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Biomedical subjects

R Wilson

Publications and source records attributed to R Wilson.

At least 721 records · Page 40Linked to original sources
PubMed1981

Potentiation of dimethylhydrazine bowel carcinogenesis in rats.

An animal model of organ-specific chemical carcinogenesis has been used to study environmental effects on the incidence of human colorectal adenocarcinoma. Wistar/Furth weanling rats underwent connection of their urinary and fecal streams (ureterosigmoidostomy), connection of their urinary and fecal streams with proximal fecal diversion (rectal bladder), or sham operations. Age-matched, unoperated control and operated animals then received either no carcinogen, 1,2-dimethylhydrazine (DMH) 20 mg/kg body weight, s.c. once weekly for 16 weeks, N-[4-(5-nitro-2-furyl)-2-thiazolylformamide (FANFT) 0.2% of the feed for 16 weeks, or DMH + FANFT concurrently. Thirty-three weeks after carcinogen exposure, surviving animals were killed and examined for bowel and urinary bladder tumors. The incidence of adenocarcinoma of the colon adjacent to the junction between bladder and bowel was significantly higher in animals after ureterosigmoidostomy compared with animals whose fecal stream had been proximally diverted (14/22 vs. 0/34, P less than 0.001). This effect was not dependent upon chemical carcinogen exposure. Nonexposed animals still developed a significantly higher incidence of colon adenocarcinomas adjacent to their bladder-bowel junctions as compared with animals with proximal fecal diversion (5/8 vs. 0/13, P less than 0.01). In unoperated or sham operated animals, adenocarcinomas of the bowel occurred in 33% of DMH-treated animals and transitional cell carcinomas of the urinary bladder in 33% of the FANFT-treated animals. After concurrent exposure to both carcinogens, no increased incidence of bladder tumors was noted when compared with FANFT treatment alone. However, the number of animals with one or more adenocarcinomas of the bowel (22/30 vs. 17/50, P less than 0.001), the mean number of tumors per animal (2.1 +/- 0.2 vs. 1.1 +/- 0.1, P less than 0.01), and the invasiveness of the tumors were all increased after DMH + FANFT as compared with DMH exposure alone. The carcinogenic potential of direct bladder to bowel connection with intact fecal and urinary streams, and the potentiation by FANFT of DMH-induced colon carcinogenesis may have implications in the genesis of human colorectal cancer.

1,2-Dimethylhydrazine↗
PubMed1981

Rearranged and germline immunoglobulin kappa genes: different states of DNase I sensitivity of constant kappa genes in immunocompetent and nonimmune cells.

The rearrangement of a variable (V) and a constant (C) gene appears to be a necessary prerequisite for immunoglobulin gene expression. Multiple different rearranged kappa genes were found in several mouse myelomas, although these cells produce only one type of kappa chain [Wilson, R., Miller, J., & Storb, U. (1979) Biochemistry 18, 5013--5021]. It is therefore of interest to understand how only one allele within a lymphoid cell becomes expressed, while the other allele remains nonfunctional ("allelic exclusion"). We have studied the chromatin conformation of kappa genes by making use of the preferential digestion of potentially active genes by DNase I described, for example, for globin genes [Weintraub, H., & Groudine, M. (1976) Science (Washington, D.C.) 193, 848--856]. The DNase I sensitivity of kappa genes in myeloma tumors, in a B cell lymphoma, and in liver was determined by hybridization with DNA on Southern blots. It was found that rearranged C kappa genes are DNase I sensitive in myelomas in which several kappa genes are rearranged, regardless of whether the rearranged genes code for the kappa chains synthesized by the cell. Furthermore, the C kappa gene in germline configuration is also DNase I sensitive in a B cell lymphoma; i.e., it is in the same chromatin state as the rearranged C kappa gene which probably codes for the kappa chains produced by the cell. The altered chromatin state appears to be localized: V kappa genes in germline context are not DNase I sensitive in myeloma or B lymphoma cells while C kappa genes present in a kappa gene cluster on the same chromosomes are sensitive. When rearranged, however, the V kappa genes are as sensitive to DNase I as are rearranged C kappa genes. V lambda and C lambda genes are not DNase I sensitive in kappa myelomas. Thus, commitment to kappa gene expression is apparently correlated with a chromatin conformation which confers increased DNase I sensitivity to the DNA in the vicinity of all C kappa genes in the cell. "Allelic exclusion" does not operate on the level of chromatin conformation which can be detected by altered DNase I sensitivity.

Animals↗
PubMed1981

Resource partitioning during reproduction in the Norway rat.

Rat pups nursed by pregnant dams grow as fast as pups reared by dams that are not pregnant. Moreover, litters that were in utero during a lactation are as numerous at birth and grow as fast as pups developing in a nonlactating, pregnant mother. These litters continue to grow as fast as pups born to nonlactating dams whether or not the first litter remains after the birth of the second litter. When pregnant and lactating dams have a restricted food supply, some dams are capable of extending the duration of their pregnancies by over 2 weeks past that of nonlactating, pregnant dams. This facultative prolongation of pregnancy apparently allows females to carry normal litters to term.

Animals↗
PubMed1981

Correlation of Plasma CEA and CEA tissue staining in poorly differentiated colorectal cancer.

A review of patients operated on for colorectal cancer disclosed poorly differentiated histologies in those whose preoperative and postoperative carcinoembryonic antigen (CEA) levels were no elevated, even in the presence of metastatic disease. CEA was therefore, of little prognostic value or predictive of disease recurrence in these patients. The amount of CEA in tumor tissue of 17 patients with poorly differentiated colorectal cancer was estimated with the immunoperoxidase staining technique and was correlated with histology and plasma CEA levels obtained during various stages of disease. Five tumors did not stain negatively for CEA and all had predominantly poorly differentiated histologies. In all of these patients metastatic disease developed but not elevated plasma CEA levels. In contrast 12 tumors stained positively for CEA and were found to contain either differentiated areas or signet ring cells. Serial plasma CEA levels correctly monitored the postoperative course of all 12 patients. Six of these had a relapse and all were detected by serial increases in plasma CEA. The remaining six were disease free greater than 48 months after resection and had normal plasma CEA levels. Among poorly differentiated tumors, those that contain glandforming areas or signet ring cells can be assumed to produce CEA and plasma CEA levels can be used effectively for monitoring. On the other hand, undifferentiated tumors which do not stain for CEA identify those patients whose plasma CEA levels do not provide a useful monitor.

Adenocarcinoma↗
PubMed1981

Effects on exercise tachycardia during forty-eight hours of a series of doses of atenolol, sotalol, and metoprolol.

Beta adrenoceptor blockers differ mainly in their plasma elimination half-lives (t 1/2 s). It has been assumed that drugs with longer t 1/2 will have a longer duration of effect on exercise tachycardia. Several factors may influence the duration of action of beta blockers; we have investigated the contribution of plasma elimination t 1/2 and dose by comparing the effects on an exercise tachycardia in healthy subjects of placebo, 25, 50, 100, and 200 mg of atenolol and of sotalol, and 50, 100, 200, and 400 mg metoprolol. Subjects exercised before and at 2, 3, 6, 8, 24, 33, and 48 hr after oral doses of each drug. Plasma samples for measurement of drug concentration were drawn before each exercise period. Twenty-four hours after 50, 100, and 200 mg atenolol and 50, 100, 200, and 400 mg sotalol there were reductions in an exercise tachycardia; at this time reductions were greater after the larger doses. The plasma elimination t 1/2s of atenolol were between 7.2 +/0 1.0 hr. Although 50, 100, and 200 mg metoprolol induced the same reductions in an exercise tachycardia 2 hr after drug as 25, 50, and 100 mg atenolol and 50, 100, and 200 mg sotalol, these doses were without effect at 24 hr. Metoprolol 400 mg reduced exercise tachycardia at 24 hr but the effect was less than that of the three largest doses of atenolol and sotalol. The plasma elimination t 1/2 for metoprolol was between 3.6 +/- 0.6 and 5.0 +/- 1.8 hr. These results show that duration of cardiac beta blocking of cardiac beta blocking activity of atenolol, sotalol, and metoprolol is determined by the elimination t 1/2 and dose.

Adolescent↗
PubMed1981

Non-O group 1 Vibrio cholerae gastroenteritis associated with eating raw oysters.

A cluster of five cases of non-O group 1 (non-O1) V. cholerae gastroenteritis occurred in one Florida locality during November 1979. Clinical findings included nausea, vomiting, and abdominal cramping in all affected persons; two had bloody diarrhea. All five persons gave a history of eating raw oysters within four days of onset of illness. A case-control study statistically associated the eating of raw oysters with development of illness (p = 0.0008); this finding was confirmed by a retrospective cohort study of patients hospitalized for diarrhea (p = 0.0001). Non-O1 V. cholerae organisms were isolated from oysters and water samples taken from areas where ill persons had obtained their oysters. In at least one instance the same serotype was isolated from a patient's stool specimen and from the water where the patient had obtained oysters. Non-O1 V. cholerae infection must be considered in the differential diagnosis of shellfish-associated gastroenteritis.

Adult↗
PubMed1981

Epidemiologic characteristics of necrotizing enterocolitis: a population-based study.

The authors studied retrospectively the epidemiologic characteristics of necrotizing enterocolitis occurring among Georgia infants born during 1977 and 1978; 148 cases of necrotizing enterocolitis were identified. The highest incidence rate for necrotizing enterocolitis occurred among infants weighing 751-1000 g at birth and declined with increasing birth weight to less than 0.2 cases per 1000 live births among infants weighing more than 2500 g at birth. The overall incidence rate for blacks was significantly greater than that for whites (1.6 vs. 0.5 cases per 1000 live births, p = 0.01). The overall case fatality ratio was 38.5%; there were no differences in these ratios between blacks and whites. Necrotizing enterocolitis accounted for 15% of all deaths after the first week of life for infants weighting 1500 g or less at birth. If Georgia incidence rates and fatality ratios are applied to 1978 US births, it is estimated that 2210 cases of necrotizing enterocolitis with over 900 associated deaths would have occurred.

Birth Weight↗
PubMed1981

Acute biliary tract disease associated with echovirus 11 infection.

A patient hospitalized with the clinical diagnosis of acute cholecystitis had a normal cholangiogram and recovered without medical or surgical intervention. During the same week, two adults in an acquainted family had a similar syndrome at home. Echovirus 11 was cultured from the stool of all three patients, as well as from four other members of the same two families who had concurrent diarrheal illness. Serologic evidence confirmed acute echovirus 11 infection in the hospitalized patient. In the absence of evidence of a communitywide epidemic of cholecystitis, the coexistence of viral infection with biliary tract symptoms could represent an ongoing endemic situation. Recognition of this syndrome could make it possible to avoid unnecessary major surgical procedures.

Adult↗
PubMed1981

Observation on the efficacy and pharmacokinetics of betaxolol (SL 75212), a cardioselective beta-adrenoceptor blocking drug.

1 Observations were made in five subjects who exercised before and at 2, 3, 6, 8, 24, 33 and 48 h after the oral administration of placebo and 5, 10, 20 and 40 mg betaxolol. 2 The exercise heart rate remained constant at all times after the placebo. All doses of betaxolol significantly reduced the exercise tachycardia at all times. The maximum effect (34.4 +/- 2.2%) occurred after 40 mg. 3 There was a small decline in effect from the peak to 24 h when 40 mg produced a 23.3 +/- 2.7% reduction and a further decline to 48 h when there was a 14.6 +/- 1.8% reduction. 4 Plasma levels of betaxolol were measured in these studies. The peak plasma concentration occurred between 3 and 8 h with different doses. The plasma elimination half-lives after 10, 20 and 40 mg were 11.4 +/- 2.5, 15.9 +/- 4.9 and 15.1 +/- 3.1 h. 5 The effects of 40 mg betaxolol, 200 mg atenolol, 160 mg propranolol, 160 mg oxprenolol, 400 mg sotalol and placebo on an exercise tachycardia were compared in five subjects who received all treatments in random order. 6 There was no significant difference in the maximum reduction produced in an exercise tachycardia by the different drugs. 7 The effect of all drugs decreased with time. The effect of oxprenolol had worn off at 24 h but at 48 h only atenolol and betaxolol produced significant reductions in the exercise tachycardia. 8 Plasma concentrations of the different drugs were measured and plasma elimination half-lives determined. The half-life for betaxolol was 24.5 h which was longer than that for any of the other drugs. 9 These observations show that betaxolol is a potent beta-adrenoceptor antagonist with a long duration of effect on an exercise tachycardia and a long plasma elimination half-life.

Adrenergic beta-Antagonists↗
PubMed1981

Non-O group 1 Vibrio cholerae gastroenteritis in the United States: clinical, epidemiologic, and laboratory characteristics of sporadic cases.

Fourteen sporadic cases of non-O group 1 Vibrio cholerae gastroenteritis were identified through isolates submitted to the Centers for Disease Control in 1979. All the ill persons had diarrhea, 13 had abdominal cramps, 10 had fever, and three had vomiting; in four cases the patients had bloody diarrhea. Five patients had traveled outside the United States before they became ill. All nine domestically acquired cases were in patients who had eaten raw oysters within 72 hours of onset of illness; in a matched case-control study, illness in these patients was strongly associated with eating raw seafood (p less than 0.0001). Only one isolate produced heat-labile toxin by a Y-1 adrenal cell assay. All isolates were susceptible to tetracycline, chloramphenicol, kanamycin, and cephalothin.

Adult↗
PubMed1980

Myeloma with multiple rearranged immunoglobulin kappa genes: only one kappa gene codes for kappa chains.

In many myelomas more than one kappa gene is rearranged (2-5). We are reporting here the results of studies undertaken to determine whether all the rearranged genes are expressed. It was found that in the myeloma NS-1 three different rearranged kappa genes exist. In a subline of NS-1 and several hybridomas produced by fusion of mouse spleen cells with NS-1 it was found that production of NS-1 kappa chains was correlated with the presence of one of the three kappa genes. Loss of this "expressed" gene eliminated the synthesis of the NS-1 kappa chains, loss of one of the other two rearranged kappa genes did not. It is hypothesized, that allelic exclusion (20) of kappa genes generally operates by the functional rearrangement of one kappa gene; other rearrangements are relatively frequent, at least in myelomas, but mostly they are nonfunctional and thus scrambled antibody molecules do not arise.

Animals↗
PubMed1980

Acute phosphine poisoning aboard a grain freighter. Epidemiologic, clinical, and pathological findings.

Two children and 29 of 31 crew members aboard a grain freighter became acutely ill after inhaling the toxic fumigant phosphine; one child died. Predominant symptoms were headache, fatigue, nausea, vomiting, cough, and shortness of breath. Abnormal physical findings included jaundice, paresthesias, ataxia, intention tremor, and diplopia. Focal myocardial infiltration with necrosis, pulmonary edema, and widespread small-vessel injury were found at postmortem examination of the dead child. The surviving child showed ECG and echocardiographic evidence of myocardial injury and transient elevation of the MB fraction of serum creatinine phosphokinase. Illness was significantly associated with living or working amidships or on the forward deck areas of the vessel. Phosphine gas was found to have escaped from the holds through a cable housing located near the midships ventilation intake and around hatch covers on the forward deck. The outbreak illustrates the hazards associated with shipboard fumigation.

Acute Disease↗