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Biomedical subjects

S Kahn

Publications and source records attributed to S Kahn.

At least 19 recordsLinked to original sources
PubMed1992

Polyreactive autoantibodies to negatively charged epitopes following Trypanosoma cruzi infection.

During the course of many human autoimmune diseases, antibodies which recognize negatively charged epitopes on self antigens are detected. Trypanosoma cruzi, an intracellular protozoan parasite capable of infecting a wide variety of vertebrates, is the cause of Chagas disease in humans. Infection with the parasite frequently results in autoimmune and inflammatory pathology. We report here on an affinity-purified population of antibodies that bind to a broad class of antigens that contain runs of acidic amino acids, including tubulin. Although these antibodies can be isolated from both uninfected and T. cruzi chronically infected C3H/He mice, the antibodies from the normal mice (the natural autoantibodies) bind to tubulin poorly at physiological pH, whereas the antibodies isolated from the infected animals bind well at physiological pH. We propose that similar processes may occur in humans following other infections accounting for the detection of antibodies to negatively charged epitopes in a variety of autoimmune diseases.

3T3 Cells↗
PubMed1992

Evaluation of recombinant trypomastigote surface antigens of Trypanosoma cruzi in screening sera from a population in rural northeastern Brazil endemic for Chagas' disease.

A perfect serologic test for infection with Trypanosoma cruzi does not exist. This study uses recombinant T. cruzi surface proteins in the antibody capture enzyme linked immunoabsorption assay (ELISA); and compares this approach to the more standard immunofluorescence assay (IFA). Three recombinant antigens are studied: F1-160 corresponding to the 160 kDa flagellar associated surface protein of trypomastigotes (the motile form of T. cruzi in mammalian infections); and SA 85-1.1 and 1.2 corresponding to different members of the 85 kDa family of surface proteins expressed by trypomastigotes and amastigotes (the replicative, non-motile form of T. cruzi in mammalian infections). Each recombinant antigen is found to be highly specific (range 86-94%) but relatively insensitive (range 36-52%) when used to screen for antibodies to T. cruzi. Defining seropositivity as reactivity to any of the three recombinant antigens markedly increases the sensitivity (72%) with only a minor reduction in specificity (82%). Thus, employing recombinant T. cruzi antigens to screen for T. cruzi infection has promise, but improvements in sensitivity must be made before widespread utilization is recommended.

Animals↗
PubMed1992

Cardiomegaly on chest x-ray: prognostic implications from a ten-year cohort study of elderly subjects: a report from the Bronx Longitudinal Aging Study.

This report is from a 10-year cohort study of community-dwelling elderly men and women. Mean age at the time of entry into the study was 79 years. Annual chest x-ray studies were performed, and data are presented regarding prevalence, incidence, and prognosis of cardiomegaly. Cardiomegaly was defined as a transverse diameter of the cardiac silhouette greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio). At the time of entry into the study 110 subjects (23%) had cardiomegaly. After 10 years, 51% of the subjects with cardiomegaly at baseline died compared with 33% of the subjects without cardiomegaly (mortality rate = 9.1 vs 4.8/100 person-years respectively; p = 0.014). Cardiovascular disease incidence was also higher for those with preexisting cardiomegaly at baseline (rate 9.1 vs 6.1/100 person-years; p = 0.0001). According to the Cox proportional hazards regression analysis, age, cardiomegaly, diabetes, and prior evidence of myocardial infarction were independent predictors for death in this cohort. Similarly, the best predictive variables for cardiovascular disease were age, diabetes, prior evidence of myocardial infarction, and cigarette smoking. Of the 359 subjects without cardiomegaly at baseline, 108 (30%) showed evidence of new cardiomegaly, and their risk of cardiovascular disease was 1.8 times that of subjects whose test results were negative for cardiomegaly throughout the study (p = 0.003). Thus cardiomegaly, as defined by an increased cardiothoracic ratio on x-ray films, irrespective of cause, is associated with a poor prognosis in very elderly men and women.

Aged↗
PubMed1992

Perceptual organization and attention.

It is widely assumed that the grouping of the visual field first described by the Gestalt psychologists and the related phenomenon of texture segregation occur very early in the processing of visual information and involve preattentive processes. All the recent evidence supporting this assumption comes from visual search experiments in which the subject is actively looking for a target and attending to the stimulus. The question at issue is whether these kinds of patterns are perceived under conditions of inattention, i.e., when observers are not searching for them. We performed six experiments to determine whether texture segregation and grouping by similarity or proximity are perceived under conditions of inattention. On the first two trials subjects were asked to report the longer arm of a briefly presented cross which was surrounded by a pattern of ungrouped small elements. On the third trial and subsequent control trials these elements were configured into grouping patterns and subjects queried about them immediately following their line length reports. The results establish that neither texture segregation nor grouping by similarity of lightness or proximity are perceived under conditions of inattention. They support the conclusion that there is an earlier stage of processing than that referred to as preattentive.

Adult↗
PubMed1991

The major 85-kDa surface antigen of the mammalian-stage forms of Trypanosoma cruzi is a family of sialidases.

Trypanosoma cruzi, an intracellular protozoan parasite infecting a wide variety of vertebrates, is the agent responsible for Chagas disease in humans. An estimated 15-20 million people in South and Central America are infected with the parasite. Chagas disease often results in severe autoimmune and inflammatory pathology and is the major cause of heart failure in endemic areas. Nevertheless, little is known about the host-parasite interactions that lead to this pathology. We have previously cloned several members of a large gene family (SA85-1) and shown that these genes encode 85-kDa T. cruzi, mammalian-stage-specific, surface antigens. Here we report that members of the SA85-1 family possess sialidase activity and are shed by the parasite. We suggest that the sialidases may contribute to the pathology during T. cruzi infection by cleaving sialic acid from cells of the immune system.

Amino Acid Sequence↗
PubMed1991

Effects of gemfibrozil and other fibric acid derivatives on blood lipids and lipoproteins.

Fibric acid derivatives (FADs) are a class of drugs that have been shown to reduce the production of very low-density lipoprotein (VLDL) while enhancing VLDL clearance due to the stimulation of lipoprotein lipase activity. The drugs can reduce plasma triglyceride levels while raising high-density lipoprotein (HDL) cholesterol levels. Their effects on low-density lipoprotein (LDL) cholesterol levels are less marked and more variable. There is evidence that oral gemfibrozil (Lopid, Parke-Davis, Morris Plains, NJ) can reduce the risk of serious coronary events, specifically in those patients who had elevations of both LDL cholesterol levels and total plasma triglyceride levels with lower HDL cholesterol levels. Newer FADs (bezafibrate, ciprofibrate, fenofibrate) have been shown to have greater efficacy in reducing LDL cholesterol than gemfibrozil but, in general, these drugs are not as effective as the other primary drugs used to lower LDL levels. The FADs are also used to treat adult patients with very high levels of triglycerides who have pancreatitis and whose disease cannot be managed with dietary therapy. The FADs are well tolerated, with dyspepsia and abdominal pain the most common adverse effects. A small risk of cholelithiasis exists with these drugs, and caution should be used when combining these drugs with HMG-CoA reductase inhibitors because the combination increases the incidence of hyperlipidemic myositis and rhabdomyolysis.

Bezafibrate↗
PubMed1991

Mimicry in Trypanosoma cruzi: fantasy and reality.

Chronic infection of mammals by Trypanosoma cruzi often results in severe autoimmune and inflammatory pathology. Extensive antigen cross-reactivity between the parasite and its mammalian hosts has also been reported. These findings have stimulated speculation that Trypanosoma cruzi uses antigenic mimicry as a mechanism for escaping the host immune system. This may not be the case and the observed antigen cross-reactivity may be a result of perturbations of the immune system such that common, normally tolerated antigens are recognized in infected animals. The parasite, however, does appear to use functional mimicry to survive in the immune competent host.

Acute-Phase Reaction↗
PubMed1991

Hypnosis and the treatment of Huntington's disease.

Huntington's Disease is an inherited fatal disorder of the central nervous system. Literature on the hypnotic treatment of this disease is extremely sparse. We treated two patients with Huntington's Disease using a wide variety of hypnotic interventions. One patient was treated for a number of years and the other for 10 consecutive sessions. We discuss the continuously interacting cycle between the primary physical symptoms caused by the disease and the secondary psychological symptoms. Hypnotic techniques and daily self-hypnosis appeared to ameliorate both physical and psychological difficulties, thereby enhancing the quality of life that remained for the patients. Systematic research into the effectiveness of hypnosis with symptoms of Huntington's Disease needs to be undertaken in the future.

Adult↗
PubMed1991

Prevalence of illicit drug use among prenatal patients and predictive validity of nurses' judgments.

The purposes of this investigation were to: (1) estimate the prevalence of illicit drug use within the prenatal population of a midwestern suburban ambulatory care center; (2) explore the relationship between nurses' judgments of patient illicit drug use and urine toxicology results; and (3) determine if a difference exists between nurses' judgments of illicit drug use by private physicians' patients (PPP) and nurses' judgments of illicit drug use by resident physicians' patients (RPP). For a 16-week period, all new prenatal patients (N = 189) were included in this study; 78 (41%) were in the RPP group and 111 (59%) were in the PPP group. Urine remaining from routine urinalysis was assayed for seven drugs or drug classes. Fourteen (7.5%) subjects tested positive for illicit drugs, 8 (10.3%) in the RPP group, and 6 (5.4%) in the PPP group (chi 2, P greater than .33). Using a Likert-type scale, nurses rated the likelihood of a positive result of each patient's urine test. Nurses' judgments of patient illicit drug use and positive results were related, r = .28. Nurses were more likely (P less than .0001) to suspect residents' patients of illicit drug use than private physicians' patients.

Adult↗
PubMed1990

The major 85-kD surface antigen of the mammalian form of Trypanosoma cruzi is encoded by a large heterogeneous family of simultaneously expressed genes.

Trypanosoma cruzi is an obligate intracellular protozoan parasite. The parasite mammalian stage surface antigens exhibit extensive antigenic diversity. We have characterized a family of T. cruzi genes that code for a polymorphic set of 85-kD surface antigens, the SA85-1 antigens. The family contains greater than 100 genes and pseudogenes, of which a minimum of nine are transcribed. The gene family is expressed in the mammalian stage only. A subset of the gene family is present in two telomere-linked copies in the genome. Telomere linkage of other expressed SA85-1 genes has not been demonstrated. We have shown that at least three members of the SA85-1 gene family encode antigens at the surface of the mammalian stage of the parasite. Interestingly, these three antigens are expressed on all the trypanosomes examined. This suggests that T. cruzi simultaneously expresses a large repertoire of similar, but diverse antigens at its surface. Thus, T. cruzi exhibits extensive antigenic diversity in a system unique from that of African trypanosomes, perhaps reflecting its intracellular niche.

Amino Acid Sequence↗
PubMed1990

Disulfiram-induced hepatitis.

We reported a case of disulfiram-induced hepatitis with unique clinical features and compared our case with others in the literature. Our patient had headache, mild fever, nausea, vomiting, rash, and eosinophilia after 3 weeks of disulfiram therapy. Subsequent liver biopsy showed low-grade lobular hepatitis. After disulfiram therapy was discontinued, symptoms subsided and results of liver function tests returned to normal.

Alcoholism↗
PubMed1990

The role of molecular epidemiology in cancer prevention.

Risk of cancer is determined by the complex interaction between "environmental" exposures and genetic and nutritional factors that modulate response to carcinogenic insults. Here, the term "environmental" encompasses lifestyle, occupation, and the ambient environment. As a promising approach in cancer prevention, a number of biologic markers are currently being evaluated in terms of their ability to identify harmful exposures and populations at risk in time to effectively intervene. These biomarkers are reflective of the molecular dose or early effect of carcinogens (such as DNA or protein adducts, gene or chromosomal alterations and oncogene activation) or they provide information on potential susceptibility (such as the genetically or nutritionally determined handling of carcinogens). Techniques as diverse as immunoassays, 32P-postlabelling and gas chromatography-mass spectroscopy (GC/MS) are being deployed to measure DNA and protein adducts in cells and tissues from persons with occupational, community or lifestyle-related exposure to chemical carcinogens. Signal changes in target oncogenes and tumor suppressor genes are also being investigated in heavily exposed, "healthy" populations and in lung cancer cases and controls using current molecular biologic techniques. Inherited predisposition to lung cancer is being evaluated through such assays as aryl hydrocarbon hydroxylase (AHH), glutathione activity and restriction fragment length polymorphism. A review of recent studies using a panoply of biomarkers provides a departure point for recommendations for future, integrated molecular epidemiologic studies of cancer.

Animals↗
PubMed1989

Motion aftereffects and retinal motion.

Two experiments are described in which it was investigated whether the adaptation on which motion aftereffects (MAEs) are based is a response to retinal image motion alone or to the motion signal derived from the process which combines the image motion signal with information about eye movement (corollary discharge). In both experiments observers either fixated a stationary point or tracked a vertically moving point while a pattern (in experiment 1, a grating; in experiment 2, a random-dot pattern) drifted horizontally across the field. In the tracking condition the adapting retinal motion was oblique. In the fixation condition it was horizontal. In every case in both conditions the MAE was horizontal, in the direction opposite to that of pattern motion. These results are consistent with the hypothesis that the adaptation is a response to the motion signal derived from the comparison of eye and image motion rather than to retinal motion per se. An alternative explanation is discussed.

Adaptation, Ocular↗
PubMed1988

Time-related changes in the Starling forces following extracorporeal circulation.

The intra- and postoperative variations of the transcapillary forces [colloid osmotic pressure of plasma (COPpl), colloid osmotic pressure of interstitial fluid (COPif), average hydrostatic pressure in the interstitium (Pif)] were studied in the subcutaneous tissue as a function of time in 13 patients operated on for coronary artery disease using extra-corporeal circulation (ECC). The measurements were performed before operation, during ECC, and during the first 24 hours postoperatively. COPif was measured subcutaneously on the chest both by the wick method and by a noninvasive blister suction method. The latter technique allowed several consecutive measurements in the same individual during the postoperative period. Pif was measured by "wick-in-needle" technique in the same area as the COPif measurements. COPpl was measured in a blood sample collected from a cubital vein. COPpl was reduced about 50% during ECC returned to pre-ECC level within the first 6 hours postoperatively. During ECC COPif was higher than COPpl, reaching its minimum level 4 to 5 hours postoperatively. Measurements performed following ECC showed return of the transcapillary COP-gradient to the normal direction (COPpl greater than COPif). Pre-ECC level of COPif was not entirely obtained during the first postoperative day. Pif increased gradually during ECC and continued to increase the first 2 to 3 hours following ECC. Pre-ECC level was reached within 24 hours postoperatively. The present investigation has demonstrated major dynamic variations in the transcapillary forces in patients undergoing open heart surgery with ECC. There was an increased net capillary filtration (F) intraoperatively predisposing to interstitial edema formation in subcutaneous tissue until several hours following the termination of ECC.

Adult↗
PubMed1986

Biochemical and immunocytochemical evidence for a deficiency of normal interfascicular oligodendroglia in the CNS of the dysmyelinating mutant (md) rat.

Carbonic anhydrase was assayed and carbonic anhydrase and 5'-nucleotidase were localized in the CNS of myelin-deficient mutant rats and normal littermates. The carbonic anhydrase specific activities were reduced by 61% and 29% in the mutants' forebrains and cerebella, respectively, and the total carbonic anhydrase activity in the spinal cords was reduced by 35%. Immunostained cells were found in gray matter from both normal and mutant rats, but, in the mutants, there was a marked deficiency of interfascicular oligodendrocytes in the regions that are normally occupied by white matter. It is suggested that a developmental study could indicate the step(s) at which normal differentiation of interfascicular oligodendroglia is blocked in this mutant.

5'-Nucleotidase↗
PubMed1985

Immunocytochemical localization of 5'-nucleotidase in oligodendroglia and myelinated fibers in the central nervous system of adult and young rats.

Rat central nervous system (CNS) tissue sections were immunostained by the peroxidase-anti-peroxidase (PAP) method using a rabbit serum directed against rat liver 5'-nucleotidase. In paraffin sections from the brains of 60-day-old rats 5'-nucleotidase immunoreactivity occurred in the same white-matter regions as myelin-basic protein immunoreactivity and histological staining of myelin. The immunostaining of cerebral white matter for 5'-nucleotidase was more intense and wide-spread at the age of 120 days than at 60 days, and the choroid plexus and blood vessels were stained consistently. In the paraffin sections from the brains of younger (20-day-old) rats the staining of 5'-nucleotidase in the white matter was faint and patchy. In paraffin sections from spinal cord, 5'-nucleotidase immunoreactivity was observed throughout the lateral white-matter columns and, frequently, in the cell bodies of interfascicular oligodendroglia. Interfascicular oligodendroglia also showed 5'-nucleotidase immunoreactivity in vibratome sections from the CNS tissue of young and adult rats. The findings were consistent with histochemical and biochemical evidence for 5'-nucleotidase in rat brain myelin and oligodendroglia, with substantial increases in activity in the myelin as rats develop from the ages of 20 to 120 days. 5'-Nucleotidase immunoreactivity was not observed in any astrocytes or in oligodendrocytes in the gray matter; however, the enzyme may occur in those glial cells at levels lower than were detectable using the present method.

5'-Nucleotidase↗