Retrospective survey of the clinical significance of cytosolic oestrogen receptor status in 287 patients with primary breast cancer.
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Biomedical subjects
Publications and source records attributed to J Levin.
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Blood clotting in Limulus is dependent on the activity of a proteinase which converts the zymogen, coagulogen, into a form that undergoes polymerization to form the clot. The abilities of a series of recently discovered endogenous proteinase inhibitors to inhibit this enzyme and thereby serve as potential regulators of its activity were explored. The blood plasma of Limulus contains a single inhibitor that is functionally and structurally homologous to vertebrate alpha 2 macroglobulin. During exocytosis, the blood cells (amebocytes) release a series of inhibitors, including small quantities of the alpha 2 macroglobulin homologue; a low molecular weight, acid-and heat-stable inhibitor; and an acid acid-labile activity. Of the three inhibitory activities, only the cell-released, acid-labile inhibitor is capable of inhibiting the clotting enzyme.
Clotting enzyme activity was detected in lysates prepared from the coelomocytes of Asterias forbesi following incubation with endotoxin-activated Limulus amebocyte lysate. This activity was not detected in the cell-free coelomic fluid. The enzymatic activity from the sea star lysate hydrolyzed the synthetic substrate S2222 but not S2238 or S2251, and polymerized partially purified Limulus clottable protein. The clotting enzyme activity was not detected following treatment of the sea star cell lysate with endotoxin or with the clotting enzyme from Limulus lysate. The enzymatic activity, generated in sea star cell lysate by the activated Limulus lysate, was inhibited by the addition of benzamidine; and its effect was suppressed with rabbit anti-sera directed against Asterias whole cell lysate, but not with anti-sera directed against the previously reported Sea Star Factor.
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A patient data storage and retrieval system has been developed for a microcomputer used in a nuclear medicine department. The advantages of coding clinical information and the problems encountered in coding are highlighted. The application of the stored patient data is briefly discussed.
A clotting enzyme, associated with the endotoxin-mediated activation of the cellularly based coagulation system of the American horseshoe crab (Limulus polyphemus), was considerably purified by a modification of the method employed to purify the corresponding enzyme from the Japanese horseshoe crab (Tachypleus tridentatus) (Nakamura, et al., 1982). This enzyme was inhibited by DFP, benzamidine, p-aminobenzamidine, antithrombin III, soybean trypsin inhibitor, and antipain, suggesting that it is a trypsin-type serine protease. The enzyme demonstrated amidolytic activity to Ac-Ile-Glu-Gly-Arg-pNA (S-2423) and related synthetic substrates (S-2222, S-2422, S-2337, and Boc-Leu-Gly-Arg-pNA) but not to other substrates (S-2160, S-2238, S-2251, S-2444, S-2266, and S-2302), indicating specificity similar to mammalian blood coagulation Factor Xa. These properties of the Limulus enzyme were identical with those of the corresponding Tachypleus enzyme. The structure and function of the enzymes in these two species probably have been highly conserved during the past few hundred million years of their evolution.
A case is described in which technetium-99m-di-isopropyl-iminodiacetic acid imaging was used to trace the passage of bile from its site of leakage into an amoebic liver abscess, through a fistulous tract connecting the liver abscess with an abscess in the right lower lobe of the lung, and into the upper respiratory tract.
The requirements for factor VIII (AHF) or factor IX (PTC) of hemophilic patients undergoing dental extractions were evaluated to determine the minimum effective regimen. Sixteen patients underwent 19 operative procedures. The mean total dose of factor VIII or IX was 45.8 U/kg for 11 procedures with preoperative replacement therapy and 34.5 U/kg for the 8 without. Four patients received no replacement therapy at all. Our results compared favorably to published studies employing factor replacement alone or in combination with antifibrinolytic agents such as epsilon-amino-caproic acid (EACA), with respect to blood products utilized and duration of hospitalization. However, our patients received less factor replacement than usually suggested. General anesthesia with intubation, a common recommendation, was not required in any patients. Dental extractions can be carried out in hemophiliacs using less replacement therapy than currently recommended. In some circumstances, no replacement therapy may be necessary. The reported efficacy of antifibrinolytic agents in reducing the requirement for replacement therapy is difficult to assess because of the relatively large amount of prophylactic factor replacement used in conjunction with these agents.
N-Nitrosobis(2-oxopropyl)amine (BOP), N-nitrosobis(2-hydroxypropyl)-amine (BHP) and N-nitroso(2-hydroxypropyl-2-oxopropyl)amine (HPOP) are pancreatic carcinogens in the Syrian golden hamster (SGH) but do not cause pancreatic tumors in rats. In this study, the ability of these three compounds to induce DNA damage in isolated pancreas cells from both species was determined by alkaline elution analysis. BOP was highly potent in SGH cells, causing DNA damage at concentrations as low as 0.5 micrograms/ml, and HPOP, although less potent than BOP, also caused considerable damage. Isolated SGH pancreas cells are thus able to metabolize BOP and HPOP to DNA-damaging species. Of the three compounds tested, only HPOP at higher doses (25-100 micrograms/ml) induced DNA damage in isolated rat pancreas cells. BHP did not damage rat or SGH pancreas cell DNA at concentrations up to 100 micrograms/ml, apparently due to lack of uptake of this compound by the cells. The observed insensitivity to DNA damage in rat cells is consistent with the resistance of the rat pancreas to carcinogenesis by these three compounds. The sensitivity of SGH pancreas cells to BOP- and HPOP-induced DNA damage correlates with the high carcinogenicity of these compounds for the SGH pancreas.
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Twenty of 22 patients with tuberculous hepatitis had abnormal Tc-99m tin colloid liver scans. However, in the majority of the patients the changes were mild and nonspecific. The most frequent scintigraphic picture was a decreased uptake of the radiocolloid by the liver, with shunting to the spleen and bone marrow. The decreased hepatic uptake was usually mildly heterogeneous, but it was sometimes homogeneous, and in five patients obvious defects were present. The liver was enlarged in six patients and the spleen in six patients. Increased extrahepatic uptake of the radiocolloid was the only abnormality in five patients. The severity of the scintigraphic changes did not correlate with the following histologic findings: number of granulomas, degree of associated fibrosis, degree of hepatocyte swelling, or extent of fatty change.
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Twenty-four-hour mean plasma concentrations of estradiol, estrone, testosterone, LH and FSH were measured in 6 men with typical alcoholic liver cirrhosis and in 17 age-matched controls. Plasma estradiol levels were markedly elevated in the cirrhotic patients, as has been reported before. Plasma levels of estrone, testosterone and LH did not differ significantly from normal. The most striking finding was marked elevation of the plasma FSH level: the mean value in the cirrhotic group was 19.5 mIU/ml (95% confidence limits, 13-29), more than twice the mean control value, 9.7 mIU/ml (95% confidence limits, 7.0-13) (p less than 0.0005). This consistent elevation of FSH in cirrhotic men may be due to a deficient testicular secretion of inhibin as a result of alcohol toxicity to the testes.
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Previous studies have demonstrated functional and histologic abnormalities of the liver, and, more recently, splenomegaly in patients with hemophilia. Since these observations usually were derived from hemophiliacs who had received intensive replacement therapy, the question was posed as to whether the frequency of splenic and hepatic abnormalities was secondary to the amount of therapy utilized. In this study, a variety of tests were employed to evaluate spleen and liver size and function to determine if abnormalities in these organs correlated with the intensity of the transfusion program. The study group was comprised of 25 hemophiliacs (mean factor replacement-18,361 U/year; median factor replacement-12,920 U/year). Over 70% of our patients had elevations of aspartate and alanine aminotransferase. Immunoglobulin and complement levels were normal in most subjects. Ninety-six percent had evidence of exposure to hepatitis B virus. Liver-spleen imaging suggested significant hepatic abnormalities in most of the patients as evidenced by inhomogeneity of tracer uptake in the liver in 33% and relatively increased colloid uptake in the spleen in 90%. Splenomegaly (palpable spleen or enlargement on liver-spleen imaging) was detected in 40% of our patients, and tended to occur in the more frequently transfused patients. These findings indicate that significant abnormalities of the spleen and liver can occur in hemophiliacs who have received moderate amounts of replacement therapy and that liver-spleen imaging may be a useful method for monitoring the development of hepatic and splenic abnormalities.
To evaluate the effect of thyroid function on the in vivo cortisol in equilibrium cortisone (F in equilibrium E) equilibrium, double-labeled cortisol tracer techniques were used to measure separately the rates of the F leads to E and E leads to F reactions in 4 euthyroid, 2 hypothyroid, and 2 hyperthyroid subjects. The rate of the F leads to E reaction was calculated from the appearance rate of 3H in body water after the i.v. injection of [11 alpha-3H]-cortisol; the rate of the E leads to F reaction was calculated from the difference in the plasma turn-over rates of [11 alpha-3H]-cortisol, and [4-14C]-cortisol after simultaneous i.v. injection of both tracers; the F in equilibrium E set-point was calculated by dividing the F leads to E rate by the E leads to F rate. In euthyroid subjects the F leads to E reaction rate averaged 1.6%/min, the E leads to F reaction rate averaged 1.0%/min, and the F in equilibrium E set-point averaged 1.6. In hyperthyroid subjects the two reaction rates were supranormal: the F leads to E rate averaged greater than or equal to 3.9%/min and the E leads to F rate averaged 1.54%/min; since the increase in the F leads to E rate was proportionally greater, the F in equilibrium E set-point (average greater than or equal to 2.6) was displaced towards cortisone. In hypothyroid subjects both reaction rates were equally slowed, to an average of 1.0%/min (F leads to E) and 0.68%/min (E leads to F); the F in equilibrium E set-point averaged 1.65, the same as in euthyroid subjects. Displacement of the F in equilibrium E equilibrium towards cortisone in hyperthyroid subjects appears to account for their elevated urinary THE/THF ratios, but the normal F in equilibrium E set-point in hypothyroid subjects makes it necessary to invoke a different mechanism for their depressed THE/THF ratio; it is suggested that increased conversion of THE to cortoic acids may be the responsible factor.
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