Selective serotonin reuptake inhibitors.
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Depressive Disorder↗
Biomedical subjects
D Harrison
Publications and source records attributed to D Harrison.
Safety of 5-HT reuptake inhibitors.
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Depressive Disorder↗
Involvement of a metalloprotease in spontaneous and phorbol ester-induced release of natural killer cell-associated Fc gamma RIII (CD16-II).
Two genes encode the CD16 low affinity IgG FcR. CD16-I (Fc gamma RIII-1) is expressed on PMN as a phosphatidylinositol-glycan anchored glycoprotein. CD16-II (Fc gamma RIII-2) is expressed on NK cells and macrophages as a transmembrane glycoprotein associated with CD3 zeta or Fc epsilon RI-gamma. NK cells spontaneously release soluble CD16-II from the cell surface and this is enhanced by activation with phorbol ester. In this study, we demonstrate that a metalloprotease is involved in the spontaneous and PMA-induced release of CD16-II from NK cells. 1,10-phenanthroline, an inhibitor of Zn(2+)-dependent metalloproteases, efficiently inhibits CD16-II release. 1,7-phenanthroline, an inactive analogue that doesn't chelate Zn2+ or other divalent metal cations, and inhibitors of serine proteases do not affect spontaneous or PMA-induced release of CD16-II. Murine P815 mastocytoma cells transfected with human CD16-II cDNA shed membrane CD16, and 1,10-phenanthroline inhibits this process. P815 transfectants expressing CD16-II molecules with truncated cytoplasmic domains also release soluble receptors, indicating that the cytoplasmic segment of CD16-II is not required for interaction with the protease or the cytoskeleton. By contrast, 1,10-phenanthroline does not inhibit PMA-induced release of CD16-I glycoprotein from PMN, indicating a different mechanism of release for this phosphatidylinositol-glycan anchored molecule. Prior studies have demonstrated that NK cells are activated via the inositol phosphate pathway after engagement of CD16-II by immune complexes or Ig-coated tumor cell targets. A membrane metalloprotease with substrate specificity for CD16-II that is activated by PKC stimulation may provide a mechanism for releasing the immune complex or target from the effector cells and halting signal transduction.
Alkaloids↗
Pharmacokinetics of ranitidine after partial gastrectomy in dogs.
The effect of gastric surgery on the pharmacokinetics of ranitidine was studied in six dogs, all serving as their own controls. Prior to and after surgery, each dog received a single oral dose (5 mg/kg of body weight) of a ranitidine solution. The surgery consisted of partial gastrectomy (antrectomy) and truncal vagotomy. Ranitidine plasma and urine concentrations were measured by reversed-phase ion-pair liquid chromatography with UV detection. Pharmacokinetic parameters were estimated by noncompartmental data analysis techniques. Gastric surgery tended to slow the absorption of ranitidine as reflected by a slight increase of the time necessary to reach the peak plasma concentration. The maximum observed plasma concentration was slightly lowered. The amount of drug absorbed remained unchanged as reflected by no change in the AUCs. Other parameters such as mean residence time, elimination half-life, apparent oral clearance, and fraction excreted unchanged in the urine remained unchanged. However, due to the small number of animals and the considerable intersubject variability, none of these trends reached statistical significance.
Absorption↗
A stratified binomial marker model for bone-marrow repopulation experiments.
The paper considers bone-marrow repopulation experiments with injected mixtures of two types, A and B, of genetically marked donor cells. The covariance of the proportions of type A erythrocytes and lymphocytes is analysed as the sum of two components, under a stratified binomial model allowing the proportions of type A cells to vary in postulated strata of the mixture and with the assumption that the genetic marker does not influence cell development. The ratio of the two components is not experimentally estimable, but each of them has an interesting "demographic" interpretation. Possible inferences about certain "two-cell probabilities" are derived, and the experimental findings that necessitated the stratified model are illustrated.
Animals↗
Effects of truncal vagotomy and partial gastrectomy on the pharmacokinetics of propranolol enantiomers in dogs.
The effect of partial gastrectomy on the pharmacokinetic parameters of (+)- and (-)-propranolol were investigated in six dogs. (+/-)-Propranolol (3 mg/kg body weight) was administered orally before and after surgery and the plasma concentrations of (+)- and (-)-propranolol were determined using an indirect enantioseparation technique. There were significant differences (p less than or equal to 0.05, paired t-test) in the area under the concentration-time curves (AUCs) and the maximum plasma concentration (Cmax) between (+)- and (-)-propranolol. The ratio AUC(+):AUC(-) was 1.73 +/- 0.28. These differences between the enantiomers remained unchanged after surgery. Other pharmacokinetic parameters showed no stereoselectivity. After partial gastrectomy, there was a slight, but nonsignificant decrease in time to reach maximum plasma concentration (tmax) and in the absorption half-life for both enantiomers. The maximum plasma concentration increased slightly. The elimination half-life and the mean residence time remained unchanged before and after surgery. Therefore, it is unlikely that there are any clinically relevant changes in the pharmacokinetics of (+)- and (-)-propranolol after partial gastrectomy.
Animals↗
Theophylline absorption and gastric emptying after partial gastrectomy in dogs.
The pharmacokinetic parameters of theophylline, administered orally as a solution (4 mg/kg body weight), were studied in six dogs before and after two different kinds of gastric surgery in which part of the stomach was removed. The theophylline absorption rate was slightly increased after this antrectomy, whereas other pharmacokinetic parameters, such as area under the concentration time curve (AUC) and the elimination half-life (t1/2), remained unchanged. Gastric emptying was quantified using radionuclide imaging; after antrectomy, it was accelerated for liquids and delayed for solids.
Animals↗
Effect of aging on epidermal dendritic cell populations in C57BL/6J mice.
The density and function of epidermal dendritic cell populations were investigated in aged C57BL/6J mice. The densities of both Langerhans cells (LC) and Thy-1+ dendritic epidermal cells were found to decrease with age. Epidermal cell suspensions from aged mice showed impaired immunologic function as assessed in vitro by the skin-lymphocyte reaction assay and by measuring the ability of epidermal cell suspensions to stimulate the proliferation of sensitized T cells in the presence of the sensitizing antigen. However, the capacity of LC to transport antigen from the skin to the draining lymph nodes was found in vivo to be comparable to that of young mice. Results of transplantation of bone marrow cells from young and old donors into irradiated recipients indicate that the decreased Langerhans cell density found in old mice may result from a deficiency in Langerhans cell bone marrow progenitors.
Aging↗
Ultrastructural localization of cytochrome b in the membranes of resting and phagocytosing human granulocytes.
Affinity-purified rabbit anti-neutrophil cytochrome b light or heavy chain antibodies were used to immunocytochemically and biochemically localize cytochrome b in neutrophils and eosinophils. The antibodies were monospecific, recognizing polypeptides of 91 and 22 kD, respectively, on Western blots of whole neutrophil extracts. The antibodies were used in Western blot analysis of subcellular fractions of purified neutrophils to confirm that the distribution of cytochrome b spectral absorbance matched that of the two subunits. Thin sections of cryofixed, molecular distillation-dried granulocytes were labeled with the anti-cytochrome b antibodies, followed by incubation with biotin-conjugated secondary antibody, and final labeling with streptavidin-conjugated colloidal gold. Electron microscopy revealed that the cytochrome b light and heavy chains were localized primarily (80%) to 0.1-0.2-micron round or elliptical granule-like structures in neutrophils and 0.4-0.5-micron granules in eosinophils. Approximately 20% of the cytochrome b was localized to the surface, confirming the subcellular fractionation studies. Double staining experiments on the neutrophils, using polyclonal rabbit anti-lactoferrin antibody, indicated that the cytochrome-bearing structures also contained lactoferrin and thus were specific granules. When the analysis was performed on neutrophils that had phagocytosed Staphylococcus aureus, cytochrome b was found in the phagosomal membrane adjoining the bacterial cell wall.
Animals↗
1990 Ogura memorial lecture: moral dilemmas in head and neck cancer.
Neither morality nor dilemma can be defined meaningfully in the concept of the practical management of head and neck cancer. Although both have important implications, particularly with regard to ethnic and social factors, they play a relatively minor role in determining management policy. With little knowledge of the intrinsic causes of cancer and with a treatment strategy limited to radiotherapy and surgery, our desire for cure must be tempered by concern to avoid any increase in patient privations. My philosophy, based upon the care of more than 3500 patients over almost 30 years, reflects some of the difficulties of applying the concept "do nothing that may cause harm," while offering each patient the opportunity for long-term cure.
Disclosure↗
Invalid information from the ear probe of a pulse oximeter in tricuspid incompetence.
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Carbon Dioxide↗
Fructosamines in uraemia and renal replacement therapy.
Serum fructosamines and glycosylated haemoglobin have been examined in groups of patients with (n = 27) and without (n = 39) diabetes mellitus and chronic renal failure, or undergoing renal replacement therapy. Elevated values of fructosamines were found in nondiabetic haemodialysis patients as compared to the other non-diabetic patients. The relationship between fructosamines and glycosylated haemoglobin appeared to be attenuated by uraemia. Successful pancreatic transplantation returned fructosamine and glycosylated haemoglobin values to normal.
Adult↗
Diagnostic pitfalls in plasma cell neoplasia.
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Adult↗
Predictors of death from chronic graft-versus-host disease after bone marrow transplantation.
Chronic graft-v-host disease (chronic GVHD) is a frequent cause of late morbidity and death after bone marrow transplantation (BMT). The actuarial survival after onset of chronic GVHD in 85 patients was 42% (95%Cl = 29%, 54%) at 10 years. Baseline characteristics present at the onset of chronic GVHD (before therapy) in 85 patients were reviewed to determine which were risk factors for death. In a multivariate proportional hazards analysis, three baseline factors emerged as independent predictors of death: progressive presentation (chronic GVHD following acute GVHD without resolution of acute GVHD; hazard ratio of 4.1, 95% Cl = 2.1 to 7.8), lichenoid changes on skin histology (hazard ratio of 2.2, 95% Cl = 1.1 to 4.3), and elevation of serum bilirubin greater than 1.2 mg/dL (hazard ratio = 2.1, 95% Cl = 1.1 to 4.1). Actuarial survival of 23 chronic GVHD patients with none of these risk factors was 70% at 6 years (95% Cl = 38%, 88%). Thirty-eight patients with one of these risk factors had a projected 6-year survival of 43% (95% Cl = 21%, 63%). The 29 patients with any combination of two or more of these factors had a projected 6-year survival of only 20% (95% Cl = 8%, 37%). Identification of baseline risk factors should facilitate design of trials of chronic GVHD therapies and assignment of high-risk patients to more aggressive innovative therapeutic regimens.
Actuarial Analysis↗
The use of intravenous pancuronium bromide to produce fetal paralysis during intravascular transfusion.
Intravascular fetal transfusion can be complicated by difficulty in maintaining vascular access because of fetal movements. Treatment by intramuscular pancuronium bromide has been proposed as a means of arresting fetal movements, although this treatment requires a separate puncture for injection. We report in this article our experience with intravenous fetal injection of pancuronium bromide to produce muscular paralysis during fetal transfusion.
Blood Transfusion, Intrauterine↗
Renal brush border glutamine transport: comparison between in situ and isolate membrane vesicle uptake.
Glutamine uptake by renal cortical brush-border vesicles was compared to transport expressed by the functioning isolated kidney. Comparisons were made with regard to sodium dependency and the adaptive increase induced by chronic metabolic acidosis in the rat. The results show an absolute dependency upon a sodium gradient; sodium-independent glutamine uptake has no counterpart in situ. In addition, acidosis-induced adaptive increase in vesicle glutamine uptake has no counterpart in situ. Rather, the apparent adaptation reflects extravesicular gamma-glutamyltransferase-mediated conversion to glutamate and subsequent accumulation; acidosis-induced adaptation of this enzyme largely explains the apparent adaptation in glutamine uptake. Consequently the role of membrane transport in glutamine flux regulation can be assessed providing metabolic conversion is controlled.
Acidosis↗
Effect of precisely identified mutations in the spoIIAC gene of Bacillus subtilis on the toxicity of the sigma-like gene product to Escherichia coli.
Yudkin (1986) has shown that the spoIIAC gene of Bacillus subtilis cannot be cloned in Escherichia coli in such an orientation that it is expressed. This toxicity of the gene product has been attributed to its close homology with the sigma subunit of the E. coli RNA polymerase. The effect of six individual mutations in spoIIAC has now been studied. All six mutant genes could be cloned in E. coli in an orientation that does not allow expression. When in the orientation that permits expression, one mutant gene could not be cloned, and a second substantially hampered growth; both mutations lie in the region that is believed to encode the DNA-binding domain of the protein. By contrast, two missense mutations in the region of the gene thought to encode the domain that binds to the core RNA polymerase rendered the protein harmless in E. coli, as did two nonsense mutations.
Bacillus subtilis↗
Hematopoietic effects of continuous intravenous infusion of mice with growth factors produced by the WEHI-3 cell line.
A method for continuous intravenous infusion of unanesthetized adult C3H/HeJ or Wx/Wv anemic mice was designed using cage immobilization and a tail vein catheter connected to a model 940 Harvard infusion pump. Infusates included: WEHI-3 cell line dialyzed, 5 times concentrated conditioned medium containing multi-colony-stimulating factor (C-SF) interleukin 3 (IL-3); purified murine IL-3; bacterial endotoxin; serum-free medium, or normal saline. Mice were monitored at days 5-7 after infusion for complete peripheral blood counts and production of granulocytes in vitro by explanted marrow in long-term bone marrow cultures. We observed a stimulatory effect of WEHI-3 conditioned medium infusion that was not attributable to endotoxin and produced significant increases in peripheral blood WBC count and neutrophils, colony-forming units in spleen and numbers of granulocyte/macrophage colony-forming unit culture responsive to both C-SF-1 (L cell C-SF) and multi-C-SF in vitro. This infusion method should prove valuable for test of the in vivo effects of purified growth factors and molecularly cloned hematopoietins.
Animals↗