CIC
Protein capicua homolog [KIAA0306]
Publications[править]
This study sheds light on cell inactivating processes with focus on the phenomenon of cell-in-cell (CIC). Cell-in-cell describes a cell process where one cell is being engulfed by another non-professional phagocyte. We determined frequency and prognostic impact of CIC structures (CICs) as well as of senescent and apoptotic cells in head and neck squamous cell carcinomas (HNSCC). These different forms of cell inactivation as well as the proportion of proliferating and tumor cells were assessed in 169 pre-radiochemotherapy biopsies and 32 post-therapy tumor resections by immunohistochemistry of tissue microarrays. Four consecutive cancer sections were stained with antibodies specific for E-cadherin for CIC detection, cleaved caspase-3 for apoptosis, H3K9Me for senescence and Ki67 as a proliferation marker. Positive events were quantified in corresponding tumor areas. CICs were found in 55.5%, senescent cells in 67.1% and apoptotic cells in 93.3% of samples. While no prognostic impact of apoptotic and senescent cells was observed, CICs turned out to significantly influence overall-survival (p = 0.016) with a lack of CICs being prognostically beneficial. There was no correlation between CICs and apoptosis and 98.9% of CICs were negative for cleaved caspase-3. CIC formation is a frequent event in HNSCC and a superior predictive marker compared to senescence and apoptosis. Independence of CIC and apoptosis and the adverse prognosis associated with numerous CICs lead to the assumption that CICs might take up necrotic rather than apoptotic cells preventing an adequate antitumoral immune response that would otherwise be initiated by necrotic cells through damage-associated molecular pattern molecules.
MeSH Terms
- Apoptosis
- Carcinoma, Squamous Cell
- Cellular Senescence
- Cohort Studies
- Female
- Head and Neck Neoplasms
- Humans
- Male
- Middle Aged
- Neoplasm Grading
- Neoplasm Staging
- Phagocytosis
- Prognosis
Keywords
- Apoptosis
- Cell death
- Cell-in-cell
- HNSCC
- Proliferation
- Senescence
Group I metabotropic glutamate receptors (mGluRs) are linked to intracellular Ca(2 ) signalling and play important roles related to synaptic plasticity and development. In neurons from the central nucleus of the inferior colliculus (CIC), the activation of these receptors evokes large [Ca(2 ) ](i) responses. By using optical imaging of the fluorescent Ca(2 ) -sensitive dye Fura-2, we have explored which [Ca(2 ) ](i) routes are triggered by group I mGluR activation in young CIC neurons and whether mGluR-induced [Ca(2 ) ](i) responses are regulated during postnatal development. In addition, real-time quantitative RT-PCR was used to study the developmental expression of both group I mGluR subtypes, mGluR1 and mGluR5. Application of DHPG, a specific agonist of group I mGluRs, was used on CIC slices from young rats to elicit [Ca(2 ) ](i) responses. A majority of responses consisted of an initial thapsigargin-sensitive Ca(2 ) peak, related to store depletion, followed by a plateau phase, sensitive to the store-operated Ca(2 ) entry blocker 2-APB. During postnatal development, from P6 to P17, DHPG-induced [Ca(2 ) ](i) responses changed. The largest Ca(2 ) responses were reached at P6, whereas lower peak and plateau responses were found after hearing onset, at P13-P14 and P17. qRT-PCR analysis also revealed important differences in the expression of both mGluR1 and mGluR5 subtypes during development, with the highest levels of both subtypes at P7 and a developmental decrease of both transcripts. Our results suggest both intra- and extracellular routes for [Ca(2 ) ](i) increases linked to group I mGluRs in CIC neurons and a regulation of group I mGluR activity and expression during auditory development.
MeSH Terms
- Aging
- Animals
- Auditory Cortex
- Calcium Channels
- Calcium Signaling
- Cell Membrane
- DNA, Complementary
- Down-Regulation
- In Vitro Techniques
- Inferior Colliculi
- Inositol 1,4,5-Trisphosphate
- Male
- Mesencephalon
- Methoxyhydroxyphenylglycol
- Neurons
- Polymerase Chain Reaction
- RNA
- Rats
- Rats, Wistar
- Receptors, Metabotropic Glutamate
- Signal Transduction
The expanding number of Americans living with chronic illness necessitates educating future physicians about chronic illness care. Weill Cornell Medical College's Chronic Illness Care in the Home Setting Program (CIC-HSP), a mandatory part of the primary care clerkship, exposes medical students to persons with chronic illness via a half day of house calls with a geriatrics team. The investigators sought to qualitatively assess the effect of the CIC-HSP on medical students and recent medical graduates. Fifty-two prospective participants were approached, and 50 (96%) with varying training levels and time since completing the program were interviewed. Most respondents (63%) found that the home visits taught them important approaches to caring for the chronically ill, such as individualizing care to meet patients' individual needs and improving quality of life as a goal of care. Students remarked that the experience enhanced their empathy (18%) and sensitivity (20%) toward chronically ill patients and increased their appreciation for chronic illness care (35%). Many participants reported that patients were more empowered in the home (55%) and perceived greater rapport and warmth between the doctor and patient (57%) in the home (vs office) setting. The vast majority of recent medical graduates (84%) related that this educational exposure continued to positively influence their approach to patient care. A home visit experience with a geriatrics team can help foster medical students' understanding of the psychosocial and medical aspects of chronic illness, teach relevant approaches to patient care, and improve students' attitudes toward caring for the chronically ill.
MeSH Terms
- Adult
- Attitude of Health Personnel
- Chronic Disease
- Female
- Geriatrics
- House Calls
- Humans
- Interviews as Topic
- Male
- Physician-Patient Relations
- Students, Medical
In this study, the effects of infestation (with Schistosoma haematobium or hookworm) during host ageing on the serum levels of circulating immune complexes (CIC), C3, IgG, IgA and IgM were examined in residents of Omi dam area of Kogi state, Nigeria. S. haematobium-infested and hookworm-infested individuals showed no significant alteration in the levels of CIC, C3, IgG, IgA and IgM in comparison with controls. These levels were the same in infested subjects and controls even when the patients were pooled. Infested old people had the same concentrations of serum CIC, C3 IgG and IgM in comparison with infested young people but IgA levels were higher in the aged group (t=2.100; P<0.05); and were significantly correlated with age (r=0.301; P<0.05). No significant increase in CIC levels with rising age (r=0.123; P>0.20) was observed in the overall population of infested subjects; and infestation in old age did not alter CIC, C3, IgG, IgA and IgM levels in comparison with uninfested young people. For the uninfested, IgG, IgA and IgM values were similar in the aged and the young but the levels of CIC were higher (t=2.156; P<0.05; r=0.280; P<0.05) and C3 lower (t=3.313; P<0.01; r=-0.236; P>0.10) in the aged. The results of this study suggest that the elevated CIC levels found in old people is age-related; and that the contribution of parasitic infestation to these raised levels is uncertain.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Ancylostomatoidea
- Animals
- Antibody Formation
- Antigen-Antibody Complex
- Child
- Complement C3
- Female
- Humans
- Immunoglobulins
- Male
- Middle Aged
- Nigeria
- Schistosoma haematobium
Temporal processing deficits in the central auditory system of aged subjects are apparent from animal and human studies but could be due to peripheral hearing loss. Sequential paired tone stimuli reveal age-related changes in temporal processing properties of neurons in the central nucleus of the inferior colliculus (CIC). A greater proportion of CIC neurons exhibit suppression of excitability following pure tone stimulation in 20 month old ("aged") compared with 3-6 month "young" Long Evans rats. The duration (time constant of exponential curve fit to recovery of excitability) of suppression is also increased in aged compared with young rats, with more neurons exhibiting suppression with time constants over 100 ms. The time course of post-stimulatory suppression is not dependent on the duration or intensity of preceding stimuli and is not correlated with either initial magnitude of suppression or best frequency of IC neurons. Although the increase in unit thresholds is greater for high-frequency units in old animals, the largest post-stimulatory suppression changes occur in neurons with best frequencies of less than 10 kHz. Since the increase in duration of post-stimulatory suppression is not correlated with peripheral hearing loss, the difference is likely attributed to central auditory neuron changes in aging. In addition, the proportion of IC neurons exhibiting other temporal patterns of excitability (post-stimulatory facilitation and delayed-maximum excitability) is reduced in aged animals. Therefore, temporal processing of acoustic information is significantly altered in aged animals. The greater post-stimulatory suppression of excitability, reduced facilitation, and delayed facilitation is expected to reduce and alter the encoded information passing from the brainstem through the IC to higher structures. These changes correlate with reduced speech understanding in noise, elevated thresholds in noisy conditions, and reduced temporal processing capabilities in the elderly.
MeSH Terms
- Acoustic Stimulation
- Aging
- Animals
- Ear
- Functional Laterality
- Inferior Colliculi
- Male
- Neurons
- Rats
- Rats, Long-Evans
- Reaction Time
- Sensory Thresholds
- Time Perception
The inferior colliculus (IC) is a processing center for monaural and binaural auditory signals. Many units in the central nucleus of the inferior colliculus (CIC) respond to amplitude and frequency modulated tones, features found in communication signals. The present study examined potential effects of age on responses to sinusoidally amplitude modulated (SAM) tones in CIC and external cortex of the inferior colliculus (ECIC) units in young and aged F344 rats. Extracellular recordings from 154 localized single units of aged (24 month) rats were compared to recordings from 135 IC units from young adult (3 month) animals. SAM tones were presented at 30 dB above threshold. Comparisons were made between CIC and ECIC regarding the percentage of units responding to SAM stimuli, the relationship between SAM responsiveness and temporal response patterns, maximum discharge rates and maximum modulation gains, shapes of rate transfer functions and synchronization modulation transfer functions (MTFs) in response to SAM tones. Sixty percent of units in young and aged rat IC were selectively responsive to SAM stimuli. Eighty-one percent of units classified as onset temporal response patterns were not tonically responsive to SAM stimuli. Median maximum discharge rate in response to SAM tones was 17.6/s in young F344 rats; median maximum modulation gain was 3.85 dB. These measurements did not change significantly with age. Thirty-seven percent of young rat units displayed bandpass MTFs and 53% had lowpass MTFs. There was a significant age-related shift in the distribution of MTF shapes in both the CIC and ECIC. Aged animals showed a lower percentage of bandpass functions and a higher percentage of lowpass functions. Age-related changes observed in SAM coding may reflect an altered balance between excitatory/inhibitory neurotransmitter efficacy in the aged rat IC, and/or possibly a change in the functional dynamic range of IC neurons.
MeSH Terms
- Acoustic Stimulation
- Aging
- Animals
- Evoked Potentials, Auditory
- Humans
- Inferior Colliculi
- Male
- Neurons
- Presbycusis
- Rats
- Rats, Inbred F344
- gamma-Aminobutyric Acid
The investigations were held on the calves of the red steppe breed and its cross-breeds with Holsteins [correction of Golshtins] in critical age periods (2, 6, 17 months and in heifers). It is established, that the immune protection of the cattle organism at the early stages of ontogenesis (2 months) is provided on the whole at the expense of the phagocytosing activity of the blood neutrophils. T- and B-systems of the immunity are formed with age. At the age of 2 and 6 months the cross-bred calves yield to pure-bred calves in majority of the indices of the immune status, though the trustworthy difference is marked only in the indices of T-helpers and CIC. By 17 month the cross-bred heifers of the first generation trustworthy excel the red steppe heifers in the quantity of T-active lymphocytes and yield to the latter in the contents of CIC in the blood. The cross-bred heifers of the second generation excel the heifers of the same age in many indices of the immune status but the difference is not trustworthy. The heifers of the all three groups have no trustworthy differences.
MeSH Terms
- Aging
- Animals
- B-Lymphocytes
- Cattle
- Crosses, Genetic
- Female
- Immunity, Cellular
- Neutrophils
- Phagocytosis
- Reference Values
- T-Lymphocytes
Circulating immune complexes (CIC) in the sera from 45 clinically healthy cats and 23 feline immunodeficiency virus (FIV) infected cats were measured by an immune adherence hemagglutination (IAHA) method. The level of CIC in the sera from FIV sera-negative healthy cats was 47.2 /- 47.3 micrograms/ml when expressed as heat aggregated feline IgG equivalent value in IAHA reactivity. On the other hand, the level of CIC in the sera from FIV infected cats was 757.4 /- 910.5 micrograms/ml, which was significantly higher than that of healthy ones. CIC levels of 11 symptomatic cats and 12 asymptomatic ones were 837.8 /- 1138.2 micrograms/ml and 683.0 /- 684.2 micrograms/ml, respectively. These results showed that IAHA method was reliable to detect CIC levels of cat sera and that CIC levels in the sera of cats infected with FIV were higher than those of healthy ones.
MeSH Terms
- Aging
- Animals
- Antigen-Antibody Complex
- Cats
- Feline Acquired Immunodeficiency Syndrome
- Female
- Hemagglutination Tests
- Immunodeficiency Virus, Feline
- Immunoglobulin G
- Male
- Reference Values
1. Presbycusis, age-related hearing loss, is an ever increasing problem in our aging society. It involves changes in both the peripheral and central portions of the auditory system. The inferior colliculus (IC) has been shown to display age-related changes including decreased gamma-aminobutryic acid (GABA) levels, decreased glutamate decarboxylase levels, and decreased binding by GABAB receptors, as well as rearrangement of axon terminals in aging Fischer 344 (F344) rats. Age-related physiological changes have also been noted in the ICs of C57 and CBA mice. 2. Given the age-related alterations in the inhibitory neurotransmitter system, we hypothesized that aged F344 rats would show alterations in the physiological response properties of their IC neurons due to an imbalance in the relative levels of inhibition and excitation affecting the neuronal firing. 3. In vivo extracellular single-unit recordings were made from 297 IC neurons in ketamine/xylazine-anesthetized aged (24 mo) F344 rats. Locations of recorded units were determined from the electrode track marks and horseradish peroxidase marks. Results were compared with those obtained from young adult (3 mo) animals. 4. Average threshold increased from 25.4 dB SPL in young rats to 56.1 dB SPL in aged rats. 5. Although there was a reduction in the percentage of units recorded at either extreme of the frequency range in aged animals, the characteristic frequency (CF) range and mean did not differ between the two groups. 6. For the IC as a whole, no differences were noted in spontaneous activity, first spike latency, dynamic range, percentage of units with nonmonotonic contralateral CF tone rate/intensity functions (RIFs), or percentage of units sensitive to change in CF tone presentation rate. 7. In aged rats, a higher percentage of units was poorly responsive to auditory stimulation. 8. In the aged rat, there was a 12% reduction in the maximum discharge rate, a 12% increase in the percentage of units classified as onset in their temporal response pattern, and an 18% increase in the breadth of the isointensity functions at 30 dB above threshold. 9. Age-related changes in the central nucleus of the IC (CIC) frequently differed from those observed in the external cortex of the IC (ECIC). The percentage of units classified as having nonmonotonic contralateral tone RIFs decreased with age in the CIC but increased with age in the ECIC, and the percentage of units classified as onset in their temporal response pattern increased with age in the CIC but did not change with age in the ECIC. 10. The results of this study support the hypothesis that there is an age-related shift to higher intensities in the working range of most CIC units along with a small, selective deficit in inhibitory processing. When considered in conjunction with the mouse aging studies conducted by other researchers and with the results of a similar study of single units in the visual system (lateral geniculate nucleus) of young and aged rhesus monkeys, these results suggest that compensatory mechanisms are highly active in sensory systems as animals age. Despite deficits that lead to reduced input to the IC and neurochemical changes affecting neurotransmitter levels, IC neurons in aged rats are able to respond to most simple auditory stimuli in a fashion quite similar to that observed in young rats.
MeSH Terms
- Age Factors
- Aging
- Animals
- Inferior Colliculi
- Male
- Mice
- Rats
- Rats, Inbred F344
- Reaction Time
- Sensory Thresholds
This study was designed to establish the young adult (3 month) Fischer 344 (F344) rat as a model of inferior colliculus (IC) physiology, providing a baseline for analysis of changes in single unit responses as the animals age and for the study of noise induced hearing loss. The response properties of units localized to the central nucleus of the IC (CIC) and those localized to the external cortex of the IC (ECIC) were compared in order to better characterize differences between these two subnuclei in the processing of simple auditory stimuli. In vivo extracellular single unit recordings were made from IC neurons in ketamine/xylazine anesthetized young adult F344 rats. When a unit was electrically isolated, the spontaneous activity level, characteristic frequency (CF) and CF threshold were determined. Rate/intensity functions (RIFs) in response to contralateral CF tones and to contralateral noise bursts were obtained as were tone isointensity functions. The recording site was marked by ejecting horseradish peroxidase (HRP) from an electrode. Locations of recorded units were determined from electrode track marks and HRP marks in serial brain sections. Recordings were made from 320 neurons in the IC; 176 were localized to the CIC and 87 to the ECIC. Thirteen percent of the units in each subdivision were found to be poorly responsive to auditory stimulation (clicks, tones or noise), and spontaneous activity was generally low. Characteristic frequencies representative of the full rat audiogram were found in each subdivision with the mean threshold significantly higher in the ECIC (28.7 dB SPL) than in the CIC (22.3 dB SPL). The mean maximum discharge rate to CF tone bursts was near 24 spikes/s in each subdivision. Dynamic range tended to be higher in the ECIC (28.3 dB) than in the CIC (23.2 dB), reflecting the lower percentage of nonmonotonic units found in the ECIC. Most units responded more robustly with a slower tone presentation rate, displayed lower levels of discharge to noise bursts than to tone bursts, and had differently shaped tone and noise RIFs. Most units were classified as onset responders to CF tone bursts in both subdivisions, with the percentage of onset responders higher in the ECIC (68.9%) than in the CIC (57.8%). First spike latency did not differ significantly between the subdivisions, but tended to be shorter in the CIC. The breadth of the excitatory receptive fields did not differ significantly between subdivisions, although the mean was slightly larger in the ECIC. These results are generally consistent with the results of CIC studies from other species, establishing the F344 rat as a model of CIC physiology. Differences between CIC and ECIC units included a higher percentage of nonmonotonic RIFs and lower percentage of onset temporal response patterns in the CIC than in the ECIC. Some properties which have been previously used as hallmarks for differentiation between CIC and ECIC units, namely broader tuning and longer first spike latencies in the ECIC, did not reach statistical significance in this study. These may reflect species differences and/or the highly variable and largely overlapping sets of responses evident in the large sample size used in this study.
MeSH Terms
- Acoustic Stimulation
- Aging
- Analysis of Variance
- Animals
- Audiometry
- Auditory Threshold
- Cochlear Nucleus
- Disease Models, Animal
- Evoked Potentials, Auditory, Brain Stem
- Hearing Loss, Noise-Induced
- Inferior Colliculi
- Male
- Rats
- Rats, Inbred F344
- Sample Size
- Statistics as Topic
Circulating immune complexes (CIC) in the sera from 102 clinically healthy dogs and from 16 Dirofilaria immitis (D. immitis) infected dogs were measured by the immune adherence hemagglutination (IAHA) method. The level of CIC in the sera from healthy dogs was 28.2 /- 29.1 micrograms/ml. There was no significant difference in the levels of CIC regarding sexes or ages. On the other hand, the level of CIC in the sera from D. immitis infected dogs was 230.3 /- 117.1 micrograms/ml, which was significantly (p < 0.01) higher than that of healthy dogs. The results of this study confirm that IAHA method is one of the reliable means of detecting and/or diagnosing immune complex mediated diseases in dogs.
MeSH Terms
- Aging
- Animals
- Antigen-Antibody Complex
- Complement System Proteins
- Dirofilaria immitis
- Dirofilariasis
- Dog Diseases
- Dogs
- Guinea Pigs
- Hemagglutination Tests
- Humans
- Rabbits
- Reference Values
- Species Specificity
The concentrations of circulating immune complexes (CICs) have been measured in healthy Nigerians aged 6-95 years by the polyethylene glycol precipitation technique. The prevalence of antinuclear antibodies (ANAs) and rheumatoid factors (RFs) was also studied in these Nigerians. Significant positive correlation between CIC concentrations and age was observed; but no sex-related differences. Weakly reacting ANAs plus age-associated increase in ANA prevalence were noted. Positivity rate for RFs detected by latex agglutination was significantly higher (chi 2 = 3.948; P < 0.05) in old subjects (> 65 years of age; 9.4%) compared to younger ones (< 65 years of age; 2.7%). Semi-quantitative Rose-Waaler technique gave 22% RF seropositivity rate in subjects with age > 65 years. The age groups 46-65 years, 26-45 years, and 6-25 years had 13.5%, 7.5% and 2.5% positivity rates, respectively. There was significant positive correlation between RF concentrations and CIC levels; and increased prevalence of RF autoantibody in subjects with CIC (10%) compared with those without (4.7%). Four percent of subjects with CICs, and none of those without, were positive for ANAs. Autoantibodies may contribute to increased prevalence of CICs in old individuals.
MeSH Terms
- Adolescent
- Adult
- Age Distribution
- Aged
- Aging
- Antibodies, Antinuclear
- Antigen-Antibody Complex
- Child
- Female
- Humans
- Male
- Middle Aged
- Nigeria
- Rheumatoid Factor
Before, we reported a higher frequency of circulating immune complexes (CIC) in the sera from institutionalized Alzheimer's disease (AD), multi-infarct dementia and Down's syndrome patients than from age-matched controls. In this study, we tested the presence of CIC in the sera from an extended series of hospitalized AD patients, AD patients living in the community, from age-associated memory impairment (AAMI) subjects as well as from nursing home and community controls. We used two methods to measure CIC, C1q binding Elisa (C1qB-Elisa) and conglutinin binding (KgB-Elisa). The AD patients showed the highest frequency of positive findings and differed from the controls in KgB (42% vs. 17%) (Chi-square, p = 0.01) and C1qB (30% vs. 11%) (p < 0.05). In severe AD, 14/19 patients were KgB positive and 11/19 were C1qB positive and differed from controls. The frequency of CIC for the patients with moderate or mild dementia, the AAMI subjects and controls was similar. In the multivariate linear regression analysis, high CIC values of the AD patients significantly associated with a long disease duration and a history of recurrent urinary infections but not with age, sex, hospitalization, or the Mini-Mental Status score. We conclude that AD patients with severe dementia frequently show CIC but those with mild or moderate disease do not. The CIC relate to a long disease duration and a history of recurrent urinary infections.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Antibodies
- Antigen-Antibody Complex
- Collectins
- Complement C1q
- Enzyme-Linked Immunosorbent Assay
- Female
- Humans
- Immunosorbents
- Male
- Memory Disorders
- Middle Aged
- Psychiatric Status Rating Scales
- Recurrence
- Serum Globulins
- Urinary Tract Infections
The experiments on 40 young and old rabbits which were given exogenous immune complexes (IC) for a month were made to study the changes in the blood levels of circulating IC (CIC), cholesterol and lipoproteins and their relation to the degree of atherosclerotic lesions to the vessels. The old animals that had low levels of minor CIC and insignificant transient increases in blood lipids were demonstrated to develop the same vascular atherosclerotic lesions as did the young animals that had higher levels of CIC and lipids. Some old animals retained a high immunological responsiveness (high CIC levels), which was accompanied by high incidence rates and extent of aortic lipid lesions. The findings make us conclude that the role of IC in atherosclerotic responsiveness increases with age.
MeSH Terms
- Aging
- Animals
- Antigen-Antibody Complex
- Arteriosclerosis
- Male
- Rabbits
This study was designed to determine if there are age-related alterations in the bio-synthetic enzyme glutamic acid decarboxylase (GAD), the degradative enzyme GABA-transaminase (GABA-T), and the uptake system for GABA in the central nucleus of the inferior colliculus (CIC), the cochlear nucleus (CN), and/or nuclei of the lateral lemniscus (NLL) of Fischer-344 rats. For purposes of comparison, the cholinergic neuronal system was studied in parallel in young adult (3-7 months), mature (15-17 months) and aged (24-26 months) rats. In young adults GAD activity was highest in the CIC (219 nmol/mg protein/h; N = 5), intermediate in NLL (82 nmol/mg protein/h), and lowest in CN (34 nmol/mg protein/h). Choline acetyltransferase (ChAT) activity was highest in NLL and CN, and approximately 35-40% lower in CIC. A more uniform pattern was observed with GABA-T activity. Reductions in GAD activity were seen in the CIC of mature (-31%) and aged (-30%) rats that were not graded with age when compared to young adult, P < 0.05 (N = 5). This effect was regionally selective, since the CN did not show any loss of GAD or ChAT activity. The neurotransmitter selectivity of this deficit in CIC is supported by the non-parallel changes in ChAT activity (-22%, aged vs. mature, P < 0.05) that occurred after the changes in GAD activity. In contrast to the loss of GABAergic biosynthetic capacity in aged CIC, high affinity uptake processes (Kd and Vmax) for 14C-GABA and 3H-D-aspartate were not significantly altered (P > 0.05). Similar to the CIC, the NLL showed remarkable age-related deficits, but these deficits were more substantial for the cholinergic system (ChAT activity: -56% aged vs. young adult, P < 0.05; GAD activity: -35% aged vs. mature). None of the areas examined showed a significant loss of GABA-T activity with aging. These data suggest: 1) Age-related loss of GABA-mediated inhibition in the CIC of Fischer-344 rats is not attributable to changes in uptake or degradation of GABA, but may be related loss of biosynthetic capacity (i.e. activity or quantity) of the GAD present; 2) processing centers of the central auditory pathway (i.e. CIC and NLL), but not necessarily primary (i.e. CN) integrative nuclei, demonstrate selective, age-related neurochemical deficits; and 3) age-related neurochemical changes in central auditory structures may contribute substantially to the abnormal perception of signals in noise and loss of speech discrimination observed in neural presbycusis.
MeSH Terms
- 4-Aminobutyrate Transaminase
- Acetylcholine
- Aging
- Animals
- Aspartic Acid
- Auditory Pathways
- Biological Transport, Active
- Brain Stem
- Choline O-Acetyltransferase
- Cochlear Nucleus
- Geniculate Bodies
- Glutamate Decarboxylase
- In Vitro Techniques
- Inferior Colliculi
- Kinetics
- Pons
- Presbycusis
- Rats
- Rats, Inbred F344
- gamma-Aminobutyric Acid
Quantitative receptor autoradiography was used to assess GABAB receptor binding in three primary subdivisions of the inferior colliculus (IC): dorsal cortex (DCIC), external cortex (ECIC), and the central nucleus (CIC) of 3-, 18-20-, and 26-month-old Fischer 344 rats. GABAB binding sites were localized using [3H]GABA in the presence of a saturating concentration of isoguvacine, a selective GABAA receptor agonist, to displace [3H]GABA bound to GABAA receptor sites. In the three IC subdivisions examined, GABAB receptor binding was significantly reduced in 26-month-old rats when compared to 3-month-old rats (DCIC, -44%; ECIC, -36%; CIC, -32%; p < 0.05). For comparison, GABAB binding was determined in the portion of cerebellum located in the recess of the IC. In the molecular layer of this region, there was no statistically significant differences in receptor binding between 3, 18-20-, and 26-month-old rats. In addition, there was not a significant age-related change in the cross-sectional area of the IC. These findings provide additional evidence to support the existence of selective age-related changes in GABA neurotransmitter function in the rat IC.
MeSH Terms
- Aging
- Animals
- Autoradiography
- Binding Sites
- Inferior Colliculi
- Rats
- Rats, Inbred F344
- Receptors, GABA-B
- gamma-Aminobutyric Acid
This paper reviews 179 patients (23 females and 156 males) with suprasacral spinal cord injury (SCI) who underwent videourodynamic evaluation to compare maximum detrusor pressure, compliance, and trabeculation with methods of bladder management, years post-injury, and age. The patients were divided into four groups based on mode of bladder management: clean intermittent catheterization (CIC), indwelling catheter (IND), external collector (EC), and voiding (V). Maximum pressure decreased significantly with increasing age for those using EC (P < 0.01) and CIC (P < 0.05). Maximum pressure also decreased significantly with years post-injury for patients on EC (P < 0.01) and was highest the first decade after injury and progressively decreased through the fifth decade. Post-hoc tests indicated more severe trabeculation in patients in the EC group than in either the CIC or IND groups. Age and trabeculation did not correlate in those on EC. We conclude that patients with long-standing suprasacral SCI using EC are more likely to have lower detrusor pressures than are those with less chronic SCI. This finding may reflect the effects of age as well as reduced survival in those using EC with chronically elevated detrusor pressure.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Analysis of Variance
- Catheterization
- Catheters, Indwelling
- Female
- Humans
- Lumbosacral Region
- Male
- Middle Aged
- Patient Compliance
- Pressure
- Spinal Cord Injuries
- Television
- Urinary Tract
- Urination
- Urodynamics
Oral contraceptives (OC) have been shown to induce in some women antiethinylestradiol antibodies which may be detected as circulating immune complexes by precipitation in ammonium sulphate at 25% saturation (CIC.AS). A reevaluation of the presence of CIC.AS in 644 women either receiving sex steroid hormones or not was made, and the respective role of estrogens and progestogens investigated, together with the influence of the dose. The study confirmed that CIC.AS levels were significantly different in controls (442 /- 246 micrograms/ml serum), healthy gonadal hormone users (754 /- 700 micrograms) and users with thrombosis (1331 /- 1099 micrograms/ml). These results indicated that: 1. CIC.AS could be induced by synthetic estrogens as well as progestogens, but not by non-synthetic hormones; 2. the induction of CIC.AS seemed poorly dose-related, and 3. was not correlated with the duration of use; 4. in reactive women, high CIC.AS levels occurred as soon as 3 weeks after the beginning of synthetic gonadal hormones use, persisted throughout treatment and decreased slowly when discontinued; 5. in women with thrombosis CIC.AS were more frequently detected (64.7%) than in healthy users (32.2%) P less than 0.001. The importance of the immunologic changes as a risk factor in thrombosis in OC users was evaluated in comparison with other predisposing factors and tobacco smoking.
MeSH Terms
- Adolescent
- Adult
- Aging
- Antigen-Antibody Complex
- Contraceptives, Oral
- Contraceptives, Oral, Combined
- Dose-Response Relationship, Immunologic
- Estradiol Congeners
- Estrogens
- Female
- Humans
- Middle Aged
- Progesterone Congeners
- Risk
- Smoking
- Thrombosis
Keywords
- Antibodies
- Biology
- Cardiovascular Effects
- Contraception
- Contraceptive Agents
- Contraceptive Agents, Estrogen
- Contraceptive Agents, Female
- Contraceptive Agents, Progestin
- Contraceptive Methods--pharmacodynamics
- Diseases
- Embolism
- Examinations And Diagnoses
- Family Planning
- Immunity
- Immunologic Factors
- Immunological Effects
- Laboratory Examinations And Diagnoses
- Laboratory Procedures
- Oral Contraceptives--pharmacodynamics
- Physiology
- Reproductive Control Agents
- Thromboembolism
- Thrombosis
- Vascular Diseases
Circulating immune complexes (CIC) were detected by a solid-phase radioassay in 34% of fifty-three insulin-dependent diabetics (IDD) as compared to 18% of forty-five non-insulin-dependent diabetics (NIDD) and 14% of 173 control subjects. In control subjects, the prevalence of CIC increased with age and was higher in males than in females. In IDD, immune complexes were found with the highest frequency before the age of 30 and after 50. There was no significant difference between the incidence of CIC in old IDD and their age-matched controls. The same sera were also tested for the presence of the following autoantibodies; nuclear , thyroid, gastric, smooth and striated muscle; mitochondria, sub-maxillary and adrenal gland and liver-kidney microsome. Sera containing at least one antibody were found in 16.4% of controls, 55.3% of IDD and 40% of NIDD. The prevalence of autoantibodies increased with age in controls but not in IDD. Islet cell antibodies were present in 28.5% of IDD and 2.9% of control subjects; they were more frequent in young patients. CIC and autoantibodies were statistically associated both in controls and IDD; in the patients, CIC were associated not only with islet cell antibodies but also with other autoantibodies. The possible relation between autoimmunity, degenerative vascular diseases and CIC is discussed.
MeSH Terms
- Adult
- Aged
- Aging
- Antibody Specificity
- Antigen-Antibody Complex
- Autoantibodies
- Diabetes Mellitus
- Female
- Humans
- Islets of Langerhans
- Male
- Middle Aged
We measured in vitro mitogen responses, delayed hypersensitivity skin tests, circulating immune complexes (CIC) and three autoantibodies in 279 healthy and 24 chronically ill individuals over 65, and in young controls. The elderly individuals had previously undergone a complete medical examination and laboratory screening tests, and were on no medications. Compared to the results of 180 young controls tested concurrently, the healthy elderly individuals had significantly depressed PHA responses and skin test responses. In addition, CIC and autoantibodies were increased in the healthy elderly group compared to young controls. There was no difference in PHA or skin test responses between the healthy and chronically ill elderly subjects, suggesting that the major determinant of depressed cellular immunity in the elderly is age per se and not age-associated diseases. Within the elderly population, aged 65-94, there was a significant decrease in PHA response with age. Previously it has been reported that correlations exist between measurements of cellular immune response (mitogen response and skin testing) and manifestations of autoimmunity (CIC or autoantibodies) in elderly subjects. However, in this well characterized healthy elderly population we could not verify an association between the cellular immune response and either autoantibodies or immune complexes. In addition, was no increased prevalence of autoantibodies in subjects with CIC.
MeSH Terms
- Aged
- Aging
- Antibodies, Antinuclear
- Antigen-Antibody Complex
- Antilymphocyte Serum
- Autoantibodies
- Female
- Humans
- Hypersensitivity, Delayed
- Lymphocyte Activation
- Male
- Phytohemagglutinins
- Rheumatoid Factor
- Skin Tests
The incidence of circulating immune complexes, anti-low density lipoprotein (LDL) autoantibodies and the anti-LDL activity of immune complexes was studied in healthy young and aged controls and in patients with vascular diseases. Circulating immune complexes (CIC) frequently occurred both in the young or old patient groups and in the aged healthy control groups, whereas they could not be found in the young controls. Marked differences were found in the incidence of anti-LDL antibodies between the groups tested. In both young and aged control groups such antibodies were very rarely observed (4-5%). In contrast anti-LDL antibodies were present in 35-45% in the aged, or young patients. Similarly, no anti-LDL activity was found in CIC of the controls, whereas in the patients with vascular diseases a significant CIC-associated anti-LDL activity was detected. These results suggest that the presence of anti-LDL antibodies are associated with the arteriosclerotic manifestations, while that of circulating immune complexes is connected by the ageing process itself.
MeSH Terms
- Adult
- Aged
- Aging
- Antigen-Antibody Complex
- Arteriosclerosis
- Autoantibodies
- Cerebrovascular Circulation
- Coronary Circulation
- Coronary Disease
- Female
- Humans
- Lipoproteins, LDL
- Male
- Middle Aged
Hematological and biochemical parameters were measured in carefully selected healthy elderly (50 males and 50 females, aged 60-97 years) and young (10 males and 10 females, aged 18-23 years) populations. Most of the parameters measured did not show any age-related variations. It means that any deviation from the present normal ranges established for healthy young subjects should be considered as pathologic in the case of elderly, too. Some parameters showed age-specific changes and hence there is a possibility that their actual normal ranges might be extended towards the upper limit (globulin, IgG, IgA, CIC, C3, BUN, AP for females), or towards the lower limit (creatinine clearance, albumin). Verification of these modifications may indicate that a lot of unnecessary investigations in the case of elderly could be avoided.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Blood Chemical Analysis
- Enzymes
- Female
- Hematologic Tests
- Humans
- Liver
- Male
- Middle Aged
- Sex Factors
Immune response parameters were studied on 1341 A-bomb survivors residing in Hiroshima, Japan. Mononuclear cells were isolated from venous blood and tested for interleukin-2 production; lymphocytes were purified and tested for natural killer (NK) cell activity and interferon (IFN) production; and serum was tested for IFN and circulating immune complex (CIC) levels. Statistical analyses were performed for each type of assay using a linear models procedure including sex, age at the time of the bomb, radiation exposure, all the interaction variables, and the categorical variable day-of-assay in the model. The findings showed that (1) none of the immunologic variables were significantly affected by radiation exposure; (2) NK activity and CIC levels were positively associated with age; and (3) NK activity was on average higher for males than females. The data exemplify the difficulty in reaching firm conclusions concerning associations with radiation exposure when the dependent variable exhibits a large degree of interindividual and day-of-assay variability.
MeSH Terms
- Aging
- Antigen-Antibody Complex
- Female
- Interferons
- Interleukin-2
- Killer Cells, Natural
- Leukocytes, Mononuclear
- Lymphocytes
- Male
- Nuclear Warfare
- Radiation Injuries
The present study describes substantial, selective, age-related loss of the putative inhibitory neurotransmitter GABA in the central nucleus of the inferior colliculus (CIC) of rat based on immunocytochemical and neurochemical data. For immunocytochemistry, neurons in the CIC were immunolabeled using an antibody against a GABA conjugate in young adult (2- to 7-month-old) and aged (18- to 29-month-old) Fischer-344 rats. Computer-assisted morphometry was then used to generate maps of GABA-immunoreactive neurons in the CIC. The number of GABA-positive neurons was reduced 36% in the ventrolateral portion of the CIC of aged animals (93 neurons/mm2) compared to their matched young adult cohorts (145 neurons/mm2; p less than 0.01). For neurochemistry, basal and K( )-evoked release of the endogenous amino acids GABA, glutamate (Glu), aspartate (Asp), and tyrosine (Tyr) from micropunches of the CIC were measured in 8 age-paired animals from the 2 age groups using high-performance liquid chromatography. Overflow of radiolabeled acetylcholine (3H-ACh) was also determined. In both age groups, K( )-evoked release of GABA, Glu, Asp, and 3H-ACh from CIC punches was significantly enhanced above basal efflux ( 200, 215, 163, and 309%, respectively), while Tyr release was unchanged. Evoked release of 3H-ACh and all amino acids except Tyr showed substantial Ca2 dependence. A significant (p less than 0.05) age-related reduction in both basal (-35%) and K( )-stimulated (-42%) efflux of GABA from the CIC was observed. A corresponding decrease in postrelease tissue content of GABA in CIC of aged rats was observed (-30%, p less than 0.05). In contrast, tissue content as well as basal and evoked release of Glu, Asp, Tyr, and 3H-ACh was similar between the 2 age groups. Age-related GABA neurochemical changes described in the CIC were not observed in the release of the other amino acids or 3H-ACh from either the rostral ventrolateral medulla or the somatosensory cortex, 2 brain regions involved in processing non-auditory sensory input. These data support previous findings that GABA, Glu, Asp, and ACh may subserve neurotransmission in the CIC. Additionally, these data provide clear evidence for a pronounced, region- and neurotransmitter-selective, age-related reduction of GABA in the CIC. These findings support the hypothesis that impairment of inhibitory GABAergic neurotransmission in the CIC may contribute to abnormal auditory perception and processing seen in neural presbycusis.
MeSH Terms
- Acetylcholine
- Aging
- Animals
- Aspartic Acid
- Calcium
- Glutamates
- Glutamic Acid
- Hearing Loss, Sensorineural
- Inferior Colliculi
- Neurons
- Potassium
- Presbycusis
- Rats
- Rats, Inbred F344
- gamma-Aminobutyric Acid
T lymphocyte subsets were investigated in 57 aged persons with Kidney Deficiency Syndrome as well as in 30 normal controls with application of the monoclonal antibody (OKT3, OKT4, OKT8). The results showed that the percentage of OKT3, OKT4 in the aged persons was significantly lower than that of control (P < 0.01), while OKT8 was significantly higher (P < 0.01). The OKT4/OKT8 ratio was significantly lower than that of control (P < 0.01). However, the above-mentioned changes were more evident in the Kidney Yang Deficiency Syndrome than those in Kidney Yin Deficiency Syndrome (P < 0.01). The further analysis indicated that the aged persons with Kidney Yang Deficiency appeared as marked positive correlation (r = 0.64, P < 0.001) between the OKT4/OKT8 ratio and IgA, and they also appeared as marked negative correlation (r = -0.89, P < 0.001 and r = -0.665, P < 0.001 respectively) between the OKT4/OKT8 ratio and C3 or CIC. The results suggested that the imbalance of the cell mediated immunity expressed by the T lymphocyte subsets in aged persons with Kidney Deficiency might be one of the essences of senility.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Antigen-Antibody Complex
- CD4-CD8 Ratio
- Female
- Humans
- Immunoglobulins
- Kidney Diseases
- Male
- Middle Aged
- T-Lymphocyte Subsets
- Yang Deficiency
- Yin Deficiency