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Biomedical subjects

L Diamond

Publications and source records attributed to L Diamond.

At least 109 records · Page 6Linked to original sources

A nonadrenergic vagal inhibitory pathway to feline airways.

In cats anesthetized with chloralose-pentobarbital and artificially ventilated, electrical stimulation of the caudal end of the cut cervical vagus nerve has a biphasic effect on the bronchoconstriction induced by an intravenous infusion of serotonin. The response consists of a brief augmentation of bronchoconstriction followed by relatively prolonged bronchodilation. After muscarinic receptor blockade with atropine, vagal stimulation causes only bronchodilation. Vagally mediated bronchodilation is not affected by beta adrenergic blockade with propranolol, alpha adrenergic blockade with phenoxybenzamine, or adrenergic neuronal blockade with guanethidine, but is abolished by autonomic ganglionic blockade with hexamethonium. These findings support the conclusion that a nonadrenergic inhibitory nervous system is present in the pulmonary airways of the cat and that the system is supplied by preganglionic fibers in the cervical vagus nerves.

Airway Resistance↗

The effects of 5-bromodeoxyuridine on the growth and morphology of transformed rat liver cells.

The effects of bromodeoxyuridine (BrdUrd) on the growth, morphology, and tumorigenicity of the spontaneously transformed rat liver cell line R72/3 were studied. These cells grow either in suspension or in a monolayer and are tumorigenic. In monolayer cultures, cells treated with low concentrations (2.5 micrograms/ml) of BrdUrd were larger, more spread out, and more firmly attached to the substratum than were untreated controls. Treated cells failed to grow in suspension or on confluent monolayers of 3T3 cells and did not form colonies in soft agar. Scanning electron microscopy revealed extensive flattening of treated cells and a dramatic reduction in the number of microvilli on the cell surface. Transmission electron microscopy showed an increase in polyribosomes and rough endoplasmic reticulum, as well as an enlargement of endoplasmic reticulum cisternae and a complete absence of the bundles of intermediate size filaments that were conspicuous in untreated cells. The persistence of these changes required the continuous presence of BrdUrd in the medium. The effects of BrdUrd were readily reversed by withdrawal of BrdUrd and were not expressed in the presence of excess thymidine.

Animals↗

Sugar transport in the LLC-PK1 renal epithelial cell line: similarity to mammalian kidney and the influence of cell density.

Cells of confluent cultures of the established pig renal epithelial line, LLC-PK1, accumulate alpha-methyl-D-glucoside against a concentration gradient. This transport system is strongly inhibited by phlorizin and 6-deoxy-D-glucose, moderately inhibited by phloretin, and only weakly inhibited by 3-0-methyl-D-glucose, paralleling the situation in mammalian kidney. The time courses for the uptake of alpha-methyl-D-glucoside and for the carrier-mediated but passive uptake of 3-0-methyl-D-glucose are identical to those seen in mammalian kidney. Subconfluent cultures of LLC-PK1 cells are unable to accumulate alpha-methyl-D-glucoside, and their transport of this glucose analog is less sensitive to phlorizin inhibition than is the transport system in confluent cultures. Transmission electron micrographs show that cells from subconfluent cultures lack the microvillous surface seen in cells from confluent cultures. Cell density is thus a factor in the occurrence of structural and functional differentiated properties related to transport in these cells.

Animals↗

Effects of ouabain and ortho vanadate on transport-related properties of the LLC-PK1 renal epithelial cell line.

Uptake of alpha-methyl-D-glucoside (AMG) by LLC-PK1 cells is inhibited by the uncoupler p-trifluoro-methoxyphenyl-hydrazone (FCCP) and by the absence of extracellular Na+, indicating that the transport system is energy- and Na+-dependent. We have previously demonstrated that transport of AMG by LLC-PK1 cells proceeds against a concentration gradient and is phlorizin-sensitive (Mullin et al., '80). Uptake of AMG was also inhibited by ouabain (OUA) but not by ortho-vanadate (VAN). Rubidium uptake also was affected by OUA but not by VAN. VAN, however, caused collapse of the three-dimensional domes of confluent LLC-PK1 monolayers much more rapidly and thoroughly than OUA. Since domes are presumably dependent upon the Na+ pump, yet VAN is not acting on transport-related functions of the OUA-sensitive (Na+ + K+)-ATPase, we hypothesize a direct effect of VAN on the water permeability of these cells. We also suggest that OUA does not act on these cells until domes collapse in normal course, and access of the OUA to the extracellular surface of antiluminal membranes is then achieved.

Animals↗

Inhibition of adipose conversion of BALB/c 3T3 cells by interferon and 12-O-tetradecanoylphorbol-13-acetate.

The adipose conversion of BALB/c 3T3 preadipose cells is inhibited by interferon; this inhibition is directly correlation with the interferon concentration. In cultures treated with low doses of interferon and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, another inhibitor of adipose conversion (Diamond et al., 1977), the two compounds act synergistically to block differentiation. Several lines of evidence suggest that the compounds differ in the mechanism by which they inhibit adipose conversion.

Adipose Tissue↗

Metabolic activation of benzo[a]pyrene by a human hepatoma cell line.

The liver-derived human cell line, Hep G2, has high benzo[a]pyrene-metabolizing activity and converts benzo[a]pyrene to intermediates that are mutagenic and that bind to DNA. This cell line will be useful for studying metabolic activation of polycyclic aromatic hydrocarbons and other xenobiotics by human tissue and as an activation system in short-term screening assays for identifying compounds with carcinogenic potential for humans.

Animals↗

Relapse after short-term drug therapy in neurotic outpatients.

A 6-month follow-up of 184 anxious depressed neurotic outpatients who reported improvement after controlled drug trials of several weeks duration revealed an astonishing relapse rate of 81% for anxious and 87% for depressed patients. Early as compared to late relapse was associated with more chronicity and less improvement at the end of the drug trial, while type of drug received did not affect relapse. Onset of relapse had no effect on help-seeking behavior. At time of follow-up, non-relapsed patients had lowest and untreated relapsed patients had highest symptom levels. It was concluded that short-term drug treatment alone does not represent sufficient therapy for chronic neurotic anxious or depressed outpatients.

Adult↗

Induction of differentiation in human promyelocytic leukemia cells by tumor promoters.

Phorbol diester tumor promoters and the promoter mezerein convert human promyelocytic leukemia cells in culture into adherent, nonproliferating cells with many of the characteristics of macrophages. Other types of promoters such as anthralin, phenobarbital, and saccharin do not have this effect. Various compounds that can inhibit some of the biological and biochemical effects of tumor promoters do not interfere with the induction of cell adherence and differentiation by the effective promoters.

Cell Adhesion↗

[3-(1,4-Cyclohexadienyl)-L-alanine,8-lysine]vasopressin: synthesis and some pharmacological properties.

[3-(1,4-Cyclohexadienyl)-L-alanine,8-lysine]vasopressin, otherwise known as [3-(2,5-dihydrophenylalanine),8-lysine]vasopressin or [DiHPhe3]lysine-vasopressin, has been synthesized in an attempt to utilize 2,5-dihydrophenylalanine (DiHPhe) to evaluate the contribution of aromaticity in position 3 to biological activity. The analogue has the same primary structure as lysine-vasopressin, except that two additional hydrogen atoms are present on the ring moiety of the phenylalanine residue in position 3. The key intermediate was the protected nonapeptide N-carbobenzoxy-S-benzyl-L-cysteinyl-L-tyrosyldihydrophenyl-L-alanyl-L-glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-N epsilon-tosyl-L-lysylglycinamide that was synthesized stepwise by the solid-phase technique. Deprotection with sodium in liquid ammonia was followed by sulfhydryl oxidation with I2 to give the hormone analogue. [DiHPhe3]lysine-vasopressin exhibited 125--130 units/mg of antidiuretic, 129--132 units/mg of rat pressor, and 6 units/mg of rat uterus contracting activity. To confirm the presence of DiHPhe in the analogue, an enzymatic procedure employing Aspergillus oryzae was developed that liberates in high yield the amino acid residue in position 3 of the posterior pituitary hormone structure. This study should be applicable to other biologically active peptides.

Aminopeptidases↗

Ornithine decarboxylase activity and DNA synthesis after treatment of cells in culture with 12-O-tetradecanoylphorbol-13-acetate.

The ability of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to induce the enzyme ornithine decarboxylase (ODC) and to stimulate DNA synthesis was studied in four different cell types in vitro. The effects of this agent on each cell type were different: (a) in hamster embryo cells, TPA induced ODC but had no effect on DNA synthesis; (b) TPA induced ODC and stimulated DNA synthesis in BALB/c 3T3 mouse cells; (c) it did not induce ODC in human fibroblasts but did stimulate DNA synthesis; and (d) it induced neither ODC nor DNA synthesis in rat embryo fibroblasts. In contrast to the effects of TPA, ODC was induced and DNA synthesis was stimulated in all cell types by fresh serum-containing medium. Treatment of the cells with a combination of fresh medium and TPA resulted in an approximate summation of the effects of treatment with each agent alone. These results emphasize the differences in the responses of various cells to TPA. They also show that in some cells, at least, the induction of ODC and stimulation of DNA synthesis following TPA treatment can be regulated independently.

Animals↗

Long-term oral bronchodilator therapy of asthma with pirbuterol.

We studied the effects of an oral beta2 selective bronchodilator, pirbuterol, in 12 male asthmatic patients over periods ranging from 6 to 23 months (mean, 13.8). Each patient was evaluated initially by physical examination, urinalysis, blood analysis, and pulmonary function tests. Patients were examined at regular intervals thereafter. Patients remained off all bronchodilator therapy for 12 hr before each visit. Blood analysis, urinalysis, and pulmonary function tests were performed and the pulmonary function tests were repeated approximately 2 hr after an oral dose of pirbuterol. We found no significant changes in the baseline resistance or in the bronchodilator response to pirbuterol during the course of the study, but there was a significant decrease in the functional residual capacity (FRC). The reduction in FRC could be due to the prolonged reduction in airways resistance with continuous therapy. We found no increase in the bronchodilator response to pirbuterol during oral prednisone therapy. There were no significant changes in serum potassium. Side effects attributable to pirbuterol, nervousness and tremor, occurred in only 2 patients and were easily controlled.

Administration, Oral↗