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Biomedical subjects

C A Watkins

Publications and source records attributed to C A Watkins.

32 records · Page 2Linked to original sources
PubMed1982

Additive effects of pentobarbital and halothane to inhibit synthesis of lung proteins.

The effect of pentobarbital on synthesis of lung proteins was investigated, both when administered alone and in combination with halothane. When rat lungs perfused in situ with Krebs-Henseleit bicarbonate buffer containing plasma levels of 19 amino acids, 690 microM phenylalanine, 5.6 mM glucose, and 4.5 per cent fraction V bovine serum albumin were exposed to pentobarbital, a dose-related inhibition of [14C]phenylalanine incorporation into protein was observed, with a maximal inhibition (74 per cent) at a pentobarbital concentration of 324 micrograms/ml. Halothane (1-4 per cent equilibrated with O2/N2/CO2, 4:15:1) also rapidly inhibited synthesis of lung proteins in a dose-dependent manner. At the maximally effective concentration of pentobarbital, exposure of the lungs to halothane enhanced the inhibition of protein synthesis; halothane concentrations ranging from 1 to 4 per cent were equally effective. Furthermore, when lungs were exposed to a combination of pentobarbital (100 micrograms/ml) and halothane (1 per cent) at doses which had no effect when given alone, protein synthesis was inhibited 35 per cent (P less than 0.001). Thus, the metabolic effects of the anesthetics were potentiated when the drugs were administered in combination. The inhibition of protein synthesis by pentobarbital (324 micrograms/ml), with or without 4 per cent halothane, was fully reversible. A similar inhibitory effect of pentobarbital was observed in perfused rat hearts.

Adenosine Triphosphate↗
PubMed1982

Effect of diabetes on metabolism of 5-hydroxytryptamine by rat lungs perfused in situ.

The effect of diabetes induced by treatment of rats with streptozotocin on metabolism of circulating 5-hydroxytryptamine (5HT) was investigated using an in situ lung perfusion preparation. Tissue uptake of 5HT and production of its metabolite, 5-hydroxyindolacetic acid, were unaffected in lungs of diabetic animals provided 2 or 20 microM exogenous 5HT. At constant perfusion pressure, pulmonary flow was not altered by substrate concentration or by streptozotocin treatment. Thus, in the experimental models of diabetes used, metabolism of circulating 5HT by the pulmonary endothelium remained unaffected.

Animals↗
PubMed1980

Measurement of protein synthesis in rat lungs perfused in situ.

Compartmentalization of amino acid was investigated to define conditions required for accurate measurements of rates of protein synthesis in rat lungs perfused in situ. Lungs were perfused with Krebs-Henseleit bicarbonate buffer containing 4.5% (w/v) bovine serum albumin, 5.6mm-glucose, normal plasma concentrations of 19 amino acids, and 8.6-690mum-[U-(14)C]phenylalanine. The perfusate was equilibrated with the same humidified gas mixture used to ventilate the lungs [O(2)/CO(2) (19:1) or O(2)/N(2)/CO(2) (4:15:1)]. [U-(14)C]Phenylalanine was shown to be a suitable precursor for studies of protein synthesis in perfused lungs: it entered the tissue rapidly (t((1/2)), 81s) and was not converted to other compounds. As perfusate phenylalanine was decreased below 5 times the normal plasma concentration, the specific radioactivity of the pool of phenylalanine serving as precursor for protein synthesis, and thus [(14)C]phenylalanine incorporation into protein, declined. In contrast, incorporation of [(14)C]histidine into lung protein was unaffected. At low perfusate phenylalanine concentrations, rates of protein synthesis that were based on the specific radioactivity of phenylalanyl-tRNA were between rates calculated from the specific radioactivity of phenylalanine in the extracellular or intracellular pools. Rates based on the specific radioactivities of these three pools of phenylalanine were the same when extracellular phenylalanine was increased. These observations suggested that: (1) phenylalanine was compartmentalized in lung tissue; (2) neither the extracellular nor the total intracellular pool of phenylalanine served as the sole source of precursor for protein; (3) at low extracellular phenylalanine concentrations, rates of protein synthesis were in error if calculated from the specific radioactivity of the free amino acid; (4) at high extracellular phenylalanine concentrations, the effects of compartmentalization were negligible and protein synthesis could be calculated accurately from the specific radioactivity of the free or tRNA-bound phenylalanine pool.

Animals↗
PubMed1979

Effects of starvation and diabetes on protein synthesis in lung.

Metabolism of lung proteins was investigated in rats starved 3 days or made diabetic with streptozotocin. Body weight was below normal in both groups, but lung weight decreased only in starved animals. Total lung protein and RNA (mg/lung) decreased during starvation and diabetes. Protein concentration (mg/g) was unchanged in either group of animals; RNA concentration decreased only during starvation. Protein synthesis, estimated in lungs perfused in situ, was reduced 22% in starvation, but remained unchanged in diabetes. Inhibition of protein synthesis was accounted for by loss of RNA. Ribosomal profiles were unchanged by starvation, suggesting an unaltered relationship between rates of peptide-chain initiation and elongation in vivo. Activity of an eIF-2-like initiation factor decreased during starvation in proportion to the loss of RNA. In diabetes, factor activity remained normal. Thus, starvation but not streptozotocin-induced diabetes, reduced the capacity of the lung to synthesize protein. No evidence for reduced efficiency of synthesis was observed.

Animals↗
PubMed1979

Rapidity of compensatory lung growth following pneumonectomy in adult rats.

The rapidity with which lung growth was initiated following pneumonectomy was investigated using rats (330 g) in which lung weight-to-body weight ratio and lung cell size had stabilized. Following removal of the left lung, right lung weight increased from 823 to 1.161 mg within 7 days. Right lung weight in sham-operated animals did not change significantly. At day 7, right lung weight-to-body weight ratio in pneumonectomized rats was equal to that of both lungs in sham-operated animals; these values remained equal through day 14. Growth of individual lobes of the right lung was generally in proportion to their initial weights. Dry-to-wet weight ratio in either lung of sham-operated or pneumonectomized animals was unchanged, as compared to unoperated controls. Total right lung RNA and protein increased significantly by day 2 and reached levels equal to those in both lungs of sham-operated animals by day 7. Synthesis of lung proteins, estimated during 120 min of perfusion in situ, was elevated 25% on day 3. Incorporation of [3H]thymidine into DNA increased somewhat on day 2 and was elevated fourfold on day 3, corresponding with the initial accumulation of total DNA within the lung. These observations suggested that increased cell size may accompany early compensatory growth following pneumonectomy, but that the major portion of the response involved cellular hyperplasia.

Animals↗
PubMed1979

In situ perfusion of rat lungs: stability and effects of oxygen tension.

A new method for perfusion of rat lungs in situ was developed for metabolic studies. The pulmonary circulation was cannulated without contacting the lungs, which remained in the thoracic cage. Perfusion was continued for up to 4 h with Krebs-Henseleit bicarbonate buffer, equilibrated with 95% O2- 5% CO2 and containing 4.5% bovine serum albumin, 5.6 mM glucose, and levels of amino acids normally found in rat plasma. At an arterial pressure of 20 cmH2O flow remained constant (10.9 ml/min.100 g body wt) and appeared evenly distributed among the lobes. Tidal volume was 1 ml/100 g body wt (72/min); positive end-expiratory pressure was 2 cmH2O. The preparation remained stable and metabolically active for 4 h, as evidenced by a minimal decline in dry-to-wet weight ratio, constant levels of ATP and glycogen, a high ratio of glucose uptake to lactate production, and a linear rate of incorporation of [14C]phenylalanine into protein. The lungs were unaffected when perfusate oxygen was reduced to a more physiological level (20% O2-75% N2-5% CO2). In the presence of 95% N2-5% CO2 dry-to-wet weight ratio, ATP, glycogen, and amino acid incorporation decreased, while lactate production doubled.

Animals↗
PubMed1975

Efficacy of phage typing epidemiologically related Staphylococcus epidermidis strains.

A total of 118 epidemiologically related Staphylococcus epidermidis strains from hospital patients, staff, and fomites were examined with a provisional set of 18 typing phages. Seventy (59.3%) of these strains were typed using phage concentrations of 100 times routine test dilution. The remainder were nontypable. Thirty-six (30.5%) of the strains were of related phage types, 71/108/275A/459 and 71/108/275A. These latter strains were associated with clinical S. epidermidis endocarditis in patients with prosthetic valve replacements. Ninety-eight strains were characterized by the Baird-Parket biotyping schema. Eighty-three (84.7%) were biotype 1, and the majority (68.4%) of these were resistant to penicillin, ampicillin, methicillin, cephalothin, erythromycin, and clindamycin. Type 71, 71/108/275A/459, 71/108/275A and 71/108/275/459 strains were generally resistant to penicillin, ampicillin, erythromycin, and methicillin, whereas a less consistent resistance pattern was noted among miscellaneous and nontypable strains.

Anti-Bacterial Agents↗
PubMedDate not supplied

Salivary concentration of secretory leukocyte protease inhibitor, an antimicrobial protein, is decreased with advanced age.

BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) exhibits antimicrobial activities that, in addition to other well-characterized proteins such as lysozyme and lactoferrin, is thought to play a critical role in mucosal defenses. Although elderly individuals are particularly susceptible to mucosal infections, salivary production of SLPI has not been assessed in an aged cohort. OBJECTIVES: Hypothesizing that oral SLPI concentrations are reduced with advanced age, this cross-sectional study compared SLPI concentrations to concentrations of lysozyme, lactoferrin and total protein in unstimulated salivary secretions of healthy, community-dwelling 79+-year-old and younger adults. METHODS: Study participants were 45 non-hospitalized dentate adults aged 79-89 (23 elderly) or 21-51 years (22 non-elderly). Home-based interviews and clinical examinations determined dentate status and confirmed the absence of dentures, oral mucosal disease, anti-infective medication use, irradiation therapy for head and neck cancer and self-perceived xerostomia. Whole unstimulated saliva was collected from all subjects and analyzed for antimicrobial protein concentration by enzyme-linked immunosorbent assay and for total protein content by the bicinchoninic acid method. Bivariate and multivariate (generalized linear modeling) analyses evaluated the relationships between age, gender and salivary protein concentrations. RESULTS: Mean salivary levels of SLPI and lysozyme were lower in elderly compared with non-elderly subjects (p < 0.001), unlike lactoferrin and total protein levels. Similar results were obtained when concentrations of the individual proteins were normalized to the total protein concentration, suggesting that glandular production of SLPI and lysozyme preferentially decreases with aging. Gender differences were detected only for SLPI concentrations; males had lower SLPI levels than females regardless of age (p < 0.01). Generalized linear models confirmed that age (p < 0.001) and gender (p < 0.05) were each associated with the SLPI concentration and together accounted for 50% of the variation in SLPI concentration in this population. CONCLUSION: These findings indicate that SLPI production is diminished among healthy community-dwelling older adults, particularly elderly males. Further investigation should determine the impact of decreased local SLPI production on the increased risk of oral mucosal disease with advanced age.

Adult↗