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Biomedical subjects

J M Howard

Publications and source records attributed to J M Howard.

At least 109 records · Page 6Linked to original sources

Comparison of cytoskeletal organization in canine distemper virus-infected and uninfected cells.

The organization of vimentin filaments, keratin filaments, microtubules and microfilaments was compared in canine distemper virus (CDV)-infected and uninfected cells by indirect immunofluorescence. Infection of tissue culture cells with CDV caused a total reorganization of all the cytoskeletal structures with the most notable changes in the microtubules and intermediate filaments. During virus infection two different patterns of staining were observed for both the intermediate filaments and microtubules, suggesting a step-by-step reorganization of the structures. While the two types of intermediate filaments (vimentin and keratin) had quite different staining patterns, the vimentin (but not keratin) filaments had a distribution pattern similar to the microtubules in both infected and uninfected cells. These results suggest that microtubules and vimentin (but not keratin) filaments may have a close association in CDV-infected cells.

Animals↗

Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload.

To determine whether or not hepatic computed tomography density is an alternative to liver biopsy for the diagnosis of body iron overload, hepatic computed tomography density was determined in healthy controls, patients with idiopathic hemochromatosis, and patients with liver disease. Hepatic computed tomography density was obtained from a single computed tomography slice taken through the liver on a General Electric CT/T 8800 scanner. In 69 controls, hepatic computed tomography density ranged from 11 to 36 units (mean = 30). Given an upper limit of normal of 36 computed tomography units, 4 of 6 untreated patients with idiopathic hemochromatosis had elevated hepatic computed tomography density compared with 0 of 8 patients after venesection (X2 = 7.5, p = 0.01). Hepatic computed tomography density correlated directly with serum ferritin (r = 0.72, p = 0.01). In 58 consecutive patients with clinical or biochemical evidence, or both, of liver disease who underwent liver biopsy for diagnostic purposes, 0 of 52 patients with normal hepatic iron had an elevated hepatic computed tomography density as compared with 4 of 6 patients with excess iron (X2 = 35, p less than 0.001). An elevated hepatic computed tomography density associated with an elevated serum ferritin indicates iron overload; however, a normal hepatic computed tomography density does not exclude iron overload. When computerized tomography is applied to patients with an unexplained elevation of the serum ferritin, it provides a noninvasive alternative to liver biopsy for the detection of excess hepatocellular iron.

Adult↗

Enkephalin inhibits relaxation of the lower oesophageal sphincter.

Five healthy volunteers were studied for the effect on oesophageal motility of a single subcutaneous injection of a synthetic analogue of enkephalin as compared with an injection of an equivalent volume (0.5 ml) of saline. The injections were given at random on separate days, and each was followed after 40 minutes by 2 mg naloxone given intravenously. Pressures were measured by manometry after dry and wet (5 ml) swallows at one-minute intervals, and traces were coded and analysed "blind". Twenty-five minutes after the injection of enkephalin the percentage relaxation of the lower oesophageal sphincter pressure was significantly less (p less than 0.005) than at the same time after saline. Within two minutes after intravenous naloxone this effect had disappeared completely. Enkephalin had no noticeable effect on pressure of the sphincter or on amplitude and duration of oesophageal peristalsis. The mechanism of action of enkephalin in selectively inhibiting relaxation of the lower oesophageal sphincter remains to be determined. That naloxone rapidly reversed the inhibition may be relevant in achalasia and warrants further study.

D-Ala(2),MePhe(4),Met(0)-ol-enkephalin↗

3H-methyl scopolamine binding to dispersed pancreatic acini.

Maximal amylase release occurred with 10(-5) M carbachol and slightly greater than half maximal response occurred with 3 x 10(-7) M carbachol in dispersed pancreatic acini. The preparation released more than 45% of its initial amylase content after 60 min of maximal carbachol stimulation. Electron microscopy revealed depletion of zymogen granules and the presence of secretory material in the ductules after carbachol stimulation. At 37 degrees C, maximal binding of methyl scopolamine occurred in about 45 min with 3 x 10(-10) M 3H-methyl scopolamine. The dissociation constant for 3H-methylscopolamine was 6.8 x 10(-10) M and saturation occurred at 109 pm/g protein. The I.C. 50 for 3H-methylscopolamine inhibition of carbachol-induced amylase secretion was 7 x 10(-10) M.

Amylases↗

How informed is informed consent? The BHAT experience.

In the Beta-blocker Heart Attack Trial (BHAT) a number of strategies were implemented to increase the probability of informed voluntary consent among survivors of an acute myocardial infarction. To evaluate the subjects' comprehension of the study, a bioethicist conducted in-depth home interviews with a random sample of 64 participants from 11 geographic areas. The great majority of respondents proved to be well informed about the study design, its scientific logic, and possible risks of the experimental drug. However, five subjects (8% of the sample) appeared to believe they were involved in a therapeutic program rather than a research project. The analysis of predictor variables indicates that education, race, and age were associated with the degree of respondent awareness of fundamental aspects of the trial.

Adrenergic beta-Antagonists↗

The effects upon blood coagulation in dogs of experimentally induced pancreatitis and the infusion of pancreatic juice.

The coagulation changes observed in acute experimental pancreatitis were compared with those after the intravenous infusion of pancreatic juice and ascitic fluid exudate obtained from bile-induced pancreatitis in dogs. The coagulation changes after acute pancreatitis was induced by the intraductal injection of autologous bile, trypsin or elastase showed decreased platelet counts, decreased plasma fibrinogen levels, prolonged partial thromboplastin and prothrombin times, shortened euglobulin clot lysis time and increased fibrin degradation products. Multiple microemboli were observed in the lung and, occasionally, in the kidney, an indication of consumption coagulopathy. The effects upon blood coagulation after the intravenous injection of pancreatic juice included decreased platelet counts, decreased plasma fibrinogen levels and prolonged partial thromboplastin and prothrombin times. The intravenous injection of pancreatic exudate produced greater changes than did those of an equal amount of pancreatic juice. There was a shortening of euglobulin clot lysis time and a marked increase in fibrin degradation products. Pancreatic exudate which accumulates during acute pancreatitis may contain a toxic substance or substances which contribute to the consumption of coagulation factors during acute pancreatitis.

Acute Disease↗

The contribution of pancreas and kidney in regulating serum amylase levels in dogs.

Amylase activity in canine serum before and after total pancreatectomy with or without additional removal of duodenum and other small intestines were determined and resulted that pancreas would provide approximately fifty per cent of amylase detected in the canine serum. Serum amylase levels were also measured before and after intravenous injection of canine pancreatic juice as a source of pancreatic amylase into normal or nephrectomized dogs in order to investigate the mode of disappearance of amylase from circulating blood and following result was obtained that intravenously injected amylase were removed from the blood of extraurinary mechanism in dogs.

Amylases↗

Fat necrosis.

Fat necrosis has been found to be associated with many forms of pancreatitis, carcinoma of the pancreas and pancreatic trauma. The causative agents seem to be pancreatic lipase and colipase, which presumably escape from the pancreas during the development of the disease. The precise mechanism by which these factors attack the adipose tissue, leading to the formation of foci of fat necrosis, is not known. The pathologic finding of fat necrosis is not restricted to the peritoneal-retroperitoneal region, where a direct contact with these factors is the most likely cause. In other patients, fat necrosis involves peripheral tissues, notably in subcutaneous adipose tissue throughout the body, in joints of the hand and foot and in bone marrow. This is associated with additional complications dependent upon the sites involved and is manifested as skin lesions, polyarthritis and osteolytic defects in patients who sometime suffer from a primary pancreatic disease.

Acute Disease↗

Lipase and colipase in canine pancreatic juice as etiologic factors in fat necrosis.

Lipase and colipase have been purified to homogeneity from canine pancreatic juice. The purity of the lipase and colipase preparations was established by acrylamide gel electrophoresis. Either lipase or colipase alone did not produce fat necrosis when injected intraperitoneally into mice. Fat necrosis was seen only when both lipase and colipase were used together. Selective removal of lipase from fresh canine pancreatic juice by immunoprecipitation with an antilipase specific antiserum also eliminated its fat necrotizing activity. Together, these results identify the fat necrotizing factors to be pancreatic lipase and colipase. Their uncontrolled release during acute pancreatitis is believed to constitute the cause of fat necrosis. The absolute amount of lipolytic activity was not found to be the crucial factor in the induction of fat necrosis. It is suggested that the colipase molecule may have other functions besides enhancing the lipolytic activity of purified lipase in causing fat cell necrosis.

Animals↗

The disintegration of surgical sutures on exposure to pancreatic juice.

The loop-breaking strength of various suture materials was tested over a period of 14 days during which time the sutures were incubated in vitro in saline or canine serum, bile, activated or nonactivated pancreatic juice. Under the conditions of the study, silk and nylon maintained their strength in each environment. Polyglycolic acid maintained its strength in saline, bile or serum, but gradually lost much of its strength when exposed to pancreatic juice. Catgut, both plain and chromic, disintegrated almost completely within 24-48 hours respectively when exposed to enterokinase activated pancreatic juice. Inhibition of trypsin by aprotinin (Trasylol) resulted in preservation of catgut strength but inhibition by soybean inhibitor did not. The latter findings suggest that proteolytic enzymes, other than trypsin, may be responsible for the disintegration.

Animals↗