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Biomedical subjects

N Lin

Publications and source records attributed to N Lin.

At least 109 records · Page 6Linked to original sources

Identification of the receptor for erythropoietin on human and murine erythroleukemia cells and modulation by phorbol ester and dimethyl sulfoxide.

Erythropoietin, a glycoprotein that regulates erythropoiesis, initiates its biological effects by binding to a cell-surface receptor. Little is known about the structure of the erythropoietin receptor and the events that follow binding of erythropoietin to its receptor, in part because of the difficulty of obtaining sufficient quantities of cells that express the erythropoietin receptor. We used both iodinated and metabolically labeled erythropoietin to characterize the receptor on a variety of erythroleukemia cell lines not previously tested, and we have identified both human and murine cell lines that display large numbers of erythropoietin receptors. Both erythropoietin-responsive and -nonresponsive cell lines exhibit a single class of binding sites. The human erythroleukemia cell line OCIM1 exhibits approximately 3000 erythropoietin receptors per cell with a Kd of 280 pM. The erythropoietin-responsive Rauscher red 5-1.5 murine erythroleukemia cell line displays approximately 1700 receptors per cell with a Kd of 440 pM. The GM979 murine erythroleukemia cell line has approximately 1600 receptors per cell with a Kd of 660 pM. Induction of the erythroid phenotype by dimethyl sulfoxide or its suppression by phorbol 12-myristate 13-acetate was accompanied by an increase or decrease, respectively, in erythropoietin receptor number. Affinity crosslinking of labeled erythropoietin to the receptor identified two proteins corresponding to estimated molecular masses of 95 and 105 kDa. The OCIM1, Rauscher, and GM979 erythroleukemia cell lines provide a useful model for the study of postreceptor signaling events, as well as a convenient source for purification of the erythropoietin receptor.

Animals↗

Interleukin 1 stimulates fibroblasts to synthesize granulocyte-macrophage and granulocyte colony-stimulating factors. Mechanism for the hematopoietic response to inflammation.

IL-1 is a family of polypeptides which play a critical role in the inflammatory response. Characteristics of this response include an enhanced release of bone marrow neutrophils, activation of circulating and tissue-phase phagocytes, and enhanced production of neutrophils and monocytes. We have sought to understand the hematopoietic response to acute and chronic inflammatory states on a cellular and molecular level. Colony-stimulating factors (CSFs) are glycoproteins involved in the production and activation of neutrophils and monocytes in vitro and in vivo. We have found that quiescent dermal fibroblasts constitutively release granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), and macrophage CSF in culture, and that picomolar concentrations of the inflammatory mediator IL-1 stimulate by at least fivefold the transcription and release of GM-CSF and G-CSF. These findings establish the role of IL-1 in the hematopoietic response to inflammation through the stimulation of the production and release of GM-CSF and G-CSF.

Animals↗

Impact of legislation raising the legal drinking age in Massachusetts from 18 to 20.

On April 16, 1979, Massachusetts raised its legal drinking age from 18 to 20 years. Massachusetts was compared with New York State, exclusive of New York City and Nassau County. New York State retained an 18-year-old drinking age. Random telephone surveys with approximately 1,000 16-19 year olds in each state were undertaken prior to the law's enactment and twice at yearly intervals after the law to assess the law's impact on teenage drinking, driving after drinking, and non-fatal accident involvement. Fatal crash data reported to the US Department of Transportation by each state from April 16, 1976-April 15, 1981 were also analyzed. After the law, although the modes of procuring alcohol changed. No significant changes were observed in Massachusetts relative to New York in the proportion of surveyed teenagers who reported that they drank or in the volume of their consumption. The proportion of teenagers who drove after drinking heavily (six or more drinks at one time) did not decline in Massachusetts relative to New York. However, the frequency that teenagers reported driving after any drinking declined significantly in Massachusetts. Frequency of teenage driving after marijuana use and non-fatal teenage accidents declined at comparable rates in both states. The numbers of teenage nighttime single vehicle fatal accidents declined more in Massachusetts than New York, in the 18-19 year age group. Overall fatal accident trends among 16-19 year olds in the two states were similar.

Accidents, Traffic↗

Properties of a human alpha-interferon purified from E. coli extracts.

A human alpha interferon, designated HuIFN-alpha A, produced in E. coli by direct expression of cloned cDNA [Goeddel et al., Nature 287, 411--416 (1980)] has been purified from bacterial extracts and characterized. The protein has a molecular weight (19,400 by SDS/PAGE) and amino acid composition consistent with the DNA sequence. The pI was determined to be 6.1. The molecule has a specific activity of 1.5 x 10(8) NIH reference units/mg of protein. The sequence of the first 35 amino acids is identical to that expected from the nucleotide sequence. About 50% of the molecules begin with the expected cysteine, and 50% begin with the initiator methionine which E. coli apparently did not remove efficiently. Analysis of a trypsin digest of the native molecule showed that all four of the molecule's cysteines are involved in disulfide bonds: Cys1 is bonded to Cys98, and Cys29 is bonded to Cys 138.

Amino Acids↗

Social support scales: a methodological note.

The relationship between social support and depression has implications for researchers studying schizophrenia. In this article, the authors attempt to conceptualize social support and assess the reliability and validity of its various measures. They then evaluate the ability of social support, along with stressors, to explain psychiatric symptoms. Representative data from a community survey of adults, ages 17-70, suggest that social support measures show strong relationships to depression and other psychiatric symptoms. The implications of these and other findings for the study of schizophrenia are discussed.

Depressive Disorder↗

Polycythemia vera. Physical separation of normal and neoplastic committed granulocyte-macrophage progenitors.

In previous studies of two patients with polycythemia vera (PV) who were heterozygous at the X-linked locus for glucose-6-phosphate dehydrogenase (G6PD), only A type enzyme was found in nonlymphoid blood cells. However, some erythroid and granulocytic colonies grown in vitro were type B and therefore arose from presumably normal progenitors. One patient had enough type B colonies (8%) that studies of the physical characteristics of normal and PV clonal colony-forming cells could be undertaken. When marrow cells were separated by velocity sedimentation at unit gravity, most PV clonal granulocyte-macrophage progenitors (CFU-C) (type A G6PD) sedimented between 6.4 and 7.2 mm/h, whereas most residual normal, type B CFU-C sedimented less than or equal to 5.9 mm/h (P = 0.04)., When blood cells were separated over a discontinuous buoyant density gradient, PV clonal CFU-C equilibrated at densities < 1.065 g/ml, whereas residual normal CFU-C were found greater than or equal to 1.065 g/ml (P < 0.01). PV clonal and residual normal erythroid burst-forming progenitors were not separable by either method. Thus PV clonal CFU-C are larger and less dense cells than are residual normal CFU-C.

Erythrocytes↗

Polycythemia vera. Further in vitro studies of hematopoietic regulation.

Further in vitro studies of hematopoietic regulation were carried out in two patients with polycythemia vera who were also heterozygotes (Gd(B)/Gd(A)) for glucose-6-phosphate-dehydrogenase (G-6-PD). While only G-6-PD type A was detectable in circulating erythrocytes, granulocytes and platelets, cultures of peripheral blood and marrow from one patient revealed a substantial number of G-6-PD type B erythroid burst-forming units (BFU-E) and granulocyte/macrophage colony-forming units. Detailed analysis demonstrated: (a) where detectable, normal BFU-E and granulocyte/macrophage colony-forming units were found with similar frequencies; (b) the same frequencies for normal progenitors characterized cultures of peripheral blood and marrow; (c) inhibition of normal erythroid differentiation between BFU-E and the more mature erythroid colony-forming unit; (d) a decline in the prevalence of normal colony-forming units with time, suggesting that disease progression is associated with further suppression of normal hematopoiesis by products of the abnormal clone.

Bone Marrow Cells↗

Locus of control and symptoms of psychological distress among Chinese-Americans.

A sample of Chinese-Americans in the District of Columbia was drawn to examine the relationship between the locus of control, the personality factor, and two indices of symptoms of psychological distress. The findings indicated that the externals scored higher on symptomatology than did the internals. A multivariate analysis further compared the predictive utility of locus of control with other determinants of psychiatric symptoms, i.e., sex, marital status, SES, kinship and friendship tie, and amount of life change. The evidence showed that locus of control is an important determinant of Chinese-Americans' symptomatology. It accounted for a greater proportion of the variance in the two indices of psychological distress than did the other independent variables.

Acculturation↗

Analysis of erythropoiesis by erythroid colony formation in culture.

The development of clonal assays for hemopoietic progenitors has provided new tools for the analysis of normal and abnormal cell regulation. Such assays have been applied to erythropoiesis and have demonstrated classes of precursors which differ significantly in their growth potential, physical characteristics, and sensitivity to the hormone, erythropoietin. A formal geneology of these classes has been established and insight into the factors that regulate the numbers of the classes provided by studies in anemic and polycythemic animals. The results suggest that commitment to the earliest erythroid progenitors recognizable in culture is not controlled by erythropoietin, whereas the most differentiated elements demonstrate a requirement for the hormone for their maintenance. Recognition of differences in the factors that control erythroid differentiation predict that a variety of mechanisms will be found to account for different forms of erythroid failure in man.

Anemia↗

The stress-buffering role of social support. Problems and prospects for systematic investigation.

Over the pase 20 years, a sizable body of literature has developed which serves to establish that stressful life events are associated with the onset, incidence, and prevalence of a wide range of physical and psychiatric disorders. As measured by the Holmes and Rahe Social Readjustment Rating Scale, or similar instruments, the stressful life events are fundamentally sociological in nature. Yet, paradoxically, the research has been largely limited in the relevant basic sociological theory and data brought to or yielded from investigation. Recently, however, several prominent researchers have emphasized the importance of studying the role of social support systems as possible buffers or mediators of stress. The most basic objective of this paper is to contribute to the advancement of such studies by clearly identifying key empirical, theoretical and methodological problems and suggesting some approaches to their resolution. Specifically, this paper offers: a) a selective review of the essential status of empirical knowledge; b) an examination of the nature and significance of social support systems; c) clarification of methodological and theoretical problems; and d) detailed proposals for approaching problems of measurement and research design.

Animals↗