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PubMed1976

Male pseudohermaphroditism presumably due to target organ unresponsiveness to androgens. Deficient 5alpha-dihydrotestosterone binding in cultured skin fibroblasts.

Maximum specific 5alpha-dihydrotestosterone (DHT) binding activity (Bmax) had been measured in intact confluent monolayers representing fibroblast strains derived form nongenital and genital (labium majus) skin of normal individuals and of 11 patients fulfilling the clinicogenetic criteria of complete testicular feminization (TF). Nine labium majus strains from adult females had a mean Bmax value three times greater than that of seven nongenital strains from adult females (33 vs. 11 fmol/mg cell protein). The Bmax results for 13 adult nongenital strains varied from 5.6 to 23.3 fmol/mg protein; the values for males and females had very similar means and ranges. The variation could not be correlated with the chronologic age of adult skin explant donors or with the in vitro age (mean population doubling level) of the cultures assayed. The Bmax activities of three nongenital strains from normal infants (two male, one female) did not exceed 5 fmol/mg protein. Seven of eight nongenital TF strains had Bmax values below 2 fmol/mg protein; the value for the eighth coincided with the lower limit of normal adults. The lower limit of DHT binding in normal labium majus strains was 15 fmol/mg protein. Three of five labial strains from patients with TF had Bmax values close to zero; the other two fell between 10 and 15 fmol/mg protein. It is apparant that labial skin fibroblast strains from clinically homogeneous patients with TF had highly variable degrees of DHT binding deficiency, and that they permit a more reliable diagnosis of severe and intermediate degrees of DHT binding deficiency than do strains of nongenital skin fibroblasts.

Adolescent↗
PubMed1996

Epithelial, possibly precancerous, lesions of the lung in relation to smoking, passive smoking, and socio-demographic variables.

We have undertaken an autopsy-based study to evaluate the etiologic importance of active and passive smoking, as well as socio-demographic variables, in the development of pathologic precursors of lung cancer. Lung specimens were taken at autopsy from 531 persons who had died within four hours from a cause other than respiratory or cancer in Athens (Greece) or the surrounding area. Specimens were examined blindly for basal cell hyperplasia, squamous cell metaplasia, cell atypia and mucous cell metaplasia, i.e., pathological entities considered as epithelial, possibly precancerous, lesions (EPPL). Interviews were conducted with next of kin of the deceased. Suitable autopsy specimens as well as completed interviews were eventually available for 275 subjects. EPPL score was regressed on the available independent variables. EPPL score was higher among active smokers than among nonsmokers, while ex-smokers occupied an intermediate position. Conditional on smoking habits, EPPL score was higher among women than among men and higher among manual than among non-manual workers, in agreement with the corresponding patterns with respect to lung cancer. Nonsmoking women married to ever smokers had significantly higher EPPL score than those married to never smokers. The overall findings of this study suggest that EPPL is a valuable indicator of lung cancer risk and that exposure to environmental tobacco smoke is associated with higher EPPL levels and therefore with higher lung cancer risk.

Adult↗
PubMed1998

Risk factors for treatment-related death in elderly patients with aggressive non-Hodgkin's lymphoma: results of a multivariate analysis.

PURPOSE: It has been suggested that age is associated with chemotherapy-related death in patients with non-Hodgkin's lymphoma (NHL) treated with doxorubicin-containing chemotherapy. The purpose of this study was to evaluate the relative influence of increasing age and other clinical parameters on the occurrence of treatment-related death in elderly patients with intermediate- or high-grade NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. METHODS: A retrospective study of patients 60 years of age or older with intermediate- or high-grade NHL treated with CHOP chemotherapy in a single cancer center. The following variables were recorded: age (60 to 69, 70 to 79, and 80 to 94 years), histology (Working Formulation [WF] D, E, F, G, and H), Ann Arbor stage, B symptoms, extranodal involvement, bulky disease (> 7 cm), performance status (Eastern Cooperative Oncology Group [ECOG] scale), International Prognostic Index (IPI score), serum lactate dehydrogenase (LDH) level and doxorubicin relative dose-intensity (RDI). The relationship between these features and treatment-related death was assessed in univariate and multivariate logistic regression analysis. RESULTS: From 1982 to 1991, 267 consecutive patients were treated. Median age was 70 years (range, 60 to 94 years). There were 35 toxic deaths. Sixty-three percent of the deaths occurred after the first cycle. Infection accounted for 82% of the toxic deaths. In the univariate analysis, the features associated with an increased risk of toxic death were ECOG performance status 2 to 4 (relative risk [RR], 7.82), B symptoms (RR, 3.38), diffuse large-cell histology (RR, 3.06), bulky disease (RR, 2.58), serum levels of LDH (RR, 2.53), and IPI score (RR, 2.46). The age groups did not show significance. In the regression model, performance status 2 to 4 was the only independent predictor of treatment-related death (RR, 3.52; 95% confidence interval [CI], 2.98 to 4.06). CONCLUSION: Our results show that in elderly patients with NHL treated with doxorubicin-based chemotherapy the risk for treatment-related death is associated with poor performance status rather than with increasing chronologic age.

Age Factors↗
PubMed2002

Effect of gender on counterregulatory responses to euglycemic exercise in type 1 diabetes.

A marked sexual dimorphism in neuroendocrine and metabolic responses to moderate, prolonged exercise occurs in healthy humans. It is unknown whether similar differences occur in type 1 diabetes mellitus (T1DM). Fifteen patients with T1DM (7 women and 8 men) were studied during 90 min of euglycemic exercise at 50% of the maximum rate of O(2) consumption. Men and women were matched for age, glycemic control, duration of diabetes, and exercise fitness, and had no history or evidence of autonomic neuropathy. Hypoglycemia was scrupulously avoided during the week preceding tests. Exercise was performed under constant infusion of regular insulin (1 U/h) and a variable 20% dextrose infusion, as needed to maintain euglycemia. At 15-min intervals, neuroendocrine, metabolic (glucose kinetics, intermediate metabolism, lipolysis), and cardiovascular responses were assessed. Indirect calorimetry was performed during the last 10 min of exercise. Plasma glucose and insulin did not differ between genders at baseline or during exercise. Key neuroendocrine responses were significantly reduced in women, compared with men, during exercise (epinephrine, 360 +/- 104 vs. 666 +/- 126 pM; norepinephrine, 2.3 +/- 0.8 vs. 4.1 +/- 1.0 nM; GH, 10 +/- 5 vs. 22 +/- 8 micro g/liter). Glucagon, cortisol, and pancreatic polypeptide responses were similar between genders. Despite reduced catecholamine responses in women, no gender differences were observed in endogenous glucose production (EGP) or exogenous glucose infusion rate during exercise. The lipolytic response to exercise (blood glycerol), on the other hand, was greater in women than in men. In conclusion, a marked sexual dimorphism exists in counterregulatory responses to exercise in T1DM, including key neuroendocrine (catecholamine, GH) and metabolic (lipolysis) responses. Other responses, including glucagon and EGP, were similar between genders, suggesting that the glucagon to insulin ratio may be the primary determinant of EGP during moderate intensity exercise in T1DM.

Adult↗
PubMedDate not supplied

Immunohistochemical study of basement membrane collagen IV in uterine cervix carcinoma.

CONTEXT: The integrity of basement membrane (BM) is damaged during the evolution of a benign or potentially malignant lesion into a malignant one, in which it may undergo several degrees of discontinuity as a necessary condition for the invasive process. Immunostaining for collagen IV, which is exclusively found in BM, has been used to evaluate its formation in neoplastic and benign lesions of several organs. OBJECTIVE: To investigate BM continuity pattern in squamous carcinoma "in situ" (CIS), microinvasive (MIC) and invasive (IC) squamous cell carcinoma of the uterine cervix, and to find out if BM expression could be useful in the diagnosis of early stromal invasion (MIC). DESIGN: Archival material between 1988 and 1993 was studied at the Pathological Anatomy Department-Unicamp. PROCEDURES: The selected cases, previously formalin fixed and paraffin embedded, were reviewed retrospectively by submitting them to immunohistochemical study via the avidin-biotin-peroxidase method using a monoclonal antibody anticollagen IV. RESULTS: In all, 17 cases of CIS, 16 of MIC and 21 of IC were evaluated. All IC cases showed evident BM discontinuity, either focal or diffuse. In the CIS group, a continuous BM pattern was predominant, being focally disrupted in only 2/17 cases (11.8%). The MIC group showed an intermediate pattern, but with a clear tendency to BM discontinuity in 10/16 cases (62.5%). Inflammatory infiltrate, a variable also studied, cannot be considered responsible for BM discontinuity, since there was no statistical correlation between them. CONCLUSION: We conclude that immunostaining for collagen IV may contribute to the diagnosis of stromal invasion by BM discontinuity.

Basement Membrane↗
PubMed1980

Behavioral and dimensional contrast in rats.

Rats pressed a nose key for brain stimulation reinforcement presented on a fixed-interval schedule. Stimuli were drawn at random from a continuum of 12 white noise intensities in the range 62-95 decibels, spaced in 3 decibel steps. Experiment 1 varied the number of stimuli and the reinforcement contingencies associated with them. In Condition I (baseline) all stimuli signaled reinforcement; in Conditions II and III stimuli from one half of the continuum signaled reinforcement and those from the other half, extinction. However, in Condition II the 6 stimuli from the middle of the continuum were omitted. Experiment 2 held constant the number of stimuli and varied their spacing. In Condition I, each of 6 sounds signaled reinforcement. In Conditions II and II, three stimuli from one half of the continuum signaled reinforcement and three from the other half, extinction. However, in Condition II the stimuli were near the extremes of the continuum (Stimuli 1, 3, 4, 9, 10, 12). Condition III replaced Stimulus 3 with Stimulus 6 and Stimulus 10 with Stimulus 7. Behavioral contrast was seen in an increase over baseline in response rate to the stimuli associated with the constant schedule component when the variable component was changed to extinction. Dimensional contrast was seen in a further elevation of rate to intermediate positive stimulus values when stimuli were added to the border region between positive and negative values.

Animals↗
PubMed2005

Clinical outcome at a minimum of five years after reconstruction of the anterior cruciate ligament.

BACKGROUND: We are not aware of any previous studies in which independent measurements of function with validated outcome questionnaires such as the Knee Injury and Osteoarthritis Outcome Score and the International Knee Documentation Committee score were evaluated five years after reconstruction of the anterior cruciate ligament. We hypothesized that patient demographics, mechanism of injury, and intra-articular injuries and their treatment are factors associated with function five years after reconstruction of the anterior cruciate ligament. METHODS: A consecutive series of unilateral, arthroscopically assisted primary reconstructions of the anterior cruciate ligament performed by one surgeon using a patellar tendon graft was evaluated. Data on patient demographics, injury variables, and intra-articular lesions noted at the time of surgery were collected prospectively. Multivariable regression analysis was used to identify independent predictors of outcomes as measured with five questionnaires. RESULTS: Sixty-nine percent (217) of 314 knees with a reconstruction of the anterior cruciate ligament were followed for an average of 5.4 years. The average age at the time of the operation was twenty-seven years. Independent predictors of a worse outcome, which was measured with the overall Knee Injury and Osteoarthritis Outcome Score, the International Knee Documentation Committee score, the Lysholm score, and the Western Ontario and McMaster Universities Osteoarthritis Index score, included the patient's recollection of hearing or feeling a pop at the time of the injury, a weight gain of >15 lb (6.8 kg), and no change in educational level since the surgery. There was a lack of association between the outcome and either the occurrence or the form of treatment of a meniscal tear or chondromalacia of the articular cartilage. CONCLUSIONS: To our knowledge, we performed the first prospective cohort study to evaluate the prognosis following reconstruction of the anterior cruciate ligament by identifying significant associations between multiple variables and clinical outcomes as measured with validated questionnaires. The clinician can counsel patients about the intermediate-term functional outcomes of reconstructions of the anterior cruciate ligament on the basis of these findings. Suggestions regarding weight control and future education may improve intermediate-term outcomes.

Adult↗
PubMed1991

Polymorphic and monomorphic expression of arylamine carcinogen N-acetyltransferase isozymes in tumor target organ cytosols of Syrian hamsters congenic at the polymorphic acetyltransferase locus.

A number of human epidemiological investigations suggest a relationship between acetylator phenotype and the incidence and/or severity of tumors caused by exposure to arylamine carcinogens. Conclusions drawn from these investigations can be compromised by a variety of environmental and other genetic factors. To eliminate variability in these other factors, our laboratory recently completed construction of homozygous rapid (Bio. 82.73/H-Patr), heterozygous intermediate (Bio. 82.73/H-Patr/Pat(s)) and homozygous slow (Bio. 82.73/H-Pat(s)) acetylator congenic hamsters. The purpose of the present study was to assess the utility of this congenic hamster model for investigations into the relationship between acetylator genotype and arylamine carcinogenesis. We report the expression of acetylator genotype-dependent (polymorphic) and acetylator genotype-independent (monomorphic) N-acetyltransferase isozymes in hepatic cytosols. The hepatic polymorphic N-acetyltransferase isozyme isolated from the congenic hamsters expressed clearly acetylator-genotype dependent (Patr greater than Patr/Pat(s) greater than Pat(s)) N-acetylation towards p-aminobenzoic acid, 4-aminobiphenyl, 2-aminofluorene, p-aminophenol, 1-aminopyrene, 5-aminosalicylic acid, beta-naphthylamine, 3,4-dichloroaniline, 3,2'-dimethyl-4-aminobiphenyl and p-phenetidine. Acetylator genotype-dependent N-acetylation for a number of arylamines also was observed in liver, colon, kidney and urinary bladder cytosols derived from the congenic hamster lines, including arylamines highly carcinogenic to hamster colon and urinary bladders. It is concluded that the congenic hamster model will be useful in studies to delineate the role of acetylator genotype in the incidence or severity of arylamine tumors.

Animals↗
PubMed1989

Myoepitheliomas and myoepithelial adenomas of salivary gland origin. Immunohistochemical evaluation of filament proteins, S-100 alpha and beta, glial fibrillary acidic proteins, neuron-specific enolase, and lactoferrin.

Immunohistochemical identification of keratin proteins (TK, KL1 and PKK1), vimentin, myosin, S-100 protein (using polyclonal antiserum) and S-100 alpha and beta subunits, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), lactoferrin, and lysozyme was made in myoepitheliomas, myoepithelial adenomas, and clear cell adenomas of salivary gland origin. Myoepithelioma cells were divided into two types: plasmacytoid cells, which showed great heterogeneity in terms of keratins and S-100 alpha and beta proteins and a lack of GFAP, NSE, lactoferrin, and lysozyme in most the cells, and fibrous and dendritic tumor cells, which displayed variable staining for keratin and S-100 alpha and beta proteins. Myoepithelial adenomas were composed of small-, intermediate-, and large-sized spindle cells that showed irregular positive reactions for keratins and S-100 alpha and beta. Immunohistochemical deposition of S-100 protein was restricted strongly to the dendritic cells present in hyalinous and myxomatous areas. Clear cell adenomas revealed uniformly slight staining of keratins and S-100 proteins, and negative staining or rarely positivity for GFAP, NSE, lactoferrin, and lysozyme. When the immunohistochemical deposition of these proteins was compared between normal glands and myoepithelial tumors, heterogeneity of expression of keratins, S-100 proteins, GFAP, and NSE was notable in the tumors. Progenitor cells of several kinds of myoepithelioma were suggested to be intercalated reserve cells, which are thought to be the same cell that gives rise to pleomorphic adenoma of salivary glands.

Adenoma↗
PubMed1984

Minimal requirements for planning control projects.

The different life cycles of trematodes causing the snail-transmitted infections, the complex interactions of the numerous groups of variables representing the five major areas of the epidemiology - human prevalence, incidence and intensity rates, parasite strains, intermediate hosts, ecological backgrounds and human behavioural factors - all combine to render control projects both area and parasite specific. Control must never be equated with eradication which is the complete and permanent cessation of transmission - and rarely, if ever, achievable. In medical and epidemiological terms, control means reduction of morbidity and mortality. Minimum requirements common to efficient planning for any control projects are: a community awareness of the problem; a community expression for the need of control; pathological, statistical and socio-economic evidence of morbidity/mortality produced and the associated economic loss to area, region or country, medical interest and governmental commitment to action as a priority in health policies; appropriate, simple, yet adequate diagnostic technology; appropriate control tools, which, for this group of infections, will rely heavily on population-based chemotherapy; a cadre of trained technicians, field workers and health educators; a programme for training trainers; a delivery system which can be used as an entry point to other health improvements, e.g. sanitation, nutrition, family planning; baseline demographic and epidemiologic information, a pre-tested system of data recording, collection, reduction and analysis; and, finally, funding support. These factors will be discussed.

Anthelmintics↗
PubMed1993

Characterization of particle- and vapor-phase organic fraction emissions from a heavy-duty diesel engine equipped with a particle trap and regeneration controls.

The effects of a ceramic particle trap on the chemical and biological character of the exhaust from a heavy-duty diesel engine have been studied during steady-state operation and during periods of trap regeneration. Phase I of this project involved developing and refining the methods using a Caterpillar 3208 engine, and Phase II involved more detailed experiments with a Cummins LTA10-300 engine, which met Federal 1988 particulate matter standards, and a ceramic particle trap with built-in regeneration controls. During the Phase I experiments, samples wee collected at the Environmental Protection Agency (EPA)* steady-state mode 4 (50% load at intermediate speed). Varying the dilution ratio to obtain a constant filter-face temperature resulted in less variability in total particulate matter (TPM), particle-associated soluble organic fraction (SOF), solids (SOL), and polynuclear aromatic hydrocarbon (PAH) levels than sampling with a constant dilution ratio and allowing filter-face temperature to vary. A modified microsuspension Ames assay detected mutagenicity in the SOF samples, and in the semivolatile organic fraction extracted from XAD-2 resin (XAD-2 resin organic component, XOC) with at least 10 times less sample mass than the standard plate incorporation assay. Measurement techniques for PAH and nitro-PAH in the SOF and XOC also were developed during this portion of the project. For the Phase II work, two EPA steady-state rated speed modes were selected: mode 11 (25% load) and mode 9 (75% load). With or without the trap, filter-face temperatures were kept at 45 degrees +/- 2 degrees C, nitrogen dioxide (NO2) levels less than 5 parts per million (ppm), and sampling times less than 60 minutes. Particle sizes were determined using an electrical aerosol analyzer. Similar sampling methods were used when the trap was regenerated, except that a separate dilution tunnel and sampling system was designed and built to collect all of the regeneration emissions. The SOF and XOC were extracted from their collection media with dichloromethane. Levels of 12 PAH and nitro-PAH compounds with known biological effects were determined using high-pressure liquid chromatography with fluorescence detection. Two additional dinitro-PAHs were analyzed semi-quantitatively, and several representative SOF and XOC samples were screened for three additional PAH compounds. Mutagenicity was assessed using the modified Ames microsuspension assay.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants↗
PubMed1997

The association of cardiovascular disease risk factors with abdominal obesity in Canada. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To assess the degree of association of abdominal obesity with blood pressure and plasma lipid levels and to determine which anthropometric measures of obesity are most closely associated with these cardiovascular risk factors. DESIGN: Population-based, cross-sectional surveys. SETTING: Five Canadian provinces (Alberta, Manitoba, Ontario, Quebec and Saskatchewan) between 1989 and 1992. PARTICIPANTS: A probability sample of 16,007 men and women aged 18 to 74 was selected using health insurance registration files in each province and invited to participate. A complete set of measurements was available for 8974 (56%) adults. OUTCOME MEASURES: Initially, simple correlation analyses by age and sex were performed between the anthropometric variables-body mass index, waist circumference (WC), hip circumference (HC), ratio of waist to hip circumference (WHR)- and cardiovascular disease risk variables-systolic blood pressure (SBP), diastolic blood pressure (DBP), levels of total cholesterol (TC), low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides (TRIG) and the TC/HDL ratio. Canonical correlation analyses were performed to determine the multivariate associations between the anthropometric and risk variables. RESULTS: The simple correlations between anthropometric variables and cardiovascular disease risk variables were highest for SBP; moderate for DBP, HDL, TRIG and TC/HDL; and lowest for LDL and TC. Of the anthropometric variables, WC demonstrated the greatest correlations with the risk variables. The first canonical correlations were significant (p < 0.0001) in men (0.58) and women (0.61) of all ages. Of the anthropometric variables, WC consistently demonstrated the highest loading values in the first canonical variable in men (0.56) and women (0.59). Of the risk variables in both sexes, the loadings of TRIG were generally the largest, those of HDL, SBP, DBP intermediate and those of LDL the smallest. In men, the strength of these associations generally decreased with age, whereas in women they peaked in the 35-54 year age group. CONCLUSION: Considerable association was seen between measures of abdominal obesity and blood pressure and plasma lipid levels. WC is the measure of abdominal obesity most highly correlated with these cardiovascular disease risk factors.

Abdomen↗
PubMed2002

[Problems of molecular systematics of the genus Salvelinus based on nucleotide sequence variability of the major noncoding region of mitochondrial DNA].

Variability of the major noncoding mitochondrial DNA region of char (Salvelinus alpinus complex) was analyzed by the median network method on the basis of the literature data on nucleotide sequences of this region. A significant portion (21%) of the polymorphic sites of char mtDNA was shown to be evolutionarily unstable, which results in mutation homoplasia at these sites. Using median-joining analysis the chars were divided into three phylogeographical groups: Arctic, Beringian, and chars occurring in the vast region from Lake Baikal and Taimyr Peninsula to the Atlantic Ocean. The latter group includes three subgroups (Siberian, Atlantic, and Acadian), which diverged from a common ancestor. In the Arctic group, the branch of Taranetz char S. taranetzi is clearly separated. It diverged from the common ancestor earlier than S. boganidae and S. elgyticus occurring on the Chukotka Peninsula species and S. a. erythrinus occurring in Alaska. The Beringian group, which includes dolly varden char from various regions of Asia and America, is an intermediate between the two char groups. The main problems of char systematics inferred from the major noncoding mtDNA region variability arise from the high level of mutation homoplasia.

3' Untranslated Regions↗
PubMed2000

The variability of practice hypothesis in motor learning: does it apply to Alzheimer's disease?

Based on Schmidt's (1975) variability of practice hypothesis, this study examined acquisition and transfer of a gross motor skill, namely tossing, in 58 patients with Alzheimer's disease (AD) and 58 healthy older adults under constant, blocked, and random practice conditions. While healthy older adults were able to learn the tossing task equally well under the three practice conditions, only AD patients receiving constant practice showed significant improvements. Tests of intermediate transfer yielded the expected random practice advantage in healthy controls but not AD patients. None of the practice conditions facilitated intermediate transfer in AD patients; however, constant practice did benefit these impaired individuals on tests of near transfer. These results indicate that the variability of practice hypothesis does not extend to AD patients. As motor learning and transfer were clearly a function of constant practice, future attempts to retrain basic activities of daily living in AD patients should emphasize consistency in training.

Aged↗
PubMed1994

Swim test immobility co-segregates with serotonergic but not cholinergic sensitivity in cross-breeds of Flinders Line rats.

The Flinders Sensitive Line (FSL) rat, a genetic animal model of depression, was cross-bred with its normal control, the Flinders Resistant Line (FRL) rat, in order to investigate the relationship between cholinergic sensitivity, the selected variable, and two apparent genetically correlated variables, serotonergic sensitivity and swim test immobility. Cross-breeding established F1, F2 and back-cross progeny, with at least 20 rats of each sex for each group. Cholinergic sensitivity was assessed as the hypothermic response to oxotremorine (0.2 mg/kg) in 30 day old rats. Serotonergic sensitivity was assessed as the hypothermic response to 8-OH-DPAT, a serotonin (5-HT)-1A agonist, in 35-40 day old rats. Immobility was assessed as the time spent immobile in a 5 min swim test in 60-70 day old rats. For each variable, there were highly significant group differences, with the parental FSL and FRL groups being at the extremes. The segregating populations tended to be intermediate between the parental lines and were generally significantly different from both FSL and FRL groups. However, the crosses more closely resembled the FRL parent for only the cholinergic responses, the distributions for 8-OH-DPAT and immobility suggesting predominantly additive genetics. Statistical analyses with chi square to compare response distributions and regression to quantify the association between variables in the segregating populations confirmed that cholinergic sensitivity was different from serotonergic sensitivity and immobility, which were significantly correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Neuropsychological aspects of multiple sclerosis: a quantitative review.

Neuropsychological studies of multiple sclerosis (MS) from a 20-year period were reviewed using meta-analytic and vote-count techniques. Mean effect sizes comparing MS and healthy control groups on variables categorized by neuropsychological domain were small to moderate in magnitude; all were statistically significant (M(r) = .22 (.13) to .46 (.15), rW = .23 to .43, all p < .05). Interhemispheric transfer, general cognitive ability, and learning/memory were more highly related to MS than were visuoperceptual, visuospatial, and visuoconstructional ability, language and conceptual ability (all p < .05); other domains were generally intermediate. Despite previous reports to the contrary, disease subtype was not shown to be consistently related to neuropsychological status independently of other potential explanatory variables. Findings were interpreted with regard to future research and clinical activities involving patients with MS, including selection of tests for brief neuropsychological screening examinations.

Adult↗
PubMed2003

Human interindividual variation in lymphocyte UDP-glucuronosyltransferases as a determinant of in vitro benzo[a]pyrene covalent binding and cytotoxicity.

UDP-glucuronosyltransterases (UGTs) catalyse the glucuronidation and elimination of most xenobiotics and, thereby, may prevent their alternative bioactivation to carcinogenic and teratogenic reactive intermediates. Previous studies have shown that glucuronidation, bioactivation, and covalent binding of the carcinogen/teratogen benzo[a]pyrene (BP) in rat lymphocytes accurately reflected those processes in hepatic microsomes from the same animals. Accordingly, lymphocytes from 12 normal human volunteers were incubated with BP metabolites to determine UGT variability and its potential toxicological relevance. Over 200-fold interindividual variability was observed in both the glucuronidation and covalent binding of BP metabolites, with decreasing total glucuronidation among subjects correlating with a decreased UGT-modulated reduction in covalent binding (R(2) = 0.8272, p < 0.01) and, in six subjects, enhanced cytotoxicity (r = -0.9338, p < 0.001). Decreased glucuronidation of both BP diols (r = -0.9106, p < 0.001) and BP diones (r = -0.9625, p < 0.005), but not BP monophenols, correlated with enhanced cytotoxicity. These results provide the first evidence for substantial interindividual variability in UGT activities for BP metabolites among the normal population and suggest that UGT-deficient individuals may be at increased risk from the reactive intermediate-mediated effects of BP and related xenobiotics.

Adolescent↗
PubMed1983

A network of transverse and longitudinal intermediate filaments is associated with sarcomeres of adult vertebrate skeletal muscle.

An extensive network of transverse and longitudinal filamentous bridges was revealed when small myofibril bundles, prepared from Triton-EGTA-treated rabbit skeletal muscles, were extracted with Kl to remove the majority of thin and thick filaments. Transmission and scanning electron microscopic studies of these salt-resistant cytoskeletal residues indicated (a) small bundles of short transverse filaments connect adjacent myofibrils by forming Z to Z and M to M bridges; (b) parallel, continuous longitudinal filaments connect the peripheries of successive Z-disks and ensheath the sarcomere. These transverse and longitudinal filaments have the characteristic morphology of intermediate filaments; (c) two rings of tightly interwoven and tangled filaments, connected laterally by short filaments, encircle each Z disk. This double-ring also encircles a weblike meshwork which penetrates the sarcomeric space. From the peripheries of these rings, transverse and longitudinal intermediate filaments emerge; and (d) a massive amount of material translocated and accumulated near Z disks during Kl extraction. The residues were fairly resistant to solubilization by urea and SDS, and complete dissolution was achieved only with guanidinium chloride. SDS PAGE indicated that the residues consisted mainly of titin, nebulin, and variable amounts of residual myosin and actin. Desmin represented only a few percent of total residual proteins; however, it may be a major component of the intermediate filament network. We suggest that the intermediate filament should be considered an integral sarcomeric component that may play important cytoskeletal roles in muscle structure and mechanics.

Animals↗