Biomedical subjects
Publications and source records attributed to F C Brown.
Epithelioma cuniculatum is a rare, slow growing, but locally destructive, low-grade epithelioma of squamous cell origin. The first case of this tumor occurring on the thumb is reported. Treatment of this case is discussed, the literature reviewed, and controversy surrounding the naming of this tumor is examined.
The incorporation of intracisternally injected L-[methyl-3H]methionine [( 3H]Met) or S-adenosyl-L-[methyl-3H]methionine (Ado[3H]Met) into rat brain AdoMet and phospholipid pools was examined. When [3H]Met was administered, both AdoMet and phospholipid pools were labeled. However, exogenously injected Ado[3H]Met did not serve as a substrate for phospholipid-N-methyltransferases. It was concluded that only Ado[3H]Met formed in situ was utilized to methylate phospholipids and that this process was initiated on the cytoplasmic side of the membrane. The apparent biological half-life in brainstem of phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine formed from [3H]Met was 1.4 and 1.7 days, respectively. The half-life of phosphatidylcholine could not be determined due to interference from peripheral sources.
The effects of vasoactive intestinal polypeptide (VIP), glucagon, and secretin on lower esophageal sphincter pressure were investigated in awake baboons. The three hormones were compared with respect to effect on (1) resting lower esophageal sphincter pressure and (2) maximal stimulatory response to pentagastrin. VIP was shown to reduce resting and pentagastrin-stimulated lower esophageal sphincter pressure with significantly greater potency than either secretin or glucagon. For reduction of resting lower esophageal sphincter pressure, the potency ratio of VIP to secretin was 16:1 and of VIP to glucagon was 32:1 (P less than 0.05). For inhibition of pentagastrin-stimulated sphincter pressure, the potency ratio of VIP to secretin was 32:1 and of VIP to glucagon was 64:1 (P less than 0.02). This demonstration of significantly increased potency of VIP over known inhibitory hormones strengthens the suggestion that VIP may have a physiologic role in the control of lower esophageal sphincter function.
The effect of somatostatin (GH-RIH) infusion (2 microgram/min) on lower esophageal sphincter pressure (LESP) responses to various stimuli was evaluated in adult male baboons. GH-RIH infusion did not affect basal LESP, but did cause a significant suppression of mean immunoreactive insulin (IRI) to 5.8% of basal values (P less than 0.05). Pentagastrin IV caused dose-related increases in LESP that were unaffected by GH-RIH. Abdominal compression caused a threefold rise in LESP (P less than 0.005) both without and with GH-RIH. However, atropine (20 microgram/kg iv bolus) completely blocked this cholinergic LES pressure response. Intragastric alkali as well as intragastric glycine caused significant increases in LESP (P less than 0.05). These LESP responses to alkali and to glycine were totally abolished by GH-RIH. In conclusion, GH-RIH infusion in the baboon does not affect basal LESP, LES smooth muscle response to exogenous stimulation, nor a cholinergically mediated LES response. GH-RIH does inhibit the response of LESP both to intragastric alkali and to glycine by the apparent suppression of a hormonally mediated mechanism.
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Under conditions that are optimum for DbetaH, ascorbic acid denatures serum albumin, gamma-globulin, catalase, and DbetaH. With ascrobate plus Cu2+, the proteins are almost completely destroyed. Pyrazole protects DbetaH and albumin, but not catalase. Superoxide dismutase (SOD) is not denatured by ascorbate, with or without Cu2+, and in combination with catalytic amounts of catalase or Fe2+ it stimulates maximum DbetaH activity. In other words, a combination of catalase and SOD, or Fe2+ and SOD, will protect DbetaH. Excessive amounts of catalase and/or other protein, either native or denatured will prevent the effects of superoxide and/or ascrobate, but cannot replace the requirements for catalytic quantities of catalase or Fe2+. The results suggest that the rate of hydroxylation of tyramine may be limited by superoxide, but that the latter per se does not denature DbetaH as does hydrogen peroxide. The in vitro activation of oxygen by DbetaH is a toxic process, involving the production of both hydrogen peroxide and superoxide and possibly other free radicals. In the absence of precise regulation of the production and concentrations of these compounds, the enzyme is denatured.
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We have studied the lower esophageal sphincter (LES) response to exogenous histamine and to H1- and H2-blocking agents in the awake baboon. Increasing intravenous bolus doses of histamine produce an increase in LES pressure with a maximum response at a dose of 12 microgram/kg. H1-receptor blockade with chlorpheniramine over a wide dose range did not alter basal LES pressure but did abolish the response of the LES to exogenous histamine. H2-receptor blockade with cimetidine at doses markedly inhibiting gastric acid secretion (2 mg/kg.h) did not alter basal LES pressure or the response of the LES to exogenous histamine. In addition, cimetidine did not alter the response of the LES to pentagastrin and bethanechol. Although histamine and histamine receptors are important in gastric secretion, they appear to have no identifiable role in the maintenance of basal LES smooth muscle tone in the baboon. These results demonstrate the presence of a stimulatory H1 receptor on baboon LES smooth muscle, but provide no evidence for the presence of an H2-inhibitory receptor. As opposed to the parietal cell, the LES response to pentagastrin and bethanechol does not require a H2 receptor.
The effectiveness of cimetidine for symptomatic relief in patients with chronic gastroesophageal reflux was studied in a multicenter, double blind clinical trial. Patients were entered into the study for a total of 8 weeks, receiving either cimetidine, 300 mg four times daily, or identical placebo tablets. Throughout the trial, frequent assessments were made of symptom severity and frequency, combined with careful measurement of antacid use. Esophagoscopy, esophageal acid sensitivity, and lower esophageal pressures were performed before and at the completion of the treatment period. Significant (P less than 0.05) decreases in symptom frequency and severity were noted throughout the study in the cimetidine-treated patients, as compared with the placebo group. This subjective improvement was corroborated by a concomitant decrease in antacid use, which was significantly (P less than 0.05) reduced in the cimetidine-treated group. In addition, significant improvement in esophageal acid sensitivity resulted from cimetidine therapy. No objective improvement in esophageal endoscopic appearance or sphincter pressures was noted. The results of this double blind trial indicate that cimetidine is more effective than the placebo for the relief of symptoms of gastroesophageal reflux.
Chronic pyrazole treatment caused a 40% decrease in rat serum dopamine beta-hydroxylase (DBH) activity. Ethanol given simultaneously with pyrazole prevented the inhibition. 4-Hydroxypyrazole, the major metabolite of pyrazole, competitively inhibited both rat serum DBH and partially purified bovine adrenal DBH in vitro. In vivo, 4-hydroxypyrazole caused large decreases in rat serum (53-84%) and adrenal (97%) DBH activity but had no effect on brain enzyme. The decrease in rat serum DBH after chronic pyrazole treatment and the pyrazole-induced changes in physiological parameters, such as body weight and temperature, may be due to the formation of 4-hydroxypyrazole.
Single large doses of pyrazole (100-200 mg/kg) given either i.p. or orally caused a decrease in brain norepinephrine and 3-methoxy-4-hydroxyphenylethylene glycol sulfate, but no change in dopamine beta-hydroxylase activity. The effects were enhanced by daily administration for 3 to 4 days. Concomitant administration of ethanol prevented the effects. With smaller doses (50 mg/kg/day) given orally for several days, there was little or no change for 3 days, but after 6 days there was an increase in both parameters. Dopamine beta-hydroxylase activity was also increased. The daily administration of ethanol alone (6.0 g/kg/day) for 6 days caused increased norepinephrine, but 3-methoxy-4-hydroxyphenylene glycol sulfate was diminished and dopamine beta-hydroxylase was unaffected. When the two drugs were given simultaneously, steady-state levels of norepinephrine were unaltered, but the sulfate metabolite was increased as was dopamine beta-hydroxylase. The results suggest that pyrazole and/or ethanol, administered daily for 6 days, leads to adaptive responses in catecholamine metabolism. Pyrazole (or a metabolite) has marked effects of its own, some or all of which are independent of its effects on alcohol dehydrogenase. When the two drugs are administered together, it is difficult to know whether the observed changes are independent or overlapping effects.
A baboon (Papio anubis) was used as a model for the study of the physiology of the esophagus. This model closely resembles the human being phylogenetically and physiologically. Base-line lower esophageal sphincter pressure and peristaltic amplitude are similar to that of man. In addition, the anatomic transition from striated to smooth muscle is identical to that of the human esophagus. The sphincter-depressing effect of ketamine anesthesia was demonstrated.
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