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Biomedical subjects

S Shin

Publications and source records attributed to S Shin.

At least 217 records · Page 12Linked to original sources
PubMed1982

Tumorigenicity of partial transformation mutants of Rous sarcoma virus.

Chicken embryo cells infected with partial transformation mutants of Rous sarcoma virus were tested for tumor-forming ability in chickens and in nude mice. Cells transformed by each of these partial transformation mutants display different combinations of transformation parameters. They therefore present a potentially favorable system for analyzing which properties of transformed cells are necessary for tumor formation. We found that the relative tumorigenicity of the virus mutants was generally similar in chickens and in nude mice, except that certain temperature-conditional mutants appeared to be sensitive to the differences in body temperature of the two experimental animals. (The body temperature of nude mice is 4 to 5 degrees C lower than that of chickens). Thus, the nude mouse appears to be a suitable system for testing the tumorigenicity of transformed chicken cells. Because mice are nonpermissive for Rous sarcoma virus infection and replication, it was possible to recover the transformed chicken cells from the tumors in this host and to determine what phenotypic changes they had undergone during tumor development. We also examined the relationship between various cellular properties of the virus-infected chicken cells in vitro and their tumorigenicity in nude mice. The combined results of these two studies indicated that anchorage independence and plasminogen activator production were highly correlated with the tumor-forming ability of these cells, whereas loss of fibronectin did not correlate with tumorigenicity. Furthermore, the inability of the least tumorigenic virus mutant to stimulate the phosphorylation of a 36,000-Mr target of pp60src raises the possibility that the 36,000-Mr protein plays a role in tumor formation.

Animals↗
PubMed1982

Preovulatory changes in luteinizing hormone releasing hormone concentrations in peripheral plasma in constant estrous rats at induced ovulation.

Cervical stimulation was used to induce synchronous ovulation in rats that were induced into constant estrus by exposure to continuous lighting. Anti-LHRH or anti-LH serum completely blocked the induced ovulation when administered iv within 5 or 40 min after cervical stimulation. Peripheral concentrations of LH and LHRH hypothalamic content of LHRH were quantified before and at various intervals (0.5-70 min) after cervical stimulation. The radioimmunoassay for LHRH employed a specific antiserum, OAL-513, with high affinity and specificity and highly purified 125I-LHRH. Measurement of LHRH in extracts of 3-5 ml of plasma gave values that were readable in the middle portion of the standard curve. A two-fold increase in the LHRH concentration in peripheral plasma was observed 30 sec after the start of cervical stimulation. The elevated LHRH level was sustained for 15 min, though associated with large fluctuations. Serum LH levels started to rise 4 to 10 min and returned to the basal level 70 min after cervical stimulation. The hypothalamic LHRH content continued to increase throughout the entire experimental period and attained 140% of the initial level. No significant deflection due to LHRH release was observed in the hypothalamic LHRH content. Changes in the peripheral hormone level after cervical stimulation were component for chronologically reasoning the effectiveness of the antihormone treatment for blockage of the induced ovulation. From these results it is concluded that LHRH release before the preovulatory LH surge in light-estrous rats was brief in duration and erratic in mode.

Animals↗
PubMed1982

Induction of insulin-dependent diabetes by streptozotocin. Inhibition by estrogens and potentiation by androgens.

Susceptibility of mice to experimental insulin-dependent diabetes as induced by multiple subdiabetogenic doses of streptozotocin has been shown to be strongly gender-dependent, males being much more susceptible than females. We examined this gender difference further in two strains of genetically susceptible mice to determine whether exogenous steroid sex hormones can both suppress the high susceptibility of males and potentiate the low susceptibility of females. Our results show that, in both BALB/cBOM and C57BL/6 mice, exogenous estrogens can suppress the high susceptibility of males. Conversely, the normally streptozotocin-resistant females become as highly susceptible as males after the administration of androgens. The inhibitory effect of estrogens and the potentiating effect of androgens can be demonstrated after the hormones are given to the mice either chronically (in slow-release capsules implanted at a subcutaneous site), or immediately prior to streptozotocin injection. These observations are consistent with the view that the critical factor that determines the susceptibility of mice to the hyperglycemic effects of streptozotocin is not the absolute concentration of androgens per se, but rather the relative overall level of androgens over estrogens in the recipient animal. Several alternative mechanisms for the effect of sex hormones on diabetogenic sensitivity are discussed.

Androgens↗
PubMed1982

Diabetes susceptibility of BALB/cBOM mice treated with streptozotocin. Inhibition by lethal irradiation and restoration by splenic lymphocytes.

In genetically susceptible strains of mice, repeated injections of a subdiabetogenic dose of streptozotocin induces the development of progressive insulin-dependent hyperglycemia. We showed previously that host T-cell functions play an obligatory etiologic role in this experimental disease by demonstrating that the athymic nude mouse is resistant to diabetes induction unless its T-cell functions are reconstituted by thymus graft (Paik et al., Proc. Natl. Acad. Sci. USA 77:6129-33, 1980). Here we show that lethal irradiation of euthymic (+/nu) mice of BALB/cBOM background causes selective resistance of the mice to the diabetogenic effects of the multiple low doses of streptozotocin without affecting their sensitivity to a high pharmacologic dose of the toxin. We also show that reconstitution of the irradiated mice with splenic lymphocytes causes the restoration of diabetes susceptibility. Lethally irradiated mice thus represent a useful experimental model for analyzing the host functions involved in the development of this disease. These results provide an additional support for the hypothesis that the induction of diabetes in this model system is mediated by an autoimmune amplification mechanism.

Animals↗
PubMed1981

Immunochemical identification of the chick HPRT gene transferred from chick erythrocytes to mammalian somatic cells.

Immunochemical methods were used to identify the genetic origin of hypoxanthine phosphoribosyltransferase (HPRT) expressed in heteroploid, HPRT-deficient mouse (A9) cells and Chinese hamster ovary (K627) cells, after these cells were fused with chick embryo erythrocytes and selected for resistance to hypoxanthine-aminopterin-thymidine (HAT) medium. All of the HAT-selected clones produced HPRT activity which was immunoprecipitable by an antiserum specific for chick HPRT, but not by an antiserum specific for mouse and hamster HPRT. Furthermore, the HPRT activity in these clones was electrophoretically indistinguishable from chick liver HPRT and clearly different from mouse liver HPRT. These data provide evidence that the HPRT activity expressed in cell hybrids produced by the fusion of HPRT-negative mammalian cells and chick erythrocytes containing genetically inactive nuclei is indeed coded by the chick HPRT gene and that an avian gene can be stably incorporated and correctly expressed in a mammalian cells.

Animals↗
PubMed1981

Specific resistance to 8-azaguanine in cells with normal hypoxanthine phosphoribosyltransferase (HPRT) activity: the role of guanine deaminase.

The role of guanine deaminase in selective cellular resistance to 8-azaguanine was examined, using eight mammalian cell lines and their subclonal derivatives isolated on the basis of increasing resistance to this drug. 8-Azaguanine and 6-thioguanine are synthetic analogs of guanine and are lethal to cells with normal hypoxanthine phosphoribosyltransferase (HPRT) activity. In principle, however, HPRT-positive cells could become selectively resistant to 8-azaguanine if, by any mechanism, the cells expressed higher levels of guanine deaminase. This is because 8-azaguanine, but not 6-thioguanine, is converted by this enzyme to a noncytotoxic metabolite, 8-azaxanthine. Our study shows that HPRT-positive cells inherently resistant to relatively high levels of 8-azaguanine contain high levels of guanine deaminase. In general, guanine deaminase activity was higher in 8-azaguanine-resistant cells, regardless of their HPRT activity. Our results support the view that elevated guanine deaminase activity constitutes a potential mechanism of selective 8-azaguanine resistance in cells with normal HPRT activity. Guanine deaminase levels were significantly elevated in HPRT-positive cells briefly exposed to sublethal concentrations of 8-azaguanine, but this elevation was transient. Long-term exposure of cells to increasingly higher levels of the drug did not lead to high stable levels of guanine deaminase, indicating that 8-azaguanine is not an inducer of guanine deaminase in the cells examined.

Aminohydrolases↗
PubMed1981

Production of antisera to des Asn28 Thr29 Homoser27-glucagon; the development of radioimmunoassay for total glucagon-like immunoreactivity in human plasma.

Antisera having a strong and strictly constant cross-reactivity for gut-GLI were raised in seven rabbits immunized with immunogen, a conjugate of BSA and des-Asn28, Thr29, Homoser27 -glucagon (CNBr-glucagon). All of the anti-CNBr-glucagon sera exhibited titer and affinity for glucagon sufficiently high enough to develop a sensitive radioimmunoassay. The relative crossreactivity of the antisera to gut-GLI was comparable to that of antiserum K-4023 which strongly crossreacted with gut-GLI. One of the anti-CNBr-glucagon sera, OAL-196, did not react with the glucagon 19-29 fragment at all. The intra- and inter-assay coefficients of variation were 3.8-5.0 and 6.0-7.3%, respectively, in the radioimmunoassay system for total GLI in human plasma using OAL-196. The fasting plasma total GLI was 374 +/- 18 pg/ml. The plasma total GLI during 50 g oral glucose load in normal subjects increased significantly, whereas the plasma IRG level measured with the anti-glucagon 19-29 serum, OAL-123, assay system was lowered. In the gastrectomized subjects, plasma total GLI measured with the present assay system elicited a marked increase following an oral glucose load. These results suggest that the radioimmunoassay using anti-CNBr-glucagon sera will be useful in measuring plasma total GLI.

Animals↗
PubMed1981

Glucagon radioimmunoassay with use of antiserum to glucagon C-terminal fragment.

In this pancreatic-glucagon-specific radioimmunoassay we used C-terminal-region-specific antiserum. OAL-123, produced against a 19-29 C-terminal fragment of porcine glucagon. On measurement of pooled plasma the ranges for intra- and inter-assay coefficients of variation were 4.8-8.1% and 7.5-10.7%, respectively. The concentration of immunoreactive glucagon in plasma of healthy subjects, as measured with the OAL-123 assay system, was 87.9 (SD 23.8) ng/L. Measurement of the same plasma samples with the 30K assay system (30K being an antiserum highly specific for pancreatic glucagon) showed a comparable value, 86.2 (SD 26.3) ng/L. We followed changes in human and dog plasma immunoreactive glucagon concentrations on arginine infusion and after glucose load, using the OAL-123 and the 30K assay systems, with identical results. Combining other results of comparative immunochemical characterization of the OAL-123 and 30K assay systems, we confirmed that the antisera raised against the C-terminal fragment of glucagon can be used in radioimmunoassay of pancreatic glucagon.

Amino Acids↗
PubMed1980

A sudden decline in ampicillin resistance in Salmonella typhimurium.

Starting in 1975, an abrupt decline in ampicillin resistance of Salmonella typhimurium (the most common and antibiotic-resistant serotype) occurred in New York City. The present lower rate of 5% to 7.9% at our hospitals represents a return to the 1965 level. At the same time, the ampicillin resistance in S typhimurium from calves and other farm animals from upper New York State, which has been rising since 1972, has reached 75%. Substantial differences between levels of resistance in Escherichia coli from animals and humans were also noted. The divergence of the trends in S typhimurium from these two sources in New York State suggests a substantial degree of separation of the respective reservoirs of Salmonella and of antibiotic resistance.

Ampicillin↗
PubMed1980

Isolation of somatic cell mutants with specified alterations in hypoxanthine phosphoribosyltransferase.

Cellular resistance to 6-thioguanine is almost always associated with a complete loss of hypoxanthine phosphoribosyltransferase (HPRT) activity, while resistance to 8-azaguanine has frequently been shown to occur independently of any changes in the HPRT activity. As a result, mutant cells selected for resistance to 6-thioguanine are also resistant to 8-azaguanine, but cells selected for 8-azaguanine resistance are not necessarily cross-resistant to 6-thioguanine. Our previous studies demonstrated that this difference is due to differential utilization of the two purine analogs by HPRT in the cells. In this paper we describe a novel selective procedure for the systematic isolation of cellular mutants that contain wild-type levels of HPRT, are sensitive to 6-thioguanine, and yet are able to survive in medium containing both HAT and a high level of 8-azaguanine. We also present evidence which shows that such mutants arise through a mutation that specifically alters the HPRT molecule so that the enzyme no longer recognizes 8-azaguanine as a substrate, while remaining catalytically functional with hypoxanthine and 6-thioguanine. Mutants of this type may be useful as a marker in gene-transfer experiments.

Animals↗
PubMed1980

Heterogeneity of plasma motilin in patients with chronic renal failure.

Plasma immunoreactive motilin (IRM) concentrations were strikingly higher in patients with chronic renal failure (CRF) than in normal subjects. IRM in azotemic plasma was heterogeneous in gel-filtration profile. The first peak eluted in the void volume of the column and the second and the third one, comprising a major portion of IRM content, came out coincidentally with insulin and authentic motilin, respectively. By contrast, no discernible amount of IRM was found in the region corresponding with the second peak in gel-filtration of the plasma from normals and very little in a patient with ileus whole plasma IRM level was elevated. The hypermotilinemia and the accumulation of this high molecular weight motilin in patients with CRF suggest that the kidney plays some role in the elimination of motilin, and further, that the clearance of the high molecular motilin is more dependent on renal function than that of authentic motilin. The present paper emphasizes the necessity for clarifying the significance of the heterogeneity of IRM in CRF.

Chromatography, Gel↗
PubMed1980

pJT2: unusual H1 plasmid in a highly virulent lactose-positive and chloramphenicol-resistant Salmonella typhimurium strain from calves.

A lactose-positive and chloramphenicol-resistant strain of Salmonella typhimurium of high virulence was isolated from an outbreak of enteric and septicemic salmonellosis in veal calves. the lactose-positive marker was located on an H1 plasmid, pJT2, together with resistance to chloramphenicol, streptomycin, sulfonamides, and tetracycline, pJT2 was unusually large and had a molecular weight of about 150 X 10(6). A similar plasmid was also present in a third of the Escherichia coli strains isolated from the intestines of septicemic calves during the outbreak. Spontaneously derived Lac- derivatives of pJT2 had an approximate molecular weight of 140 X 10(6).

Animals↗
PubMed1980

Heterogeneity of immunoreactive motilin.

Motilin-like immunoreactivities were examined in extracts of duodena of pig, human, dog, rat, cat, rabbit and guinea pig with a combination of radioimmunoassays using three different antisera possessing distinct region-specificities. Antisera GP-1103 and R-1104 were rather C-terminal specific, but the immunological feature of GP-1103 was different from that of R-1104. In the case of antiserum GP-1103, the Glu residue in position 15 in the motilin molecule participated in antigen-antibody interaction, but not in the case of R-1104. Antiserum MBR-02 was N-terminal specific, with of the three assay systems, only a single major peak was detected in the elution profile from BioGel P-10 column of motilin-like immunoreactivity in the porcine duodenal extract, of which the elution volume corresponded to that for synthetic porcine motilin. On the other hand, the gel filtration profiles of the human and canine duodenal extracts consisted of two or three peaks of the immunoreactivity. The major peak emerged in the elution volume identical with that for synthetic porcine motilin and the other two peaks were eluted earlier. The peak which was eluted in the volume corresponding to that for BSA marker was detectable only by the assay system with N-terminal specific antiserum MBR-02. The immunoreactivity of the major peak component in the human, canine or rat extract was found to be lower than that in the porcine extract. The present data may indicate the existence of heterogeneity of motilin-like immunoreactivity and species variation of the structure of the immunoreactive motilin.

Animals↗
PubMed1979

Tumorigenicity of revertant from an SV40-transformed line.

A syndrome of in vitro properties correlates with the tumorigenicity of SV40-transformed rodent cells. These properties are: plasminogen activator production, loss of large actin cables, and anchorage-independent growth. An established rat fibroblast line, its SV40 transformant, several T-antigen negative revertants, and a spontaneous retransformant isolated from one of the revertants were analyzed in vivo for their tumorigenicity and in vitro for the syndrome. The two transformed lines were highly tumorigenic, and had clearly abnormal in vitro properties. The parental rat line was weakly tumorigenic in nude mice and demonstrated a slightly transformed response in the in vitro assays. The revertants were completely nontumorigenic. Expression of the in vitro syndrome was not uniform for all revertants; however, most cell lines maintained the correlation of the syndrome and tumorigenicity.

Animals↗
PubMed1979

Cellular tumorigenicity in nude mice. Role of susceptibility to natural killer cells.

The athymic nude mouse is a useful animal model for assaying the neoplastic growth potential in vivo of animal cells transformed in vitro. Despite the demonstrated absence of thymus-dependent immunological functions, however, the nude mouse has now been shown to reject transplants of certain highly malignant heterologous tumors. In addition, a few transformed mammalian cell lines that exhibit all or most of the cellular phenotypes usually associated with malignancy fail to grow as tumors when injected into nude mice. In a continuing study to identify the in vitro phenotypes associated with tumor-forming ability in vivo, we investigated the role of cellular susceptibility to the naturally occurring, thymus-independent lymphocytes (natural killer or NK cells) in determining tumor induction by animal cells in nude mice. A representative collection of animal cells (ranging from normal human diploid cell strains to highly tumorigenic clonal cell lines, either transformed in vitro or derived from experimental tumors) was tested to see if the ability of cells to form tumors is consistently correlated with their susceptibility to NK cell-mediated lysis measured in vitro with splenic leukocytes from nude mice. If the physiological role of the NK cells in vivo were to recognize, and possibly to destroy, incipient tumor cells in situ, a direct association between cellular tumorigenicity and susceptibility to NK activity, might be expected. If, on the other hand, the formation of growing tumors by animal cells in nude mice depended on their ability to escape the cytolytic activity of NK cells, cellular tumorigenicity would be associated with cellular resistance to NK cells. Results obtained in this study failed to confirm either of these associations. Thus, cellular suscepbibility to NK cells, at least as determined by direct cytotoxicity assay in vitro, is not a useful predictive indicator of cellular tumorigenicity in nude mice.

Animals↗