Multiple primary tumors in a 72-year-old woman.
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Biomedical subjects
Publications and source records attributed to P Ray.
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A case is presented of a patient with separate primaries of the cervix, breast, bladder, and kidney. In a review of 352,073 cancer patients in the literature, the genitourinary system appears to be at a greater risk of this phenomenon. The entity of multiple primary malignant neoplasms is reviewed with an analysis of the involvement of the genitourinary system.
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Various cryoprotective agents [glycerol, dimethylsulphoxide, polyvinylpyrrolidone (PVP 40)], all dissolved in Krebs phosphate medium were tested for their effects on cytoplasmic preservation in oligodendroglia isolated from bovine white matter sorted at -30 degrees C. Of these agents, only PVP 40 (15% wt/vol) produced a significant improvement in recovery of oligodendroglial cytoplasm compared with untreated frozen brain. Cels isolated after PVP 40 pretreatment contained levels of membrane-bound enzymes similar to those found in cells isolated from fresh white matter. There was however, some loss of soluble protein. Studies of galactocerebroside synthesis in neuronal and oligodendroglial perikarya have shown that the glial cells contain ceramide galactosyltransferase at much higher specific activity than the neurones.
A series of 205 patients with inoperable, non-oat cell carcinoma of the lung were treated with three different dose-fractionation schedules. Fifty-six patients received 5000 rads in 25 fractions over five weeks (continuous, A); 79 patients received 2000 rads in five fractions over five days, with two weeks' rest, followed by 2000 rads in five fractions over five days (split-course, B); 70 patients received 3000 rads in 10 fractions over two weeks, followed by three weeks' rest and another 3000 rads (split course, C). The 24-month survival was 33% for A, 15% for B and 25% for C. The split course was better tolerated and radiation fibrosis was dose-related.
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Evaluation of regional node involvement in patients with bronchogenic carcinoma is a crucial step in determining therapy and prognosis. Mediastinoscopy has been recommended for staging all potentially operable cases, but technical limitations and the need for anesthesia make this impractical. Gallium-67 scanning and chest radiography were prospectively compared as noninvasive means of evaluating spread to regional nodes in 75 patients with bronchogenic carcinoma in whom histologic evaluation of hilar and mediastinal nodes was performed. Gallium scanning was more accurate than chest radiography in assessing regional nodes (overall accuracy 85.3% vs. 56%, P less than 0.05). When positive, both procedures correctly indicate malignant involvement of regional nodes (85% vs. 87.3%). A negative gallium scan, however, was significantly more accurate in predicting the absence of such involvement (80% vs. 40%, P less than 0.01). Gallium scanning appears to be a reliable, noninvasive means of assessing mediastinal spread of bronchogenic carcinoma and when used in conjunction with radiographic findings, allows selection of appropriate patients for surgical staging procedures.
Since August 1975, 69 patients with localized pancreatic carcinoma (extent of tumor confined to a 15 cm x 15 cm radiotherapy port) have received either Regimen A, comprising radiotherapy (6,000 rad) to the tumor area with simultaneous combination chemotherapy utilizing methyl-CCNU, 125 mg/m2 orally, every six weeks, and 5-fluorouracil, 400 mg/m2 intravenously, weekly; or Regimen B, comprising Regimen A with the addition of testolactone, 200 mg, orally every day. Thirty-eight patients on Regimen A and 30 patients on Regimen B are currently evaluable. Median survival, which appeared not to be affected by the addition of testolactone, was 38 weeks for those on Regimen A and 30 weeks for those on Regimen B (P = 0.677). The median survival time for all patients was 38 weeks. Good performance status did correlate with improved survival vs. poor performance status (46 weeks vs. 20 weeks, P = .008). Fifteen patients have survived for more than 52 weeks, with the longest survival time being 160 + weeks, and in 3 cases all therapy has been discontinued. However, most patients experienced moderate to severe hematologic toxic reactions. There was one treatment-related death and significant gastrointestinal bleeding developed in 6. Because of the toxic reactions of this program, it should not be considered in favor of similar less aggressive programs.
The mean number of lymphocytes, response to phytohemagglutinin (PHA), and response to concanavalin A (Con A) in whole-blood cultures for 106 patients with head and neck cancer were 83%, 73%, and 64%, respectively, of values for healthy control individuals. During radiotherapy, lymphocyte counts declined to 44% and PHA and Con A responses declined to about one third of control values. Lymphocyte counts slowly increased after treatment to 77% of control values after two years, but responses to mitogens remained at about 40%. Responses to PHA and Con A for 38 patients who lived beyond 18 months were significantly greater before and after treatment than responses for 39 patients who died within 18 months. In general, a poor pretreatment response to PHA and Con A correlated with a poor clinical course, whereas responses near the control level indicated a good clinical course.
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Microtubules from the cow adrenal cortex and brain were purified by three cycles of the temperature-dependent polymerization-depolymerization procedure. Whereas tubulin comprised approximately 8--10% of soluble brain protein, it comprised only 0.5-1.0% of the soluble adrenocortical protein. The partially purified tubulin from both sources gave similar results in the following studies: (1) [3H]colchicine binding examined by Scatchard analysis revealed an apparent Ka of 1 . 10(6) M-1 and a colchicine/tubulin molar binding ratio of 0.4-0.6; (2) tyrosylation studies using a specific tubulin-tyrosine ligase (which adds a tyrosine residue to the C-terminal glutamate or glutamine of the alpha-chain) in conjunction with carboxypeptidase A (which recovers the tyrosine) and (3) amino acid analysis. Examination of protein bands, in addition to the tubulin doublet of 55 000 molecular weight, on sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a difference between the two tubulin preparations. The adrenocortical preparation had protein bands corresponding to apparent molecular weight of 36 000, 60 000, and 68 000. In contrast the brain preparation had only proteins of molecular weights greater than 200 000 (these bands were absent in all adrenal preparations). It would thus appear that if proteins which copurify with tubulin through repeated cycles of polymerization-depolymerization play a role in either microtubule formation or function there is a distinct difference between neural and non-neural tissue.
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The role of cytoplasmic microtubules in the process of steroidogenesis was examined in enzyme-dispersed and mechanically dispersed adrenocortical cells obtained from adult male rats. These cells were maintained in culture for periods of 2 h to 2 days and tested with various antimicrotubular drugs as well as ACTH and N6,O2-dibutyryl adenosine 3',5'-monophosphoric acid [(Bu)2cAMP]. The drugs tested, viz. colchicine, vinblastine, and nocodazole, were found to stimulate steroid synthesis in a dose-dependent fashion; the maximal degree of stimulation was found to be the same as that obtained with either ACTH or (Bu)2cAMP. When a maximal concentration of an antimicrotubular drug was mixed with a maximal concentration of either (Bu)2cAMP or ACTH, no additive effect on steroidogenesis was observed. The mixture of maximal concentrations of two antimicrotubular drugs produced a steroidogenic response that was less than when either drug was used alone. However, when submaximal concentrations of two antimicrotubular drugs were mixed, a synergistic response was noted. These antimicrotubular drugs are known to interfere with microtubular function by binding to specific sites on the tubulin protomer and inhibiting normal polymerization. Lumicolchicine, the photoinactivated form of colchicine, does not bind to tubulin and did not stimulate steroid synthesis. These studies support the notion that microtubules can influence the process of steroidogenesis.
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