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Biomedical subjects

R S Bush

Publications and source records attributed to R S Bush.

At least 73 records · Page 4Linked to original sources

Evidence for separate enzymes of pyruvate decarboxylation and pyruvate synthesis in soluble extracts of Clostridium pasteurianum.

Additional evidence to that already presented (Sauer, F. D., Bush, R. S., and Stevenson, I. L. (1976) Biochim. Biophys. Acta 445, 518-520) suggests that pyruvate-ferredoxin oxidoreductase isolated from Clostridium pasteurianum consists of two separate enzymes: (a) pyruvate lyase, which catalyzes the CoA and electron acceptor-dependent decarboxylation of pyruvate, and (b) pyruvate synthase, which catalyzes the reduced ferredoxin-dependent carboxylation of acetyl-CoA to pyruvate. The enzymes separated on Sephadex G-200 and with acrylamide gel electrophoresis but complete separation of one enzyme free of the other was not achieved. Extensive purification procedures were not used because both enzymes are unstable. The results confirm published reports that pyruvate lyase contains thiamin and a chromophore which participates in electron transfer. Pyruvate synthase, however, did not appear to be a thiamin enzyme and there was no evidence to indicate participation of an enzyme chromophore in the pyruvate synthase reaction.

Carboxy-Lyases↗

Treatment of epithelial carcinoma of the ovary: operation, irradiation, and chemotherapy.

This paper presents an interim analysis of 279 patients with epithelial carcinoma of the ovary who were entered into a prospective study started in April, 1971. One hundred and three patients were available for analysis three years after diagnosis. Apart from the survival differences by stage and treatment method, this study has shown that the completeness of the initial pelvic operation, in Stages II and III, is of greater prognostic importance than the stage. The importance of the features of the pelvic disease which interfere with the removal of all pelvic organs led the authors to conclude that factors other than stage should be considered in prescribing postoperative treatment. To date, the disease-free survival trends in Stages IB, II, and asymptomatic Stage III show that physicians should place much greater emphasis on the initial operative features when they are seeking the most effective combination of irradiation and chemotherapy. Analysis of failures shows that upper abdominal irradiation is more effective than daily chlorambucil in preventing progression of disease to that area. However, early evidence indicates that chlorambucil added to pelvic irradiation improves the control of pelvic disease. Improved methods of treatment have not yet been identified for early Stage I (IA) and advanced presentations (symptomatic Stages III and IV).

Abdomen↗

A quantitative measurement of peritoneal drainage in malignant ascites.

With a two-compartment model, a method is described for quantitative determination of peritoneal drainage rates in malignant ascites. Data on twenty-four patients are presented and comparison is made with the qualitative assessment of the integrity of diaphragmatic and mediastinal lymphatics on the basis of lymphoscintigrams. It is concluded that flow rates less than 50 ml/hour are usually associated with abnormalities of the diaphragmatic and mediastinal lymphatics, indicating that tumor permeation of these structures is a significant contributing factor to persistent, intractable ascites in patients with malignant diseases.

Ascites↗

The separation of pyruvate-ferredoxin oxidoreductase from Clostridium pasteurianum into two enzymes catalyzing different reactions.

The ferredoxin requiring cleavage of pyruvate to acetyl-CoA and CO2 is catalyzed by pyruvate ferredoxin oxidoreductase (pyruvate:ferredoxin oxidoreductase (CoA-acetylating):, EC 1.2.7.1). The same enzyme is thought to catalyze the reversal of this reaction, i.e. the synthesis of pyruvate from acetyl-CoA and CO2 in the presence of reduced ferredoxin. Evidence is presented that the forward and reverse reactions are catalyzed not by one, but by two proteins that are clearly separable by Sephadex G-200 gel filtration.

Clostridium↗

Enzymes of 2-oxo acid degradation and biosynthesis in cell-free extracts of mixed rumen micro-organisms.

The enzymes of 2-oxo acid decarboxylation and 2-oxo acid synthesis (EC 1.2.7.1 and EC 1.2.7.2) were isolated and partially purified from cell-free extracts of rumen micro-organisms. The lyase was active with pyruvate, 3-hydroxypyruvate and 2-oxobutyrate. The synthase was active with acetate, 2-oxoglutarate or succinate. Pyruvate synthase was separated from pyruvate lyase by Sephadex G-200 gel filtration. With Sephadex filtration, approximate mol.wts. of 310000 and 210000 were determined for pyruvate lyase and pyruvate synthase respectively.

Acetoin↗

Placenta-like alkaline phosphatase in gynecological cancers.

In 302 patients with tumors of the cervix, corpus uteri, and ovaries, assessment by clinical staging (tumors-nodules-metastasis system) (4) and histopathology has been related to the presence of serum heat-stable, placenta-lide alkaline phosphatase (PLAP) activity. Early stages of cervical tumors show the highest incidence of this isoenzyme. In advanced stages of this disease, a decrease in frequency was observed that might be interpreted as the result of gradual dedifferentiation of the tumor cells to a point where synthesis of PLAP became undetectable. The same observation was made in adenocarcinomas of the corpus uteri, i.e., patients with advanced disease tended to have the lowest incidence of serum PLAP. Only in cancers of the ovaries did we find a positive correlation between this enzyme marker and the extent of the disease. In more than one-third of the patients examined, PLAP levels were an index of the tumor burden.

Adenocarcinoma↗

Radiation injuries to the bowel associated with the treatment of carcinoma of the cervix.

Advances in radiation techniques and increased dosage have improved the cure rate of patients with cancer of the cervix to 65 percent. Associated with this increased dosage (betatron, 5,250 r and intracavitary 137-cesium, 4,000 r at point A) has been a serious complication incidence of 10 percent. Major intestinal complications usually become manifest within an 8 to 24 month period following radiation. Few are associated with tumor and the majority are amenable to surgical correction. Rectosigmoid stenosis is a common and frequently unrecognized complication. The 8 to 12 cm. segment of rectosigmoid, with its rigid wall and narrowed lumen, can be recognized on barium examination. The symptoms are those on incomplete obstruction and deterioration, frequently confused with tumor progression. Thirty-one patients have been treated by resection and low anterior anastomosis with relief of symptoms. Rectosigmoid stenosis progressing to necrosis, perforation, or fistula (an additional 29 patients) is treated best by the Hartmann operation as a first stage. This procedure has been less complicated than either colostomy alone or resection and anastomosis. Fifteen patients with low level rectovaginal fistula or stenosis were treated by defunctioning sigmoid colostomy. A loop transverse colostomy was unsatisfactory. Ileorectovaginal fistulas occurred in an additional six patients. Preoperative investigation should establish the presence or absence of an ileal component in all fistulas. Radiation ileitis is rare as an isolated finding but frequently is associated with severe rectosigmoid damage. Surgical treatment is seldom necessary but, if indicated (ten patients), resection appears to be preferable to bypass.

Colectomy↗

The relationship between mouse arterial partial pressure of oxygen (PaO2) and the effectiveness of localized tumour irradiation.

The effectiveness of localized X-irradiation on the transplantable KHT sarcoma was investigated while the host mice breathed gas mixtures ranging from 5% O2 : 95% N2 to 100% O2. Subcutaneous tumours in the flank of C3H mice anaesthetized with Nembutal (sodium pentobarbitol), Valium (diazepam), or urethane, were irradiated with doses of 1,500 or 2,500 rads and the delay in days for the tumours to grow from 4 to 10 mm in diameter was determined. Measurements of the arterial partial pressure of oxygen (PaO2) were made under conditions identical to the irradiation experiments. For PaO2 values less than 100 mm Hg (animals breathing air), growth delay decreased linearly, while for PaO2 values greater than 100 mm Hg, growth delay increased and reached a plateau at a PaO2 between 200 and 300 mm Hg, (animals breathing congruent to 50% O2). This relationship holds for the two doses and the three anaesthetics studied, and indicates the importance of investigating the Pa02 levels of patients undergoing radiotherapy treatment.

Animals↗

Clinical trials with new radiation modalities.

I would suggest that the investigation of a new clinical modality involves a major commitment by the whole clinical group of the department involved and not just by the people chosen to be the primary investigators. As a base for comparison, it requires a detailed knowledge of the results and sites of failures and complications of the therapy used by that department. To make adequate relative biologic effect studies for the new modality, suitable comparative, quantitative tissue and tumor assays have to be done with photons and these could be done and established before the new modality came on line. For the Phase III trial, which is usually considered a randomized comparative trial, it can be argued (and a method is proposed) for the use of a non-randomized study to make the maximum use of patients coming to the centre.

Clinical Trials as Topic↗