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Biomedical subjects

L Diamond

Publications and source records attributed to L Diamond.

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

Survival analysis of patients undergoing dialysis.

We analyzed the five-year survival of 4661 patients with end-stage renal disease whose first dialysis occurred in 1977. The analysis incorporated characteristics of patients and dialysis institutions. Results showed that mortality was positively correlated with patient age, initial conditions leading to renal failure, being male and white, open staffing, and the number of staff physicians. In addition, lower death rates were observed for patients treated in larger dialysis units and units that had been long-term reusers of dialyzers. Patients treated in for-profit and not-for-profit units appeared to have the same mortality, although patients treated in freestanding units had lower mortality. The direction of causation was not always clear in these results.

Adult↗
PubMed1987

Augmentation of elastase-induced emphysema by cigarette smoke: effects of reducing tar and nicotine content.

The effects of reducing the tar and nicotine concentration of cigarette smoke were examined in a rat model of smoke-augmented, porcine pancreatic elastase- (PPE-) induced, pulmonary emphysema. Sixty-eight female Long-Evans rats were divided approximately evenly into seven groups: control, PPE, PPE plus sham smoke, high-tar/nicotine cigarette smoke (2R1; 38.8 mg total particulate matter and 2.2 mg nicotine per cigarette), low-tar/nicotine cigarette smoke (1R4F; 10.8 mg total particulate matter and 0.8 mg nicotine per cigarette), PPE + 2R1, and PPE + 1R4F. Three days after intratracheal administration of PPE (400 IU/kg), animals in the smoke-treated groups were exposed to 8-10 puffs of cigarette smoke daily, 7 d/wk for 12 wk. Sham-treated animals received room air in place of cigarette smoke. At the conclusion of the exposures, pulmonary function tests were performed under general anesthesia. Cigarette-smoke exposure alone did not produce significant changes in pulmonary function. Elastase-treated groups demonstrated significant increases in total lung capacity, functional residual capacity, and dynamic and static compliance, as well as significant decreases in carbon monoxide (CO) diffusing capacity and CO diffusion coefficient. Morphometric measurements of mean linear intercept demonstrated a loss of alveolar fine structure with enlargement of distal airspaces in PPE-treated rats. Exposure to either 2R1 or 1R4F cigarette smoke significantly enhanced many of the emphysematous changes produced by PPE, but there were no significant differences between the effects of the two smokes. These data indicate that reducing the tar and nicotine concentration of cigarette smoke does not lessen its ability to augment PPE-induced pulmonary emphysema in the rat.

Animals↗
PubMed1987

The effect of oral zindotrine (MDL-257), a bronchial smooth muscle relaxant, on histamine airways responsiveness in asymptomatic asthmatics.

We evaluated the efficacy of an oral dosage form of the investigational smooth muscle relaxant, zindotrine, a novel pyridazine derivative, in counteracting histamine-induced bronchospasm in a group of 12 non-medicated asymptomatic asthmatics. Histamine inhalation challenges were performed before (control) and 45, 150, and 300 minutes after zindotrine (200 and 300 mg), or the corresponding dose of placebo was administered orally in a randomized, double-blind crossover fashion. When compared to the control state, the 300-mg zindotrine dose markedly lowered histamine airway responsiveness as indicated by a significant (P less than .01) increase in the inhaled histamine dose necessary to provoke a 20% decrease in the forced expired volume in one second (PD20FEV1) 45 minutes after drug administration. The PD20FEV1 then decreased linearly over time but remained higher than the control PD20FEV1 value (P less than .05) during the entire observation period. The 200-mg zindotrine dose failed to affect the PD20FEV1. Our data indicate that orally administered zindotrine lowers airways responsiveness to inhaled histamine in asymptomatic asthmatics in a dose-dependent and time-dependent fashion.

Administration, Oral↗
PubMed1986

Comparison of five methods of analyzing respiratory pressure-volume curves.

Five methods of analyzing the deflation limb of respiratory pressure-volume (PV) curves obtained from seven groups of rats that had undergone various treatments were compared. The five methods utilized measurements of: y intercept and slope with simple exponential curve fitting; area under the curve; volumes at fixed pressures; shape constant, k, of the sigmoid curve described by Paiva et al. (Respir. Physiol. 23:317, 1975); and quasi-static compliance. The seven groups of rats were treated as follows: control (n = 10); high tar/nicotine cigarette smoke exposure (n = 10); low tar/nicotine cigarette smoke exposure (n = 9); intratracheal elastase (n = 10); intratracheal elastase plus sham smoke exposure (n = 10); intratracheal elastase plus high tar/nicotine cigarette smoke exposure (n = 9); and intratracheal elastase plus low tar/nicotine cigarette smoke exposure (n = 10). Elastase treatment caused a leftward and upward shift of the PV curve and this shift was augmented by exposure to either high tar/nicotine or low tar/nicotine cigarette smoke. Using Duncan's multiple range test, we found that the y-intercept measurement of method 1, the area under the curve, volumes at fixed pressures, and quasi-static compliance methods were better able to differentiate PV curves between groups than were the slope measurement of method 1 and the shape constant measurement of method 4.

Animals↗
PubMed1986

Oncogene activation and surface markers in mouse lymphomas induced by radiation and nitrosomethylurea.

Thymic lymphomas have been induced by gamma-radiation and treatment with the chemical nitrosomethylurea in different mice strains. As indicated by the NIH 3T3 focus forming assay, a significant percentage of the tumors contain activated oncogenes of the ras family (K or N). Cloning and sequencing has enabled us to identify single base mutations as the only significant alteration present in the activated oncogenes. These alterations result in the substitution of amino-acid 12 or 61 of the p21 product of the ras genes. With the use of synthetic oligonucleotides it has been found that the tumors do not all contain the same mutation and in one case so far the normal allele is absent.

Animals↗
PubMed1986

Reflex activation of the nonadrenergic noncholinergic inhibitory nervous system in feline airways.

Experiments were undertaken to learn if the nonadrenergic noncholinergic inhibitory nervous system (NANCIS) in feline airways could be activated reflexly either by mechanically stimulating the laryngeal mucosa or by inducing acute bronchospasm with boluses of 5-hydroxytryptamine (5HT) injected intravenously. Mechanical stimulation of the dorsal laryngeal mucosa evoked a biphasic bronchomotor response in anesthetized cats that had received intravenously an infusion of 5HT to raise their basal airway smooth muscle tone. The response consisted of a transient augmentation of bronchoconstriction followed by a prolonged bronchodilation. After muscarinic cholinergic receptor blockade with atropine, the constriction phase of the response disappeared, but the relaxation phase persisted. Bronchodilation elicited by laryngeal stimulation was resistant to beta-adrenergic receptor blockade with propranolol but was abolished by autonomic ganglionic blockade with hexamethonium and blocked reversibly by vagal cooling. The latter interventions, when imposed between successive dose-response curves generated by intravenous 5HT in animals pretreated with atropine and propranolol, did not alter the positions or slopes of the curves. These findings support the conclusion that mechanical stimulation of the larynx reflexly activates not only the well-known vagal cholinergic excitatory pathway to the airways but also the more recently described vagal, nonadrenergic noncholinergic inhibitory pathway. The results further indicate that bronchoconstriction is neither a prerequisite for the bronchodilator component of the laryngeal bronchomotor reflex nor an independent initiating stimulus for NANCIS-mediated reflex bronchodilation.

Airway Resistance↗
PubMed1986

Up regulation of the phorbol ester receptor-protein kinase C in HL-60 variant cells.

The human promyelocytic leukemia cell line HL-60 can be induced to differentiate into macrophage-like cells by nanomolar concentrations of phorbol esters. A phorbol ester-resistant variant R1B6 obtained by culturing HL-60 cells with increasing concentrations of 12-O-tetradecanoylphorbol-13-acetate, is reversibly resistant. These cells have been growing continuously in the presence of phorbol esters for more than 1 yr, but when the phorbol ester is removed, the cells gradually regain their sensitivity and express characteristics of macrophage-like cells upon readdition of phorbol ester. The concentration of phorbol ester receptors in R1B6 is about one-third that in the parental HL-60 cells. The reversion of the variants to sensitivity to phorbol esters is associated with the up regulation of the cytosol and membrane phorbol ester receptors. When partially purified, these receptor populations contain protein kinase C activity, in support of the identity of protein kinase C and the receptor. This study demonstrates that a phenotypic change in a clonal cell population correlates with the up regulation of the phorbol ester receptor-calcium-activated phospholipid-dependent protein kinase. This variant cell line is a useful model for analyzing the relationship between phorbol ester binding and protein kinase C during differentiation of HL-60 cells.

Caenorhabditis elegans Proteins↗
PubMed1985

Tumor-initiating activity of the 9,10-dihydrodiol- and 9,10-dihydrodiol-7,8-epoxide of 3-methylcholanthrene in SENCAR mice.

The skin tumor-initiating activities of several bay-region metabolites of 3-methylcholanthrene (3-MCA) were determined in SENCAR mice. 3-MCA-anti-9,10-diol-7,8-epoxide possessed weak tumor-initiating activity when tested at 100 and 200 nmol/mouse doses (0.27 and 0.67 papillomas per mouse after 18 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA)). 3-MCA-trans-9,10-diol at initiating doses of 50 and 100 nmol/mouse was as active as 3-MCA. 3-MCA-trans-9,10-diol was also tested for mutagenic activity toward V79 cells in cell-mediated assays and found to be approximately 2-times more potent than 3-MCA. The data suggest that 3-MCA-trans-9,10-diol is a proximate carcinogen for mouse skin.

Animals↗
PubMed1985

Effect of alpha-chymotrypsin on the nonadrenergic noncholinergic inhibitory system in cat airways.

Electrical field stimulation of 5-hydroxytryptamine contracted cat trachea and bronchi in the presence of cholinergic and adrenergic blockade caused relaxation by activating intrinsic nonadrenergic noncholinergic (NANC) inhibitory nerves. Pretreatment of the tissues with the proteolytic enzyme, alpha-chymotrypsin, did not affect NANC inhibitory responses. Relaxations induced by vasoactive intestinal peptide (VIP) were abolished by alpha-chymotrypsin. These results suggest that VIP or related peptides may not act as the NANC inhibitory transmitter in cat airways. However, the possibility remains that peptides not susceptible to degradation by alpha-chymotrypsin may mediate these NANC inhibitory responses.

Animals↗
PubMed1985

Morphologic and physiologic response of lungs to steroid and cigarette smoke: an animal model.

The combined effects of cigarette smoke inhalation and hydrocortisone acetate (HCA) treatment induce prominent abnormalities in lungs of C57BL/6 male mice. These abnormalities include (1) a marked reduction of pulmonary macrophage population which is normally elevated by smoke inhalation, (2) an accumulation of surfactant and flocculent material in alveoli, (3) a decrease in alveolar space surrounded by normal septal tissue, and (4) an increase in hypertrophied alveolar parenchyma. Concomitant with altered lung morphology, lung volume and gas diffusing capacity were significantly compromised in animals subjected to smoke exposure and steroid treatment. It was found that smoke inhalation or HCA administration alone had no ill effects on the animals. The data presented indicate that manifestation of pathologic conditions resembling pulmonary fibrosis and pulmonary alveolar proteinosis is a result of cigarette smoke-drug interaction. The information reported provides a basis for an animal model which might be applicable to assessment of factors related to smoke inhalation and development of pulmonary disorders.

Animals↗
PubMed1985

Augmentation of elastase-induced emphysema by cigarette smoke. Description of a model and a review of possible mechanisms.

Rats were treated with a single endotracheal dose of purified porcine pancreatic elastase (400 IU/kg), exposed to undiluted cigarette smoke from Kentucky 2RI reference cigarettes (one 35-ml puff/min for 10 min daily, 5 days per week, for 12 wk) or with a combination of elastase followed by smoke exposure. A number of significant functional abnormalities were observed in the lungs of rats receiving elastase; these included reduced spontaneous ventilation, enlarged subdivisions of lung volume, loss of elastic recoil, and diminished gas exchange capacity. Rats receiving both elastase and cigarette smoke had significantly more severe pulmonary dysfunction than did rats treated with elastase alone. Morphometric measurements of mean linear intercept demonstrated a loss of alveolar fine structure, with enlargement of distal air spaces in elastase-treated rats. These changes were significantly more severe in rats treated with both elastase and cigarette smoke. Pulmonary function tests and morphometric measurements in sham-treated rats and in rats exposed to cigarette smoke only were not significantly different from those in untreated control animals. It is concluded that elastase-induced emphysema in rats is enhanced by exposure to whole cigarette smoke.

Animals↗
PubMed1985

Neurally mediated nonadrenergic relaxation in cat airways occurs independent of cholinergic mechanisms.

Activation of the nonadrenergic noncholinergic (NANC) inhibitory system in cat airways causes coincident release of acetylcholine from vagal nerve terminals. The present study was undertaken to determine if neurally released acetylcholine is involved in initiating or modulating activity in the lung NANC inhibitory system. Electrical field stimulation experiments were performed on isolated segments of cat trachea and bronchi and additional studies were conducted in intact anesthetized, mechanically ventilated cats. In isolated airways, frequency-dependent NANC relaxations of bethanechol contracted tissues were identical to NANC responses of airways contracted with 5-hydroxytryptamine. This result suggested that muscarinic receptor activation did not influence NANC inhibitory system function. In additional studies where agents that inhibited or potentiated the actions of acetylcholine were used, similar results were obtained. Pretreatment of tissues with hexamethonium or atropine did not alter NANC frequency response curves. Contractile responses evoked by field stimulation were potentiated by neostigmine and abolished by hemicholinium treatment; NANC relaxation responses were not significantly affected by either agent. In intact cats, neostigmine pretreatment did not alter the magnitude or duration of vagally mediated NANC bronchodilation. Acetylcholine administered as an aerosol to cats treated with atropine did not mimic the NANC response. These findings suggest that NANC inhibitory system function in cat airways is neither dependent upon nor modulated by neurally released acetylcholine.

Acetylcholine↗