Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 235 records · Page 13Linked to original sources

PubMed1990

Regulation of interleukin 1 generation in immune-activated fibroblasts.

In the present study we have demonstrated that fibroblasts can generate the inflammatory cytokine interleukin 1 (IL 1) under conditions similar to those abundant in cellular immune responses. Thus, induction of IL 1 requires a sequential two-step protocol which consists of preactivation of mouse embryo fibroblasts (MEF) with crude preparations of T cell or macrophage-derived conditioned media (CM; 72 h), followed by a challenge with lipopolysaccharide (LPS; 24 h). Unstimulated fibroblasts or such cells activated by either CM or LPS produced only low levels of IL 1, while a synergism between both signals was observed for obtaining maximal IL 1-like activity in MEF. Each of a series of individual recombinant lymphokines and cytokines (IL 2, granulocyte/macrophage-colony-stimulating factor, tumor necrosis factor, IL 1 beta and interferons-alpha, beta and gamma) was shown to serve as an efficient priming signal for the induction of IL 1. IL 1-like activity in fibroblasts was detected in cell lysates or associated with the producing-cell membrane but not in culture fluids. Immune-stimulated fibroblasts, activated under such experimental conditions, were shown to actively transcribe mRNA of both IL 1 genes (alpha and beta). For the expression of IL 1-specific mRNA in fibroblasts a single stimulus, provided by either LPS or a lymphokine/cytokine, was sufficient; however, a more intense signal was observed when both stimuli were applied. The IL 1-like biological activity of fibroblast origin was significantly reduced by anti-IL 1 alpha antibodies. Thus, fibroblasts, when activated by immune and bacterial products, generate IL 1 which in turn possibly amplifies cellular immune responses or inflammatory processes in connective tissues.

Animals↗

PubMed1990

Topoisomerase I activity associated with human immunodeficiency virus (HIV) particles and equine infectious anemia virus core.

In the present study, we found a topoisomerase I (topo I) activity in two strains of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV) particles. The topo I activity was located in the EIAV cores and differed from the cellular topo I in its ionic requirements and response to ATP, indicating that these were two distinct forms of this enzyme. Topo I activity was removed from the viral lysates and viral cores by anti-topo I antiserum. The only protein recognized by this antiserum was an 11.5 kd protein in HIV lysate and 11 kd in EIAV lysate. We showed that the 11 kd protein recognized by the anti-topo I antiserum is the EIAV p11 nucleocapsid protein. Furthermore, purified topo I protein blocked the binding of the antibodies to the p11 protein and vice versa, purified p11 protein blocked the binding of these antibodies to the cellular topo I. These results suggest that the EIAV p11 nucleocapsid protein and the cellular topo I share similar epitopes.

Antibodies↗

PubMed1990

Cystine and dibasic amino acid uptake by opossum kidney cells.

The characteristics of the uptake of L-cystine by the continuous opossum kidney cell line, OK, were examined. Uptake of cystine is rapid and, in contrast to other continuous cultured cell lines, these cells retain the cystine/dibasic amino acid transport system which is found in vivo and in freshly isolated kidney tissue. Confluent monolayers of cells also fail to show the presence of the cystine/glutamate transport system present in LLC-PK1 cells, fibroblasts, and cultured hepatocytes. Uptake of cystine occurs via a high-affinity saturable process which is independent of medium sodium concentration. The predominant site of cystine transport is across the apical cell membrane. The intracellular concentration of GSH far exceeds that of cystine with a ratio greater than 100:1 for GSH:cysteine. Incubation of cells for 5 minutes with a physiological level of labelled cystine resulted in the labelling of 66% and 5% of the total intracellular cysteine and glutathione, respectively. The ability of these cells to reflect the shared cystine/dibasic amino acid transport system makes them a suitable model for investigation of the cystine carrier which is altered in human cystinuria.

Amino Acids↗

PubMed1990

Regulation of galactose metabolism: implications for therapy.

In view of evidence that dietary therapy of galactose-1-phosphate uridyltransferase deficiency has failed to prevent complications of the disorder, there is a need for new strategies in treatment. The enhancement of residual enzyme activity in tissues of galactosaemic patients should provide such an approach. This possibility is derived from knowledge of the regulation of transferase activity in normal animal tissues. The pertinent observations summarized herein are: (1) that hepatic transferase activity is modulated by various cellular metabolites, uridine nucleotides being of particular significance; (2) that transferase activity in the young rat liver is subject to developmental programming with a several-fold increase after birth; (3) that transferase activity in pregnant rat liver is significantly increased which may be related to hormonal effects of progesterone; and (4) that pharmacological doses of folic acid may increase transferase activity. The basis of such regulation can give insight into sufficient augmentation of the residual activity to increase galactose utilization and thereby better the long-term outcome.

Animals↗

PubMed1990

Cystine uptake by cultured cells originating from dog proximal tubule segments.

Large numbers of kidney epithelial cells were cultured successfully from isolated dog proximal tubule segments. Cells in primary culture and in first passage retained the cystine-dibasic amino acid co-transporter system which is found in vivo and in freshly isolated proximal tubule segments. In contrast to other cultured cells, the cystine-glutamate anti-porter was absent in primary cultures. However, this anti-porter system seemed to be developing in cells in first passage. The intracellular ratio of cysteine:reduced glutathione (CSH:GSH) was maintained at 1:36 in both primary cultures and in low passage cells. Incubation of cells in primary culture for 5 min at 37 degrees C with 0.025 mM [35S]L-cystine resulted in incorporation of approximately 36 and 8.5% of the label into intracellular CSH and GSH, respectively. These cultured cells, therefore, seem to be an excellent model system for the eventual elucidation of a) the inticacies of cystine metabolism and b) regulation of 1) the cystine-dibasic amino acid co-transporter system and 2) the development of the cysteine-glutamate anti-porter system.

Amino Acids↗

PubMed1990

Typing of Pseudomonas aeruginosa ear infections related to outcome of treatment.

Of 142 patients with Pseudomonas aeruginosa (PSA) ear infections, 88 (62 per cent) had chronic otitis media and 54 (38 per cent) external otitis. Following serotyping and pyocin typing of their bacteria, and relating the type to outcome, patients could be divided into three groups: (1) 120 patients who had no recurrence with isolation of only one PSA strain, (2) 13 patients who had recurrent infections and in whom the same PSA strain was isolated in repeated cultures, and (3) nine patients who had recurrent disease, but who had a change in their PSA strains. Most of the PSA strains isolated from patients in groups (1) and (2) were stable to pyocin, and resistent to gentamicin. Patients in the first group were all cured initially by medical management. Of the nine patients in group (3) who had a different serotype on repeated cultures, medical treatment was successful in eight (89 per cent), but of the 13 patients in group (2) who had the same Pseudomonas aeruginosa serotype cultured, medical therapy failed in six (46 per cent) and mastoid surgery was required. Serotyping of Pseudomonas aeruginosa otitis may be helpful in predicting the type of management in patients who have recurrent infections.

Adolescent↗

PubMed1990

Chemical-retroviral cooperative carcinogenesis and its molecular basis in NIH/3T3 cells.

We demonstrate in this study that infection with Moloney murine leukemia virus (M-MLV) and exposure to 3-methylcholanthrene (3-MC) can cooperate to transform NIH/3T3 mouse fibroblasts. M-MLV seems to stimulate the expression of c-myc and of a certain major histocompatibility complex (MHC) class I gene. Yet M-MLV infection by itself is insufficient to transform these cells. However, exposure of the infected cells to 3-MC resulted in a rapid cell transformation with concomitant enhancement of c-Ha-ras and H-2K class I MHC gene expression in the transformed cells. No such transformation was observed when uninfected NIH/3T3 cells were similarly treated with this carcinogen. Clones of cells transformed by this combined effect of M-MLV and 3-MC were found to be highly tumorigenic in fully immunocompetent allogeneic BALB/c mice. We provide evidence to suggest that the enhanced expression of the H-2K gene in these transformed cells plays an important role in overcoming the BALB/c allogeneic barrier and allowing tumor growth in these mice.

Animals↗

PubMed1990

The response to ovarian hyperstimulation and in-vitro fertilization in women older than 35 years.

There are conflicting reports concerning the effect of female age and potential reproductive function. We assessed the response to ovarian hyperstimulation in two consecutive IVF cycles in 25 women greater than 35 years of age and compared their response to a control group of 48 women less than 35 years of age who conceived in our IVF programme. In the older women, the maximal oestradiol response was proportional to the number of vials of HMG used and did not differ from the response of the younger women. Similarly, the number of follicles of diameter greater than 1.0 cm, the number of oocytes recovered and the number of embryos which cleaved did not differ between the older and the younger women. However, conception rates were markedly lower in the older women than the overall pregnancy rate in the IVF programme during the same time period. We conclude that the older women in this study have a normal response to ovarian stimulation but may have a decreased receptivity of the endometrium or increased numbers of embryos with chromosomal abnormalities, leading to a reduced rate of implantation.

Clomiphene↗

PubMed1990

The association between students' research involvement in medical school and their postgraduate medical activities.

The authors examined the impact of students' research involvement during medical school on their postresidency medical activities. The three medical schools involved--The Pennsylvania State University College of Medicine (PSU), The University of Connecticut School of Medicine (UCONN), and The University of Massachusetts Medical School (UMASS)--have nearly indistinguishable applicant, matriculant, and curriculum profiles. However, at PSU a research project is a curriculum requirement for students who did not do medical research prior to entering medical school. Questionnaires were sent to all graduates from the classes of 1980, 1981, and 1982. A total of 567 graduates completed the questionnaires, an overall response rate of approximately 76%. Medical school research experience was reported by 83% (183) of the PSU graduates, 34% (52) of the UCONN graduates, and 28% (54) of the UMASS graduates. When compared on a school-by-school basis, the graduates from the three schools did not differ with respect to residency specialty training, fellowship training, academic appointments, career practice choices, or postgraduate research involvement. However, when all the graduates studied were examined as a single group, medical school research experience was found to be strongly associated with postgraduate research involvement.

Academic Medical Centers↗

PubMed1990

Usefulness of a short femur in the in utero detection of skeletal dysplasias.

In 28 fetuses studied during a 4 1/2-year period, the initial femur was below 2 standard deviations (SDs) of the mean when compared with the biparietal diameter. These fetuses were considered at risk for skeletal dysplasias and were followed up. Studies were performed at a mean gestational age of 26.7 weeks (range, 15.3-41.0 weeks). Group 1 had a femur length 1-4 mm below the 2-SDs line (range, -2.0 to -4.0 SDs); no other abnormalities were detected. Interval examination of 12 femurs showed that 10 either remained shortened to the same degree or had a growth spurt. At birth, all subjects were healthy except one with mild growth retardation and one with a chromosomal abnormality. Of the two subjects that failed to continue normal growth, one was healthy and the other was a heterozygous achondroplastic dwarf. Group 2 had greater femoral shortness; all measurements were more than 5 mm below the 2-SD line (range, -4.3 to -31.0 SDs). All had fetal abnormalities and significant skeletal dysplasias. The authors conclude that the number of millimeters below the 2-SDs line is an accurate, easy criterion for evaluation of femoral length.

Bone Diseases, Developmental↗

PubMed1990

Postprandial changes in cytosolic free calcium and glucose uptake in adipocytes in obesity and non-insulin-dependent diabetes mellitus.

We evaluated the possible relationship between [Ca2+]i and glucose uptake in the postabsorptive state and postprandially in adipocytes obtained from normal and obese subjects, as well as from patients with non-insulin-dependent diabetes mellitus (NIDDM). Adipocytes isolated from overnight-fasted obese and NIDDM patients revealed high levels of [Ca2+]i (p less than 0.05 vs. control) in association with a decreased insulin-stimulated glucose uptake (p less than 0.05 vs. controls). In obese and NIDDM patients treated with oral hypoglycemic agents, the overnight fasting levels of [Ca2+]i were increased postprandially (p less than 0.05), concomitantly with a further decrease in insulin-stimulated 2-deoxyglucose uptake. Although the precise nature of the relationship between [Ca2+]i in specific insulin target tissues and diminished insulin action remains unknown, it is clear that high levels of [Ca2+]i may contribute to the development of insulin resistance.

Adipose Tissue↗

PubMed1990

[Epiglottitis in adults].

Acute epiglottitis in the child is an emergency, well known to pediatricians, that requires rapid diagnosis and treatment. Aggressive treatment in recent years has markedly decreased mortality (17). Acute epiglottitis in adults has been thought to be rare, but lately numerous studies have shown an increase in the disease. We present 19 older patients, aged 13-72 (mean 44.7 years), with acute epiglottitis. A most important finding was the relatively long time from onset of symptoms until diagnosis, averaging 2.5 days. All the blood and throat cultures were negative, except for a single throat culture which yielded Pseudomonas aeruginosa. The most common presenting symptoms were severe sore-throat and dysphagia; half presented with some respiratory distress. Diagnosis was usually made on indirect laryngoscopy, but lateral X-ray of the soft tissues of the neck was found to be highly reliable. Treatment was usually conservative, including antibiotics, rehydration and steroids to alleviate edema. All patients were under strict observation for the first 48 hours, but only 1 required intubation. There were no deaths.

Acute Disease↗

PubMed1990

Variation of HLA-ABC surface antigen expression on adenocarcinoma of the colon in correlation with the degree of differentiation.

The expression of HLA class I antigens was tested on biopsy specimens originating from 90 patients suffering from adenocarcinoma of the colon. Three different samples were examined from each specimen: one from the tumor and the other two from the neighboring surrounding surgical margins. Twenty-seven out of 27 well-differentiated carcinomas were found highly positive for the presence of HLA class I antigens. Most of the moderately well differentiated tumors (37 out of 46) were weakly positive. None of the poorly differentiated tumors (n = 11) nor the mucin-producing tumors (n = 6) expressed HLA class I antigens. In 180 histologically normal colonic epithelia from patients suffering from adenocarcinoma of the colon (surgical edges free from tumorous tissue of the same specimens) no positive expressions were found. These results tend to suggest that class I HLA-ABC deficient, poorly differentiated tumors may possibly evade lethal immune aggression by HLA-restricted cytotoxic T cells and thus progress to overt malignancy. This negative expression may provide an explanation for the poorer prognosis observed among patients afflicted by a poorly differentiated adenocarcinoma or mucin-producing adenocarcinoma of the colon. Furthermore, these results tend to suggest that enhanced expression of HLA class I antigens on colonic epithelium could serve as a clinical laboratory indication for further examination looking for the possible emergence of neoplasm. If further verified, this may prove to serve as a predictive diagnostic tool for screening populations at risk.

Adenocarcinoma↗

PubMed1989

jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun.

We have cloned the human jun-B gene and determined its sequence and transforming and trans-activating activities. jun-B is less potent that c-jun in transforming and immortalizing primary rat embryo cells in cooperation with activated ras (effects enhanced by c-fos and TPA); unlike c-jun, jun-B does not transform Rat-1A cells alone. However, cotransfection of c-jun and jun-B into primary rat embryo cells with c-Ha-ras results in a significant decrease in transformation compared with c-jun alone, an event reversed by TPA. Cotransfection of c-jun and jun-B with or without c-fos into F9 teratocarcinoma cells results in decreased trans-activation of AP-1 compared with either gene alone. Introduction of jun-B into primary rat c-jun/ras transformants or c-jun into jun-B/ras transformants also results in a decrease in trans-activation. These findings demonstrate that, whereas jun-B and c-jun each participate in AP-1 trans-activation and malignant transformation, interactions between them involve negative regulation.

Amino Acid Sequence↗

PubMed1989

Effect of persistent measles virus infection on protein kinase C activity and c-fos protooncogene expression in neuroblastoma cells.

The effect of persistent measles virus infection on c-fos protooncogene and protein kinase C (PKC-I) gene expression in a murine neuroblastoma cell line was studied. Overexpression of c-fos protooncogene by infected NS20Y/MS cells was detected when compared with uninfected NS20Y cells. The level of PKC-I-specific mRNA was increased in infected NS20Y/MS cells. In addition, the level of total PKC activity in these cells was also enhanced. We conclude that persistent measles virus infection can alter both protooncogene expression and signal transduction in cells of neuronal origin.

Animals↗

PubMed1989

Human peritoneal macrophage activity is increased by tuftsin.

Peritonitis caused by Candida albicans is a major complication of continuous ambulatory peritoneal dialysis (CAPD). Increasing the activity of the peritoneal macrophages--the predominant cell type found in the peritoneal cavity--may be of great importance in the prevention and therapy of peritonitis. Therefore, the activating effect of tuftsin was studied on human peritoneal macrophages from CAPD patients. Tuftsin induced a biphasic effect on macrophage activity within a range of 2 X 10(-9)-2 X 10(-6) M, with a maximal activity of 2 X 10(-7) M. At this concentration, tuftsin enhanced by twofold cell association with radiolabelled candida (from 2 +/- 0.2 to 4 +/- 0.2 candida per macrophage) and superoxide anion production in response to exposure to candida (from 150 +/- 20 to 300 +/- 20 nmoles/mg). These results suggest the potential use of tuftsin as a therapeutic drug.

Adult↗

PubMed1989

Galactose-1-phosphate uridyl transferase in density-fractionated erythrocytes. Studies of normal and mutant enzymes.

Galactose-1-phosphate uridyl transferase (GALT), the deficient enzyme in classical galactosemia, was studied by Percoll-gradient age-fractionation of erythrocytes. For normal GALT, a rapid and substantial decrease in GALT activity and loss of most of two isozymes was found to occur in the reticulocyte fractions. The loss of activity was then followed by relative stabilization of both GALT-specific activity and microheterogeneity in mature and aging erythrocytes. When applied to the study of mutant GALT from galactosemic patients, the Percoll-gradient fractionation method permitted detection in the reticulocyte-enriched fractions of up to 5% of normal GALT-specific activity and an isoelectric focusing pattern essentially the same as that of normal GALT. Percoll-gradient fractionation of erythrocytes offers a simple and direct method to study characteristics of GALT activity and microheterogeneity in normal and galactosemic human erythrocytes.

Cell Separation↗

PubMed1989

Characteristics of L-proline and sodium transport in renal brush border membranes isolated from 7-day-old and adult rats.

To explore the nature of differences in uptake by renal brush border vesicles from animals of different ages, vesicles were isolated from 7-day old and adult rats by a Mg-aggregation method. A number of criteria were compared in vesicles from the young and mature animals. The vesicles isolated from animals of both ages appear similar on electron microscopy, in response to osmotic changes, and in uptake kinetics for L-glucose. Despite these parameters which indicate no basic differences between the membranes of young and mature kidney, differences in proline and sodium handling are seen. When compared to the uptake pattern seen in vesicles from adult animals, the height of the sodium gradient-stimulated proline overshoot is diminished and sodium entry is faster in vesicles of the 7-day old rats. These are the same differences which were found in vesicles prepared by differential centrifugation from 7-day old animals. In addition, although sodium efflux was faster from vesicles of immature kidney and mirrored the faster sodium entry, proline efflux was slower. The data indicate a dissociation of proline and sodium fluxes in brush borders of the young rat kidney.

Aging↗