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S L Friedman

Publications and source records attributed to S L Friedman.

At least 91 records · Page 5Linked to original sources
PubMed1989

Lipocytes from normal rat liver release a neutral metalloproteinase that degrades basement membrane (type IV) collagen.

We report a proteinase that degrades basement-membrane (type IV) collagen and is produced by the liver. Its cellular source is lipocytes (fat-storing or Ito cells). Lipocytes were isolated from normal rat liver and established in primary culture. The cells synthesize and secrete a neutral proteinase, which by gelatin-substrate gel electrophoresis and gel filtration chromatography, has a molecular mass of 65,000 D. The enzyme is secreted in latent form and is activated by p-aminophenylmercuric acetate but not by trypsin. Enzyme activity in the presence of EDTA is restored selectively by zinc and is unaffected by serine-protease inhibitors. In assays with radiolabeled soluble substrates, it degrades native type IV (basement membrane) collagen but not interstitial collagen types I or V and exhibits no activity against laminin or casein. At temperatures causing partial denaturation of soluble collagen in vitro, it rapidly degrades types I and V. Thus, it is both a type IV collagenase and gelatinase. The enzyme may play a role in initiating breakdown of the subendothelial matrix in the Disse space as well as augmenting the effects of collagenases that attack native interstitial collagen.

Animals↗
PubMed1989

Activation of cultured rat hepatic lipocytes by Kupffer cell conditioned medium. Direct enhancement of matrix synthesis and stimulation of cell proliferation via induction of platelet-derived growth factor receptors.

Hepatic lipocytes appear to be central to the pathogenesis of hepatic fibrosis, undergoing activation during inflammation to a matrix-producing, proliferative cell type. We have studied the activation process in culture by examining the response of lipocytes to conditioned medium from hepatic macrophages (Kupffer cells). Lipocytes exposed to Kupffer cell medium (KCM) exhibited cellular and nuclear enlargement associated with up to a threefold increase in collagen and total protein synthesis per cell. Cell proliferation was also stimulated as measured by [3H]thymidine incorporation and direct cell counting. The latter effect was serum dependent and inhibited by antibodies to platelet-derived growth factor (PDGF). Proliferation could be stimulated by recombinant PDGF, but only after preincubation of cells with KCM. These findings suggested that KCM was eliciting expression of the PDGF receptor in lipocytes, and this was confirmed by immunoblot analysis with antibodies to the PDGF receptor. DNA synthesis in lipocytes exposed to KCM occurred at 48 h, which reflected the time required for PDGF receptor expression (24 h) plus initiation of [3H]thymidine incorporation (24 h). These results indicate that KCM has multiple stimulatory effects on cultured lipocytes similar to activation of these cells observed in vivo.

Animals↗
PubMed1988

Formation of extracellular matrix in normal rat liver: lipocytes as a major source of proteoglycan.

Proteoglycans are a major component of the normal hepatic extracellular matrix and undergo quantitative and qualitative changes in hepatic fibrosis. The cellular sources of proteoglycans are as yet incompletely defined. We examined this question using primary cultures of hepatocytes and lipocytes isolated from normal rat liver. Proteoglycan synthesis was assessed by measuring production of sulfated glycosaminoglycan, the polysaccharide moiety of proteoglycans. The findings indicate that lipocytes produce sixfold more glycosaminoglycan, per cell, than do hepatocytes. Two-thirds of the newly synthesized material is cell- or matrix-associated. Of the individual glycosaminoglycan species produced by lipocytes, dermatan sulfate represents 60% of the total; heparan sulfate and chondroitin sulfate are measurable but relatively minor. In hepatocyte cultures, heparan sulfate accounted for essentially all of the glycosaminoglycan detected. We conclude that lipocytes are an important source of proteoglycan in normal liver and may be the principal source of dermatan sulfate associated with hepatic fibrosis.

Animals↗
PubMed1988

Immunolocalization of laminin in normal rat liver and biosynthesis of laminin by hepatic lipocytes in primary culture.

Laminin, a glycoprotein with a molecular weight of approximately 850,000 daltons, is a major constituent of most epithelial basement membranes. Its presence in the extracellular matrix of normal liver, however, is debated. Using two affinity-purified antibodies directed against laminin, we have localized the glycoprotein within normal rat liver and identified its cellular source. Immunofluorescent staining of rat liver sections revealed laminin in a continuous distribution around hepatic sinusoids, adjacent to hepatocytes and sinusoidal lining cells. To determine the cellular origin of laminin, three perisinusoidal cell populations (hepatocytes, sinusoidal endothelial cells, and lipocytes) were purified from enzymatically dispersed rat liver and were established in primary culture. By immunofluorescence, laminin was associated almost exclusively with lipocytes. Synthesis of laminin was demonstrated by immunoprecipitation of the protein from lipocyte culture medium pulse-labeled with radioactive methionine. These results show that in adult liver, laminin is present in the perisinusoidal matrix and is produced by hepatic lipocytes. Lipocytes, which have the capacity to produce collagen as well as laminin, may be the principal source of extracellular matrix proteins in the perisinusoidal space, and may contribute to subendothelial fibrosis resulting from liver injury.

Animals↗
PubMed1988

Toddlers' concentration: does maternal depression make a difference?

Twenty-five mother-toddler dyads with depressed mothers were compared with 25 dyads with well mothers on measures of attention during 20 min of spontaneous play in a home-like setting. Children of depressed women focused attention on more objects for shorter durations. Group differences could be accounted for by mothers' involvement in their children's play. Depressed women initiated and terminated more instances of attention to objects than well mothers. Correlations between maternal behaviors and children's attention were statistically significant. Results support the hypothesis that poorer attention of children of depressed women is at least in part mediated by inculcation.

Adult↗
PubMed1988

Collagen measured in primary cultures of normal rat hepatocytes derives from lipocytes within the monolayer.

The cellular origin of hepatic collagen is under active investigation. Several recent studies using cells in primary culture suggest that hepatocytes are the source of much of the collagen in normal rat liver. In view of other data indicating that lipocytes produce substantial amounts of this protein, we have reexamined collagen biosynthesis in hepatocyte cultures that have been carefully characterized with respect to the presence of lipocytes. We find that routinely prepared hepatocyte isolates contain, by number, approximately 10% lipocytes. Lipocytes in early culture are difficult to visualize by phase-contrast microscopy but after 4 d proliferate and eventually replace the parenchymal cells. The size of the lipocyte subpopulation in these cultures correlates positively with collagen production. Similarly, removal of lipocytes by further processing of the initial hepatocyte isolate significantly reduces collagen production. Moreover, the only cells within hepatocyte cultures that display type I collagen by immunohistochemistry are lipocytes. We conclude that lipocytes are the principal source of collagen in primary hepatocyte cultures. The findings indicate also that these cells are the previously described "fibroblast" that appear in relatively long-term hepatocyte cultures.

Animals↗
PubMed1988

Gastrointestinal and hepatobiliary neoplasms in AIDS.

There is an increased frequency of Kaposi's sarcoma and non-Hodgkin's lymphomas in patients with AIDS. These "opportunistic malignancies" establish the diagnosis of AIDS in an HIV-positive patient and are associated with a high likelihood of gastrointestinal and hepatobiliary involvement. Kaposi's sarcoma is a multicentric cutaneous spindle-cell tumor that is associated with luminal lesions in at least 40 per cent of patients. Gastrointestinal KS is usually asymptomatic but may rarely bleed or obstruct. Treatment of KS with either radiation or chemotherapy can reduce tumor bulk, without affecting survival. Non-Hodgkin's lymphomas in AIDS are B-cell neoplasms composed of either noncleaved or blast cells, similar to those seen in Burkitt's lymphoma. The tumors are usually highly aggressive and present in extranodal sites in the majority of cases. Primary or secondary gastrointestinal involvement is frequent, with hepatic and rectal tumors being particularly common. Unlike KS, gastrointestinal lymphomas are usually symptomatic. Obstruction, perforation, and bleeding can occur in patients with luminal involvement. Jaundice due to hepatic infiltration or biliary obstruction may be seen. Treatment with chemotherapy is usually indicated because of the rapid progression of the tumor, although no prolongation of survival has been demonstrated. There may also be an increased incidence of Hodgkin's disease and anorectal neoplasia in patients with AIDS; however, these malignancies do not establish the diagnosis of AIDS in an HIV-positive patient.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Isolation and culture of hepatic lipocytes, Kupffer cells, and sinusoidal endothelial cells by density gradient centrifugation with Stractan.

A method for isolating purified populations of hepatic lipocytes, Kupffer cells, and sinusoidal endothelial cells suitable for culture, using density gradient centrifugation on the polysaccharide material Stractan is described. A nonparenchymal cell digest of liver from either normal rats or rats treated with modest doses of vitamin A is layered on a discontinuous gradient of 6, 8, 12, ind 20% Stractan; lipocytes are separated efficiently from other nonparenchymal cells and are removed from the top of the gradient. Kupffer cells and sinusoidal endothelial cells, which migrate to denser interfaces in the gradient, are further purified by differential plating and selective trypsinization, respectively. Isolated highly viable lipocytes free of contaminants adhere and spread progressively over several days in primary culture and display both intrinsic vitamin A fluorescence and positive immunostaining for desmin. Lipocytes survive for prolonged periods on plain plastic, and collagen synthesis by these cells remains relatively constant for at least 28 days. Based on serial assay of DNA content, lipocytes in primary culture proliferate, beginning 7 days after plating. Kupffer cells and sinusoidal endothelial cells isolated by Stractan density centrifugation likewise retain their typical morphologic and functional characteristics in culture; the purity of these cell isolates has been confirmed by using specific fluorescent markers. This investigation demonstrates that Stractan density gradient centrifugation is an efficient, sensitive, and reproducible method for isolating pure populations of hepatic nonparenchymal cells.

Animals↗
PubMed1985

Gastrointestinal Kaposi's sarcoma in patients with acquired immunodeficiency syndrome. Endoscopic and autopsy findings.

Homosexual men with acquired immunodeficiency syndrome and Kaposi's sarcoma (KS) have been studied to define the extent of gastrointestinal KS. In 50 patients examined by both upper endoscopy and flexible fiberoptic sigmoidoscopy, 20 (40%) had visible lesions consistent with KS. Ten patients (20%) had upper and lower tract involvement, 6 (12%) patients had upper tract involvement alone, and 4 (8%) had lower tract disease alone. Only 23% of endoscopic biopsies of KS lesions were positive for KS. Gastrointestinal KS was not more frequent in patients with nodal KS (41%) than in patients with skin KS (50%). No clinical sequelae of gastrointestinal KS lesions were seen. Mortality was significantly greater in those patients with endoscopic evidence of gastrointestinal KS. Postmortem examination of 13 men with KS and acquired immunodeficiency syndrome revealed abdominal visceral involvement in 10 patients (77%). Antemortem endoscopic findings correlated with subsequent autopsy data in 5 patients. Our findings suggest that visceral involvement, though rarely symptomatic, may be associated with a poorer prognosis.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Hepatic lipocytes: the principal collagen-producing cells of normal rat liver.

Hepatic lipocytes were isolated from normal rat liver and established in culture. A virtually pure isolate was obtained by fractionating enzymatically digested liver on a discontinuous gradient of arabinogalactan. Isolated cells displayed prominent rough endoplasmic reticulum and typical cytoplasmic droplets containing vitamin A. Lipocytes in primary culture were shown by immunofluorescence to secrete collagen types I, III, and IV and also laminin. Immunoassay of culture media showed that lipocytes during the first week in culture secrete type I (72.1-86.2% of total measured soluble collagen), type III (2.6-7.2%), and type IV (11.2-29.7%) collagens. Five percent of total secreted protein was collagen compared with 0.2% in similarly cultured hepatocytes and 1.7% in sinusoidal endothelial cells, as measured by the production of peptide-bound [3H]hydroxyproline in cells incubated with [3H]proline. The calculated amount of collagen synthesized by lipocytes per microgram of cellular DNA was 10-fold greater than that produced by hepatocytes and over 20-fold greater than that produced by endothelial cells. The findings indicate that collagen synthesis and secretion are specialized functions of hepatic lipocytes, and that, in cells from normal liver, this represents production primarily of type I collagen. The phenotypic resemblance of these cells to fibroblasts supports the hypothesis that lipocytes are a major source of collagen in pathologic fibrosis and may be precursors of the fibroblast-like cells observed in liver injury.

Animals↗
PubMed1984

Gastrointestinal Kaposi's sarcoma in AIDS: radiographic manifestations.

About one-third of all patients with the acquired immunodeficiency syndrome (AIDS) have Kaposi's sarcoma. Gastrointestinal involvement has been noted in 50% of homosexual men with cutaneous Kaposi's sarcoma and AIDS. We report the abnormalities on barium studies of nine homosexual men from the San Francisco bay area who have AIDS and documented gastrointestinal Kaposi's sarcoma. Submucosal nodularity and infiltrative irregularity were the most frequently noted findings and were demonstrated in the stomach, duodenum, small bowel, and colon. The duodenum was the most frequent site of abnormality. Coalescent plaques, some with umbilications, were seen in the colon. Although nonspecific, these radiographic abnormalities are highly suspicious for Kaposi's sarcoma, particularly in patients with or at high risk for AIDS, especially homosexual men.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Children's emotions and behaviors in response to infants' cries.

Infant crying can elicit in others both a range of emotions and contrasting behavioral reactions, such as altruistic caregiving versus aggression. Variations in reactions to young infants' cries were examined in 60 children ranging in age from late preschool to preadolescence. Each child over-heard either a preterm or a full-term tape-recorded cry from an adjacent room. Then a mother, carrying her infant, came looking for her (previously) "crying" infant's bottle. Later each child was interviewed after hearing a tape recording of a preterm and a full-term cry. Children's emotions and behaviors thus were assessed in response to simulated, real distresses and hypothetical representations of distress. Children's self-reports of empathy, their verbalized intentions to help, their actual helping responses, and observers' ratings of negative emotion were common responses to cries at all ages. In addition there were significant increases with age in prosocial, behavioral interventions. Expressions of negative emotion were inversely related to subsequent forms of prosocial behavior that required direct interaction with the infant. The emotions and behaviors of most children were not influenced by whether they heard preterm or full-term cries. They were, however, able to discriminate between such cries and some articulated "theories" about the impact of the cries on the listener.

Arousal↗
PubMed1982

Complementing the success of medical intervention.

In this article we have placed the studies reported in this issue of Seminars in Perinatology in the context of research that has been conducted to evaluate the psychologic integrity of preterms. We have focused on the limitations of standardized tests of intelligence as indices of mental competencies, since these tests have been used extensively in studies that evaluate preterms throughout childhood. We described alternative methods for the evaluation of intelligence that are congruent with current theory and data about the nature of intelligence. We have implied that (A) theoretical considerations regarding the mutual and interdependent influences of biology and environment on the course of normal and abnormal human development suggest that intervention aimed at enhancing the psychologic adjustment of preterm children will complement the benefits gained through medical interventions in the neonatal period, and that (B) theoretical and methodological advances in cognitive psychology make it now possible to embark on research programs of evaluation and intervention that could improve the mental functioning of many preterms and hopefully repair some of the damage their central nervous system suffered in early infancy.

Adolescent↗
PubMed1975

Developmental changes in the understanding of implied motion in two-dimensional pictures.

The power of various pictorial movement cues in eliciting a reading of movement was studied to determine the relationship between the ease with which a picture is interpreted and the degree to which the picture retains the structure of reality. Movement was indicated in 2 ways: pictorial conventions indicated movement by lines, blurs, and vibration marks; and pictorial postures indicated movement by figures which were isomorphic with the postures involved in real movement. Preschoolers, first graders, sixth graders, and college students were asked to label and sort pictures of human figures as "moving" or "still". Members of the 2 young groups did not classify pictures with conventional cues as "moving" as often as they did pictures with postural cues. Members of the 2 older groups classified both types of pictures as "moving". Since postural cues for movement are recognized at an earlier age than conventional cues, those that are more similar to reality may be easier to understand.

Adult↗