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Biomedical subjects

N Katz

Publications and source records attributed to N Katz.

At least 19 recordsLinked to original sources
PubMed1992

Hepatocyte heterogeneity in the metabolism of fatty acids: discrepancies on zonation of acetyl-CoA carboxylase.

Lipid metabolism appears to be less zonated than carbohydrate and protein metabolism. Studies on the zonation of lipid metabolism have been centered in particular on fatty acid synthesis which, according to the concept of metabolic zonation, should be a predominantly perivenous process while fatty acid oxidation should be periportal. There are, however, conflicting data on the activity gradients of lipogenic enzymes as well as measurements of actual synthesis of fatty acid and very low density lipoprotein. Data obtained by microdissection show a 1.5- to 2-fold higher activity of acetyl-CoA carboxylase and citrate lyase in the perivenous zone in agreement with measurements of the actual rate of fatty acid synthesis in preparations of hepatocyte, enriched in periportal or perivenous cells. On the other hand, results obtained with the dual-digitonin-pulse perfusion technique demonstrate the opposite gradient in the form of a 2- to 3-fold higher specific activity of acetyl-CoA carboxylase in the periportal zone based on measurements of the acetyl-CoA carboxylase protein proper. This specific activity gradient, which applies to male and not female rats, disappears almost completely in the fasted-refed animal, were lipogenesis is strongly induced. In this review we attempt to rationalize these discrepancies in the results as methodological differences which in particular apply to the following parameters: (1) expression of results (reference substance); (2) selectivity of zonal sampling, and (3) differences in methodology of acetyl-CoA carboxylase measurements. It is concluded that these factors could account for the discrepancies, but further studies, in particular on the zonation acetyl-CoA carboxylase mRNA, are required in order to further understand the zonation of lipid metabolism and its possible role in the metabolic regulation of the liver.

Acetyl-CoA Carboxylase↗
PubMed1992

Vaccination in murine schistosomiasis with adult worm derived antigens--II. Protective and immune response in inbred mice.

Previous work in our laboratory, mainly focused the prospects of achieving resistance against Schistosoma mansoni infection with adult worm-derived antigens in the form of a soluble extract (SE). This extract obtained by incubation of living adult schistosomes in saline, contains a large number of distinct molecules and was actually shown to be significantly protective in different outbred animals models such as Swiss mice and rabbits. It thus appeared worthwhile to investigate the potential protective activity of SE in different inbred strains of mice, known to be highly susceptible to the infection. Herein we present data showing that DBA/2 mice, once immunized with SE acquire significant levels of resistance to a S. mansoni cercarial challenge. In addition, preliminary studies on the immune system of immunized animals revealed that, injection of SE caused no general imbalance of B or T cell responses.

Animals↗
PubMed1992

Brazilian contributions to epidemiological aspects of schistosomiasis mansoni.

A review of epidemiological aspects of endemic areas for schistosomiasis, especially in Brazil, will be presented. These studies, performed by several authors from different states of the country, have been very useful in indicating the relative efficacy of control measures. For example quoting only one aspect, specific treatment was demonstrated by Brazilian researchers to be the most important individual tool for morbidity control. More recently the study of risk factors in endemic areas has been seen to be a very important approach when transmission control is the final goal.

Brazil↗
PubMed1992

Hormone-sensitive carbohydrate metabolism in rat hepatocyte-hepatoma hybrid cells.

Hepatocyte-hepatoma hybrid cells were obtained by fusion of hepatocytes from adult rats and Fao hepatoma cells in the presence of polyethylene glycol. These hybrids were called hepatocytoma cells. The preservation of liver-specific enzyme activities and metabolic functions was studied in the hybrid clone 1E3. 1) The proliferating hepatocytoma cells formed monolayers presenting morphological similarity to primary cultures of hepatocytes. 2) In contrast to Fao hepatoma cells, activities of all gluconeogenic key enzymes were preserved at normal or reduced levels. 3) Lactate-dependent glucose formation was maintained at a state reduced to 36% of the gluconeogenesis in hepatocytes; no glucose formation was detected in Fao hepatoma cells. 4) The activity of the liver-specific glucokinase was reduced in hepatocytoma cells, but it was still present in contrast to Fao cells. The liver-specific isoenzyme pyruvate kinase type L was replaced by the isoenzyme type M2. 5) Gluconeogenic and glycolytic enzyme activities were regulated in hepatocytoma cells by glucagon (0.1 microM) and by insulin (0.1 microM). 6) The genome of hepatocytoma cells and its expression were stable for at least one year, when spontaneously dedifferentiating cells were removed by recloning in hypoxanthine-aminopterine-thymidine (HAT) medium.

Animals↗
PubMed1992

A Piagetian framework as a basis for the assessment of cognitive organization in schizophrenia: a comparison of adolescent and adult patients to a normal control group.

Piaget's theoretical framework was utilized in this study to investigate the cognitive organization of schizophrenic patients. Data from a battery of eight Piagetian tasks of concrete and formal operations was collected for adolescent and adult-acute and chronic schizophrenic patients, and was compared to matched normal control groups. Findings show significant differences between patients and controls; among the patients' chronicity, age and hospitalization are contributing variables to lower cognitive performance. Concrete operational tasks in the physical and spatial domains are retained better than in the logico-mathematical domain, or formal operational tasks in all domains. Major problems appear in the ability to abstract general criteria and to mentally work with more than one dimension at a time. A logical approach to the solution of concrete problems and solving problems which seem to present a contradiction, or cause problems in the accommodation and integration of one's thinking. Further studies are needed in order to draw conclusions and to understand the implications for every day functioning, deficient in the schizophrenic patient.

Acute Disease↗
PubMed1991

Autoregulatory control of actin synthesis in cultured rat hepatocytes.

ADP-ribosylation of actin by Clostridium botulinum C2 toxin resulted in a depolymerization of filamentous F-actin and an increase of monomeric G-actin in cultured hepatocytes. Simultaneously the de novo synthesis of actin was largely reduced, while the synthesis of albumin and of other proteins was not significantly impaired. The specific decrease of actin mRNA to 30% of the control indicates a down-regulation of actin synthesis at a pretranslational level. On the other hand, treatment with the mycotoxin phalloidin resulted in an increase of F-actin and a decrease of monomeric G-actin. Under this condition the de novo synthesis of actin was specifically enhanced and the level of actin mRNA was increased to 600% of the control. The data suggest an autoregulatory control of the actin synthesis.

Actins↗
PubMed1991

Vaccination in murine schistosomiasis with adult worm-derived antigens: variables influencing protection in outbred mice.

Previous studies have shown that both permissive (mouse) and partially permissive (rabbit) hosts develop high levels of resistance against Schistosoma mansoni infection after vaccination with a multiple antigen extract (SE) obtained by incubation of living adult worms in saline, plus bacterial adjuvant. To investigate variables influencing SE-induced protection in murine schistosomiasis, a series of distinct vaccination protocols were performed focussing on the immunization dose, carrier systems, route, site and amplitude of challenge infection, and time between immunization and challenge. In addition, a new approach was adopted to evaluate SE protective activity, by means of population analysis of worm burden frequency distributions in a large scale study of vaccination in outbred Swiss mice. Distinct curves of frequency and a drastic difference in worm burden distribution of frequencies from SE-vaccinated x non-vaccinated mice were found. It was shown that SE could generate 75% mean protection in outbred mice even in the absence of adjuvant. In addition SE immunization was also able to induce full protection against lethal infection. SE-induced protection could be modulated by such parameters as dose of SE immunization/challenge interval, and route of cercariae injection. These data show that SE yields very high protective activity in outbred mice, and may provide a further insight for rational design of a vaccine in experimental schistosomiasis.

Animals↗
PubMed1991

International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC publication No. 18. Review of the genotoxicity and carcinogenicity of antischistosomal drugs; is there a case for a study of mutation epidemiology? Report of a task group on mutagenic antischistosomals.

One of the interests of ICPEMC is to identify situations in which the possible induction of inherited defects in man by mutagen exposure could actually be studied. The large-scale use of mutagenic drugs in field programmes against schistosomiasis, mainly during the 1970's, was considered a possible case. An ICPEMC task group approached the problem by (1) updating the genetic toxicology data base for antischistosomal drugs, and (2) reviewing possible study areas. Expertise was combined from genetic toxicology, mutation epidemiology and tropical medicine. It was considered that: (a) if any, hycanthone would be the most appropriate candidate drug for study; (b) it would be virtually impossible to meet the basic requirements of an appropriate mutation epidemiology study, in endemic countries; (c) as more defined genetic endpoints would be selected (e.g. sentinel phenotypes) the required large sample sizes would seem prohibitive, since documentation on past programmes is limited and local demography would render the reliable tracking of substantial numbers of offspring of treated persons an almost impossible task; (d) in most endemic countries proper diagnosis and registration of inherited defects is largely lacking; (e) the problems encountered in demonstrating inherited effects in humans after heavy or chronic exposure to established animal mutagens such as ionizing radiation and cancer chemotherapy, in combination with the ambiguous nature of the animal germ cell data with hycanthone, do not particularly warrant large expectations; (f) since non-mutagenic antischistosomal drugs are now in use, the problem is academic and of low priority in the endemic countries whose medical and research resources are often limited. Thus, studying offspring of hycanthone-treated people to demonstrate the mutagenic potential of the drug in man is not a viable enterprise.

Animals↗
PubMed1991

Activity of the artemether in experimental schistosomiasis mansoni.

The action of the ether of artemisinin (artemether) on Schistosoma mansoni in mice and hamsters experimentally infected with the LE strain was studied. In mice, the drug showed high schistosomicidal activity using a single intramuscular dose of 100 mg/kg/day. By the oral route, this dose showed a low activity. Mice treated with a single intramuscular dose of 200 mg/kg/day, and examined 15 days after treatment, presented 100% alteration of the oogram; when examined 45 days after treatment, the oogram was normal. With doses of 100 mg/kg/day, i.m., during 3 or 5 consecutive days, the death rate of mice was very high. Morphologic analysis of the worms collected by perfusion of mice treated with a single dose of 100 mg/kg/day, i.m., detected a marked decrease in the length of male and female worms, degenerative alterations in the parenchyma and in the reproductive system of the females, with the reduction of vitellinic material and in ovary volume; the intestinal contents presented a marked despigmentation. In the male worms significant alteration was not apparent by optical microscopy.

Animals↗
PubMed1991

Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. III. In vitro granuloma modulation induced by immune complexes.

Granulomatous hypersensitivity to parasite eggs of Schistosoma mansoni is an important factor in the development of morbidity in chronic schistosomiasis. It has been demonstrated previously that the chronic, well-tolerated, intestinal form of schistosomiasis is associated with the establishment and maintenance of a variety of immunoregulatory mechanisms. We have used an in vitro model of granuloma formation for the purpose of studying the regulation of granulomatous hypersensitivity to S. mansoni egg antigens, mediated by immune complexes (IC). Our results show that the peripheral blood mononuclear cells (PBMCs) from patients with active schistosome infections, when treated with sera from chronic schistosomiasis patients, were able to induce an inhibitory activity on in vitro granuloma formation. Significant modulation of the in vitro granuloma reaction remained after treatment of PBMCs with isolated IC or manufactured IC with soluble egg antigen (SEA) and purified IgG from pooled chronic schistosomiasis sera. In contrast to granuloma modulation stimulated with whole molecule IgG-SEA IC, the incubation of PBMCs with F(ab')2 IgG-SEA IC did not induce any suppression of the granulomatous hypersensitivity to SEA. It appears in this model system that IC may inhibit the activity of granuloma formation by stimulating macrophages to release suppressive mediators. We have demonstrated this possibility by inhibition of prostaglandin activity using indomethacin. The addition of indomethacin to the granuloma culture significantly reduced in vitro granulomatous hypersensitivity to S. mansoni eggs in patients with chronic intestinal schistosomiasis and do so by inducing macrophages to secrete prostaglandins.

Alprostadil↗
PubMed1991

Efficacy of alternating therapy with oxamniquine and praziquantel to treat Schistosoma mansoni in children following failure of first treatment.

Two hundred children infected with Schistosoma mansoni were treated with either 20 mg/kg oxamniquine or 60 mg/kg praziquantel. Cure rates (about 85%) were similar as was the percentage reduction (80%) in egg counts in uncured children. Treatment with the alternative drug of children not cured with the first treatment resulted in negative stools in 11 of 12 cases examined one month after the second round of therapy. In order to minimize the risk of the development of drug resistance, our data suggest that infected patients be treated with one drug, and therapeutic failures with another. Evidence from experiments in mice with isolates obtained after failures of one treatment in children suggests that therapeutic failure does not necessarily indicate the presence of drug-resistant schistosomes. The value of using mice to assess drug resistance in schistosomes is questioned.

Adolescent↗
PubMed1991

Genomic variability in field populations of Schistosoma mansoni in Brazil as detected with a ribosomal gene probe.

A cloned fragment of the ribosomal gene of Schistosoma mansoni, pSM 389, which contains part of the small rRNA gene plus a portion of the nontranscribed intergenic spacer, was used in Southern hybridization analyses to investigate genomic variation in natural populations of S. mansoni in Brazil. Genomic DNAs were isolated from schistosomes from infected patients (some of whom did not respond to antischistosomal chemotherapy), and from snails from disparate geographic locations in Brazil. Restriction fragment length polymorphisms (RFLPs) were evident in Southern blot hybridizations of these schistosome DNAs, and the RFLPs indicated that the genomic profiles of a number of Brazilian strains were more similar to each other than they were to parasites from two laboratory reference strains of Puerto Rican origin. In addition, the Brazilian isolates could generally be separated from each other based on these RFLPs. Isolates from the southeastern state of Minas Gerais were more similar to each other than they were to parasites isolated in the northeastern states of Alagoas and Pernambuco. Variation was evident among individual worms from some of the isolates, and these individual variations contributed to the complex RFLP patterns that were characteristic for particular isolates. The variation within a natural population isolated directly from snails at Ressaca, Belo Horizonte, may be more marked than that exhibited by more established strains maintained in the laboratory for numerous generations.

Animals↗
PubMed1991

Meaning ascribed to major professional concepts: a comparison of occupational therapy students and practitioners in the United States and Israel.

A number of concepts related to human performance, such as occupation, purposeful activity, function, work, doing, and play/leisure, are widely used in occupational therapy. Because these concepts are essential to the profession, we seek to understand their meaning. Many theorists in occupational therapy define and attribute different levels of importance to each of these concepts. The present study examines the professional (student vs. practitioner) and universal (American vs. Israeli) meanings of the six concepts named above. Four statistical methods were used: (a) a multivariate analysis of variance, (b) t tests and a sign test to analyze the Osgood semantic differential, and (c) Individual Differences in Multidimensional Scaling (Carroll & Chang, 1970). The results indicate that the American occupational therapists ascribed higher affective meanings than did all of the other groups to the concepts of purposeful activity, function, doing, and work. No difference was found for occupation and hobby, which rated high for all groups. Differences in the dimensions underlying the concepts between American and Israeli subjects suggest a cultural and linguistic influence on the meaning ascribed to the concepts.

Analysis of Variance↗
PubMed1991

A problem-solving version of the Allen Cognitive Level Test.

The purpose of this study was to construct and validate a problem-solving version of the existing Allen Cognitive Level Test (ACL) (Allen, 1985). The new problem-solving version of the ACL (ACL-PS) follows the theoretical developments of the cognitive disability theory and the information processing approach. It was constructed to provide a more accurate assessment of the problem-solving process as well as task performance, especially at the higher cognitive levels. Both tests were administered to a psychiatric adolescent group (n = 49) who were subdivided according to diagnosis and to a matched nondysfunctional control group (n = 29). The results showed that both the ACL and the ACL-PS differentiated significantly between the patients and the control subjects and among the patient groups. At Level 6 of the ACL, none of the subjects needed any demonstration, with all scores distributed between independent performance or performance following verbal instructions only, that is, problem-solving phases that were added with the ACL-PS. The scoring of the ACL-PS is provided in addition to detailed scoring of the cognitive levels. It is suggested that the ACL-PS be implemented as a clinical evaluative tool with adolescents.

Adolescent↗
PubMed1991

[Effects of eugenol and derivatives on Biomphalaria glabrata].

Biomphalaria glabrata snails and egg-masses were exposed, for six to twenty-four hours to concentrations of 1, 10, 100 and 1000 ppm of Eugenol, O-methyleugenol, O-benzyleugenol and dehydrodieugenol. Only at 10 ppm O-benzyleugenol enhanced mortality of snails and egg-masses. The other substances showed ovicidal and molluscicidal activity only at 100 and 1000 ppm concentrations, causing a significant cardiac frequency reduction in snails after 6 to 24 hours of exposure as well as perduring low cardiac rates until 24 hours afterwards. Two specimen exposed to 100 ppm O-methyleugenol presented anesthetic effect and extrusion of copulator and urethral organs. No schistosomicide or anesthetic effects were observed in mice experimentally infected with Schistosoma mansoni and treated during 5 days with oral doses of 150 mg/kg of Eugenol, O-methyleugenol and O-benzyleugenol.

Administration, Oral↗
PubMed1991

Schistosoma mansoni-New Zealand rabbit model: resistance induced by infection followed by active immunization with protective antigens.

In previous studies, rabbits immunized with adult worm antigens released from fresh adult schistosomes incubated in saline media showed a significant level of protection against challenge parasites. Focusing on the rabbit-Schistosoma mansoni model, concomitant immunity was investigated. A peculiar form of response to cercarial infection was observed: rabbits subjected to percutaneous infection and similar reinfections at different times after primary infection killed schistosomula from the challenge infection as well as established parasites from the primary infection. In this study the challenge infection stimulus was replaced by active immunization with an adult worm-derived protective antigenic mixture. The results show that immunization of New Zealand rabbits with an adult worm antigenic extract is capable of inducing a response that results in a significant reduction of the mean worm burden of the primary infection earlier than did homologous infection, as compared to worm reduction due to a second infection.

Animals↗
PubMed1990

Hepatocyte specific long lasting inhibition of protein N-glycosylation by D-galactosamine.

The effect of D-galactosamine on protein N-glycosylation was studied in rat hepatocyte primary cultures for alpha 1-antitrypsin (three complex type oligosaccharide chains) and alpha 1-acid glycoprotein (six complex type oligosaccharide chains). D-Galactosamine at a concentration of 4 mM inhibited partially de novo N-glycosylation leading to the formation of alpha 1-antitrypsin lacking one to two and of alpha 1-acid glycoprotein lacking one to five of its carbohydrate side chains. In addition D-galactosamine interfered with oligosaccharide processing, leading to the formation of some carbohydrate side chains remaining in an endoglucosaminidase H sensitive, i.e., not completely processed, form. D-Galactosamine impaired the secretion of alpha 1-antitrypsin and of alpha 1-acid glycoprotein but did not inhibit the secretion of the unglycosylated albumin. The inhibitory effect of D-galactosamine on de novo glycosylation as well as on oligosaccharide processing lasted for at least 24 h after it had been removed from the cells. D-Galactosamine impaired the glycosylation of alpha 1-antitrypsin only in hepatocytes, but not in human monocytes. Furthermore, D-galactosamine did not impair the N- and O-glycosylation of interleukin-6 in human monocytes and in MRC 5 fibroblasts. The results indicate that the effect of D-galactosamine on protein glycosylation is restricted to D-galactosamine metabolizing hepatocytes and is not exerted by the drug itself but by its metabolites.

Acetylglucosaminidase↗