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Biomedical subjects

R Stern

Publications and source records attributed to R Stern.

At least 163 records · Page 9Linked to original sources
PubMed1990

Hyaluronic acid determinations: optimizing assay parameters.

Assay conditions for determining hyaluronic acid levels in cultured cells have been examined. In cultures labeled with [3H]glucosamine, hyaluronic acid is measured by digestion with a highly specific hyaluronidase from Streptomyces hyaluronlyticus. Products obtained in the presence and absence of preliminary enzyme digestion are precipitated with cetylpyridinium chloride. The precipitation step has been optimized for ion concentration, glycosaminoglycan carrier and for cetylpyridinium chloride levels. Chondroitin sulfate is an effective carrier in the precipitation of radiolabeled product, while unlabeled hyaluronic acid is not. Addition of sulfate to the mixture yields a flocculent precipitate that facilitates subsequent steps of the determination. Optimizing these steps in hyaluronic acid determination can generate two- to three-fold increases in apparent levels of deposition in cultured cells.

Animals↗
PubMed1990

Levels of [3H]glucosamine incorporation into hyaluronic acid by fibroblasts is modulated by culture conditions.

Tissue culture conditions can modulate apparent levels of incorporation of the radiolabeled precursor [3H]glucosamine into hyaluronic acid in cells. A careful study was made on the effects of culture conditions on human skin fibroblasts. A newly described technique to measure hyaluronic acid was utilized based on incorporation of [3H]glucosamine into cetylpyridinium chloride-precipitable hyaluronidase-digestible material. The precipitate was collected on glass fiber filters using a manifold suction apparatus. A six-fold greater level of incorporation occurred in rapidly growing preconfluent than in confluent fibroblasts. Ascorbic acid stimulated incorporation with a maximum at 25 micrograms/ml. The same ascorbic acid optimum was observed for collagen prolylhydroxylation. When beta-hydroxybutyrate was used as an energy source instead of D-glucose, a 3.5-fold increase in levels was observed. All tissue-culture media examined supported comparable levels of incorporation, except for Roswell Park Memorial Institute Media-1640, in which cells had only half the level. Fetal calf serum supported high levels of incorporation in a dose-dependent manner, while newborn calf and calf sera supported much lower levels of incorporation. Under serum-free conditions, lactalbumin hydrolysate was best able to support incorporation of hyaluronic acid. In the search for mechanisms that modulate hyaluronic acid, it is critical to consider the tissue culture conditions under which incorporation of radiolabeled precursors are being examined.

3-Hydroxybutyric Acid↗
PubMed1990

Hyaluronic acid deposition in cardiac myxomas: localization using a hyaluronate-specific binding protein.

Myxomas are the most common primary tumors of the heart. These lesions contain a gelatinous, ground-substancelike material which has been described as glycosaminoglycan in nature. Using a newly developed, cartilage-derived hyaluronic acid-binding protein and a modification of the avidin-biotin immunostaining procedure, we demonstrate that hyaluronic acid is contained in the jellylike material of cardiac myxomas.

Adult↗
PubMed1990

The therapeutical implication of a strike in a psychiatric ward.

This paper compares patient functioning during a maintenance workers' strike. Four criteria were used to assess change: 1) patients' functioning as evaluated by five independent judges on a questionnaire; 2) number of days out of the hospital; 3) number of days of closed intensive therapeutic ward hospitalization and 4) number of patients that underwent a major improvement during that period. A positive therapeutical effect in patients as a result of the strike has been found. This effect is thought to be due to the staff's higher expectations towards the patients, and not due to a need of the patients to restore a sense of balance in the threatened family-like system of the ward--as was believed in a previous study (1). The role of the staff in helping the patient to constructively cope with the strike is discussed.

Activities of Daily Living↗
PubMed1989

Hyaluronic acid-stimulating activity in sera from the bovine fetus and from breast cancer patients.

The sine qua non of malignancy is the ability of tumor cells to migrate and invade surrounding tissue. There are many substances that have been described that enhance cell motility and hyaluronic acid is prominent among these. Hyaluronic acid is a high molecular weight alternating disaccharide polymer found in abundance in extracellular matrices whenever rapid cell proliferation or tissue regeneration and repair occur. It creates a permissive environment for cell motility during embryogenesis, and high levels of hyaluronic acid also correlate with increased tumor cell invasion and aggressiveness. Little is known about the regulation of hyaluronic acid production, either in normal tissue or in malignancy. In this study, we characterize a hyaluronic acid-stimulating activity in fetal calf serum and describe a similar activity in the sera of breast cancer patients. The stimulating activity was measured by placing aliquots of test substance on fibrosarcoma cells. These indicator cells, which synthesize copious quantities of hyaluronic acid, respond to stimulation in a time- and dose-dependent fashion. The fetal calf serum hyaluronic acid-stimulating activity is maximum early in gestation and then falls rapidly to essentially no activity at term. This activity was partially purified from 120-day fetal calf serum by concanavalin A-Sepharose affinity and ion exchange chromatography and is accounted for by a glycoprotein with a molecular weight of 150,000 on gel filtration under native conditions. The sera of breast cancer patients with measurable burden of disease also contained hyaluronic acid-stimulating activity, which was not present in normal serum donors or in breast cancer patients without evidence of disease. The production of this stimulating activity may contribute to the development of the malignant phenotype by inducing hyaluronic acid-rich microenvironments that are permissive to tumor cell invasion and metastases.

Animals↗
PubMed1989

Studies in fetal wound healing: I. A factor in fetal serum that stimulates deposition of hyaluronic acid.

Fetal wound healing without scar formations, fibrosis, or contracture might be accompanied by major differences in the wound extracellular matrix. The matrix of fetal wounds is rich in hyaluronic acid, a glycosaminoglycan found in high concentrations whenever there is tissue proliferation, regeneration, and repair. Although hyaluronic acid is a critical molecule for both embryonic development and wound healing, no factor has yet been identified that modulates hyaluronic acid in a consistent manner. We describe here a substance present in fetal sheep serum that stimulates hyaluronic acid synthesis by cultured fibroblasts. This glycoprotein factor appears to be ubiquitous, present in fetal sheep and bovine serum, reaching a peak in each at 40% of the way through gestation. This factor is also present in amniotic fluid. It might control hyaluronic acid deposition. In turn, hyaluronic acid, by creating an extracellular environment permissive for cell motility and proliferation, might be critical for fetal development. We suggest that the same sequence of events underlie the unique properties observed in fetal wound healing.

Animals↗
PubMed1989

Studies in fetal wound healing: II. A fetal environment accelerates fibroblast migration in vitro.

We have used an in vitro model of wound healing using scratches made in a confluent monolayer of fibroblasts. The effects of fetal calf and postnatal calf serum on the migration of fibroblasts were compared. Differences between fetal and calf serum-incubated fibroblasts grown on coverslips were observed within 15 minutes of exposure. Cells in fetal serum began to change both shape and orientation and to move into the trough created by the scratch. The fibroblasts incubated in fetal calf serum completely filled in the trough within 16 hours while those incubated in calf serum did not do so even after 24 hours. We estimate that, at any point, there was a 50% lag time in the migration of the fibroblasts in the presence of postnatal calf serum. This difference in migration and filling was not a function of mitogenesis; the mitogenicity of the two sera were comparable. The results suggest that fibroblast migration in vitro is accelerated by the fetal serum. A similar mechanism may occur in vivo and may underlie the ability of the fetal wound to heal more rapidly.

Animals↗
PubMed1989

Studies in fetal wound healing: III. Early deposition of fibronectin distinguishes fetal from adult wound healing.

Wound healing in the fetus proceeds through a series of steps that differ in the fetus and the adult. At each phase of this complex process, there is signaling between the tissue cells and the wound microenvironment, signals that are mediated by and through the extracellular matrix. We postulate that these signals occur earlier in fetal wounds, resulting in more rapid repair. To investigate this, we compared the first 24 hours of wound healing in the rabbit fetus and adult, using antibodies against key extracellular matrix macromolecular components: laminin, fibronectin, and type-specific collagens I, III, IV, and V. Fibronectin was the first matrix component to be deposited, and was visualized as early as four hours after fetal wounding and 12 hours after adult wounding. There was no evidence of new laminin or collagen deposition in either the fetal or adult wounds at any time point examined. The early deposition of fibronectin, a matrix adhesion molecule that provides a scaffolding for epithelial migration, may underlie the rapid reepithelialization observed in fetal wounds.

Animals↗
PubMed1989

Studies in fetal wound healing. IV. Hyaluronic acid-stimulating activity distinguishes fetal wound fluid from adult wound fluid.

Recent clinical and experimental evidence suggests that the fetus responds to injury in a fashion fundamentally different from that of the adult. Our initial experience with human open fetal surgery reinforces experimental observations that the fetal wounds heal without the scarring, inflammation, and contraction that often accompany adult wounds. In this study we examine fetal wound fluid in an attempt to elucidate the control mechanisms that endow the fetus with unique healing properties. The extracellular matrix of fetal wounds is rich in hyaluronic acid, a glycosaminoglycan found in high concentrations whenever there is tissue proliferation, regeneration, and repair. We establish that wound fluid from the fetus contains high levels of hyaluronic acid-stimulating activity that may underlie the elevated deposition of hyaluronic acid in the fetal wound matrix. In contrast there was no hyaluronic acid-stimulating activity present in adult wound fluid. Hyaluronic acid, in turn, fosters an extracellular environment permissive for cell motility and proliferation that may account for the unique properties observed in fetal wound healing.

Age Factors↗
PubMed1989

Bleeding Meckel's diverticulum in an adult.

The 99mtechnetium pertechnetate nuclear red blood cell scan proved to be a valuable diagnostic tool in localizing the site of bleeding, from a Meckel's diverticulum, in a 41-year-old man. When peptic ulcer or colorectal disease has been excluded by panendoscopy, bleeding Meckel's diverticulum remains a diagnostic consideration, even in adults. We provide a 20-year list of bleeding Meckel's diverticula reported in adults, along with a brief discussion.

Adult↗
PubMed1989

Isolation and partial purification of growth factors with TGF-like activity from human malignant gliomas.

The effect of concentrated conditioned medium from each of eight human malignant glioma cell lines on the growth of indicator cells (normal rat kidney fibroblasts (NRK), clone 14) was determined in monolayer and in soft agar assay systems. The conditioned medium from all cell lines was mitogenic in the monolayer assay, but only SF-210, U-343 MG-A, and U-251 MG produced soluble factors that caused NRK cells to grow in soft agar. The soluble growth-promoting factors from these three cell lines were acid- and heat-stable (60 degrees C for 30 minutes) but were inactivated by trypsin (100 microns/ml) and dithiothreitol (50 microM). The growth factors from SF-210 and U-343 MG-A were further purified by molecular-sieve chromatography. The partially purified growth factor from U-343 MG-A retained transforming growth factor (TGF)-like activity, had a molecular weight of 9 kD, was potentiated by TGF-beta in the soft agar assay, competed effectively with 125I-epidermal growth factor (EGF) radiolabeled for the EGF receptor on A 431 epidermoid carcinoma cells, and was completely inhibited by monoclonal antibodies to TGF-alpha. The partially purified growth factor from SF-210 had a molecular weight of 17 kD, was not inhibited by monoclonal antibodies to platelet-derived growth factor (PDGF) or TGF-alpha, and did not bind to a heparin-Sepharose column. These results imply that U-343 MG-A secretes a growth factor with TGF-alpha-like activity, and SF-210 secretes a TGF with neither TGF-alpha nor TGF-beta activity.

Agar↗
PubMed1989

Cutaneous adverse reactions associated with calcium channel blockers.

The calcium channel blockers, nifedipine, verapamil, and diltiazem, are widely used for the treatment of cardiovascular disease. In spite of their widespread use, little data about the frequency and spectrum of cutaneous reactions associated with these agents have been published. Based on reports provided to the FDA's Division of Epidemiology and Drug Surveillance, and the American Academy of Dermatology's Adverse Drug Reaction Reporting System, it appears that the frequency of adverse cutaneous events associated with these drugs is low, but that occasionally severe reactions are associated with the use of these drugs. Among the more serious reactions associated with the calcium channel blockers are toxic epidermal necrolysis with diltiazem, Stevens-Johnson syndrome and erythema multiforme, which have been associated with all three drugs in this class, and exfoliative dermatitis, which has also been reported with all three agents. Most serious reactions associated with these agents occur within two weeks of initiating drug therapy. These findings suggest that calcium channel blockers are occasional causes of a wide spectrum of cutaneous reactions and should be considered as possible causative factors in patients who develop adverse cutaneous reactions while using these drugs.

Adult↗
PubMed1989

Massive hepatic necrosis in a child after administration of phenobarbital.

A 2-yr-old child developed massive hepatic necrosis caused by an unusual hypersensitivity response to phenobarbital that was prescribed for presumed febrile seizures. Despite discontinuation of the barbiturate, this child experienced fulminant hepatic failure and died. Review of the literature indicates that phenobarbital-induced hepatic injury is uncommon and usually mild. Prompt and permanent cessation of the drug results in resolution of symptoms in most patients.

Chemical and Drug Induced Liver Injury↗