Resident's view of the autopsy.
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Biomedical subjects
Publications and source records attributed to M S Murthy.
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Intravascular bronchiolo-alveolar tumor (IVBAT) is a rare and highly distinctive pulmonary tumor of disputed cellular nature. Both epithelial and endothelial differentiation of this neoplasm have been suggested. We have studied multiple nodules of IVBATs from three patients by light and electron microscopy and by immunohistochemical methods for Factor VIII-related antigen (FVIII RAG). Our light and ultrastructural studies are in essential agreement with the previous suggestion of the endothelial nature of the neoplasm and our demonstration of the presence of FVIII RAG in many of the tumor cells offers new evidence strongly supportive of their endothelial differentiation. We believe that IVBAT and a group of extrapulmonary tumors described as epithelioid hemangioendothelioma and endovascular papillary angioendothelioma are similar biologically indolent neoplasms of epithelioid and dendritic endothelial cells characterized by stromal sclerosis, intravascular spread, a low incidence of metastases and slow clinical evolution. Thus, we regard IVBAT as a low-grade sclerosing angiosarcoma of the lung.
Chronic vitamin B6 deficiency in male rats, 1, 2 and 3 months of age, led to increases in the activities of liver glycolate oxidase and kidney glycolate dehydrogenase as compared to pair-fed controls. Lactate dehydrogenase activity either decreased or showed no change in all three age groups. It is postulated that hyperoxaluria observed in vitamin B6 deficiency is due to two different pathways operative in the liver and kidney separately. A general increase seen in the enzyme activities of livers and kidneys of B6-deficient and pair-fed rats was age related.
Twelve recurrent stone formers with hyperoxaluria were administered pyridoxine-HCl (10 mg/day) daily for a period of 180 days. The pyridoxine status of the patients, as assessed by their erythrocyte transaminase activation indexes, improved significantly (p less than 0.001) after 180 days of supplementation as compared with the basal levels. Although urinary oxalate decreased significantly (p less than 0.05) by the 90th day of pyridoxine therapy, other parameters, e.g., urinary calcium, phosphorus, and creatinine, remained unaltered. Significant correlation was observed between erythrocyte glutamate pyruvate transaminase (EGPT) or erythrocyte glutamate oxaloacetate transaminase (EGOT) activation index and urinary oxalate excretion (p less than 0.01). Pyridoxine in low doses (10 mg/day) is of therapeutic value for hyperoxaluric stone formers.
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A mechanism for quality assurance in surgical pathology based on a review of the surgical pathology reports is described. The setting up of performance standards by the participating pathologists before the institution in quality assurance helped in acceptance of the critique of the reviewer. Suggestions are made to improve the quality of the surgical pathology report by incorporating the needs of th surgeons and oncologists, in the hope that the quality assurance process becomes oriented to patients care.
Thomsen-Friedenreich (T) antigenic specificity as determined with human serum anti-T was found in reactive form in breast adenocarcinomata but not in healthy and generally not in benign breast tissues. T-antigenic specificity was demonstrable in all metastatic breast carcinoma lesions. T specificity was also present in adeno- and squamous cell carcinomata from other organs; it was not found in the four melanomata, one glioblastoma, and seven benign non-breast tumors. Breast carcinoma patients but not healthy people showed cellular immunity to T antigen in vivo and in vitro. Most striking was the delayed-type cutaneous hypersensitivity reaction that was positive in over 85% of the ductal breast carcinoma patients tested, negative in over 94% benign breast disease patients, and in all presumably healthy individuals investigated. T antigen is readily available from healthy red blood cells in uncontaminated form, and free of HL-A and Australia antigens.
The genetic activity of AF-2 in both bacteria and yeast rapidly disappeared in the presence of rat-liver microsomal fraction (S9 mix). Incubation of AF-2 with S9 mix even for 10 min at 37 degrees C was sufficient to inactivate it completely. Data available in the literature suggest that activation of AF-2 is necessary for its geno-toxic effect. The activation step may involve reduction of the nitrofuran to an amino group probably by the enzyme reductase I. Most cultured cell systems, such as bacteria, yeast, Neurospora, mammalian cells and human lymphocytes, can probably bring about this reduction. However, the rapid disappearance of the genetic activity of AF-2 in the presence of rat-liver homogenate suggests that rat-liver microsomes may further metabolize the reduction products to inactive forms. Thus, it becomes necessary to test even those chemicals that are mutagenic per se, with mammalian microsomal preparations before their mutagenic/carcinogenic potentialities can be assessed in short-term tests.
One intradermal (i.d.) injection of human erythrocyte T antigen in the upper outer arm contralateral to any breast lesion elicits a delayed tuberculin-type hypersensitivity reaction (DTH) in breast carcinoma patients. It is necessary to inject simultaneously but separately the same quantity of MN antigen (about 6--8 cm apart), from which the T Antigen has been prepared, since particularly patients with Stage I breast carcinoma (Internatl. nomenclature) and those with benign breast disease may significantly react to it. The extent of reaction to MN antigen must be subtracted from the reaction to T antigen before interpreting results. DTH response to T antigen was 85% accurate among 67 patients with ductal breast carcinoma of all Stages (including non-invasive), 95% accurate (5% so far falsely positive) among 95 patients with benign breast disease and it was 100% accurate (no false positives) among 36 "healthy" persons tested. Among 18 patients with the comparatively rare and less ominous lobular and tubular breast carcinomata, the DTH reaction was positive in 8 of 16 (50%) patients with lobular, and in none of 2 patients with tubular breast carcinoma.
Blood group NM specificities occur in healthy, benign and carcinomatous breast glands and those of the gastrointestinal (G.I.) tract, but the precursors in their biosynthesis, T (Thomsen-Friedenreich) and Tn, are found in adenocarcinomata and not in benign or healthy tissues. T- and Tn-antigenic specificities are thus human carcinoma-associated. All humans possess anti-T and anti-Tn antibodies. Patients with breast or G.I. tract carcinoma show statistically significant alteration of anti-T titer levels when compared to patients with benign disease and to healthy controls. Breast carcinoma patients but not healthy people showed cellular immunity to T antigen in vitro and in vivo. Most striking was the delayed-type hypersensitivity reaction, which was positive in over 90% of ductal breast carcinoma patients tested and negative in all presumably healthy individuals. T antigen is readily prepared from healthy human red blood cells in uncontaminated form, and free of HL-A and Au antigens. T antigen and anti-T antibodies may be useful in combating some human adenocarcinomata.
More than 200 chemicals, comprising drugs, pesticides, herbicides, industrial chemicals, food additives, etc. tested by various workers for their ability to induce gene conversion in diploid yeast, have been reviewed. This review shows that a strong correlation exists between the convertogenic and mutagenic abilities of these chemicals. This conclusion confirms the earlier one by Zimmermann which was based on fewer mutagenic chemicals. Published data have further been analysed to confirm quantitatively Zimmermann's other important conclusion that gene conversion is not mutagen-specific. This is a positive advantage in using gene conversion in preliminary screening of chemicals because it reduces the chances of false negatives.
12 permitted food colours in use were screened for geno-toxicity. Mitotic gene conversion in Saccharomyces cerevisiae was used as the end-point. Each food colour was tested in stationary-phase as well as log-phase cells but without microsomal activation. These food colours did not cause any increase in mitotic gene conversion in diploid yeast BZ 34.
Inactivation of diploid yeast by hyperthermia has been studied. DO and Dq decrease with temperature for euoxic and anoxic conditions. The Arrhenius plot shows a break at 52 degrees C; the inactivation energies above and below this temperature are 153 and 94kcal/mol respectively. Hyperthermia (20 min at 51 degrees C) also potentiates the lethal action of gamma rays in diploid yeast cells under both euoxic and anoxic conditions. The interaction between hyperthermic and radiation damage appears to be largely at the sublethal level. The euoxic cells, the hyperthermic potentiation decreases with increasing time between the application of hyperthermia and radiation, being completely lost after 24 hours. However, in the anoxic cells there was no decrease in the hyperthermic potentiation with increasing time interval. These results suggest that yeast cells are capable of repairing hyperthermic sublethal damage, but require oxygen to do so. Thus there is a similarity in the process of repair of sublethal damage caused by ionizing radiation on the one hand and hyperthermia on the other.
The lethal response of a diploid yeast strain BZ34 to densely ionizing radiations from the reaction 10B(n, alpha)7 Li was studied. The values for relative biological effectiveness (r.b.e.) and oxygen enhancement ratio (o.e.r.) for this radiation compare favourably with the data obtained with charged particles on the same strain of yeast. Recovery from potentially lethal damage was also studied by post-irradiation holding under non-nutrient conditions. In order to understand the role of oxygen in the recovery process, the investigation covered the following treatment regimens: (a) aerobic irradiation and aerobic holding (A-A), (b) aerobic irradiation and hypoxic holding (A-H), (c) hypoxic irradiation and hypoxic holding (H-H) and (d) hypoxic irradiation and aerobic holding (H-A). It has been found that the presence of oxygen is essential for recovery from the damage induced by both gamma rays and high linear energy transfer (LET) radiations. The extent of recovery was larger for gamma-induced damage than for damage induced by high LET radiation (alpha + 7Li) for the A-A condition. In the H-H condition, while only a slight recovery was seen for gamma-induced damage, it was totally absent for high LET damage. For the modality A-H, it was found that there is not recovery from the sparsely ionising gamma radiation-induced damage. The implications of these results for the treatment of malignant tumours by radiotherapy are briefly discussed.
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