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Biomedical subjects

J J Berman

Publications and source records attributed to J J Berman.

At least 73 records · Page 4Linked to original sources

Effects of program characteristics on treatment outcome: an interrupted time-series analysis.

The methodological difficulties in comparing the effectiveness of alternative alcoholism treatment programs were addressed. An interrupted time-series design and MMPI scores were employed with 408 men veterans to test the effectiveness of four changes in an 8-week inpatient alcoholism treatment program: The program was given its own ward; the amount of time patients spent in common activities was increased; the staff: patient ratio was improved; and contract with the outside community was broadened. The scores of MMPI tests administered at treatment termination were available for the periods of 3 yr prior to and 3 yr after the change. The results of the time-series analysis indicated that the new program was indeed more effective than the old one because nine of the 13 subscales used and the Disturbance Index (a weighted combination of all the subscales) showed a reliable decline coincident with the introduction of the new program. However, the results also showed most of these effects to be short-lived. Implications of these results and issues involved in implementing this design are discussed.

Alcoholism↗

Differences between rat liver epithelial and fibroblast cells in metabolism of purines.

Epithelial and fibroblast cells from adult rat liver were found to differ markedly in their metabolism of the purine hypoxanthine. Both cell types took up hypoxanthine and possessed hypoxanthine-guanine phosphoribosyl transferase for phosphoribosylating the purine. However, in the transferase assay, lysates from epithelial cells converted hypoxanthine predominantly to inosine monophosphate, with small amounts of the nucleoside inosine as product, whereas fibroblast cell lysates converted hypoxanthine predominantly to inosine. The inosine appeared not to be produced by direct ribosylation of the base, since fibroblast cell lysates had less purine nucleoside phosphorylase activity than epithelial cell lysates. Rather, the inosine produced by fibroblast lysates appeared to be derived from inosine monophosphate through catabolism of the mononucleotide by 5' nucleotidase. An inhibitor of 5' nucleotidase, thymidine triphosphate, reduced the amount of inosine formed.

Adenosine Monophosphate↗

5'-Nucleotidase activities in cultured rat liver epithelial and fibroblast cells.

Cell cultures of adult rat liver produced two distinct morphologic cell types: epithelial cells polygonal in shape and growing in nests of closely apposed cells, and fibroblast cells stellate in shape with little cell-cell contact at low density growth, but aligning in parallel arrays at high density. These two morphologic variants displayed dramatic differences in histochemically demonstrable 5'-nucleotidase activities. Fibroblast cells exhibited great activity throughout the cytoplasm with no concentration of activity in the cell membrane. The lesser activity in epithelial cells was concentrated on the cell membrane. The importance of this finding to the interpretation of data derived from experiments with whole liver homogenates is discussed.

Animals↗

Endocardial schwannomas in rats. Their characterization by light and electron microscopy.

Thirty male Sprague-Dawley rats were given a single intravenous injection of methyl(acetoxymethyl)nitrosamine. Primary endocardial tumors developed in ten rats. By light and electron microscopy, the tumors had many of the typical features of schwannomas (neurinomas) in rats. Tumors were composed of masses of elongated cells surrounded by a fine reticulin network, occasionally forming Verocay bodies. Basement membrane was observed on the external surfaces of tumor cells, which had convoluted plasma membranes. To our knowledge, this is the first report of a spontaneous endocardial schwannoma in a rat. The literature addressing endocardial tumors in rodents and man is discussed, and criteria for distinguishing this neoplastic entity from other tumors and non-neoplastic endocardial proliferations are described.

Animals↗

Synthesis of fibronectin, laminin, and several collagens by a liver-derived epithelial line.

We have investigated the ability of ARL-6 cells, a cell line derived from rat liver, to synthesize various collagens and two glycoproteins of the extracellular matrix, fibronectin, and laminin. Using immunofluorescence, we detected types I, II, and IV collagen plus laminin and fibronectin. Antibodies to types I and III collagen and to fibronectin were associated with most cells and showed a similar distribution. Type IV collagen and laminin were found in thin filaments associated with a small proportion of the cells. Chemical studies showed that ARL-6 cells synthesize predominantly types I and III collagens. The level of collagen synthesis was greatly affected by the presence of exogenous fibronectin added to the cells in the media. Cells maintained in fibronectin-free serum synthesized much less collagen. These studies indicate that liver-derived cells can synthesize a variety of connective tissue proteins and that collagen synthesis by these cells is enhanced by the presence of fibronectin.

Animals↗

Mesotheliomas and proliferative lesions of the testicular mesothelium produced in Fischer, Sprague-Dawley and Buffalo rats by methyl(acetoxymethyl)nitrosamine (DMN-OAc).

A single intraperitoneal dose of methyl(acetoxymethyl)nitrosamine (13 mg/kg body weight) given to 78 5-week-old male rats induced 25 mesotheliomas; two mesotheliomas were found in 67 control rats. All mesotheliomas arose from the peritesticular mesothelium and had a typical microscopic appearance of branching papillary fronds with a collagenous core covered by one or many layers of plump tumor cells. Cytoplasm of tumor cells contained material that reacted positively to a colloidal iron stain and was labile to hyaluronidase. In addition to frank mesotheliomas, 16 lesions, which we called atypical mesothelial proliferations, were found. These consisted of a single focus of plump mesothelial cells overlying an area of thick stroma. Often these foci included short, non-branched papillary projections above the surface of adjacent normal mesothelium. Twelve of the 16 lesions occurred in methyl(acetoxymethyl)nitrosamine-treated rats.

Animals↗

Characterization of analog resistance and purine metabolism of adult rat-liver epithelial cell 8-azaguanine-resistant mutants.

Adult rat-liver epithelial cultures were sensitive to the lethal effects of 8-azaguanine (AG), but lines contained variants resistant to AG. The frequency of retrievable AG-resistant colonies varied with both the concentration of AG used and the seeding density of the population under selection. Cells resistant to AG were also cross-resistant to 6-thioguanine and unable to grow in medium containing hypoxanthine, aminopterin and thymidine. Resistance was stable. AG resistance was due to a deficiency of hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) activity which was not caused by an inhibitor. In the assay for HGPRTase, a substantial amount of product appeared as inosine (In) in addition to inosine monophosphate (IMP). Purine nucleoside phosphorylase will generate In from hypoxanthine and, indeed, the cells did possess this activity. However, several findings indicated that the In was derived from IMP by catabolism by 5'-nucleotidase (NTase): (1) IMP decreased as In increased and (2) the inhibitors of NTase, adenosine monophosphate and thymidine triphosphate, reduced the generation of In by over 90% without inhibiting purine nucleoside phosphorylase. The cells possessed substantial NTase activity, 35% of which was located in the cytosol along with 69% of HGPRTase. Several lines of evidence suggested that the NTase activity limited the amount of 8-azaguanylic acid presented to the cells by catabolising the nucleotide and, thereby, reducing the toxicity of available AG.

Animals↗

Enhancement of mutagenesis during cell replication of cultured liver epithelial cells.

The susceptibility to mutagenesis of proliferating and non-proliferating mammalian cells was studied in cultured rat liver epithelial cells. Cells brought to growth quiescence by a non-toxic means were stimulated to proliferate and both types of cultures were exposed to methyl methanesulfonate (MMS). Cultures enriched in proliferating cells were more susceptible to both the toxic and mutagenic action of the mutagen than were quiescent cultures with a low level of proliferation.

Cell Cycle↗