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Biomedical subjects

G L Huber

Publications and source records attributed to G L Huber.

At least 19 recordsLinked to original sources
PubMed1992

A dose-response trial of once-daily diltiazem.

This trial was performed to determine the safe and effective dosage range of once daily diltiazem (diltiazem CD) capsules for treatment of essential hypertension. Patients with essential hypertension having supine diastolic blood pressure values greater than or equal to 95 mm Hg and less than or equal to 110 mm Hg were randomly assigned to receive placebo or one of four doses of diltiazem CD: 90, 180, 360, or 540 mg. Blood pressure was measured at trough, 24 hours after the dose, and at the time of peak effect, 10 hours after the dose. Diltiazem CD lowered both supine diastolic and systolic blood pressure. A linear dose response was seen with changes in diastolic and systolic blood pressure and heart rate for trough and peak measurements. Trough/peak ratios for the 180, 360, and 540 mg doses were all greater than 0.50. Adverse effects were dose related; those most commonly reported were headache (8.6%), bradycardia (8.1%), and edema (7%), with bradycardia and edema possibly dose related. It is therefore concluded that diltiazem CD is a safe and effective antihypertensive agent.

Adolescent↗
PubMed1991

Marijuana and tobacco smoke gas-phase cytotoxins.

To evaluate the in vivo versus in vitro paradoxical effects of marijuana and tobacco smoke on pulmonary defenses, the responses to smoke constituents were assessed with an alveolar macrophage tissue culture bioassay. A dose-response impairment of macrophage bactericidal activity was associated with water-soluble, gas-phase constituents. A model airway surface was constructed to examine the behavior of specific gas-phase constituents removed as they passed over wetted surfaces simulating the characteristics of the human respiratory system. Chemical analyses in the bioassay flask and in the model airway were compared. Gas-phase cytotoxins were measured after passage over wetted surface areas analogous to the trachea between the larynx and second-order bronchus. A wetted surface comparable to only 5% of the human airway, or less than 0.05% of the gas-exchanging surface of the entire lung, was capable of complete detoxification of the highly water-soluble gas-phase cytotoxins. In conclusion, gas-phase cytotoxins demonstrable by in vitro bioassays may have no cytotoxic potential when inhaled by humans.

Acetaldehyde↗
PubMed1990

Theoretical and experimentally quantifiable determinants of tobacco smoking behavior for the development of successful smoking cessation strategies.

Death rates from a number of diseases linked epidemiologically to tobacco use continue to rise despite major reductions in per capita tobacco consumption, despite reductions in the total number of smokers, and despite very significant reductions in "tar", in other tumorigens and in essentially all classes of potential toxins in smoke delivered to the consumer. One concern is that smokers consume low delivery cigarettes differently and in a potentially more hazardous way than higher delivery cigarettes. The effect of nicotine reduction in cigarettes on human smoking behavior was studied in 102 human subjects by quantifiable determinants of tobacco-smoking behavior. This study indicates that reduction in nicotine delivery results in some accommodation in smoking behavior to titrate nicotine needs. In addition, smokers appear to adjust their smoking behavior as a function of taste preference, and this adjustment is as strong as the accommodation for nicotine. The theoretical application of these observations to the development of successful smoking cessation strategies is reviewed.

Administration, Inhalation↗
PubMed1979

Tobacco smoke and the pulmonary alveolar macrophage.

Our results indicate that tobacco smoke exposure to varying duration causes morphological, biochemical and functional alterations in pulmonary alveolar macrophages. The results of these changes is a population of alveolar macrophages made up of larger cells, with a reduced nucleus-cytoplasmic ratio, which are heavily loaded with heterolysosomes containing lipid. Though their fractional complement of mitochondria remains the same, an increase in the inner mitochondrial membrane surface area may be related to an enhanced oxidative metabolism. The cell is biochemically activated particularly following chronic exposure and is functionally impaired with respect to phagocytosis.

Animals↗
PubMed1979

Tobacco smoke. Effects on pulmonary host defense.

Tobacco smoke affected both the metabolism and function of pulmonary alveolar macrophages (PAM). Phagocytosis of viable Staphylococcus aureus and inert starch particles was minimally but consistently depressed in PAM from rats exposed to tobacco smoke for six months. Oxygen consumption, superoxide and hydrogen peroxide release, and hexose monophosphate shunt activity were elevated in cells from smokers. Oxidation of glucose, labelled in the carbon-six position, remained unchanged. All observed effects of tobacco smoke on oxygen metabolism occurred during phagocytosis and did not affect the basal metabolism of the nonstimulated cell.

Animals↗
PubMed1979

Metabolic and functional characteristics of alveolar macrophages recovered from rats exposed to marijuana smoke.

Pulmonary alveolar macrophages were obtained by bronchopulmonary lavage from male rats after 30 consecutive days of in vivo exposure to marijuana and tobacco smoke. No significant differences were found between either group of experimental animals and controls in the number of cells recovered, the protein content per 10(6) cells, or the percentage of cells that adhered to plastic surfaces. The ability of macrophages to phagocytize viable bacteria was not affected by exposure to either marijuana or tobacco smoke in that both treatment groups ingested Staphylococcus aureus over a 60-min period as well as did control cells. Differences were found between the groups, however, with respect to cellular metabolism. Marijuana smoke inhalation caused a small decrease in the amount of oxygen consumed by macrophages during phagocytosis, as compared with control cells. This may have been reflected in the even greater decrease in superoxide formation observed during particle engulfment by these treated cells. Tobacco smoke, on the other hand, increased oxygen consumption and was without effect on superoxide release. Neither tobacco nor marijuana smoke treatment had an effect on the direct oxidation of glucose via the hexose monophosphate shunt. Our results indicate that, despite several metabolic alterations in response to marijuana and tobacco smoke, alveolar macrophages were not compromised with respect to their ability to ingest a particulate challenge.

Animals↗
PubMed1979

Hydroxyl radical formation in phagocytic cells of the rat.

Polymorphonuclear leukocytes (PMN) and macrophages, harvested from the peritoneum and lung, release superoxide (O-.2) and hydrogen peroxide (H2O2) during phagocytosis. These two agents are thought to react with each other to produce a highly active oxidative substance known as hydroxyl radical (OH.). We present evidence suggesting that these radicals are generated by phagocytic cells of the rat. Our findings are based upon an assay where ethylene gas is generated from methional by the action of this radical. Ethylene generation was shown to be inhibited by superoxide dismutase, catalase, and scavengers of OH.. Of the cells examined, PMN generated the most ethylene from methional, exhibiting a fourfold increase during phagocytosis. Pulmonary and peritoneal macrophages caused smaller amounts of this gas to be formed. Regardless of cell type, an intact cell was required for ethylene generation. Zymosan appeared to be the most effective particle for all cells in ethylene formation from methional, although opsonization was critical only for PMN. Ethylene generation was dependent on cell concentration to an extent and increased with time.

Animals↗
PubMed1979

Morphometric analyses of tracheal gland secretion and hypertrophy in male and female rats after experimental exposure to tobacco smoke.

Quantitative morphologic analyses were performed by stereologic methods on the tracheal glands of male and female rats after exposure to tobacco smoke for 30 consecutive days. The female rats were evaluated at 2 stages of their estrous cycle. The upper segment of trachea from each animal was embedded in glycol methacrylate, sectioned, and stained with a combined Alcian blue and periodic acid-Schiff stain for glycoproteins. Exposure to tobacco smoke caused an increase in the relative proportion of gland cells in each sex when expressed in reference to the total tissue within the cartilage ring, and an increase in mucins in the gland by 50% in both sexes. Although the relative proportions of gland cells and lumina were equivalent between the sexes, male rats had a larger quantity of mucin. The volume proportion in the glands of Alcian blue-positive mucin was 80 to 84% greater in males, and periodic acid-Schiff-positive mucin was 18 to 19 per cent greater in males than in females, both in control animals and those exposed to tobacco smoke. This study demonstrated that sexual differences were present in the mucin composition of the tracheal glands of normal male and female rats, that the female glycoproteins varied during the estrous cycle, and that these differences were retained after exposure to tobacco smoke.

Animals↗
PubMed1979

Reexpansion pulmonary edema.

A case of pulmonary edema following reexpansion of a collapsed lung due to pneumothorax is described and illustrated. The importance of recognizing this relatively uncommon phenomenon is stressed. The development of such edema can be prevented by avoiding application of sudden and excessive negative pleural pressures during the evacuation of a pneumothorax or a pleural effusion. The edema generally occurs in a lung that has been collapsed for more than three days. The importance of the duration of pulmonary collapse in the causation of edema is demonstrated in this patient.

Adolescent↗
PubMed1979

Effects of experimental marijuana and tobacco smoke inhalation on alveolar macrophages. A comparative stereologic study.

Male rats were exposed for 30 consecutive days to whole smoke from either marijuana or tobacco cigarettes. At the end of this period, anesthetized animals from the two smoke-exposed groups together with their age-matched, nonexposed controls underwent bronchopulmonary lavage, and the free lung cells obtained were fixed and collected for light and electron microscopy. Measurements made on 1-micrometer. sections indicated slight, but statistically nonsignificant, shifts in the frequency distributions of alveolar macrophage profile diameters after both exposure regimens. Stereologic techniques were used to study the subcellular morphology of alveolar macrophages from the three groups of animals. Statistically significant changes were found in cells from tobacco-exposed animals in the volume densities of mitochondria, lipid inclusions, lysosomes, remaining cytoplasm, and the surface to volume ratio of the cell. In contrast, only two parameters in the cells from marijuana-exposed animals were found to have changed significantly, with a 3-fold increase in the volume density of lipid inclusions and a slight reduction in the volume density of the remaining cytoplasm. Possible reasons for the differences in the response of the cells in the two smoke-exposed groups are discussed.

Animals↗
PubMed1979

The localization of catalase in the pulmonary alveolar macrophage.

A combined biochemical and cytochemical study of catalase was performed on alveolar macrophages lavaged from the lungs of adult male rats. Biochemically, catalase activity was present in both a high-speed granule fraction and in the supernatant. The granule-associated activity exhibited latency. Two methods of cell breakage, sonication and homogenization, yielded similar levels and distributions of catalase activity. Catalase activity in whole cells was identified cytochemically by the alkaline diaminobenzidine method and was localized within membrane-lined cytoplasmic granules similar in size to microperoxisomes and associated with cisternae of smooth endoplasmic reticulum. Localization of the reaction product was inhibited by 0.04 M aminotriazole, by cyanide, and by boiling prior to incubation. The cytochemical reaction continued in the absence of exogenous peroxide, but could be prevented by addition of catalase or pyruvate to the peroxide-free medium. Enzyme activity was also localized within a portion of the membrane-bound granules present in the cell fractions used for the biochemical assays.

Amitrole↗
PubMed1978

The effect of tobacco smoke on the metabolism and function of rat alveolar macrophages.

Alveolar macrophages harvested by bronchopulmonary lavage from rats exposed to tobacco smoke for 30 days ("smokers") showed alterations in oxidative metabolism, lactate production and phagocytosis of inert starch particles when compared with control macrophages. Phagocytosis of viable Staphylococcus aureus was unaffected by tobacco smoke. Glucose oxidation measured by conversion of glucose-1-14C to 14CO2 moderately affected while oxidation of glucose-6-14C to 14CO2 was not. Smokers routinely yielded fewer cells than controls, though these cells contained approximately 17% more protein than did controls. Opsonization of particles was not necessary for macrophages from either smoker or control animals to manifest a respiratory burst and increased superoxide and hydrogen peroxide release during phagocytosis. The glycolytic inhibitors, sodium fluoride and iodoacetamide, while effectively blocking glycolysis, did not inhibit phagocytosis by macrophages from either group. The results reported clearly distinguish alveolar macrophages from other phagocytic cells (peritoneal macrophages and polymorphonuclear leukocytes) and suggest a state of non-specific activation caused by exposure to tobacco smoke.

Animals↗