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Biomedical subjects

L Wasserman

Publications and source records attributed to L Wasserman.

At least 55 records · Page 3Linked to original sources
PubMed1987

The anti-proliferative effect of lithium chloride on melanoma cells and its reversion by myo-inositol.

The effect of LiCl on melanoma cell growth and differentiation was studied in mouse and human melanoma cell lines. LiCl markedly inhibited B16 and HT-144 melanoma cell growth in vitro. Clonogenicity in soft agar of the melanoma cells was also markedly inhibited by LiCl. Pretreatment of B16 mouse melanoma cells with LiCl delayed the appearance of melanoma tumours in syngeneic mice. Growth inhibition of cells was accompanied by morphological and biochemical alterations. LiCl induced cell enlargement and formation of dendrite-like structures. The activity of NADPH cytochrome c reductase, an enzymatic marker of endoplasmic reticulum was significantly (2-3 fold) increased. Addition of myo-inositol to cell cultures partially reversed the anti-proliferative and morphological effects of LiCl on melanoma cells. This finding may suggest that the anti-proliferative effect of LiCl is related to its effect on phosphatidylinositol metabolism.

Animals↗
PubMed1987

Differential effects of sodium butyrate and dimethylsulfoxide on gamma-glutamyl transpeptidase and alkaline phosphatase activities in MCF-7 breast cancer cells.

Sodium butyrate and dimethylsulfoxide (DMSO), two known chemical inducers of cell differentiation, were examined on MCF-7 breast cancer cells. Both agents reduce the proliferative capacity of MCF-7 cells, as reflected by inhibition of colony formation in semisolid agar. Sodium butyrate is shown to enhance markedly the activity of two plasma membrane-bound enzymes, alkaline phosphatase and gamma-glutamyl transpeptidase. DMSO does not enhance the activity of these enzymes, but rather induces a small decrease in gamma-glutamyl transpeptidase activity. The present results show that although both agents inhibit cell proliferation, they have a distinct effect on phenotypic expression.

Alkaline Phosphatase↗
PubMed1987

Inhibition of heparanase-mediated degradation of extracellular matrix heparan sulfate by non-anticoagulant heparin species.

Incubation of human platelets, human neutrophils, or highly metastatic mouse lymphoma cells with sulfate-labeled extracellular matrix (ECM) results in heparanase-mediated release of labeled heparan sulfate cleavage fragments (0.5 less than Kav less than 0.85 on Sepharose 6B). This degradation was inhibited by native heparin both when brought about by intact cells or their released heparanase activity. Degradation of heparan sulfate in ECM may facilitate invasion of normal and malignant cells through basement membranes. The present study tested the heparanase inhibitory effect of nonanticoagulant species of heparin that might be of potential use in preventing heparanase mediated extravasation of bloodborne cells. For this purpose, we prepared various species of low-sulfated or low-mol-wt heparins, all of which exhibited less than 7% of the anticoagulant activity of native heparin. N-sulfate groups of heparin are necessary for its heparanase inhibitory activity but can be substituted by an acetyl group provided that the O-sulfate groups are retained. O-sulfate groups could be removed provided that the N positions were resulfated. Total desulfation of heparin abolished its heparanase inhibitory activity. Heparan sulfate was a 25-fold less potent heparanase inhibitor than native heparin. Efficiency of low-mol-wt heparins to inhibit degradation of heparan sulfate in ECM decreased with their main molecular size, and a synthetic pentasaccharide, representing the binding site to antithrombin III, was devoid of inhibitory activity. Similar results were obtained with heparanase activities released from platelets, neutrophils, and lymphoma cells. We propose that heparanase inhibiting nonanticoagulant heparins may interfere with dissemination of bloodborne tumor cells and development of experimental autoimmune diseases.

Animals↗
PubMed1986

Growth inhibition of murine melanoma by butyric acid and dimethylsulfoxide.

Treatment of B16-F10 melanoma cells with dimethylsulfoxide (DMSO) or butyric acid (BA) inhibits cell growth and delays tumor appearance in syngeneic mice. Both agents induce morphological changes in these cells. Treatment of melanoma cells with DMSO results in a marked increase in tyrosinase activity and melanin content. BA, on the other hand, does not increase melanin content and decreases tyrosinase activity. The data show that there are marked differences in the effect of DMSO and BA on melanin biosynthesis, whereas both agents inhibit cell growth and cause a delay in tumor appearance. These findings indicate that decreased proliferation of melanoma cells and induction of melanin biosynthesis are not necessarily associated phenomena.

Animals↗
PubMed1986

Factors that determine the long-term results of percutaneous transluminal dilatation for peripheral arterial occlusive disease.

Seven hundred thirty-one percutaneous transluminal dilatations (TLDs) for peripheral arterial occlusive disease were performed between 1978 and 1984. From this prospective study 666 dilatations were analyzed with a combination of clinical and objective vascular laboratory tests to determine which factors could be used to predict long-term successful results. Eleven variables were recorded at the time of TLD. The proportional hazards model (Cox regression) identified four significant variables predictive of long-term success: the indication for the procedure (claudication or salvage), site of the dilatation (aortoiliac or femoropopliteal), runoff (poor or good), and whether a previous TLD was done at the same site. With these significant variables, the Cox model was used to estimate the chances of success at 1, 2, and 3 years for all combinations of variables. The accuracy of the Cox model was confirmed by the close approximation between the number of observed and predicted successful TLDs at 1, 2, and 3 years. We concluded that the chances of success of TLD in terms of percentage at 1, 2, and 3 years can be predicted from the combinations of these four significant variables. Knowledge of these factors should permit better selection of patients for this procedure.

Aged↗
PubMed1985

Dimethylthiourea inhibition of melanoma cell growth in vitro and in vivo.

The effect of dimethylthiourea (DMTU), an agent known as a hydroxyl radical scavenger, was determined on growth and differentiation of the B16 murine melanoma cell line. DMTU inhibited melanoma cell growth in vitro and induced changes in the morphology of melanoma cells. Prolonged treatment of cells with DMTU resulted in an increase in melanin content. DMTU-treated melanoma cells had a decreased capacity to form tumors in syngeneic mice. Systemic administration of DMT to C57BL/6J mice inoculated with melanoma cells resulted in a delay in tumor appearance and a prolongation of survival. The doses of DMTU used did not cause any apparent toxic effects. A potential therapeutic role for DMTU in the treatment of melanoma is suggested.

Animals↗
PubMed1985

Structure-activity relationships for the irreversible blockade of nicotinic receptor agonist sites by lophotoxin and congeneric diterpene lactones.

Lophotoxin, a diterpene lactone paralytic toxin from gorgonian corals of the genus Lophogorgia, inhibits [125I]-alpha-toxin binding to surface nicotinic receptors of BC3H-1 cells by irreversible occupation of the primary agonist sites. In contrast, receptor-bearing membrane fragments or detergent-solubilized receptors prepared from BC3H-1 cells are not susceptible to lophotoxin block. Thus, lophotoxin inhibition requires intact cells. However, when intact cells were incubated with lophotoxin, subsequent membrane-fragment preparation or detergent solubilization of the receptors did not diminish lophotoxin occupation of [125I]-alpha-toxin-binding sites, indicating that lophotoxin binds very tightly to nicotinic receptors. These studies further demonstrate that both surface and nonsurface nicotinic receptors of BC3H-1 cells are susceptible to irreversible occupation by lophotoxin, indicating that the lipophilic toxin freely permeates intact cells. We also examined several structural analogs of lophotoxin, one of which was equipotent with lophotoxin for inhibition of [125I]-alpha-toxin binding to intact cells and, notably, also blocked alpha-toxin binding to detergent-extracted receptor. Furthermore, this active analog inhibited [125I]-alpha-toxin binding to receptor-rich membrane fragments prepared from Torpedo electric organ, a preparation in which lophotoxin was inactive. Structure-activity relationships exhibited by the lophotoxin congeners suggest mechanisms for covalent bonding to the receptor by way of a Michael addition or by Schiff base formation.

Animals↗
PubMed1984

Characterization of purine nucleotide metabolism in primary rat cardiomyocyte cultures.

Primary rat cardiomyocyte cultures were utilized as a model for the study of purine nucleotide metabolism in the heart muscle, especially in connection with the mechanisms operating for the conservation of adenine nucleotides. The cultures exhibited capacity to produce purine nucleotides from nonpurine molecules (de novo synthesis), as well as from preformed purines (salvage synthesis). The conversion of adenosine to AMP, catalyzed by adenosine kinase, appears to be the most important physiological salvage pathway of adenine nucleotide synthesis in the cardiomyocytes. The study of the metabolic fate of IMP formed from [14C]formate or [14C]hypoxanthine and that of AMP formed from [14C]adenine or [14C]adenosine revealed that in the cardiomyocyte the main flow in the nucleotide interconversion pathways is from IMP to AMP, whereas the flux from AMP to IMP appeared to be markedly slower. Following synthesis from labeled precursors by either de novo or salvage pathways, most of the radioactivity in purine nucleotides accumulated in adenine nucleotides, and only a small proportion of it resided in IMP. The results suggest that the main pathway of AMP degradation in the cardiomyocyte proceeds through adenosine rather than through IMP. About 90% of the total radioactivity in purines effluxed from the cells during de novo synthesis from [14C]formate or following prelabeling of adenine nucleotides with [14C]adenine were found to reside in hypoxanthine. The activities in cell extracts of AMP 5'-nucleotidase and IMP 5'-nucleotidase, which catalyze nucleotide degradation, and of AMP deaminase, a key enzyme in the purine nucleotide cycle, were low. The nucleotidase activity resembles, and that of the AMP deaminase contrasts the respective enzyme activities in extracts of cultured skeletal-muscle myotubes. The results indicate that in the cardiomyocyte, in contrast to the myotube, the main mechanism operating for conservation of nucleotides is prompt phosphorylation of AMP, rather than operation of the purine nucleotide cycle. The primary cardiomyocyte cultures are a plausible model for the study of purine nucleotide metabolism in the heart muscle.

5'-Nucleotidase↗
PubMed1984

Cardiomyocytes cultured in serum-free medium. Growth and creatine kinase activity.

Primary cultures of newborn rat heart cells were grown for up to 3 weeks in serum-free medium supplemented by insulin, hydrocortisone, transferrin and fetuin. The cells resumed spontaneous beating at 20 h post plating. Mean rates of beating on the second and third day were 79.5 and 94 beats per min, respectively. Cell proliferation occurred during the first 3 days of culture with maximal rates of DNA and protein synthesis on the second day. The highest values of creatine kinase activity were observed on days 2-5 and the three cytoplasmic isozymes, MM, MB and BB, were present in the cultures in proportions similar to those of the newborn heart, indicating stability of the differentiated state of the cells. The relative amount of each isozyme remained unchanged throughout the experiments, MM constituted 70-90% of enzyme activity, MB contributed up to 30% and BB did not exceed 15% of activity. The very low proportion of BB and the lack of increase in this isozyme with age of culture support our earlier morphological observations that non-myocytes do not overgrow the culture.

Animals↗
PubMed1983

Pattern of glycosaminoglycan distribution in tissue and blood vessels of human placenta.

The composition of separate crude glycosaminoglycan preparations from placental tissue and corresponding villous blood vessels was investigated in normal human placentas at various stages of maturation and in placentas from diabetic, toxemic and insufficient pregnancies. The crude preparations were separated into individual glycosaminoglycans and identified by means of electrophoresis on cellulose acetate prior or after specific enzymatic or chemical treatments. Relative amounts of individual glycosaminoglycans were estimated by densitometric scanning of the alcian blue-reactive electrophoretic bands. Irrespective of the nature of placenta, the contents of uronic acid and neutral sugar were higher in the preparations derived from blood vessels, as compared to placental tissue. Hyaluronic acid, chondroitin sulfates, heparan sulfate and dermatan sulfate were found in both preparations. The proportion of dermatan sulfate was higher while that of heparan sulfate was lower in the blood vessel preparations, compared to placental tissue. It is suggested that both heparan sulfate and dermatan sulfate may function as anticoagulants in their specific locations, namely, the maternal sinuses and the villous fetal blood vessels. The type of the glycosaminoglycan present may also influence the permeability of the tissue.

Blood Vessels↗
PubMed1980

Changes in glycosaminoglycan composition of normal human placentas with maturation.

Crude glycosaminoglycan preparations were isolated from acetone-powder of first-, second-, and third-trimester human placentas. Glycosaminoglycan composition was examined by electrophoresis and densitometric scanning before and after treatment with testicular hyaluronidase and chondroitinase ABC. Hexosamines were determined in electrophoretic fractions in order to identify the individual glycosaminoglycans. The results showed a decrease in glycosaminoglycans and an increase in protein contents in the preparations as the placenta matured. The main glycosaminoglycans in all placentas were dermatan sulfate, chondroitin sulfates, hyaluronic acid, and heparan sulfate. With aging of the placenta, the proportion of hyaluronic acid remained unchanged and that of chondroitin sulfate decreased, whereas the proportions of dermatan and heparan sulfates increased. Age-dependent changes in the glycosaminoglycan composition of the placenta appear to follow a pattern similar to that reported for other mammalian tissues.

Chondroitin Sulfates↗
PubMed1980

Glycosaminoglycan patterns in diabetic and toxemic term placentas.

Crude glycosaminoglycans were prepared from acetone powder of diabetic, toxemic, and normal term placentas. Glycosaminoglycan composition was determined by electrophoresis and densitometric scanning with and without treatment with testicular hyaluronidase and chondroitinase ABC. The identity of individual glycosaminoglycans was confirmed by the nature of their hexosamine. Glycosaminoglycan content was found to be significantly increased in diabetic placentas and increased to a lesser degree in the toxemic placentas. The amount of hyaluronic acid was elevated in both abnormal tissues, and heparan sulfate was slightly higher in diabetes, while unchanged in toxemia. Dermatan sulfate was markedly reduced in the abnormal placentas while chondroitin 4/6 sulfate was unaltered. An attempt was made to correlate the histopathologic changes reported to occur in these conditions with the alterations in the glycosaminoglycans patterns of placentas.

Chondroitin Sulfates↗
PubMed1980

Thallium 201 myocardial scintigraphy. Advantages and limitations.

Myocardial scintigraphy with thallium 201 is a simple, safe, and valuable noninvasive technique in evaluating the condition of patients with cardiac disorders. Images obtained at rest appear to have limited usefulness at the present time. However, rest imaging may prove to have advantages in the future for early diagnosis of myocardial infarction, thus aiding in the selection of patients to be admitted to the coronary care unit. Exercise imaging, on the other hand, has a high degree of sensitivity and specificity in detecting ischemic heart disease; when combined with treadmill exercise testing, imaging improves the diagnostic accuracy even further.

Acute Disease↗
PubMed1979

Composition of acidic glycosaminoglycans in human term placenta blood vessels.

The composition of acidic glycosaminoglycans in pooled blood vessels, mostly of fetal origin, from a normal human term placenta was investigated by a series of procedures consisting of chromatography on a cetyl pyridinium chloride-cellulose column, cellulose acetate electrophoresis, susceptibility to testicular hyaluronidase and thin layer chromatography of the products of digestion with bacterial chondroitinases. The results indicate the presence of hyaluronic acid (36%), chondroitin-6-sulfate (27%), dermatan sulfate (21%), heparan sulfate (8%) and chondroitin-4-sulfate (8%). Several of the fractions obtained from the cetyl pyridinium chloride-cellulose column exhibited anticoagulant activity, which might be physiological importance for the maintainance of the fluidity of the intensively circulating placental blood.

Blood Vessels↗
PubMed1978

Sudden death in severe aortic stenosis following cardiac catheterization.

Five patients with critical aortic stenosis (aortic valve area 0.6 cm2 or less) died 2 days to 21 days following cardiac catheterization performed in anticipation of cardiac surgery. A sixth patient was successfully resuscitated for spontaneous ventricular fibrillation, and successful aortic valve replacement was accomplished. Two patients had prior history of syncope; one patient, of ventricular tachycardia; three patients, of pulmonary edema; and three patients, of crescendo angina. One patient had severe hypotension during maintenance hemodialysis for chronic renal failure. The mode of death was sudden but not witnessed in two patients. The terminal cardiac rhythms were slow junctional in one patient, idioventricular in one, ventricular tachycardia in one, and ventricular fibrillation in the fourth patient. We conclude that symptomatic patients with critical aortic stenosis should be monitored after cardiac catheterization, and surgery should be performed as soon as possible since sudden death is not unusual.

Aged↗