ACR
Acrosin precursor (EC 3.4.21.10) [Contains: Acrosin light chain; Acrosin heavy chain] [ACRS]
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Salivary gland (SG) progenitor cells (SGPCs) maintain SG homeostasis. We have previously shown that in primary Sjögren's syndrome (pSS), SGPCs are likely to be senescent, and may underpin SG dysfunction. This study assessed the extent of senescence of cells in a SGPC niche in pSS patients' SGs, and its correlation with functional and clinical parameters. The expression of p16 and p21 as markers of senescence in both total SG epithelium and a SGPC niche (basal striated duct cells, BSD) was examined in SGs of pSS (n = 35), incomplete pSS (n = 13) (patients with some signs of pSS, but not fulfilling all classification criteria) and non-SS sicca control (n = 21) patients. This was correlated with functional and clinical parameters. pSS patient SGs contained significantly more p16 cells both in the epithelium in general (P <0.01) and in the BSD layer (P <0.001), than non-SS SGs. Significant correlations were found in pSS patients between p16 BSD cells and secretion of unstimulated whole saliva, stimulated whole saliva, stimulated parotid saliva, CD45 infiltrate, ultrasound total score and ACR-EULAR classification score, but not with EULAR Sjögren's syndrome disease activity index (ESSDAI) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) scores. Correlations with total epithelium p16 cells were weaker. Incomplete pSS patients also had increased numbers of p16 epithelial and BSD cells. Based on protein and mRNA expression, p21 appears not to play a significant role in the SG in pSS. These findings suggest SGPC senescence may be an early feature of primary Sjögren's syndrome and may contribute to defective SG function in pSS but not to systemic disease activity.
Keywords
- p16
- primary Sjögren’s syndrome
- salivary gland
- salivary gland progenitor cells
- senescence
We investigated the relationship between lower limb osteoarthritis (OA) and muscle strength and power (assessed by jumping mechanography) in UK community-dwelling older adults. We recruited 249 older adults (144 males, 105 females). OA was assessed clinically at the knee according to ACR criteria and radiographically, at the knee and hip, using Kellgren and Lawrence grading. Two-footed jumping tests were performed using a Leonardo Mechanography Ground Reaction Force Platform to assess maximum muscle force, power and Esslinger Fitness Index. Linear regression was used to assess the relationship between OA and jumping outcomes. Results are presented as β (95% confidence interval). The mean age of participants was 75.2 years (SD 2.6). Males had a significantly higher maximum relative power during lift off (mean 25.7 W/kg vs. 19.9 W/kg) and maximum total force during lift off (mean 21.0 N/kg vs. 19.1 N/kg) than females. In adjusted models, we found significant associations in males between clinical knee OA and maximum relative power [- 6.00 (CI - 9.10, - 2.94)] and Esslinger Fitness Index [- 19.3 (- 29.0, - 9.7)]. In females, radiographic knee OA was associated with total maximum power [- 2.0 (- 3.9, - 0.1)] and Esslinger Fitness Index [- 8.2 (- 15.9, - 0.4)]. No significant associations were observed for maximum total force. We observed significant negative associations between maximum relative power and Esslinger Fitness Index and clinical knee OA in males and radiographic knee OA in females. We have used novel methodology to demonstrate relationships between muscle function and OA in older adults.
Keywords
- Aging
- Jumping mechanography
- Muscle
- Osteoarthritis
- Sarcopenia
Stress-induced cell senescence, which contributes to cell cycle arrest and is independent of age, plays an important role in chronic kidney disease (CKD) progression. DcR2, as a senescent marker, exclusively expressed in senescent tubular epithelia. The objective of this study was to examine whether urinary DcR2 (uDcR2) could be a potential biomarker for tubulointerstitial fibrosis (TIF) in patients with immunoglobulin A nephropathy (IgAN). This study included 210 IgAN patients and 80 healthy volunteers, with uDcR2 levels measured using enzyme-linked immunosorbent assay. We examined the relationship among uDcR2/Cr levels, renal function, and pathological parameters, using regression analysis to identify risk factors for TIF and the area under the curve (AUC) approach to predict TIF. Renal DcR2 expression was quantified by immunohistochemistry. Co-expression of DcR2 with fibrotic markers (α-smooth muscle actin [α-SMA], collagen III) was analyzed by confocal microscopy. Levels of uDcR2/Cr were significantly higher in IgAN patients and in those with more severe TIF, compared with healthy controls. Serum DcR2 levels were similar across groups. The proportion of IgAN patients with stages 1-2 CKD and T0 was highest among those with uDcR2/Cr <130 ng/g. In contrast, the majority of those with uDcR2/Cr >201 ng/g had stages 4-5 CKD and T2. Levels of uDcR2/Cr were positively associated with urinary albumin to creatinine ratio (ACR), urinary N-acetyl-β-D-glucosaminidase (uNAG)/Cr, and TIF scores and negatively associated with estimated glomerular filtration rate (eGFR). uDcR2/Cr, uNAG, ACR, and eGFR were independent predictors for TIF, with AUC of 0.907 for uDcR2/Cr. This AUC value was higher than that observed for eGFR, uNAG/Cr, or ACR. The sensitivity and specificity of uDcR2/Cr in predicting TIF were 87.0 and 80.5%, respectively. Moreover, uDcR2/Cr levels were positively associated with the percentage of renal DcR2 expression. Renal DcR2 co-localized with α-SMA and collagen III in the kidneys of IgAN patients. Levels of uDcR2/Cr were closely associated with the severity of TIF and renal function parameters. uDcR2/Cr represents a potential biomarker for predicting TIF in IgAN patients.
MeSH Terms
- Adolescent
- Adult
- Aged
- Female
- Glomerulonephritis, IGA
- Humans
- Kidney
- Kidney Function Tests
- Male
- Middle Aged
- Nephritis, Interstitial
- Tumor Necrosis Factor Decoy Receptors
- Young Adult
Keywords
- Cell senescence
- Immunoglobulin A nephropathy
- Tubulointerstitial fibrosis
- Urinary DcR2
Chronic kidney disease (CKD) risk staging is based on estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR). However, the relationship between all-cause hospitalization risk and the current CKD staging system has not been well studied among older adults, despite a high prevalence of CKD and a high risk of hospitalization in old age. Among 4,766 participants of the Atherosclerosis Risk in Communities study, CKD was staged according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, using creatinine-based eGFR (eGFRcr) and ACR. Incidence rates of all-cause hospitalization associated with each CKD risk group were analyzed using negative binomial regression. Additionally, cause-specific hospitalization risks for cardiovascular, infectious, kidney, and other diseases were estimated. The impacts of using cystatin C-based eGFR (eGFRcys) to estimate the prevalence of CKD and risks of hospitalization were also quantified. Participants experienced 5,548 hospitalizations and 29% had CKD. Hospitalization rates per 1,000 person-years according to KDIGO risk categories were 208-223 ("low risk"), 288-376 ("moderately increased risk"), 363-548 ("high risk"), and 499-1083 ("very high risk"). The increased risk associated with low eGFR and high ACR persisted in adjusted analyses, examinations of cause-specific hospitalizations, and when CKD was staged by eGFRcys or eGFRcr-cys, a combined equation based on both creatinine and cystatin C. In comparison to eGFRcr, staging by eGFRcys increased the prevalence of CKD to 50%, but hospitalization risks remained similarly high. In older adults, decreased eGFR, increased ACR, and KDIGO risk stages based on a combination of these measures, were strong risk factors for hospitalization. These relationships were consistent, regardless of the marker used to estimate GFR, but the use of cystatin C resulted in a substantially higher prevalence of CKD than the use of creatinine. Older adults in the population with very high risk stages of CKD have hospitalization rates exceeding 500 per 1,000 person-years.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Albumins
- Albuminuria
- Creatinine
- Cystatin C
- Female
- Glomerular Filtration Rate
- Hospitalization
- Humans
- Kidney
- Male
- Middle Aged
- Quality of Life
- Regression Analysis
- Renal Insufficiency, Chronic
- Risk
Keywords
- Aging
- Albuminuria
- Chronic kidney disease
- Estimated glomerular filtration rate
- Hospitalization
The aim of this study was to investigate the associations between carotid wall shear stress (WSS) and renal function impairment (RFI) and albuminuria in aging adults. A total of 1,447 subjects aged 60 years and older with normal estimated glomerular filtration rate (eGFR ≥ 60 mL·min ·1.72 m ) and albumin/creatinine ratio (ACR < 30 mg·g ) were enrolled between April 2007 and October 2009 in the Shandong area, China. Carotid WSS was assessed at baseline, and eGFR, which is based on serum creatinine and cystatin C, and ACR were assessed at baseline and at the annual follow-up visits. After an average of 62.9 months of follow-up, the reduction in eGFR and the increase in ACR were significantly higher in the Q group than the Q group, as classified by either the interquartile of the mean WSS or the interquartile of the peak WSS after adjustment for multi-variabilities, including the average blood pressures at every annual visit and baseline eGFR and ACR. For groups classified by mean WSS, the hazard ratios (95% confidence intervals) were 3.45 (1.36-8.75, p = 0.008) in the incident RFI and 3.24 3.22 (1.37-7.57, p = 0.009) in the incident albuminuria for the Q group compared with the Q group. Similar results were observed among groups classified by peak WSS. The Q group was associated with endothelial dysfunction and inflammation with respect to the Q group as classified by mean or peak WSS. The results indicate that carotid WSS plays an important role in RFI and albuminuria progression in aging adults. Lower WSS was associated with a higher risk of RFI and albuminuria compared with higher WSS.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Albuminuria
- Carotid Arteries
- China
- Cohort Studies
- Creatinine
- Disease Progression
- Female
- Glomerular Filtration Rate
- Humans
- Male
- Middle Aged
- Renal Insufficiency
- Risk Factors
- Serum Albumin, Human
- Stress, Mechanical
Data are limited with regard to the relationship of albuminuria and major adverse cardiovascular events (MACE) in Chinese elder patients with high cardiovascular risk. We did a retrospective cohort study using Chinese elder patients with high cardiovascular risks ([i]n[/i] = 1474) to identify the association of albumin-to-creatinine ratio (ACR) and the incidence of MACE and all-cause mortality. Individuals were followed up from January, 2002 to November, 2007. The all-cause mortality and MACE, composite outcome of cardiovascular death, myocardial infarction, stroke and hospitalization of congestive heart failure were defined as primary endpoint. During the median following up of 56 months, 213 patients developed primary endpoint and 117 patients died. Patients with higher baseline urinary ACR (> 30 mg/g) experienced a nearly 2-fold of all-cause mortality and a 3-fold of heart failure hospitalization than those with lower baseline urinary ACR (≤10 mg/g).MACE, cardiovascular death, stoke and myocardial infarction showed no difference in three grades of urinary ACR (> 30 mg/g, 10 mg/g-30 mg/g, ≤10 mg/g) in this cohort. Patients above 65 years with increased ACR tended to experience higher mortality risks, and the association of increased ACR with higher hospitalization of congestive heart failure seemed to be more prominent in patients below 65 years than above 65 years. In this post hoc analysis of Chinese individuals with high cardiovascular risks, higher urinary ACR was associated with higher all-cause mortality and heart failure hospitalization. Further studies are needed to find out whether there is age-specific ACR cutoff point.
Keywords
- Aging
- Albumin-to-creatinine ratio
- Cardiovascular disease
- Heart failure hospitalization
- Mortality
In aging populations with an ever-growing burden of risk factors such as obesity, diabetes, and hypertension, chronic kidney disease (CKD) is on the rise. However, little is known about its exact prevalence among elderly adults, and often albuminuria is not included in the definition of CKD. Moreover, novel equations for the estimated glomerular filtration rate (eGFR) have recently emerged, which have not been applied comprehensively to older adults. Data on CKD awareness among the elderly are sparse. To determine the prevalence of CKD among older adults by eGFR and albumin/creatinine ratio (ACR), compare the performance of 6 established and novel eGFR formulas, explore risk factors, and determine the awareness of CKD in a large cohort of community-dwelling elderly from Germany. A total of 1,628 subjects from the Berlin Aging Study II (BASE-II) were included in this analysis (mean age 68.7 years; 51.2% female). Extensive cross-sectional data on sociodemographics, lifestyle, medication, and diagnoses were inquired during structured interviews and a medical examination, and blood and urine parameters were measured. In all, 77.1% of the subjects had hypertension, 12.4% had diabetes, and 18.3% were obese. The prevalence of CKD strongly depended on the eGFR equations used: 25.4% (full age spectrum [[[FAS]]] equation), 24.6% (Berlin Initiative Study), 23.1% (Lund-Malmö revised), 19.3% (Cockcroft-Gault), 16.4% (Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI]), and 14.7% (Modification of Diet in Renal Disease [MDRD]). Of the subjects with an eGFRFAS <60 mL/min/1.73 m2 and/or an ACR >30 mg/g, only 3.9% were aware of having CKD. Polypharmacy, age, BMI, coronary artery disease, non-HDL cholesterol, and female sex were independently associated with CKD. CKD is prevalent among older adults in Germany, but awareness is low. The FAS equation detects higher rates of CKD than MDRD and CKD-EPI, which are most widely used at present. Also, when CKD is defined based on eGFR and albuminuria, considerably more people are identified than by eGFR alone. Finally, polypharmacy is associated with an increased risk for CKD in the elderly.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Albuminuria
- Berlin
- Cross-Sectional Studies
- Female
- Glomerular Filtration Rate
- Humans
- Male
- Middle Aged
- Polypharmacy
- Prevalence
- Renal Insufficiency, Chronic
- Risk Factors
Whilst the hypothalamic-pituitary-adrenal (HPA) Axis is a major stress axis, and is necessarily perturbed in opioid dependency, and stress is a major contributor to aging mechanisms, the HPA axis has not been studied in opioid dependency in an age-dependent manner. Hypothesis - Differences in age dependent levels of HPA components. Cross-sectional comparison of general medical and opioid dependent patients (ODP, GMP). Setting - Primary Care. Patients - 51 GMC, 233 ODP. Ages 37.92 1.95 v. 37.12 0.62 years (P - N.S.) and 33.33% v. 71.67% male (p<0.0001). Intervention(s) - Measurement ACTH, cortisol and their ratio (ACR). Main Outcome Measure(s) - Pre-planned analysis ACR. Impact of immune and metabolic markers. ACTH/cortisol was a negative biomarker for age in female patients. Whilst the mean ACR were not different, the (log) ACTH/cortisol showed a positive relationship with age:sex:status (p=0.0396) and age:status (p=0.0437). The effect of addictive status was confined to hepatitis C (HCV) positive female ODP (p=0.0355), and the age:status interaction was also stronger in female HCV (p=0.0075) compared to HCV - (p=0.0667) patients. Multiple regression of ACR against age, status, ALT, CRP, and Globulins confirmed many significant interactions. ACTH/cortisol ratio interacted significantly from p=0.0008 in males and p=0.0079 in females, and in both sexes four terms included addictive status. These data establish the ACTH/cortisol ratio as a negative biomarker of aging in females, and show that this decline is more pronounced in ODP an effect which is partly related to HCV seropositivity, immune and metabolic factors. Dementias are one of the most serious health and socioeconomic issues. Multi-infarct dementia (MID) and Alzheimer´s type dementia (AD) exhibit differences in cerebrovascular blood flow velocity profiles and in presence of microemboli, detected by transcranial Doppler sonography.
MeSH Terms
- Adrenocorticotropic Hormone
- Adult
- Aging
- Alanine Transaminase
- Biomarkers
- C-Reactive Protein
- Case-Control Studies
- Cross-Sectional Studies
- Female
- Hepatitis C, Chronic
- Humans
- Hydrocortisone
- Hypothalamo-Hypophyseal System
- Male
- Opioid-Related Disorders
- Pituitary-Adrenal System
- Sex Factors
The association between low levels of vitamin D and the occurrence of chronic widespread pain (CWP) remains unclear. The aim of our analysis was to determine the relationship between low vitamin D levels and the risk of developing CWP in a population sample of middle age and elderly men. Three thousand three hundred sixty nine men aged 40-79 were recruited from 8 European centres for a longitudinal study of male ageing, the European Male Ageing Study. At baseline participants underwent assessment of lifestyle, health factors, physical characteristics and gave a fasting blood sample. The occurrence of pain was assessed at baseline and follow up (a mean of 4.3 years later) by shading painful sites on a body manikin. The presence of CWP was determined using the ACR criteria for fibromyalgia. Serum 25-hydroxyvitamin D (25-(OH) D) was assessed by radioimmunoassay. Logistic regression was used to determine the relationship between baseline vitamin D levels and the new occurrence of CWP. Two thousand three hundred thirteen men, mean age 58.8 years (SD = 10.6), had complete pain and vitamin data available and contributed to this analysis. 151 (6.5%) developed new CWP at follow up and 577 (24.9%) were pain free at both time points, the comparator group. After adjustment for age and centre, physical performance and number of comorbidities, compared to those in upper quintile of 25-(OH) D ( ≥36.3 ng/mL), those in the lowest quintile (<15.6 ng/mL) were more likely to develop CWP (Odds Ratio [OR] = 1.93; 95% CI = 1.0-3.6). Further adjustment for BMI (OR = 1.67; 95% CI = 0.93-3.02) or depression (OR = 1.77; 95% CI = 0.98-3.21), however rendered the association non-significant. Low vitamin D is linked with the new occurrence of CWP, although this may be explained by underlying adverse health factors, particularly obesity and depression.
MeSH Terms
- Adult
- Aged
- Aging
- Biomarkers
- Chronic Pain
- Europe
- Follow-Up Studies
- Humans
- Longitudinal Studies
- Male
- Middle Aged
- Pain Measurement
- Risk Factors
- Vitamin D
The aim of our study was to investigate characteristics of late-onset lupus after 65 years compared to younger ones. Patients with lupus revealed after 65 years were investigated in four French hospitals between 1985 and 2013. Patients with 4 ACR criteria or more were included. Clinical and biological characteristics, prognosis, treatment, comorbidities were described retrospectively and compared to the cohort of 1000 lupus patients of Cervera et al. Eighteen patients were included (14 women and 4 men). The most frequent features were arthritis (13/18), skin involvement (9/18). Hemolytic anemia and thrombosis were more frequently found in elderly lupus (p<0.05). During evolution, only cutaneous involvement were less frequent than in young subjects (p <0.05). Corticosteroids were often used (16/18), but iatrogenic complications were frequent (10/16). Diagnosis is difficult because of non-specific clinical features. Treatment needed a rigourous follow-up because of iatrogenic complications.
MeSH Terms
- Adolescent
- Adrenal Cortex Hormones
- Adult
- Age of Onset
- Aged
- Aged, 80 and over
- Aging
- Child
- Child, Preschool
- Female
- France
- Humans
- Lupus Erythematosus, Systemic
- Male
- Middle Aged
- Prognosis
- Retrospective Studies
- Young Adult
Keywords
- follow-up
- hematological complications
- late-onset lupus
Fibromyalgia (FM) is common in older adults suffering from mood disorders. However, clinical diagnosis of FM is challenging, particularly in psychiatric settings. We examined the prevalence of FM and the sensitivity of three simple screeners for FM. Using cross-sectional data, we evaluated three tests against the American College of Rheumatology (ACR) 1990 Criteria for the Classification of FM: a "Do you often feel like you hurt all over?" question, a pain map score, and the Pope and Hudson (PH) interview for FM. Participants were 185 community-dwelling adults ≥ 60 years old with comorbid depression and chronic low back pain evaluated at a late-life mental health clinic. Fifty three of 185 participants (29%) met the ACR 1990 FM criteria. Compared to those without FM, the FM group had more "yes" answers to the "hurt all over?" question and higher pain map scores. To reach a sensitivity of at least 0.90, the cut-off score for the pain map was 8. The sensitivity of the pain map, "hurt all over?" question, and PH criteria were 0.92 [95%CI 0.82-0.98], 0.91 [95%CI 0.79-0.97], and 0.94 [95%CI 0.843-0.99] respectively. Nearly one in three older adults suffering from depression and chronic low back pain met ACR 1990 FM criteria. Three short screening tests showed high sensitivity when compared to the ACR 1990 FM criteria. Implementation of one of the simple screeners for FM in geriatric psychiatry settings may guide the need for further diagnostic evaluation.
MeSH Terms
- Aged
- Aged, 80 and over
- Comorbidity
- Cross-Sectional Studies
- Depression
- Female
- Fibromyalgia
- Humans
- Low Back Pain
- Male
- Mass Screening
- Middle Aged
- Pain Measurement
- ROC Curve
- Severity of Illness Index
- Surveys and Questionnaires
Keywords
- aging
- depression
- fibromyalgia
- pain
- screening
The degree to which genetic or environmental factors are associated with early kidney damage among African Americans (AAs) is unknown. Among 462 AAs in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, we examined the cross-sectional association between apolipoprotein L1 (APOL1) risk variants and income with: 1) mildly reduced eGFR (<75 mL/min/1.73 m(2), creatinine-cystatin C equation) and 2) elevated urine albumin-to-creatinine ratio (ACR) (≥17 in men and ≥25 mg/g in women). High risk APOL1 status was defined by 2 copies of high-risk variants; low risk if 0 or 1 copy. Income groups were dichotomized as < $14,000/year (lowest income group) or ≥ $14,000/year. Logistic regression models were adjusted for age, sex, and % European ancestry. Overall, participants' mean age was 47 years and 16% (n = 73) had high risk APOL1 status. Mean eGFR was 99 mL/min/1.73 m(2). Mildly reduced eGFR was prevalent among 11% (n = 51). The lowest income group had higher adjusted odds (aOR) of mildly reduced eGFR than the higher income group (aOR 1.8, 95% CI 1.2-2.7). High-risk APOL1 was not significantly associated with reduced eGFR (aOR 1.5, 95% CI 0.9-2.5). Among 301 participants with ACR data, 7% (n = 21) had elevated ACR. Compared to low-risk, persons with high-risk APOL1 had higher odds of elevated ACR (aOR 3.8, 95% CI 2.0-7.3). Income was not significantly associated with elevated ACR (aOR 1.8, 95% CI 0.7-4.5). There were no significant interactions between APOL1 and income. Both genetic and socioeconomic factors may be important determinants of early kidney damage among AAs.
MeSH Terms
- African Americans
- Age Factors
- Aged
- Aging
- Albuminuria
- Apolipoprotein A-I
- Creatinine
- Cross-Sectional Studies
- Databases, Factual
- Environment
- Female
- Genetic Predisposition to Disease
- Geriatric Assessment
- Glomerular Filtration Rate
- Humans
- Income
- Logistic Models
- Male
- Middle Aged
- Prognosis
- Renal Insufficiency, Chronic
- Risk Assessment
- Sex Factors
- Socioeconomic Factors
Kidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure. Retrospective cohort study. 2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort. Ratios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively). Incident heart failure over a median follow-up of 12 years. Median values of each marker at baseline were 812 (IQR, 497-1,235)pg/mg for KIM-1:Cr, 31 (IQR, 19-56)pg/mg for IL-18:Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51). Generalizability to other populations is uncertain. Higher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude.
MeSH Terms
- Aged
- Aging
- Albuminuria
- Biomarkers
- Body Composition
- Cohort Studies
- Creatinine
- Female
- Follow-Up Studies
- Health Status
- Heart Failure
- Hepatitis A Virus Cellular Receptor 1
- Humans
- Incidence
- Interleukin-18
- Longitudinal Studies
- Male
- Membrane Glycoproteins
- Receptors, Virus
- Renal Insufficiency, Chronic
- Retrospective Studies
- Risk Factors
Keywords
- Interleukin 18 (IL-18)
- albuminuria
- cardiovascular disease (CVD)
- chronic kidney disease (CKD)
- cystatin C
- heart failure
- kidney injury molecule 1 (KIM-1)
- kidney tubular injury
- risk marker
The reference value for the urine albumin/creatinine ratio (ACR) varies between races and has not been previously validated in children. We assessed the ACR reference values and the factors that affect them in a population of healthy Chinese children. A total of 1986 healthy children (1078 males, 908 females) aged 6-19 y were enrolled. The 95th percentile of ACR was used as the normal upper limit. The associations between ACR and gender, age, body mass index (BMI), systolic blood pressure (SBP), preterm birth, intake of fruits, smoking, and geographical area were examined. The normal upper limit of ACR was 14.7 mg/g for male children and 19.8 mg/g for female children. The ACR value for girls was significantly higher than that for boys (P<0.001). ACR was inversely correlated with age (P<0.001) and positively correlated with BMI, SBP, and smoking (all P<0.01). The ACR reference value for healthy children in southwest China is approximately the same as the value for adults, but lower than that for the Western population. Age, SBP, BMI, and smoking in children influence ACR.
MeSH Terms
- Adolescent
- Aging
- Albuminuria
- Blood Pressure
- Child
- China
- Creatinine
- Female
- Humans
- Male
- Reference Values
- Renal Insufficiency, Chronic
- Sex Characteristics
- Smoking
- Young Adult
Keywords
- Children
- Chinese
- Chronic kidney disease (CKD)
- Reference value
- Urine albumin–creatinine ratio (ACR)
Musculoskeletal hand pain is common in the general population. This study aims to investigate the inter- and intra-observer reliability of two trained observers conducting a simple clinical interview and physical examination for hand problems in older adults. The reliability of applying the American College of Rheumatology (ACR) criteria for hand osteoarthritis to community-dwelling older adults will also be investigated. Fifty-five participants aged 50 years and over with a current self-reported hand problem and registered with one general practice were recruited from a previous health questionnaire study. Participants underwent a standardised, structured clinical interview and physical examination by two independent trained observers and again by one of these observers a month later. Agreement beyond chance was summarised using Kappa statistics and intra-class correlation coefficients. Median values for inter- and intra-observer reliability for clinical interview questions were found to be "substantial" and "moderate" respectively [median agreement beyond chance (Kappa) was 0.75 (range: -0.03, 0.93) for inter-observer ratings and 0.57 (range: -0.02, 1.00) for intra-observer ratings]. Inter- and intra-observer reliability for physical examination items was variable, with good reliability observed for some items, such as grip and pinch strength, and poor reliability observed for others, notably assessment of altered sensation, pain on resisted movement and judgements based on observation and palpation of individual features at single joints, such as bony enlargement, nodes and swelling. Moderate agreement was observed both between and within observers when applying the ACR criteria for hand osteoarthritis. Standardised, structured clinical interview is reliable for taking a history in community-dwelling older adults with self reported hand problems. Agreement between and within observers for physical examination items is variable. Low Kappa values may have resulted, in part, from a low prevalence of clinical signs and symptoms in the study participants. The decision to use clinical interview and hand assessment variables in clinical practice or further research in primary care should include consideration of clinical applicability and training alongside reliability. Further investigation is required to determine the relationship between these clinical questions and assessments and the clinical course of hand pain and hand problems in community-dwelling older adults.
MeSH Terms
- Aged
- Aging
- Disability Evaluation
- Female
- Hand
- Humans
- Interviews as Topic
- Male
- Middle Aged
- Musculoskeletal Diseases
- Pain Measurement
- Physical Examination
- Reproducibility of Results
- Surveys and Questionnaires
In order to assess age-dependence of susceptibility to acrylamide (ACR)-induced neural and testicular toxicity, 3- and 7-week-old male SD rats were given ACR at 0, 50, 100, or 200 ppm in the drinking water for 4 weeks, and the nervous and male reproductive systems were examined histopathologically. Testicular genotoxicity was evaluated with the comet assay and the micronucleus (MN) test. Glutathione S-transferase (GST) activity and glutathione (GSH) content in the liver and testis were also measured. In both young and adult animals, neurotoxicity was evident from 100 ppm and increased in proportion to ACR intake per body weight. In the testis, marked degeneration and exfoliation, mainly of spermatids, were observed from 100 ppm limited to young animals. The comet assay revealed ACR to significantly induce DNA damage from 100 ppm in both life stages, while MNs were found only in young rats from 100 ppm. The level of GST activity in the testis of young rats at the end of experiment was significantly lower than that of adult animals, regardless of the ACR treatment. There were no life stage-related differences in GSH contents in the liver and testis. These results suggest that susceptibility to neurotoxicity might not differ between young and adult rats when exposure levels are adjusted for body weight. Regarding testicular toxicity, young animals around puberty proved more susceptible than adult animals, possibly due to their lower level of testicular GST activity than that in adult animals.
MeSH Terms
- Acrylamide
- Aging
- Animals
- Body Weight
- Cerebellum
- Comet Assay
- Dose-Response Relationship, Drug
- Glutathione
- Glutathione Transferase
- Immunohistochemistry
- Liver
- Male
- Micronuclei, Chromosome-Defective
- Micronucleus Tests
- Neurotoxicity Syndromes
- Rats
- Rats, Sprague-Dawley
- Sciatic Nerve
- Testis
- Trigeminal Ganglion
As it is unclear, whether or not, urinary albumin excretion (UAE) differs between patients classified as latent autoimmune diabetes in adults (LADA) and other forms of diabetes, our study aimed to investigate the distribution of the albumin-to-creatinine ratio (ACR) in LADA compared with those in the "classical" types 1 (T1D) and 2 (T2D) diabetes. We used data from the Nord-Trøndelag Health Study (HUNT) (n=64,931) of 1995-1997. ACR (mg/mmol) was measured in three urine samples from all diabetic patients (n=1525) and from 5% of the non-diabetic study population (n=2104). We calculated the geometric means and 95% confidence intervals (CI) using a general linear model. The unadjusted mean ACR in LADA was similar to that in T2D (1.45, CI: 1.23-1.71 vs 1.41, CI: 1.33-1.49, respectively) but was significantly higher than those in T1D (0.99, CI: 0.83-1.19; P=0.002) and non-diabetics (0.72, CI: 0.69-0.74; P<0.001). These results remained similar even after multiple adjustments. In this cross-sectional study, the ACR in LADA and in T2D were similar and higher than in T1D. This similarity between LADA and T2D makes it unlikely that the autoimmune processes that operate in LADA promote albuminuria.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Albuminuria
- Autoimmune Diseases
- Body Mass Index
- Confidence Intervals
- Creatinine
- Cross-Sectional Studies
- Diabetes Mellitus
- Diabetic Nephropathies
- Female
- Glycated Hemoglobin A
- Health Surveys
- Humans
- Linear Models
- Male
- Middle Aged
- Norway
- Odds Ratio
- Prevalence
- Sex Factors
- Surveys and Questionnaires
- Young Adult
This study investigated the relationship of brain white matter (WM) lesions affecting specific neural networks with decreased mobility in ninety-nine healthy community-dwelling subjects ≥75 years old prospectively enrolled by age and mobility status. We assessed lesion burden in the genu, body and splenium of corpus callosum; anterior, superior and posterior corona radiata; anterior and posterior limbs of internal capsule; corticospinal tract; and superior longitudinal fasciculus. Burden in the splenium of corpus callosum (SCC) demonstrated the highest correlation particularly with walking speed (r=0.4, p<10(-4)), and in logistic regression it was the best regional predictor of low mobility performance. We also found that independent of mobility, corona radiata has the largest lesion burden with anterior (ACR) and posterior (PCR) aspects being the most frequently affected. The results suggest that compromised inter-hemispheric integration of visuospatial information through the SCC plays an important role in mobility impairment in the elderly. The relatively high lesion susceptibility of ACR and PCR in all subjects may obscure the importance of these lesions in mobility impairment.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Brain
- Female
- Gait
- Humans
- Image Processing, Computer-Assisted
- Logistic Models
- Magnetic Resonance Imaging
- Male
- Nerve Fibers, Myelinated
- Prospective Studies
- Walking
The reference value of urine albumin-creatinine ratio (ACR) has racial disparities. The ACR reference value in a healthy Beijing population is reported. A reference Beijing population was sampled via a multistage, clustered complex sampling method. By excluding subjects with self-reported kidney disease, hypertension, diabetes, dyslipidemia, cardiovascular disease, obesity or underweight condition, overt proteinuria, hematuria, or pyuria, as well as those with an estimated glomerular filtration rate (eGFR) > 200ml/min/1.73m2 or < 60ml/min/1.73m2, apparently healthy subjects (1260 males, 2305 females, aged 18-84y) were selected to be included in the current analysis. Urine albumin was measured using the immunoturbidimetic method, creatinine was measured using Jaffe's kinetic method on a morning spot-urine sample, and ACR was calculated. The 95th percentile of ACR was used as the normal upper limit. The association between ACR and each of gender, age, systolic blood pressure, body mass index, serum glucose, lipids, and eGFR was examined. The normal upper limit of ACR was 14mg/g (1.58mg/mmol) for males and 20mg/g (2.26mg/mmol) for females. Females had higher ACR values than males, and age, systolic blood pressure, and eGFR were positively correlated with ACR. The ACR reference value in the healthy Beijing population is lower than that of the Western population. Age, systolic blood pressure, and eGFR were found to correlate with ACR.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Albuminuria
- Blood Pressure
- China
- Creatinine
- Female
- Glomerular Filtration Rate
- Humans
- Kidney Failure, Chronic
- Lipids
- Male
- Middle Aged
- Reference Standards
- Reproducibility of Results
- Sex Characteristics
- Young Adult
This study aimed to evaluate the prevalence of chronic kidney disease (CKD) and the risk factors associated with CKD among Chinese patients diagnosed with type 2 diabetes aged over 30 in downtown Shanghai and to assess the relationship between CKD and diabetic retinopathy (DR). We investigated 1039 Chinese patients diagnosed with type 2 diabetes aged over 30 by randomized cluster sampling in downtown Shanghai, and 1009 patients in this study were analyzed based on data integrity. Body measurements including height, weight, waist circumference and hip circumference, resting blood pressure, fasting blood measures, and urinary albumin-to-creatinine ratio (ACR), as well as the digitally stored fundus images, were investigated. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault equation. The prevalence of CKD was calculated, and the risk factors associated with CKD were evaluated using stepwise logistic regression. The relationship between CKD and DR was evaluated using Spearman correlation and the chi-square test. The following were the results found in this study: (a) The prevalence rate of CKD (Stages 1-5) was 63.9% in Chinese patients diagnosed with type 2 diabetes, 8.8% in those with CKD Stage 1, 22.3% in those with CKD Stage 2, and 32.8% in those with CKD Stages 3-5 (GFR<60 ml/min/1.73 m(2)). The prevalence of CKD increased with age. (b) CKD patients were older and had higher duration of diabetes, systolic blood pressure, urea nitrogen, uric acid, creatinine, and ACR of the first urine than those without CKD. (c) Male patients had a higher percentage of CKD Stages 3-5, and female patients had a higher percentage of CKD Stages 1-2. (d) CKD was significantly associated with duration of diabetes, older age, systolic blood pressure, and serum urea nitrogen based on logistic regression analysis. (e) Of the patients without CKD, 15.6% had DR, and of those with CKD, 27.6% had DR. The decrease in GFR was significantly correlated with DR after controlling for sex, age, and albuminuria staging. The high prevalence of CKD observed in Chinese patients diagnosed with type 2 diabetes aged over 30 in downtown Shanghai was similar to that in Western patients, and the cause of CKD is likely to be any of the following: type 2 diabetes, IgA nephropathy, hypertension, or any combination of these. The screening program for GFR in type 2 diabetic patients should be performed even on those with normoalbuminuria. The decrease in GFR might predict the occurrence of DR among patients diagnosed with type 2 diabetes.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Albuminuria
- Body Mass Index
- China
- Cross-Sectional Studies
- Diabetes Mellitus, Type 2
- Diabetic Nephropathies
- Female
- Glycated Hemoglobin A
- Humans
- Male
- Middle Aged
- Prevalence
- Smoking
To analyse the proportion of individuals in the general population over age 50 who do not meet American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA) remission, and OMERACT criteria for minimal disease activity (MDA), and to compare results to RA patients. A self-report questionnaire was completed by 1400 community control subjects and 1705 RA patients, including the Health Assessment Questionnaire (HAQ), gradual rating scales for pain, fatigue and global health, duration of morning stiffness and painful joints. The prevalence of 4/6 ACR remission criteria and 4/7 OMERACT criteria for MDA was analysed in community control subjects and patients with RA over age 50. For ACR criteria, 76% of control subjects reported painful joints, 37% morning stiffness, 62% pain and 66% fatigue, vs 94, 65, 84 and 84% of patients with RA. MDA criteria were not met by 64% of control subjects for painful joints, 38% for pain, 45% for global health and 18% for HAQ, vs 89, 60, 69 and 52% of RA patients. The four ACR remission criteria were met by only 15% of control subjects over age 50 and 3% of RA patients, and MDA criteria by 28% of controls and 7% of patients. The majority of community population over age 50 did not meet criteria for remission or MDA in RA. Although a self-report format may differ from results involving an assessor, the current criteria may not be accurate to identify remission or MDA in people with RA who are older than age 50.
MeSH Terms
- Aged
- Aging
- Arthritis, Rheumatoid
- Female
- Health Status Indicators
- Humans
- Male
- Middle Aged
- Pain Measurement
- Remission Induction
- Severity of Illness Index
- Treatment Outcome
The ratio between urinary albumin concentration (UAC) and urinary creatinine concentration (UCC) is widely used to estimate renal involvement. We examined how UAC and UCC associate with each other, with other risk factors, and with diabetic complications in a population-based sample of Type 2 diabetic patients. A freshly voided morning urine specimen was provided by 1,284 consecutive, newly diagnosed diabetic patients aged 40 years or over in general practice. Albumin was measured by a polyethyleneglycol radioimmunoassay and creatinine by a modified Jaffe method. In a multivariate model including UAC, UCC, age, sex, HbA1c, and urinary glucose concentration, UAC increased with both age (P=.042) and HbA1c (P=.014), while UCC decreased (P<.001 and P<.001, respectively). In two regression models, the prevalence of diabetic retinopathy (P<.001) and relatively high resting heart rate (P<.001) increased with increasing UAC but decreased with increasing UCC (P=.002 and P=.005, respectively). The use of albumin/creatinine ratio (ACR) may introduce bias of unpredictable size and direction in comparisons of ACR with variables that are associated with UCC in their own right. In daily clinical practice, renal involvement in the individual patient can be estimated reliably with UAC or ACR measured in a freshly voided morning urine specimen, especially when considered together. However, the associations of the combined measure ACR should be interpreted with great caution in clinical and epidemiological research.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Albuminuria
- Creatinine
- Diabetes Mellitus, Type 2
- Diabetic Retinopathy
- Female
- Glycated Hemoglobin A
- Glycosuria
- Humans
- Male
- Middle Aged
- Multivariate Analysis
- Peripheral Vascular Diseases
- Regression Analysis
Recent studies suggest that patients with active rheumatoid arthritis (RA) have adverse serum lipid profiles. We examined lipid profiles among individuals with RA in a national sample of persons aged 60 years and older. Using data from 4862 participants (2379 men and 2483 women) aged 60 years and older in the Third National Health and Nutrition Examination Survey (1988-94), we examined lipid profiles among participants with RA who met the American College of Rheumatology (ACR) 1987 criteria and who were not taking glucocorticoids or disease modifying antirheumatic drugs (DMARD). Participants with RA had lower high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I concentrations than those without RA. After adjusting for age and sex, the differences in HDL-C level between those with and those without RA were 2.5 mg/dl (95% CI 0.8 to 4.9) using > or = 3 of the ACR criteria (n of RA cases = 104) and 8.8 mg/dl (95% CI 3.2 to 14.3) using > or = 4 criteria (n of RA cases = 26). Adjusting for age, sex, race, education, smoking status, body mass index, alcohol consumption, physical activity, dietary factors, and other potential confounders attenuated the differences slightly. The multivariate difference in serum apolipoprotein A-I levels between those with and those without RA was 4.5 mg/dl (95% CI -0.8 to 9.8) using > or = 3 ACR criteria and 13.6 mg/dl (95% CI 3.2 to 24.1) using > or = 4 criteria. All individual RA disease activity measures tended to have inverse relations with HDL-C levels, but significant inverse associations were present only with the following variables: C-reactive protein [[[CRP]]; multivariate difference per 1 mg/dl of CRP, -1.3 mg/dl (95% CI -2.0 to -0.5)], presence of hand arthritis [-2.6 mg/dl (95% CI -5.0 to -0.2)], and positive rheumatoid factor [-3.4 mg/dl (95% CI -5.5 to -1.3)]. These national survey data indicate that RA not treated with DMARD or glucocorticoids is associated with adverse lipid profiles characterized by lower HDL-C and apolipoprotein A-I levels in persons aged > or = 60 years.
MeSH Terms
- Aged
- Aging
- Apolipoprotein A-I
- Arthritis, Rheumatoid
- C-Reactive Protein
- Case-Control Studies
- Cholesterol
- Cholesterol, HDL
- Female
- Hand
- Humans
- Lipids
- Male
- Multivariate Analysis
- Nutrition Surveys
- Rheumatoid Factor
- United States
Development of microalbuminuria increases the risk for cardiovascular disease (CVD) in type 2 diabetes. The nature of this relationship is unclear but may involve arterial stiffness, an independent risk marker for CVD mortality. Aortic pulse wave velocity (Ao-PWV) and albumin creatinine ratio (ACR) were measured in 134 consecutive patients with type 2 diabetes without overt renal impairment (serum creatinine <150 micromol/L). ACR ranged from 0.2 to 153 mg/mmol. Patients with raised ACR (>/=3 mg/mmol) had higher Ao-PWV, poorer diabetic control, and higher pulse pressure (PP) and systolic BP (SBP) (all P < 0.05) than those with normal ACR. The closest univariate associations of Ao-PWV were positively with age, duration of diabetes, SBP, PP, ACR, and insulin treatment and negatively with GFR and weight (all P < 0.01). In a multiple linear step-down regression analysis, the significant predictors of Ao-PWV were age, SBP or PP, duration of diabetes, gender, number of antihypertensive medications, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which together explained 55% of the variance of Ao-PWV. When ACR was offered in place of arterial pressure to a separate model, ACR emerged as a significant predictor of Ao-PWV. After age adjustment, patients with lower, below median GFR had higher Ao-PWV than those with GFR above the median (P = 0.043). In patients with type 2 diabetes without overt renal impairment, raised ACR is associated with higher Ao-PWV, a relationship most likely mediated by raised BP. The association of Ao-PWV with reduced GFR suggests that even modest renal dysfunction may affect the viscoelastic properties of large arteries.
MeSH Terms
- Adult
- Aged
- Aging
- Albuminuria
- Antihypertensive Agents
- Aorta
- Blood Flow Velocity
- Blood Pressure
- Creatinine
- Diabetes Mellitus, Type 2
- Female
- Glomerular Filtration Rate
- Humans
- Linear Models
- Male
- Middle Aged
- Pulse
- Sex Factors
- Time Factors
The effects of proprioceptive neuromuscular facilitation (PNF) stretch techniques on older adults are unknown and the physiological changes associated with aging may lead to differential responses to PNF stretching. Therefore, the purpose of this experiment was to examine the effects of PNF stretch techniques and EMG activity in older adults. Three PNF stretch techniques: static stretch (SS), contract-relax (CR), and agonist contract-relax (ACR) were applied to 24 older adults aged 50-75 years. The subjects were tested for knee extension range of motion (ROM) and knee flexor muscle EMG activity. The results indicated that ACR produced 29-34% more ROM and 65-119% more EMG activity than CR and SS, respectively. It was concluded that PNF stretch techniques can increase ROM in older adults. However, a paradoxical effect was observed in that PNF stretching may not induce muscular relaxation even though ROM about a joint increases. Care should be taken when applying PNF stretch techniques to older adults due to age-related alterations in muscle elasticity.
MeSH Terms
- Aged
- Aging
- Electromyography
- Humans
- Knee Joint
- Male
- Middle Aged
- Muscle Contraction
- Muscle Relaxation
- Muscle, Skeletal
- Physical Therapy Modalities
- Range of Motion, Articular
We sought to determine the relationship between age, and other clinical characteristics such as parity, oestrogen use, dietary factors and menstrual history on breast density in Jamaican women. A retrospective study was done of 891 patients who attended the breast imaging unit. The clinical characteristics were extracted from the patient records. Mammograms were assessed independently by two radiologists who were blinded to the patient clinical characteristics. Breast densities were assigned using the American College of Radiology (ACR) classification. The concordance between the ACR classification of breast density between the two independent radiologists was 92% with k = 0.76 (SE = 0.02, P < 0.001). Women with low breast density were heavier (81.3 /- 15.5 kg vs 68.4 /- 14.3 kg, P < 0.0001, mean /- standard deviation (SD)) and more obese (body mass index (BMI), 30.3 /- 5.8 kg m(-2) vs 26.0 /- 5.2 kg m(-2), P < 0.0001). Mammographic breast density decreased with age. The age adjusted odds ratios (ORs) for predictors significantly related to high breast density were parity, OR = 0.79 (95%CIratio0.71, 0.88), weight, OR = 0.92 (95% CIratio0.91, 0.95), BMI, OR = 0.83 (95% CIratio0.78, 0.89), menopause, OR = 0.51 (95% CIratio0.36, 0.74) and a history of previous breast surgery, OR 1.6 (95% CIratio1.1, 2.3). The rate decline of breast density with age in our population was influenced by parity and body composition.
MeSH Terms
- Adult
- African Americans
- Aged
- Aging
- Anthropometry
- Body Mass Index
- Breast
- Estrogen Replacement Therapy
- Female
- Humans
- Jamaica
- Mammography
- Middle Aged
- Obesity
- Odds Ratio
- Parity
- Retrospective Studies
Our purpose was to determine the 5-year longitudinal effects of running and aging on the development of radiographic and clinical osteoarthritis (OA) of the knees, hands and lumbar spine. Thirty-five running subjects and 38 controls, with a mean age of 63 years, were matched for age ( /- 2 years), years of education, and occupation; 33 matched pairs were constructed. All subjects underwent rheumatologic examination, completed questionnaires, and had radiographs taken of the hands, lateral lumbar spine, and knees in 1984 and in 1989. Five year radiographic results for both the runner and control groups showed OA progression for the knees, hands, and lumbar spine. In 1989, 10 (13%) of the 73 subjects fit American College of Rheumatology (ACR) criteria for clinical OA of the hand, and 9 subjects (12%) fit ACR criteria for OA of the knee. In summary, running did not accelerate the development of radiographic or clinical OA of the knees, but with aging, 13% of all subjects developed OA of the hands and 12% of all subjects developed OA of the knees.
MeSH Terms
- Aged
- Aging
- Cohort Studies
- Female
- Hand
- Humans
- Knee
- Longitudinal Studies
- Lumbar Vertebrae
- Male
- Middle Aged
- Osteoarthritis
- Radiography
- Risk Factors
- Running
- Surveys and Questionnaires
- Time Factors
About 80% to 90% of females are informative for X-inactivation/methylation analysis with the probe M27 beta, which would therefore seem attractive in assessing clonality in hematologic cell populations. Eighteen acute lymphoid or myeloid leukemias, three chronic lymphocytic leukemias, and three chronic myelogenous leukemias as well as 12 malignant non-Hodgkin's lymphomas mostly showed extremely skewed clonal X inactivation (median allelic cleavage ratio [[[ACR]]] of unmethylated/inactive M27 beta alleles was 50, range 1 to 100) or hypermethylation of both alleles. Two lymphomas showed random M27 beta X inactivation but clonal antigen-receptor gene rearrangements. In normal peripheral blood leukocytes from 105 healthy females aged 2 to 96 years, the median ACR was 2 (range 1 to 100). Thus, it was significantly lower than in the leukemias (P = .0001, Mann-Whitney test), but extremely skewed patterns (ACR > 10.8, ie, > 80th percentile) were seen not only in the leukemias but also in 21/105 samples (20%) of normal leukocytes, and significantly more frequent in a population of elderly women (aged 75 to 96 years) compared with healthy children (aged 2 to 8 years) and younger women (aged 20 to 58 years) (P = .00125; chi 2 test). We conclude that in a population of cells derived from the hematopoietic system where clonality is uncertain, skewed M27 beta patterns are not reliable indicators for the presence of a clonal neoplastic disorder. The basis for severe X-inactivation skewing is unclear at present, but this finding raises interesting questions regarding the composition of the hematopoietic stem cell pool.
MeSH Terms
- Acute Disease
- Adult
- Aged
- Aged, 80 and over
- Aging
- Base Sequence
- Blotting, Southern
- Child
- Child, Preschool
- Chronic Disease
- Cloning, Molecular
- DNA Primers
- DNA Probes
- Female
- Hematopoiesis
- Humans
- Leukemia
- Leukocytes
- Lymphoma, Non-Hodgkin
- Methylation
- Middle Aged
- Molecular Sequence Data
- Polymerase Chain Reaction
- Polymorphism, Genetic
- Reference Values
- Restriction Mapping
- X Chromosome