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Biomedical subjects

K Rubin

Publications and source records attributed to K Rubin.

At least 55 records · Page 3Linked to original sources
PubMed1993

Predictors of axial and peripheral bone mineral density in healthy children and adolescents, with special attention to the role of puberty.

The role of various physical and lifestyle factors in determining axial bone mineral density (BMD) at the lumbar segment of the spine, as measured by dual-photon absorptiometry, and peripheral BMD at the distal third of the radius, as measured by single-photon absorptiometry, was assessed in 299 healthy white children of both sexes, aged 6 to 18 years. The BMD measurements were correlated with age, height, weight, body mass index, and pubertal status. Peripheral and axial BMD were highly correlated with age, height, weight, and pubertal stage, and more weakly with body mass index. Approximately 76% of the observed changes in peripheral BMD were accounted for by age, height, weight, and pubertal stage, with weight being the single strongest predictor. Up to 80% of the variation in axial BMD was explained by weight and pubertal stage, with pubertal stage being the strongest single predictor. After adjustment for weight, the effect of puberty on axial BMD in both sexes was greatest between middle and late puberty. These data indicate that a large amount of the observed changes on BMD is accounted for by standard measures of growth and development, which are largely genetically determined. Peripheral BMD rose steadily with age. Axial BMD increased steadily before puberty, followed by accelerated increases during puberty, beginning at 10 years of age in girls and 13 years of age in boys. A significant positive effect of dietary calcium intake on peripheral BMD and of physical activity on axial BMD indicated a potentially important impact of physical activity and calcium intake on peak bone mass.

Adolescent↗
PubMed1993

Impaired regulation of collagen pro-alpha 1(I) mRNA and change in pattern of collagen-binding integrins on scleroderma fibroblasts.

We explored the hypothesis that dermal fibroblasts isolated from patients suffering from systemic sclerosis are disturbed in their ability to interact functionally with native collagen fibers. Additionally, we investigated the expression of one collagen-binding integrin matrix receptor, alpha 1 beta 1 on those cells. Two populations of primary dermal fibroblasts were established, one from patients with systemic sclerosis and one from normal subjects. When cultured for 24 h in free-floating collagen gels, both types of fibroblasts down-regulated the cellular content of collagen pro-alpha 1(I) messenger ribonucleic acid, the systemic sclerosis fibroblasts less markedly than the normals. In normal, but not in systemic sclerosis fibroblasts, the kinetics of collagen gel contraction were directly proportional to the extent of the down-regulation. Fetal bovine serum stimulated collagen gel contraction in both populations. When grown in collagen gels in the presence of fetal bovine serum, no difference between systemic sclerosis and normal fibroblasts in capacity to down-regulate pro-alpha 1(I) was observed. Collagen-binding beta 1 integrins mediate the functional interactions between fibroblasts and the collagen fibers. To assess the cell surface expression of collagen-binding beta 1 integrins on fibroblasts, we labeled cells with 125I and subjected Triton X-100 extracts from them to immunoprecipitation with anti-beta 1 integrin immunoglobulin G. Among the systemic sclerosis fibroblasts, a larger number of isolates expressed low amount of alpha 1 beta 1 than did the fibroblasts isolated from normal individuals. Our data are compatible with the hypothesis that systemic sclerosis fibroblasts have a disturbed interaction with collagen fibers; this disturbance may in part be the result of an aberrant expression of collagen-binding beta 1 integrins.

Cell Line↗
PubMed1993

Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans.

The expression and localization of PDGF beta receptors and PDGF-AB/BB in human healing wounds was evaluated by immunohistochemical techniques and in situ hybridization. Expression of PDGF beta receptor protein and PDGF-AB/BB were analyzed in wound margin biopsies using the PDGFR-B2 and PDGF 007 antibodies. PDGF beta receptor expression was minor in normal skin. An increased expression of PDGF beta receptor protein was prominent in vessels in the proliferating tissue zone in wounds as early as 1 d after surgery and was apparent < or = 4 wk after surgery. There was also a concordant increase in PDGF beta receptor mRNA detected by in situ hybridization. PDGF-AB/BB was present in healing wounds as well as in normal skin. In normal skin, expression of PDGF-AB/BB was confined to peripheral nerve fibers and to solitary cells of the epidermis and of the superficial dermis. In wounds, infiltrating mononuclear cells also stained for PDGF-AB/BB. To identify cell types expressing PDGF AB/BB and PDGF beta receptors, respectively, we performed double immunofluorescence stainings. PDGF beta receptors were expressed by vascular smooth muscle cells and cells in capillary walls; the receptor protein could not be detected in neurofilament containing structures, T lymphocytes, or CD68 expressing macrophages. PDGF-AB/BB colocalized with neurofilaments, it was present in Langerhans cells of the epidermis and in HLA-DR positive cells located in the epidermal/dermal junction area. Of the macrophages infiltrating the wound, 43 +/- 18% stained positively for PDGF AB/BB. Since PDGF-AB/BB and PDGF beta receptors are expressed in the healing wound, two essential prerequisites for a role of PDGF in wound healing are fulfilled.

Adult↗
PubMed1993

Microvascular pericytes express platelet-derived growth factor-beta receptors in human healing wounds and colorectal adenocarcinoma.

The expression of platelet-derived growth factor- beta (PDGF-beta) receptors in the microvasculature of human healing wounds and colorectal adenocarcinoma was investigated. Frozen sections were subjected to double immunofluorescence staining using monoclonal antibodies (MAbs) specific for pericytes (MAb 225.28 recognizing the high-molecular weight-melanoma-associated antigen, expressed by activated pericytes during angiogenesis), endothelial cells (MAb PAL-E), laminin, as well as PDGF-beta receptors (MAb PDGFR-B2) and its ligand PDGF-B chain (MAb PDGF 007). Stained sections were analyzed by computer-aided imaging processing that allowed for a numerical quantification of the degree of colocalization of the investigated antigens. An apparent background colocalization, varying between 23 and 35%, between markers for cells not expected to co-localize was recorded. This background could be due to limitations of camera resolution, to out-of-focus fluorescence, and to interdigitations of the investigated structures. In all six tumor specimens, co-localization of PDGF-beta receptors and PAL-E was not different from the background co-localization, whereas that of PDGF-beta receptors and high-molecular weight-melanoma-associated antigen was significantly higher with mean values between 57 and 71%. Qualitatively, the same pattern was obtained in the two investigated healing wounds. PDGF-B chain did not co-localize with either PAL-E or high-molecular weight-melanoma-associated antigen, but PDGF-B chain-expressing cells were, however, frequently found juxtaposed to the microvasculature. The expression of PDGF-beta receptors on pericytes in activated microvessels and the presence of PDGF-B chain-expressing cells in close proximity to the microvasculature of healing wounds and colorectal adenocarcinoma is compatible with a role for PDGF in the physiology of the microvasculature in these conditions.

Adenocarcinoma↗
PubMed1993

Stromal expression of platelet-derived growth factor beta-receptor and platelet-derived growth factor B-chain in colorectal cancer.

BACKGROUND: The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal activation in colorectal cancer is unclear. EXPERIMENTAL DESIGN: The expression of beta-receptors for PDGF, and PDGF B-chain (PDGF AB and PDGF BB) was investigated by immunohistologic techniques in full-thickness biopsies from 210 colorectal cancers. These antigens were detected by the monoclonal antibodies PDGFR-B2 and PDGF 007, respectively. RESULTS: All tumors contained granular clusters of PDGF beta-receptor expressing stromal cells, whereas tumor epithelium was invariably negative. The staining was most prominent in vascular cells. There were several cells in the tumor stroma that expressed PDGF AB/BB. Double immunofluorescence stainings in specimens from four patients performed in order to characterize PDGF beta-receptor- and PDGF AB/BB expressing cells showed that cells expressing PDGF beta-receptors did not express PDGF AB/BB. About 20% of cells in the stroma expressing PDGF AB/BB were macrophages (CD68-positive cells), whereas the nature of the remaining stromal cells expressing PDGF AB/BB could not be disclosed. Furthermore, about 30% of CD68-positive macrophages expressed PDGF AB/BB, but not PDGF beta-receptors. The extent of clusters of PDGF beta-receptor expressing cells varied considerably between tumors, and its prognostic value was considered in the entire tumor material. The number of clusters did, however, not correlate to tumor differentiation, tumor stage according to Dukes', or outcome. CONCLUSIONS: The presence of cells expressing PDGF beta-receptor and PDGF AB/BB respectively, i.e., expression of the receptor and its ligand, fulfills two of the prerequisites for a role of PDGF in the activation of stromal cells in colorectal cancers. The data suggest that stromal activation, characterized by clusters of PDGF beta-receptor expressing cells, is of importance for the formation of tumor stroma per se. However, the expression of the PDGF beta-receptor has no potential as a prognostic marker.

Carcinoma↗
PubMed1993

Interconnection of integrins alpha 2 and alpha 3 and structure of the basal membrane in colorectal cancer: relation to survival.

The expression and distribution of integrin subunits alpha 2 and alpha 3 and two of their putative ligands, type IV collagen and laminin, were examined by immunohistochemistry in specimens from 33 consecutive patients operated on for colorectal adenocarcinomas. Both tumour cells and normal epithelium expressed the alpha 2 and alpha 3 subunits. Two typical patterns of expression could be discerned; a basolateral expression and a diffuse cytoplasmic expression. The stained tumour specimens were assessed according to (i) distribution of integrin expression (diffusely cytoplasmic or basolateral), (ii) continuity in basolateral integrin expression, and (iii) interconnection of integrin expression and expression of type IV collagen and laminin. These parameters were then related to tumour differentiation, tumour stage according to Dukes' classification, DNA-ploidy and patient survival (median observation time was 30 months; range 24-35). The continuity in the basolateral expression of alpha 3 but not of alpha 2, correlated with the basal membrane expression of type IV collagen (P < 0.001). Loss of continuity in the basolateral expression of both integrins was significantly related to impaired tumour differentiation (alpha 2 P = 0.02; alpha 3 P = 0.01), more advanced Dukes' stage (alpha 2 = 0.07, alpha 3 P < 0.001), survival rate (both integrins P < 0.05), but not to DNA-ploidy. These data suggest that determination of the pattern of expression of the integrin subunits alpha 2 and alpha 3 in the preoperative biopsy and the surgical specimen could be used as a prognostic indicator.

Adenocarcinoma↗
PubMed1992

Expression of platelet-derived growth factor-beta receptors on human fibroblasts. Regulation by recombinant platelet-derived growth factor-BB, IL-1, and tumor necrosis factor-alpha.

Stimulation of human fibroblasts by platelet-derived growth factor (PDGF)-BB leads to a down-regulation of PDGF beta-receptors and a concomitant appearance of intracellular granular accumulations of receptors, as determined by stainings with the mAb PDGFR-B2. The granules contained both the ligand and PDGF beta-receptors, as revealed by double-immunofluorescence staining, and were formed in response to PDGF-BB but not in response to other cytokines tested. The formation of intracellular PDGF beta-receptor granules was dependent on PDGF-BB concentration and time of stimulation. The granular PDGF beta-receptor staining on cells treated with PDGF-BB for 1 h at 37 degrees C was used to investigate the effects of macrophage-derived cytokines on PDGF beta-receptor expression. The number of PDGF beta-receptor granules was found to be reduced in fibroblasts grown for 48 h in the presence of PDGF-BB, TNF-alpha, or IL-1; PDGF-AA under the same conditions had no effect. The reduction observed was paralleled by a decrease in cell surface expression of PDGF beta-receptors, measured as binding of 125I-PDGF-BB and of the PDGFR-B2 antibody. Furthermore, both TNF-alpha and IL-1 decreased the detergent-extractable pool of PDGF-beta receptors in the fibroblasts, as revealed by immunoblotting of detergent cell extracts. Finally, the decrease in PDGF beta-receptors after culturing of the cells in the presence of TNF-alpha and IL-1 was accompanied by a decreased incorporation of [3H]thymidine in response to PDGF-BB stimulation. In conclusion, our data suggest that certain macrophage-derived cytokines can modulate the expression of PDGF beta-receptors by cultured fibroblasts, which may contribute in part to their reduced responsiveness to PDGF.

Cells, Cultured↗
PubMed1992

Analysis of alpha 1 beta 1, alpha 2 beta 1 and alpha 3 beta 1 integrins in cell--collagen interactions: identification of conformation dependent alpha 1 beta 1 binding sites in collagen type I.

Integrins can mediate the attachment of cells to collagen type I. In the present study we have investigated the possible differences in collagen type I recognition sites for the alpha 1 beta 1 and alpha 2 beta 1 integrins. Different cyanogen bromide (CB) fragments of the alpha 1 (I) collagen chain were used in cell attachment experiments with three rat cell types, defined with regard to expression of collagen binding integrins. Primary rat hepatocytes expressed alpha 1 beta 1, primary rat cardiac fibroblasts alpha 1 beta 1 and alpha 2 beta 1, and Rat-1 cells only alpha 2 beta 1. All three cell types expressed alpha 3 beta 1 but this integrin did not bind to collagen--Sepharose or to immobilized collagen type I in a radioreceptor assay. Hepatocytes and cardiac fibroblasts attached to substrata coated with alpha 1(I)CB3 and alpha 1(I)CB8; Rat-1 cells attached to alpha 1(I)CB3 but only poorly to alpha 1(I)CB8-coated substrata. Cardiac fibroblasts and Rat-1 cells spread and formed beta 1-integrin-containing focal adhesions when grown on substrata coated with native collagen or alpha 1(I)CB3; focal adhesions were also detected in cardiac fibroblasts cultured on alpha 1(I)CB8. The rat alpha 1 specific monoclonal antibody 3A3 completely inhibited hepatocyte attachment to alpha 1(I)CB3 and alpha 1(I)CB8, as well as the attachment of cardiac fibroblasts to alpha 1(I)CB8, but only partially inhibited the attachment of cardiac fibroblasts to alpha 1(I)CB3. 3A3 IgG did not inhibit the attachment of Rat-1 cells to collagen type I or to alpha 1(I)CB3.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Modulation of growth factor responsiveness of murine mammary carcinoma cells by cell matrix interactions: correlation of cell proliferation and spreading.

We have examined the role of growth factors and extracellular matrix in the proliferation and cell adhesion of a murine mammary carcinoma, SP1, and a stable highly metastatic variant, SP1-3M. On fibronectin, both cell types proliferated strongly in response to basic fibroblast growth factor (bFGF) and platelet-derived growth factor BB (PDGF-BB) after culture for 24 h and 72 h. In contrast, on collagen type I, SP1 cells proliferated only weakly to PDGF-BB at either time, and SP1-3M cells showed a response to PDGF-BB only at 72 h. The proliferative response to bFGF was also consistently lower when the cells were cultured on collagen than on fibronectin. No significant proliferative responses were detected to epithelial growth factor (EGF), transforming growth factor-beta (TGF-beta), or estrogen on any substratum. The lack of responsiveness to PDGF-BB of cells cultured on collagen type I was not due to differences in numbers or affinity of PDGF receptors. We therefore examined the adhesion and spreading properties of SP1 and SP1-3M cells. Without exogenous growth factors, both cell lines adhered to fibronectin and laminin. SP1-3M cells did not bind to collagen type I, whereas SP1 cells did. Attachment to all three substrata was inhibited by anti-beta 1 integrin IgG, suggesting that the primary adhesion to these substrata is mediated by beta 1 integrins. SP1 and SP1-3M cells showed similar integrin patterns following immunoprecipitation by anti-beta 1 integrin IgG. bFGF stimulated increased adhesion and spreading of both SP1 and SP1-3M cells to collagen type I within 24 h, whereas PDGF-BB was less capable of this effect. Our results suggest that the proliferative response of SP1 and SP1-3M cells to PDGF-BB and bFGF is dependent on the extracellular matrix environment, and imply that modification of extracellular matrix and/or surface integrin receptors may regulate responsiveness to these growth factors in the SP1 tumor model.

Adenocarcinoma↗
PubMed1992

Neuritogenesis on collagen substrates. Involvement of integrin-like matrix receptors in retinal fibre outgrowth on collagen.

Extracellular matrix molecules such as laminin, fibronectin and collagen promote neurite outgrowth in vitro. We have investigated the capacity of hydrated gels of collagen types I-III and monomeric collagen types I-VI on plastic surfaces to support neuritogenesis. The attachment and survival of explants from the day 6 chick embryo were studied and neurite outgrowth measured as mean elongation rate and maximal neurite length. Collagen types I and III, both as three-dimensional gels or as native monomers supported neuritogenesis equal to or better than laminin. Collagen type V also supported neurite out-growth although less effectively. Collagen types II, IV and VI, as well as denatured collagens of all types tested, did not support outgrowth. The monoclonal anti-beta 1 integrin antibody (CSAT), as well as rabbit polyclonal antibodies directed to the integrin beta 1-chain, effectively inhibited neurite outgrowth on permissive collagenous substrata, indicating that collagen-binding integrins were involved in the neuritogenesis. These beta 1-integrins were independent of Arg-Gly-Asp (RGD) since neurite formation proceeded in the presence of synthetic RGD-containing peptides. Fluorescence immunohistochemistry revealed the presence of the integrin beta 1-chain on the outgrowing neurites. The results suggest a possible function of collagen and collagen-binding integrins in the development of the visual system.

Animals↗
PubMed1992

Effect of growth hormone treatment on hyperinsulinemia associated with Turner syndrome.

To determine whether the insulin resistance in patients with Turner syndrome, which may be exaggerated by treatment with human growth hormone, leads to excessive insulin secretion, we applied the hyperglycemic glucose-clamp technique to produce a standard hyperglycemic stimulus (6.9 mmol/L, or 125 mg/dl, greater than fasting plasma glucose level for 120 minutes) in seven patients with Turner syndrome and in seven healthy children. These studies were repeated in the patients after 6 to 12 months of therapy with growth hormone. Fasting plasma levels of insulin were comparable in control subjects and patients before therapy but increased significantly in the patients after 6 to 12 months of treatment with growth hormone. Despite identical glucose increments in the two groups during the glucose-clamp procedure, both first- and second-phase insulin responses were significantly greater in the patients than in the control subjects. Moreover, the hyperinsulinemic responses to glucose were markedly exaggerated in the patients after their treatment with growth hormone, reaching values (first phase 474 +/- 100 pmol and second phase 826 +/- 100 pmol; p less than 0.02 vs pretreatment values) that were almost threefold greater than those in control subjects (p less than 0.001). Nevertheless, the rate of insulin-stimulated glucose metabolism during the last 60 minutes of the clamp procedure was similar in all three groups of studies. Glycosylated hemoglobin, total cholesterol level, and blood pressure remained normal in patients after therapy with growth hormone. We conclude that glucose-stimulated insulin response is increased in patients with Turner syndrome and that these alterations are further exaggerated by treatment with growth hormone. These hyperinsulinemic responses appear to compensate for reductions in insulin sensitivity.

Adolescent↗
PubMed1992

Blockade of beta 1-integrins in skin causes edema through lowering of interstitial fluid pressure.

The increased capillary fluid filtration required to rapidly create edema in acute inflammation can be generated by increased negativity of the interstitial fluid pressure (Pif). This observation suggests that connective tissues can "actively" enhance capillary fluid filtration. We now show that in vivo blockade of beta 1-integrin adhesion receptors in rat skin causes local edema concomitant with increased negativity of Pif. Experiments were performed on the dorsal side of the hind paw, and Pif was measured with sharpened glass capillaries (tip diameter, 3-7 microns) connected to a servo-controlled counterpressure system. Measurements were made after circulatory arrest had been induced with intracardiac potassium chloride in pentobarbital anesthesia. This procedure prevents the vascular phenomena of increased fluid and protein flux leading to edema formation, which in turn can increase Pif and therefore potentially mask an increased negativity of Pif. Control Pif averaged -0.58 +/- 0.81 (mean +/- SD) mm Hg (n = 37). Subdermal injection of 5 microliters monospecific rabbit anti-rat integrin beta 1-subunit immunoglobulin G caused increased negativity of Pif to average values between -4 and -6 mm Hg within 10 minutes after injection. Subdermal injection of 0.9% NaCl, preimmune immunoglobulin G, rat anti-fibronectin, and peptides with Arg-Gly-Asp and Arg-Gly-Glu sequences did not change Pif significantly. In another series of experiments, 5 microliters anti-beta 1 integrin immunoglobulin G was injected subdermally in rats with intact circulation and resulted in an increase in total tissue water corresponding to a doubling of the interstitial fluid volume in 10 minutes (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Regulation of fibroblast-mediated collagen gel contraction by platelet-derived growth factor, interleukin-1 alpha and transforming growth factor-beta 1.

We have examined the effects of three macrophage-derived cytokines, platelet-derived growth factor (PDGF), transforming growth factor-beta 1 (TGF-beta 1) and interleukin-1 alpha (IL-1 alpha) on the contraction of collagen type I gels populated by human foreskin fibroblasts. Contraction was quantified as loss in gel weight. Both PDGF-AA and PDGF-BB were found to induce a rapid collagen-gel contraction. TGF-beta 1 also stimulated gel contraction but with a delayed onset and at a slower rate than the PDGF-stimulated contraction. Rabbit polyclonal IgGs recognizing PDGF-AA and PDGF-BB, respectively, specifically inhibited the effects of the corresponding PDGF isoforms. However, the stimulatory effect of TGF-beta 1 was not affected by any of the anti-PDGF antibodies. The ability of PDGF to stimulate contraction became less pronounced in collagen gel cultures grown in the absence of growth factors over periods of several days. Under the same conditions, the stimulatory effect of TGF-beta 1 was not reduced. The reduced response to PDGF may be due to reduced tension on fibroblasts growing in collagen gels, since fibroblasts on free-floating gels showed a marked reduction in PDGF-BB-induced PDGF beta-receptor aggregates when compared to fibroblasts on attached collagen gels. IL-1 alpha inhibited initial collagen gel contraction, and at later stages induced a visible degradation of the collagen gels, presumably due to the generation of collagenase activity. The combination of IL-1 alpha and PDGF-BB stimulated initial collagen gel contraction, although less effectively than PDGF-BB alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A monoclonal antibody-based immunodiagnostic assay for onchocerciasis.

Five murine monoclonal antibodies raised against Onchocerca volvulus cuticular extracts and termed MOVs (1-4 and 6) were selected based on reactivity with O. volvulus cryosections, and non-reactivity with cryosections of human skin and/or nodular tissue. Two others MOVs 5 and 7 reacted with both. Using the peroxidase-anti- peroxidase (PAP) histochemical method, the target epitopes of MOV 1 were located in the cuticle's basal and cortical layers, those of MOV 2 in the cortical layer; whilst MOV 3-7 stained the basal layer. A sandwich ELISA was then developed. The trapping polyclonal antibody was raised in rabbits utilising the same antigens as for preparation of the MOVs. Once captured on microtiter plates, target antigens were identified by the sequential binding of a MOV, followed by a goat anti-mouse globulin/peroxidase or alkaline phosphatase conjugate that catalysed a colorimetric reaction in the presence of appropriate substrates. In this system, MOV 1 emerged as the most specific and potent reagent capable of recognizing antigens of Onchocerca sp. with a minimal detection limit of 78 ng per test. MOV 1, failed to react with extracts of Loa Loa, Ascaris lumbricoides and Ascaris suum in the test. The developed assay relied on the use of MOV 1, required only 1 ml of urine or 0.05 ml serum. About 97.8% of the 47 urines and 50% of the 20 sera from patients studied gave positive results. Only 1 (3%) of 32 control urines and up to 80% of the 10 control sera studied tested positive, suggesting urine as a better specimen source.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Expression of collagen binding integrins during cardiac development and hypertrophy.

The interaction between components of the extracellular matrix and the cell surface of cardiac myocytes appears to be regulated in part by receptors belonging to the integrin superfamily. The expression of the integrins was investigated at different stages of development of the heart as well as during cardiac hypertrophy. The characterization of the membrane proteins showed that a beta 1-integrin and associated alpha-chains were responsible for the interaction with collagen, laminin, and fibronectin. Immunoprecipitation data indicated that the presence of specific alpha-chains varied with development. These data were correlated with the ability of the isolated myocytes to attach to specific components of the extracellular matrix. The expression of the alpha 1-chain was prominently associated with the recognition of interstitial collagens. The presence of the alpha 1-chain was also associated with stages when collagen synthesis was increased, especially during fetal and neonatal growth and cardiac hypertrophy. Immunohistochemical localization with the antiserum against beta 1-integrin demonstrated its specific localization near the Z lines of cardiac myocytes. The localization both in vitro and in vivo indicated that the beta 1-integrin may play a role in myofibrillogenesis during development. The present immunohistochemical, cell adhesion, and biochemical data clearly indicate that integrins play a major role in the regulation of the interaction between cardiac myocytes and the extracellular matrix during development and disease.

Animals↗
PubMed1991

Insulin resistance: an early metabolic defect of Turner's syndrome.

To evaluate whether insulin resistance contributes to the increased risk of diabetes in patients with Turner's syndrome, we measured insulin sensitivity (using the euglycemic insulin clamp technique, 40 mU/m2.min) and whole body glucose and lipid oxidation (assessed by indirect calorimetry) in two groups of nondiabetic patients with Turner's syndrome and age-matched normal controls. Group 1 consisted of eight young patients (mean age, 10 +/- 0.8 yr) who had never received hormone therapy, and group 2 consisted of five patients (mean age, 17.6 +/- 1.4 yr) who had been or were on estrogen therapy. In group 2, [3-3H]glucose was also infused during the euglycemic clamp to assess hepatic sensitivity to insulin. During the euglycemic clamp, insulin-stimulated glucose metabolism was decreased in both groups of patients [group 1, 8.4 +/- 1.0 vs. 14.7 +/- 2 mM/m2.min in controls (P less than 0.05); group 2, 9 +/- 0.7 vs. 11.7 +/- 0.9 mM/m2.min in controls (P less than 0.05)]. The impairment of insulin-stimulated glucose metabolism in patients with Turner's syndrome was accounted for by reduced nonoxidative glucose disposal; glucose oxidation rose to a similar extent in Turner patients and normal controls. Insulin-induced suppression of hepatic glucose production (group 2) and plasma FFA and branched chain amino acid levels in Turner patients was also indistinguishable from that in normal controls. Our data suggest that in patients with Turner's syndrome, insulin resistance is a very early metabolic defect that may be restricted to nonoxidative pathways of intracellular glucose metabolism.

Adolescent↗
PubMed1991

Characterization of platelet-derived growth factor beta-receptor expressing cells in the vasculature of human rheumatoid synovium.

Platelet-derived growth factor (PDGF) beta-receptor expression in normal and rheumatoid synovia was investigated by double immunofluorescence staining of frozen sections and by in situ hybridization. In the inflamed synovia, PDGF beta-receptor mRNA was present in vascular cells, as well as in discrete stromal cells. PDGF beta-receptor expressing cells in rheumatoid synovia were characterized by double immunofluorescence staining using the PDGFR-B2 monoclonal antibody at a concentration at which this antibody merely stained granular accumulations of PDGF beta-receptors. Granular accumulations of PDGF beta-receptors were articulate in blood vessel cells, but also appeared in discrete stromal cells. Thus, the overall distribution of cells having granular accumulations of PDGF beta-receptors was similar to the distribution of cells expressing PDGF beta-receptor mRNA. Double immunofluorescence stainings showed that: (a) a majority (greater than 90%) of resident macrophages did not express granular PDGF beta-receptor staining, but macrophages were often juxtaposed to PDGF beta-receptor-positive cells; (b) T lymphocytes did not express PDGF beta-receptors, but these cells were frequently found in the proximity of cells stained by PDGFR-B2; (c) in some blood vessels both HLA-DR expressing cells and PDGF beta-receptor expressing cells could be visualized, whereas in other blood vessels, cells expressing only one of these activation markers could be detected; (d) smooth muscle cells in blood vessels contained PDGF beta-receptors; and (e) capillary endothelial cells in the inflamed synovia recurrently displayed granular PDGF beta-receptor staining. The granular accumulations of PDGF beta-receptors may reflect internalization of the receptor as a result of paracrine or autocrine ligand stimulation. In support of such a possibility are the findings that elevated levels of PDGF B chain mRNA were detected by in situ hybridization in the inflamed synovia, and that cells expressing PDGF B chain mRNA were distributed similarly to cells expressing PDGF beta-receptor mRNA. Taken together, the results indicate that PDGF has a role in the inflammatory process in rheumatoid synovitis, most likely by stimulating proliferative events in the vasculature.

Arthritis, Rheumatoid↗