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D N Foster

Publications and source records attributed to D N Foster.

84 records · Page 5Linked to original sources

Stigmata of recent haemorrhage in diagnosis and prognosis of upper gastrointestinal bleeding.

In 277 consecutive episodes of suspected upper gastrointestinal bleeding, lesions bearing stigmata of recent haemorrhage (stigmata) were found by endoscopy in 110 (47%) out of 233 patients who were judged to have bled; 78 (33%) had lesions without stigmata, and in 45 (19%) no lesion was seen. Results in 176 entirely unselected admissions for upper gastrointestinal bleeding were similar.Forty-eight chronic duodenal and 41 chronic gastric ulcers were identified by endoscopy. Stigmata were found in 27 (56%) and 33 (80%) of these cases respectively. Sixteen patients had multiple lesions, and in 12 (75%) the presence of stigmata permitted diagnosis of the source of the haemorrhage. Stigmata were more likely to be seen in cases of duodenal ulcer, Mallory-Weiss lesions, and oesophageal varices when endoscopy was performed within 12 hours of bleeding, but were as common in cases of gastric ulcer after longer intervals.In the absence of stigmata one out of 21 patients with duodenal ulcer had further haemorrhage and one other needed emergency surgery; no patient with gastric ulcer had further haemorrhage or needed emergency surgery. In contrast, when stigmata were present 15 of the 27 patients with duodenal ulcer (56%) had further haemorrhage and 17 (63%) needed emergency surgery; of the 33 patients with gastric ulcer, 10 (30%) had further haemorrhage and 15 (45%) required emergency surgery. Superficial mucosal lesions may have been the source of haemorrhage when an ulcer unmarked by stigmata was seen at endoscopy. Stigmata were superior to any other single factor or combination of factors in predicting rebleeding and the need for emergency surgery.

Duodenal Ulcer↗

Hepatofugal portal blood flow in hepatic cirrhosis.

A variety of indirect techniques has been claimed to provide evidence of spontaneous reversal of portal blood flow in hepatic cirrhosis but the existence of the phenomenon has been doubted by some who do not accept the validity of the indirect evidence. There are few reports of the demonstration of hepatofugal portal flow by selective hepatic arteriography, which is the only acceptable technique. We report three patients with histologically confirmed cirrhosis in whom hepatofugal portal blood flow was unequivocally demonstrated by arteriography, in whom no surgical portosystemic shunt had been performed and in whom there was no evidence of the Budd-Chiari Syndrome or hepatoma, situations accepted as associated with reversed portal blood flow. Theoretical considerations suggest that shunt surgery for bleeding esophageal varices should not be ruled out on the grounds of hepatofugal portal flow. However, end-to-side portacaval anastomosis and distal splenorenal shunt might predispose to the early redevelopment of esophageal varices when reversed portal flow is present. Side-to-side portacaval and conventional splenorenal shunts might be preferable in having less effect on hepatic parenchyma perfusion than when orthograde portal flow in the case.

Adult↗

DNA synthesis and DNA polymerase activity in Leydig cells of diethylstilbestrol-stimulated mouse testes.

Using a modification of the collagenase dispersion method of Dufau et al., we examined changes in DNA synthesis produced by estrogens in the interstitial cells of mice that develop malignant Leydig cell tumors after prolonged estrogen administration. Previous work in cryptorchid mice indicated that during continuous estrogen administration [3H]thymidine incorporation into DNA rises to a maximum in 3 to 4 days and then falls to approximately base levels within 2 to 3 weeks. This was confirmed both in Leydig cell concentrates of estrogen-treated mice after either injection with [3H]thymidine or incubation with [3H]thymidine in vitro. This DNA synthesis was blocked by hydroxyurea. DNA synthesis in cells of estrogen-treated BALB/c mice of the Huseby substrain, which have a high incidence of Leydig cell tumors, was 5 to 11 times that in untreated controls. Cells from estrogen-treated C3H/Bi mice, which have a low incidence of Leydig cell tumors, showed only a 2- to 3-fold increase. In the Huseby substrain the rise of DNA synthesis is a peak and subsequent recession were paralleled by a rise and fall in DNA polymerase alpha activity. DNA polymerase beta did not show this variation. In C3H/Bi mice, neither polymerase showed significant change. The evidence suggests that the early estrogen-stimulated DNA synthesis is probably replicative and is associated with increased DNA polymerase alpha activity.

Animals↗

Nuclear location of mammalian DNA polymerase activities.

Nuclei were isolated from monolayer cultures of mouse and human cells using a nonaqueous procedure of cell fractionation in which lyophilized cells were homogenized and centrifuged in 100% glycerol. In previous work we have shown that the nuclear pellet and cytoplasmic supernatant fraction contained 10% or less of the nucleic acids characteristic of the other cell fraction. Aqueous extracts made from fresh cultures and from nonaqueous material at each step of the fractionation procedure were assayed fro DNA polymerase activity. Activities were normalized to DNA contents of extracted material. Specific activity was preserved quantitatively through freezing and drying the cells, but was found to be unstable in glycerol suspensions with approximate half-lives and 1 h at 23 degrees and 4 h at 0-4 degrees. Activities were relatively stable at -25 degrees, however, so that by homogenizing only 15 min at 4 degrees and centrifuging at -25 degrees we preserved approximately 85% of the specific activity of fresh cultures in the nonaqueous nuclear fraction. Sedimentation analyses showed that the nuclear fraction contained both DNA polymerase-alpha and-beta in approximately the proportions expected if all polymerase activities were confined to the nucleus in living cells. DNA polymerase-alpha was found to be more unstable in glycerol suspensions than DNA polymerase-beta. Nuclear location of both activities was found in exponential cultures and in 3T3 mouse cultures synchronized in the G1 and S phases of the cell division cycle. We found no evidence for cytoplasmic factors affecting nuclear polymerase activities. We have concluded that the two major DNA polymerases are nuclear although one, DNA polymerase-alpha, frequently is present as a weakly bound nuclear protein.

Cell Division↗

Diagnosis of Mallory-Weiss lesions. A common cause of upper gastrointestinal bleeding.

Mallory-Weiss lesions were considered to be the source of bleeding 21 (13.4%) of 157 unselected patients admitted to a general medical unit because of suspected upper gastrointestinal haemorrhage over a period of 30 months. They represented 16.7% of the 126 patients in whom there was ultimately good evidence of upper gastrointestinal blood-loss. In the total series of 200 suspected bleeding episodes the incidence was 11.5%. It is suggested that endoscopy of the upper gastrointestinal tract, peformed as early as possible after resuscitation, enables the diagnosis of the Mallory-Weiss lesion to be made, shows that it is a relatively common source of haemorrhage, and establishes whether bleeding has stopped, thereby helping to identify patients who can be managed without transfusion and those who are likely to require surgery.

Adult↗

Mapping of the growth hormone gene by in situ hybridization to chicken chromosome 1.

In situ hybridization of a tritium-labeled chicken growth hormone cDNA to 62 chicken metaphase chromosome spreads was examined by analysis of silver grain distribution. A total of 554 chromosomally located grains were recorded. There was a highly significant P value for the association of silver grains to the long arm of chromosome 1. The chicken growth hormone gene can be assigned to chromosomal G-band region 1q4 because 41.3% of silver grains on chromosome 1q were located in this region.

Animals↗

Reproductive tract secretions and bull spermatozoa contain different clusterin isoforms that cluster cells and inhibit complement-induced cytolysis.

Clusterin from bull rete testis fluid (RTF), cauda epididymal fluid (CEF), and octyl-beta-D-glucopyranoside extract of cauda epididymal sperm (CES) was identified and characterized using monoclonal and polyclonal antibodies (Abs) developed against ram clusterin and a beta-subunit-specific oligopeptide of porcine clusterin. One-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blotting showed that bovine RTF clusterin had dimeric and monomeric molecular weights (M(r)s) of approximately 94 kDa and of 42 and 43 kDa, respectively. Clusterin in CEF and CES had similar dimeric M(r)s (74 kDa). Reduced CEF clusterin appeared as three monomers (M(r)=40, 39, and 38 kDa), whereas reduced CES clusterin appeared only at M(r)40 kDa. Enzymatic deglycosylation resulted in similar M(r)s of clusterin from RTF, CEF, and CES. The M(r) of RTF clusterin decreased from 94 kDa to 51 kDa, indicating a carbohydrate content of 45%. After deglycosylation, the M(r) of the CEF clusterin decreased from 74 kDa to two distinct bands at 51 and 50 kDa (with carbohydrate contents of 31 and 32%, respectively), suggesting that two isoforms of the heterodimeric protein are present because of the two isoforms of the alpha-subunit. Under nonreduced conditions, a beta-subunit-specific Ab reacted with M(r) of 36-38 kDa, indicating the existence of free clusterin beta-subunits in CES. RTF, CEF, and CES extracts all caused mouse fibroblastic L-cell aggregation. CEF cell aggregation was inhibited by Hyb-17 Ab but not by other Abs. Both RTF and CEF caused a dose-dependent inhibition of complement-induced cytolysis, although RTF clusterin was more potent than CEF clusterin. We conclude that several isoforms of clusterin occur in the bull reproductive tract and that the variation in carbohydrate content among these isoforms may affect the biological or functional activity of the protein.

Animals↗

Localization of clusterin on freeze-preserved bull spermatozoa before and after glass wool-sephadex filtration.

Clusterin is a major protein in bull reproductive tract secretions and sperm membrane extract. A polyclonal antibody was produced against clusterin from bull cauda epididymal fluid (CEF) and used for the localization of the protein on bull spermatozoa. Immunoblotting of unreduced bovine samples showed that the anticlusterin antibody reacted with a protein of approximately 94- to 100-kd in rete testis fluid (RTF), a approximately 57- to 76-kd protein in CEF, and with a approximately 57- to 60-kd protein from cauda epididymal sperm membrane extract. The antibody also reacted with stallion RTF and both ram CEF and RTF at relative molecular weights (Mr) that were consistent with the anticipated size of clusterin in these species. Less intense immunostaining was observed for a protein of about 2 times the predicted size of clusterin in unreduced ovine RTF, suggesting the presence of multimers of clusterin in ovine RTF. Also, a dimeric clusterin-sized protein was detected in reduced bovine CEF, suggesting the presence of unprocessed clusterin in bovine CEF. By immunofluorescence, clusterin was detected on only a small fraction of bull spermatozoa, which were morphologically abnormal. Neither permeabilization nor the method of dilution affected the reactivity of the antibody with spermatozoa (P > .05). Average clusterin-positive spermatozoa (CPS) in unpermeabilized, permeabilized, abruptly diluted, and gradually diluted semen were 10.1%, 11.3%, 15.0%, and 14.4%, respectively. CPS were eliminated from semen after filtration through glass wool-Sephadex (GWS) columns. Average CPS in unfiltered and filtered semen were 14.3% and 1.1%, respectively. We conclude that sperm clusterin in bull semen is associated with morphologically abnormal spermatozoa and that clusterin is implicated in the process of abnormal spermatozoa trapping in GWS columns. We suggest that the fraction of CPS in bull semen is a potential marker for poor semen quality.

Animals↗