Saline immersion and the length-tension properties of alveolar wall.
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Animals↗
Biomedical subjects
C Young
Publications and source records attributed to C Young.
[Timed bacteriostatic and bactericidal activities of latamoxef against clinical strains of gram-negative bacteria].
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Bacteroides fragilis↗
Characterization of the phenotype and function of lymphocytes infiltrating the salivary gland in patients with primary Sjogren syndrome.
Monoclonal antibodies directed against T-cell subsets, B-cell subsets, and monocytes were used to characterize the cells infiltrating the salivary glands of patients with primary Sjogren syndrome (1 degree SS). Analysis of stained frozen tissue sections and lymphocyte suspensions derived from salivary glands revealed the majority of infiltrating cells to be T cells (reactive with antibodies SC1 and Leu 4) of the Leu 3a+ subset (greater than 70% reactive). Of particular interest, a high frequency of Ia+ T cells (up to 50% of T cells) and B cells reactive with antibody B532 (5-15% of infiltrating cells) were found in salivary gland lymphocytes (SGL) but not in peripheral blood lymphocytes (PBL) of the same patients. Our finding that the phenotype of SGL was significantly different from PBL emphasizes the need to characterize lymphocytes at the site of tissue destruction. In vitro functional assays demonstrated that the OKT4+ SGL exhibited T-helper activity but not natural killer, antibody-dependent cellular cytotoxicity, or cytotoxic T-lymphocyte activity. Of note, rheumatoid factor (IgM anti-IgG) was produced by SGL but not by the corresponding PBL. Our studies on SG-lymphocyte function represent an early step in elucidating the cellular and subcellular events responsible for this autoimmune disease.
Antibodies, Monoclonal↗
Immunogenicity of Ty21a attenuated "Salmonella typhi" given with sodium bicarbonate or in enteric-coated capsules.
Ty21a, a stable attenuated mutant of Salmonella typhi, is a safe, protective oral vaccine when 3 doses of 10(9) cells in saline are taken after neutralization of gastric acidity by 1 g NaHCO3. To identify a more convenient method to administer vaccine and to determine the feasibility of immunizing with a single dose, we studied the immune response of children and adults to different formulations of Ty21a with a newly developed, sensitive, enzyme-linked immunosorbent assay (ELISA). In this ELISA, a rise in S. typhi O antibody was defined as a change in net optical density of greater than or equal to 0.15 (more than 3 SD from the mean difference in optical density in a negative control population). Three hundred and thirty-five Chilean children were given 3 doses of 10(9) Ty21a in 150 ml of milk with 0.8 g NaHCO3 or in enteric-coated capsules. In each group, 5% seroconverted by Widal O but 41% by IgG ELISA O antibody titers; mean antibody levels by group were identical. Studies were also carried out in healthy college students in a non-endemic area (U.S.A.) who had no history of prior typhoid immunization. In total, 141 U.S. adults received vaccine formulated in either one of two ways: 1) in gelatin capsules administered with two additional gelatin capsules containing a total of 0.8 gm NaHCO3 or 2) in enteric-coated capsules. Thirty-six persons received one dose, 30 got two doses and 16 ingested three doses of enteric-coated vaccines, while 44 persons receiving one dose and 15 got two doses of vaccine in the gelatin capsule formulation. Rates of seroconversion of ELISA O antibody were similar in all the groups. Ty21a vaccine was not recovered from multiple stool, jejunal fluid or blood cultures of the U.S. vaccine recipients. Based on these observations a large-scale field trial of efficacy has been initiated in 90.000 schoolchildren 6-20 years of age in Santiago, Chile, of whom one-third received one dose of enteric-coated vaccine, one-third got two doses and the remainder received placebo.
Adolescent↗
Pharmacokinetics of cisplatin regional hepatic infusions.
Cisplatin (DDP), a potent antineoplastic agent, is usually administered via a peripheral vein. Recently, there has been considerable interest in intraarterial regional infusions of DDP. The pharmacokinetics of DDP when administered by this technique have not been explored in detail. We studied DDP pharmacokinetics in dogs given DDP by infusion and bolus injection in the hepatic artery (H.A.), portal vein (portal V), and peripheral vein (P.V.). Blood and biliary platinum concentrations ([Pt]) were assayed by flameless atomic absorption spectrophotometry. During an infusion into the H.S., peak [Pt] in the vessel were markedly higher (mean value 19 micrograms/ml) than those found, simultaneously, in the portal V or superior vena cava. Following a bolus injection of DDP into the H.A., higher H.A. [Pt] were also seen, but [Pt] rapidly (within 5-10 minutes) equilibrated in all sites sampled. During the H.A. infusion, most [Pt] was in its free (active) form. Bile and hepatic tissue were also sampled. Hepatic artery infusions of DDP give high drug concentrations in the perfusing blood, while systemic [Pt] are much lower. During the infusion, the majority of DDP is in its active (unbound) state.
Animals↗
Anatomical and immunological responses of rabbit gallbladders to bacterial infections.
To study the sequential morphological and immunological response of the rabbit gallbladder to bacterial infection and to compare the inflammatory responses with different pathogens, gallbladders were infected with Streptococcus faecalis and two strains of Escherichia coli, one of which produced enterotoxin. Gallbladder infection was produced either by intravenously injecting bacteria into rabbits with a small liver infarct or by injecting bacteria directly into the gallbladder of normal rabbits. The percentage of gallbladders infected intravenously with a nonenterotoxigenic E. coli strain was 86% at 1 week, 70% at 3 weeks, and 15% at 6 weeks. Epithelial necrosis and leukocyte infiltration were prominent 1 week after infection. At 3 and 6 weeks after infection, there was crypt distortion and increased mucus secretion in the epithelium as shown by periodic acid-Schiff staining. The lamina propria was infiltrated with mononuclear cells, many of which were plasma cells. Myofibroblasts (contractile fibroblasts) were also identified on transmission microscopy, In addition to these changes, toxigenic E. coli produced subepithelial capillary dilation in the villus core. Morphological changes (excluding toxin-associated changes) were related to the duration of infection rather than to the specific species of infecting bacteria. Infected gallbladders studied by immunofluorescence had a greater than 50-fold increase in plasma cells compared with control cells. In addition, the number increased with the duration of infection. Immunoglobulin A cells were the major cell type in gallbladders infected by intravesical injection, whereas immunoglobulin G cells predominated in gallbladders infected intravenously. The gallbladder appears to mount a local immune response to bacterial infection.
Animals↗
Assessment of timed bacteriostatic and bactericidal activities of cephalothin against gram-positive and gram-negative bacteria.
The comparative bacteriostatic and bactericidal activities of cephalothin were assessed in broth medium with special reference to the period of exposure of microbes to the drug. The bacteriostatic concentration with a brief period of exposure (6 h) was lower than the conventional MIC for Escherichia coli and Klebsiella sp. When the period of exposure was prolonged (18-42 h), the bacteriostatic concentration almost corresponded with the MIC. In contrast to these gram-negatives, the bacteriostatic concentration with a brief period of exposure roughly corresponded with the MIC for strains of Staphylococcus aureus and was higher for enterococcus. When a comparison of the bacteriostatic and the bactericidal concentrations was used as the criterion for assessment, the mode of action of cephalothin appeared to be bactericidal to most of the gram-negatives. This drug was bacteriostatic to a number of strains of gram-positives, in particular to enterococcus, especially when microbes were exposed to the drug over a brief period of time.
Cephalothin↗
The effects of pituitary hormones on hepatic drug metabolism in the rat.
Sex differences exist in the hepatic microsomal metabolism of drugs in the rat. These differences have been shown to be related to the presence of androgen in the male and the pituitary gland in the female. The present study was designed to identify the pituitary 'feminizing factor' by continuously infusing hormones via an osmotic mini-pump. Rat somatotropin and prolactin mimicked somewhat the 'feminizing' effect of pituitary extract infused into male animals while human somatotropin, which binds to both lactogenic and somatogenic receptors in rat liver, completely reversed the effect of hypophysectomy of female rats with respect to most of the parameters studied. It thus appears that the somatogenic/lactogenic receptors in the rat liver are involved in the maintenance of the sex differences in drug metabolism but the identity of the hormone that normally acts on these receptors in the rat is still uncertain.
Animals↗
[Timed bacteriostatic and bactericidal activities of cefmetazole against selected gram-negative bacteria].
Antibacterial activities of cefmetazole, a new preparation of cephamycin antibiotic, were determined against selected clinical strains of Escherichia coli (27 strains), Klebsiella sp. (27 strains) and Bacteroides fragilis (27 strains). Activities were evaluated at bacteriostatic and also bactericidal levels with particular reference to time of exposure of microbes to the drug. The minimal drug concentrations producing minimal reduction of colony-forming units at time intervals of 3, 6 and 24 hours after exposure to the drug--approximations to the theoretical bacteriostatic concentrations--were designated as 3-h, 6-h and 24-h MRCs, respectively. Conventional MIC yielding no turbidity after incubation of antibiotic-containing broth for 24 hours was also determined. The minimal concentrations of the drug producing 99.9% killing at time intervals of 3, 6 and 24 hours after exposure to the drug were designated as 3-h, 6-h and 24-h MLCs, respectively. Assuming that the apparent mode of action of a drug is bactericidal when the ratio of bactericidal-bacteriostatic concentrations is low (less than or equal to 4) and bacteriostatic when high (greater than or equal to 8), then cefmetazole appeared to be a bactericidal drug to a considerable number of Gram-negative strains when the exposure time exceeded a period of 6 hours. The data that the mode of action of this drug is bactericidal with such relatively brief exposure times--indicating rapid decrease of colony-forming units--would suggest cefmetazole is an excellent antibacterial agent and would be a useful drug in treatment of bacterial infections.
Anti-Bacterial Agents↗
Phase II evaluation of 4'-epi-doxorubicin in patients with advanced colorectal carcinoma.
4'-Epi-doxorubicin (4'-epi-DX) is a new doxorubicin derivative that is more active than the parent compound against murine sarcoma virus tumors and Lewis lung carcinoma and may be less toxic. Thirty-five patients with advanced measureable colorectal carcinoma were treated with 4'-epi-DX (85 mg/m2) every 3 weeks. The major toxic effect was leukopenia less than 2000 cells/mm3 in 28% of the patients. One of 29 patients (3%) had a partial response. At this dose and schedule, 4'-epi-DX has minimal activity in colorectal carcinoma.
Adult↗
Factors determining temporal pattern of isobaric supersaturation.
It is possible to produce a transient supersaturation or undersaturation in tissues and blood by sequentially breathing gases with different equilibration rates. If the ambient gas pressure is sufficiently high, the induced supersaturation can produce vascular bubbles. By means of the classical perfusion-dependent model of inert gas elimination, which assumes that the effects of diffusion are minimal, the magnitude of the total inert gas pressure can be predicted. If, however, the effects of diffusion cannot be ignored, the supersaturation could be substantially larger. This paper estimates the effects of diffusion in a Krogh cylinder on the supersaturation produced by suddenly changing the inert gas partial pressure in the blood. The results of these estimates indicate that diffusion plays a role in this transient supersaturation only in long Krogh cylinders with high blood flows. The effects of diffusion are further reduced by the finite time necessary to switch the inert gases in arterial blood. The conclusions are supported by experiments that measure vascular bubble production after a switch of the inert portion of the inspired gas. These experiments further show that the formation of vascular bubbles after such a switch cannot be entirely explained by the different diffusion constants of the gases used.
Animals↗
Phase II trial of methylglyoxal-bis-(guanylhydrazone) in non-small-cell lung cancer.
Fifty-two patients with metastatic or recurrent non-small-cell lung cancer (NSCLC) were treated, during a phase II trial, with methylglyoxal-bis-(guanylhydrazone) (MGBG). Of the 44 patients who had adequate trials, 4 had partial responses (PR), for an overall 9% PR rate. Response durations ranged from 3 to 5+ months. Prior treatment with chemotherapy may have adversely affected response rate; 15% of previously untreated patients responded, compared to only 4% of previously treated patients. A syndrome of weakness and fatigue was the most serious side effect. Anorexia and weight loss, stomatitis, nausea and vomiting, diarrhea, and peripheral neuropathy were the other toxic effects. We conclude that MGBG has activity in NSCLC, especially in previously untreated patients, and further studies are indicated in that population.
Adenocarcinoma↗
Growing up with diabetes mellitus.
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Adolescent↗
Notes on midgut cell nuclear coats in various tsetse species.
Coats were found on the midgut cell nuclei of G.m. morsitans, G. austeni, G. tachinoides, G. f. fuscipes and G. p. palpalis. No coat was found in G. p. gambiensis. The coats were of differing ultrastructural design and of different dimensions in each species. The appearance of the coat seems to be linked to the physiological train of events following the bloodmeal rather than to novel events such as viral or protozoal infection. The timing of its appearance varied among the different species examined.
Animals↗
[Mixed colony containing macrophages and plasma cells in hemopoietic dysplasia (author's transl)].
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Bone Marrow↗
Pharmacokinetics of gallium nitrate in man.
Gallium nitrate is a new antineoplastic agent that has shown activity in a number of in vitro tumor systems. During a Phase I clinical trial, the pharmacokinetics of two methods of administration of gallium nitrate were studied: a seven-day continuous intravenous infusion, and a weekly rapid intravenous infusion. During the continuous infusion of 200 mg/M2 of gallium nitrate, plasma gallium concentrations of 0.9 +/- 0.2 microgram/ml in one patient, and 1.9 +/- 0.4 microgram/ml in a second were noted. Urine excretion of gallium approximated the daily administered dose by day 2-3. Overall, 68-107% of the total administered dose was recovered in the urine. Following a rapid intravenous infusion, a biphasic curve was generated. The T1/2 alpha ranged from 8.3-26 minutes; the T1/2 beta from 6.3-196 hours. From 69-91% of the administered dose was recovered in the urine. The effects of gallium nitrate on tissue localization and body retention of 67Ga are also presented.
Adolescent↗
Effect of dietary fat on the fluidity of platelet membranes.
Dietary fat type was reflected in the phospholipid fatty acid composition of the plasma membrane of rabbit platelets and apparently controlled the fluidity of these membranes. Rabbits were maintained for 6 months on diets that varied in stearic and polyunsaturated fatty acids and thus had different potentials for thrombosis. Microviscosities at 37 C, calculated from the arisotropy of fluorescence from the probe 1,6-diphenyl-1,3,5-hexatriene, were 3.5, 3.4, 2.8 and 2.2 poise for platelet membranes isolated from rabbits whose only source of dietary fat was cocoa butter, milkfat, coconut oil, or corn oil, respectively. The relative findings of the membrane isolates were correlated with the polyunsaturated fatty acid contents of the membrane phospholipids.
Animals↗
Influence of dietary fats on the fluidity of the lipid domains of rabbit plasma lipoproteins.
The effects of dietary stearic and other saturated fatty acids on the fluidity of the plasma lipoproteins were assessed with fluorescence polarization techniques. Rabbits were maintained on diets containing either cocoa butter, milkfat, coconut oil, or corn oil as the only source of fat. Microviscosities eta, of the lipid regions of plasma very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL) were determined by measuring the anisotropy of fluorescence from the probe 1,6-diphenyl-1,3,5-hexatriene. The microviscosity values followed the sequence eta HDL greater than eta LDL greater than eta VLDL when the lipoproteins were isolated from the plasma of rabbits fed cocoa butter, milkfat, or corn oil, HDL and LDL consist of an invariant phase in the temperature range 0--50 degrees C regardless of diet. VLDL from rabbits fed milkfat, corn oil, or cocoa butter displayed monophasic behavior in the same range, while VLDL, from rabbits fed coconut oil showed a phase transition at 31.9 +/- 3.7 degrees C. Lipoproteins were less fluid in fasted than in non-fasted rabbits and VLDL and LDL from fasted milkfat-fed rabbits showed phase transitions. Despite the fatty acid compositions of the dietary fats, VLDL and LDL were more fluid from rabbits fed cocoa butter than from rabbits fed corn oil; apparently metabolism influences microviscosity.
Animals↗