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Biomedical subjects

N Katz

Publications and source records attributed to N Katz.

At least 181 records · Page 10Linked to original sources

Demonstration of leukocyte inhibitory factor in human Schistosomiasis mansoni and its evaluation from patients in an endemic setting.

Leukocyte migration inhibitory Factor (LIF) is produced by the peripheral blood mononuclear cells (PBMN) of most patients with Schistosoma mansoni infection upon their exposure to soluble egg antigens (SEA). PBMN of some patients also respond to adult worm (SWAP) antigens by LIF production. LIF is stable at 37 degrees C for 60 min but is sensitive to heating at 56 degrees C for even 30 min. The serine protease inhibitor PMSF destroyed LIF activity at concentrations of 10(-2) to 10(-3) M. Concanavalin A stimulated production of detectable levels of LIF by 8 hr, while SEA and SWAP did so by 15 and 39 hr, respectively. PBMN of healthy normal controls did not produce LIF upon exposure to SEA or SWAP. PBMN of a few field controls (stool negative subjects from an endemic area) produced detectable LIF activity when exposed to SEA or SWAP. PBMN from most infected (stool positive) patients from an endemic area produced LIF when exposed to SEA and only occasionally did so to SWAP. Previous studies have shown that most often only the PBMN of former, cured patients, and not chronically infected patients, produce the lymphokine activity termed mitogenic factor (MF). The current data indicate that because LIF is primarily produced by actively infected patients, its production may be controlled by different immunoregulatory mechanisms. Furthermore, although most SEA-related responses are highly immunoregulated in active, chronically infected patients, SEA appears to be a better stimulus for patient PBMN production of LIF than SWAP.

Chronic Disease↗

Occupational therapy's domain of concern: reconsidered.

This paper focuses on the domain of concern part of a professional model presented by Mosey in her book Occupational Therapy: Configuration of a Profession (Raven, 1981). Based on additional review of the literature, I suggest two principal alterations. A change in core versus parameter. "Human occupation" replaces "occupational performance" and is presented as the core of the domain of concern because this is the focus of occupational therapy practice; the "performance components" defined here as "competence components" actually serve as a parameter of practice. A reconceptualization of two parameters: "time" and "cultural environment." Time should be considered a separate parameter, including categories of time practice, balance of activities over time, and time perspective. Cultural environment is perceived as a parameter that is composed of four categories: the symbolic, social, physical, and natural environments. This paper emphasizes the interrelatedness of all parts of the model and points out the qualitative differences between the parameters.

Culture↗

Antepartum nonstress test and the postmature pregnancy.

A review of 4320 consecutive term deliveries identified 258 women (6%) delivered at a gestational age of 42 weeks or longer. The group accounted for 30% of all cesarean sections for fetal distress, 30% of all infants with a low five-minute Apgar score, 40% of neonatal intensive care admissions, 60% of neonatal deaths, and 30% of all stillbirths. Nonstress tests were performed on 228 women with a postmature pregnancy. Results were defined as normal (score 7 to 10) in 83.4%, inconclusive (score 5 to 6) in 12.2%, and abnormal (score 1 to 4) in 4.4% of these cases. Monitored patients did significantly better than patients in the nonmonitored group, and so did those with normal nonstress test scores when compared with the abnormal scores. Whereas perinatal mortality in the monitored group was similar to that in the nonpostmature population, the perinatal morbidity was significantly higher.

Apgar Score↗

Immune responses during human Schistosomiasis mansoni. XI. Immunologic status of patients with acute infections and after treatment.

Sixteen patients, 8 to 30 yr of age, with acute (toxemic) phase schistosomiasis mansoni were studied immunologically within 2 to 3 mo of their exposure to Schistosoma mansoni cercariae, and were monitored after chemotherapy. Total leukocyte levels and peripheral blood eosinophilias were higher in these patients than in similar individuals with chronic schistosomiasis mansoni. In contrast to chronic patients, the eosinophilias of the acute cases were decreased rather than elevated upon treatment. Total lymphocyte population (T and B cell) percentages were not altered during acute infection. Lymphoid subset (T3+, T4+, and T8+) analysis revealed elevated levels of both T4+ and T8+ cells. In vitro blastogenic responses of peripheral blood mononuclear cells (PBMN) to heterogeneous schistosome-derived antigens (eggs, SEA; adult worms, AW; and cercariae, CERC) were evaluated. SEA responsiveness was considerably higher than that of patients with chronic S. mansoni infections. The ratios of SEA to AW responses in acute cases gave a mean of 2.0, as opposed to 0.5 for a comparable group of chronically infected patients. The sera of most acute patients already contained suppressive factors that specifically decreased schistosomal antigen-induced PBMN blastogenesis. Chemotherapy of acute cases lead to a diminution of PBMN responsiveness to SEA and CERC. Treatment of patients with chronic infections lead to the elevation of such responses. PBMN from patients with acute infections produced lymphokine leukocyte inhibition factor upon exposure of the cells to SEA but not AW. A similar pattern was true for production of the lymphokine activity mitogenic factor. Levels of antibody in sera of acutely infected patients against SEA, CERC, and AW were considerably higher than levels in sera of chronically infected patients matched for age and intensity of their infections. These high antibody titers persisted for at least 6 mo after treatment, and were unrelated to the intensity of infection. The immunologic status of these patients with acute schistosomiasis mansoni differed considerably from patients with chronic infections. These findings re-emphasize the immunoregulatory events that apparently develop upon continued exposure to schistosomes and their products during chronic infection.

Acute Disease↗

Intralobular distribution of UDP-glucuronosyltransferase in livers from untreated, 3-methylcholanthrene- and phenobarbital-treated rats.

A 3-methylcholanthrene-inducible enzyme form of UDP-glucuronosyltransferase has been localized within the liver lobule both immunohistochemically and enzymatically in microdissected centrilobular and periportal liver tissue. Livers of untreated, 3-methylcholanthrene- and phenobarbital-treated rats have been compared. The enzyme was detected in hepatocytes throughout the liver. However both immunohistochemical determination of the enzyme level and biochemical determination of its activity towards 1-naphthol revealed a heterogeneous distribution of the enzyme. In untreated controls and 3-methylcholanthrene-treated rats both enzyme activity and histochemical staining was highest in centrilobular hepatocytes. However, after phenobarbital-treatment enzyme staining and activity was highest in periportal hepatocytes, suggesting that the differentially inducible enzyme activities may be localized in different zones of the liver lobule. The results demonstrate that the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase is preferentially expressed in centrilobular hepatocytes.

Animals↗

Evaluation of natural killer activity in human schistosomiasis.

Natural killer (NK) activity was assayed in peripheral blood mononuclear cells of patients with schistosomiasis, of patients following treatment, and of uninfected control subjects. The patient populations were from villages in the Qalyub Province, Egypt and around Belo Horizonte , Brazil. NK activity was assayed by the cytotoxicity of 51Cr-labelled K562 target tumor cells. In neither infected population were significant alterations from normal levels found in the percent cytotoxicity per 10(6) cells, or in the lytic units that expressed 25% cytotoxicity. Likewise, prior treatment (2 and 6 months previously) did not alter the group NK activity detected. Similarly, in the Egyptian study there was no difference in the percentage of large granular lymphocytes between the infected and uninfected groups. In parallel studies in Egyptian and Brazilian schistosomiasis patients we did not find any evidence that this chronic infection consistently altered circulating NK activity.

Adolescent↗

Comparative study of Schistosoma mansoni isolated from patients with hepatosplenic and intestinal clinical forms of schistosomiasis.

Six Schistosoma mansoni isolates obtained from the same endemic area were compared experimentally; three were from patients with the hepatosplenic form and three from patients with the intestinal form of schistosomiasis. The following features were analyzed in mice: body weight, liver and spleen weights, mortality, infectivity, number of S. mansoni eggs/female worm, egg distribution in the viscera, and hemogram. Three groups of mice, used as controls, were infected with the LE strain of S. mansoni which is routinely maintained in the laboratory. The group of isolates from patients with the hepatosplenic form of schistosomiasis did not show important differences in relation to those from nonhepatosplenic patients; in almost all features analyzed the differences among these six isolates were within the variation limits observed with the LE strain of S. mansoni.

Adolescent↗

Early stages of chemically induced liver carcinogenesis by oral administration of the antihistaminic methapyrilene hydrochloride.

The antihistaminic drug methapyrilene hydrochloride, which induces liver tumors in rats, was administrated orally to female Wistar rats. The animals were killed after 21, 38, 77, 119, 181, and 196 days. The activities of adenosine-5-triphosphatase (ATPase) and gamma-glutamyltranspeptidase (gamma-GT) in the liver were investigated histochemically. At 21 days, a homogeneous decrease of ATPase activity as well as a slight increase of gamma-GT activity was found in the periportal zone. Additionally, after 38 days hepatocellular foci with reappearance of gamma-GT occurred mainly in the periportal zone. After 119 days, foci with increased gamma-GT activity as well as a significant reduction of ATPase activity could be observed predominantly in the periportal region. The size and number of these putative preneoplastic foci were increased according to the time of administration of methapyrilene hydrochloride. After 181 days of methapyrilene hydrochloride treatment three of five animals developed hyperplastic nodules with corresponding alterations of enzyme activities. Methapyrilene hydrochloride-a carcinogen with an unknown mechanism of reaction-produces preneoplastic changes that are analogous to the well known preneoplastic lesions in the liver observed after administration of other carcinogenic agents.

Adenosine Triphosphatases↗

Immunohistochemical and biochemical detection of uridine-diphosphate-glucuronyltransferase (UDP-GT) activity in putative preneoplastic liver foci.

Preneoplastic liver foci were produced in female Wistar rats by the administration of 2-acetylaminofluorene (0.03% w/w) in the diet for 174 days. Increased UDP-glucuronyltransferase (UDP-GT) could be visualized immunohistochemically in the same focal areas which were ATPase-negative and gamma-glutamyltranspeptidase-positive. Immunohistochemical detection was possible using rabbit anti-UDP-GT and peroxidase-labeled swine anti-rabbit immunoglobulins. The results of immunohistochemistry were substantiated by enzyme determination in microdissected material. UDP-GT activity was 5-fold higher in focal areas in comparison with the surrounding liver tissue. Increased UDP-GT activity in conjunction with the altered pattern of other drug-metabolizing enzymes is consistent with increased resistance of preneoplastic cells to the cytotoxicity of carcinogens. Immunohistochemical detection of UDP-GT may provide a new marker for preneoplastic lesions which, in conjunction with other markers, may prove useful in analyzing the various stages of liver carcinogenesis and the remodeling of preneoplastic lesions after cessation of carcinogenic stimuli.

2-Acetylaminofluorene↗

Schistosoma mansoni: inhibition in vitro of granulocyte cytotoxicity against schistosomula by autologous mononuclear cells from patients.

Granulocytes and mononuclear cells from normal subjects are able to kill Schistosoma mansoni schistosomula in the presence of human complement in vitro. In contrast, mononuclear cells from chronic schistosomiasis patients failed to kill the parasites. The relative efficiencies expressed in terms of the mean percentage killing of schistosomula for 15 experiments were 50.5 +/- 3.2 and 49.7 +/- 3.5 for granulocytes from normal and infected patients, and 50.8 +/- 2.8 against 23.0 +/- 3.2 for mononuclear cells from normal and infected patients, respectively. The killing effect of granulocytes dropped from 48.7 +/- 2.8 to 22.1 +/- 2.2 when autologous mononuclear cells from chronically infected patients were added to the system. Similar inhibitory effect of granulocyte function was obtained when these cells were incubated with normal mononuclear cells precultured with concanavalin A. Extracts prepared from mononuclear cells obtained from infected patients had the same inhibitory effect of intact cells on the complement-dependent granulocyte cytotoxicity.

Complement System Proteins↗

Immune responses during human schistosomiasis mansoni. IX. T-lymphocyte subset analysis by monoclonal antibodies in hepatosplenic disease.

T lymphocyte immunoregulatory subsets (T4+ and T8+ cells) have been analysed in eight cases of hepatosplenic schistosomiasis mansoni, and compared to parallel analyses of seven intestinal Schistosoma mansoni-infected patients and four uninfected control subjects. The mean T4+:T8+ ratio in hepatosplenic cases was markedly less than observed in other groups (0.94 vs 1.86 vs 2.22, respectively). Proliferative responses stimulated by a soluble adult worm extract correlated directly with the observed T4:T8 ratios. Normal levels of E rosette-positive and surface immunoglobulin-bearing lymphoid cells were observed in intestinal patients, while hepatosplenic patients demonstrated normal B lymphocyte proportions but highly erratic E rosette-positive percentages. Curiously, in hepatosplenic patients the percentage of E rosette-positive cells often did not correlate with the proportion of T3+ cells.

Antibodies, Monoclonal↗

Distribution of pyruvate kinase type L and M2 in microdissected periportal and perivenous rat liver tissue with different dietary states.

Pyruvate kinase type L and M2 activities were measured in microdissected periportal and perivenous liver tissue from rats in different dietary states. A specific antibody against pyruvate kinase type L was used to distinguish the two isoenzymes. Using separated cells it was found that the L-isoenzyme was essentially restricted to the parenchymal and the M2-isoenzyme to the non-parenchymal cells. Pyruvate kinase type L activity in the perivenous zone was about twice as high as in the periportal zone in both male and female fed rats. Starvation for 48 h led to a decrease of the overall activity and to a lower perivenous-periportal gradient. After refeeding for 48 h the overall activity and the gradient were increased to above the normal level. Pyruvate kinase type M2 was homogenously distributed within the liver acinus. After 48 h starvation no change in the overall activity nor in the zonal distribution was observed. Refed rats exhibited a slightly reduced overall activity. Since the hepatocytes contain the total regulatory L- but no M2-pyruvate kinase the heterogeneous distribution of the L-isoenzyme under different dietary states supports the model of metabolic zonation of liver parenchyma with glycolysis predominantly in the perivenous zone.

Animals↗

Biochemical quantification of ATPase activities during liver carcinogenesis.

In the course of chemically induced liver carcinogenesis as one of the earliest changes, the histochemically demonstrable focal loss of nucleoside 5'-triphosphatase activities (ATPase) is detectable. The exact quantitation and differentiation of these alterations can be achieved by biochemical analysis in microdissected preneoplastic foci. The preparation of focal tissue was facilitated using a microscopic-microdissecting apparatus [1]. By microanalytic determination of hydrolytic cleavage of 32P from gamma 32P-ATP a decrease of total ATPase activity to about 70% was found. Furthermore, the alteration of ATPase activities in course of chemically induced liver carcinogenesis in rats will be described.

Adenosine Triphosphatases↗

Immune responses during human schistosomiasis mansoni. X. Production and standardization of an antigen-induced mitogenic activity by peripheral blood mononuclear cells from treated, but not active cases of schistosomiasis.

Peripheral blood mononuclear cells (PBMN) from patients with active schistosomiasis mansoni are generally induced to proliferate upon exposure to a soluble worm antigenic preparation (SWAP). In contrast, only 25% of such patients responded to SWAP exposure by the production of detectable levels of a mitogenic factor (MF) activity capable of stimulating proliferation of resting cultures of allogeneic PBMN. When former schistosomal patients (chemotherapeutically cured 10 to 40 yr previously) were tested for these two responses to SWAP, all manifested blastogenesis; 80% also responded by the production of MF activity. Only 9% of control subjects with no history of schistosomiasis produced MF activity when exposed to SWAP. The production and assay of MF activity by former schistosomiasis patients was standardized. Reliable, optimal production was achieved by using 6 X 10(6) PBMN in 2-ml cultures upon exposure to 15 micrograms protein SWAP/ml. The cells were incubated for 20 hr in the presence or absence of SWAP, at which time they were washed and recultured in fresh medium for at least 28 more hours. Subject to subject variability occurred in the optimal time of detection of MF activity in culture supernatant fluids, but detection was assured between 24 and 48 hr after the wash. The assay system for MF detection required a 5 to 7-day culture. The consistent production of MF activity by former schistosomal patients emphasized the longevity of immunologic memory to SWAP, and may indicate a post-treatment decline of immunoregulatory mechanisms that are operative in patients with active schistosome infections.

Antigens↗