Profound radiosensitivity in "leukemic" T-cell lines and T-cell-type acute lymphoblastic leukemia demonstrated by sodium [51Cr]chromate labeling.

Radiation sensitivity was determined by measuring spontaneous release from 51Cr-labeled cells in various lymphoid cell populations. Among six leukemia T-cell lines originating from acute lymphoblastic leukemia, four such lines were found to be highly radiosensitive. In contrast, two of the leukemic T-cell lines and four normal control B-cell lines were not radiosensitive. Thymocytes from six patients and leukemia T-cell blasts from three patients with T-cell leukemia were likewise found to be highly radiosensitive, whereas leukemic blasts from six patients with null-cell (non-T, non-B-cell) acute lymphoblastic leukemia were not radiosensitive. Normal peripheral blood lymphocytes and mitogen-induced normal lymphoblasts were found not to be radiosensitive. The results indicate that measurement of the radiation sensitivity of acute leukemic blasts may have a therapeutic significance in coping with the heterogeneous nature of individual leukemia cases.     

An outbreak of hypervitaminosis D associated with the overfortification of milk from a home-delivery dairy.

OBJECTIVES. The purpose of the study was to identify cases of hypervitaminosis D caused by the inadvertent overfortification of milk from a home-delivery dairy and to identify risk factors for this illness. METHODS. Hospital discharge, laboratory, and state health department data were used to define, identify, and describe cases of hypervitaminosis D diagnosed in the exposed communities between January 1, 1985, and June 30, 1991. To identify disease risk factors, community-based sex- and age-matched controls were used in a case-control study. RESULTS. Of the 56 case patients identified, at least 41 were hospitalized; 2 died. The study included 33 case patients and 93 control subjects. Nineteen of the 33 case patients had been customers of the implicated dairy. Risk of illness rose with increasing consumption of the dairy's milk and was also associated with vitamin D supplement use, sunburn susceptibility, and cancer history. Accounting for these factors did not alter the association between drinking the dairy's milk and developing hypervitaminosis D. CONCLUSIONS. Overfortification of milk with vitamin D can lead to hypervitaminosis D, manifested by severe illness and death. The episode highlights the need for monitoring the fortification process and enforcing the upper limit for vitamin D addition to milk.     

3,5-甾二烯化合物的合成及抗早孕活性

以18-甲基-17β-羟基-17α-乙炔基-雌甾-4-烯-3-酮(18-甲基炔诺酮),17β-羟基-17α-乙缺基-雌甾-4-烯-3-酮(炔诺酮),17β-羟基-17α-乙炔基-雄甾-4-烯-3-酮(妊娠素)和17a-羟基孕甾-4-烯-3,20二酮(17α-羟基黄体酮)为原料,经NaBH,还原、脱水、双键转位和酯化等反应合成一系列3,5-甾二烯化合物,用¹HNMR和MS证明了它们的结构。动物筛选结果表明,17β-丙酰氧基-17α-乙炔基-雌甾-3,5-二烯(IV_b2有明显的抗早孕活性。中断早期妊娠的作用似与其雌激素活性有关。     

羧烷基化合成萘普生工艺改进

１－溴－２－甲氧基萘与０－对在苯磺酰乳酸乙酯（１）在无水氯化铝催化下化Ｆｒｉｅｄｅｌ－Ｃｒａｆｔｓ反应，还原脱溴直接合成ｄｌ－１ａ萘普生（３），以上反应均在“一锅”内完成，收率达９５。     

Desmoplastic fibroma of the proximal ulna

A young man presented with desmoplastic fibroma in the proximal ulna. This rare tumour was treated by curettage and bone grafting.     

Prostate Tumor Growth Can Be Modulated by Dietarily Targeting the 15-Lipoxygenase-1 and Cyclooxygenase-2 Enzymes

The main objectives of our study were to determine the bioavailability of omega-3 (ω-3) to the tumor, to understand its mechanisms, and to determine the feasibility of targeting the ω-6 polyunsaturated fatty acids (PUFAs) metabolizing 15-lipoxygenase-1 (15-LO-1) and cyclooxygenase-2 (COX-2) pathways. Nude mice injected subcutaneously with LAPC-4 prostate cancer cells were randomly divided into three different isocaloric (and same percent [%] of total fat) diet groups: high ω-6 linoleic acid (LA), high ω-3 stearidonic acid (SDA) PUFAs, and normal (control) diets. Tumor growth and apoptosis were examined as end points after administration of short-term (5 weeks) ω-3 and ω-6 fatty acid diets. Tumor tissue membranes were examined for growth, lipids, enzyme activities, apoptosis, and proliferation. Tumors from the LA diet-fed mice exhibited the most rapid growth compared with tumors from the control and SDA diet-fed mice. Moreover, a diet switch from LA to SDA caused a dramatic decrease in the growth of tumors in 5 weeks, whereas tumors grew more aggressively when mice were switched from an SDA to an LA diet. Evaluating tumor proliferation (Ki-67) and apoptosis (caspase-3) in mice fed the LA and SDA diets suggested increased percentage proliferation index from the ω-6 diet-fed mice compared with the tumors from the ω-3 SDA-fed mice. Further, increased apoptosis was observed in tumors from ω-3 SDA diet-fed mice versus tumors from ω-6 diet-fed mice. Levels of membrane phospholipids of red blood cells reflected dietary changes and correlated with the levels observed in tumors. Linoleic or arachidonic acid and metabolites (eicosanoid/prostaglandins) were analyzed for 15-LO-1 and COX-2 activities by high-performance liquid chromatography. We also examined the percent unsaturated or saturated fatty acids in the total phospholipids, PUFA ω-6/ω-3 ratios, and other major enzymes (elongase, Delta [Δ]-5-desaturase, and Δ-6-desaturase) of ω-6 catabolic pathways from the tumors. We observed a 2.7-fold increase in the ω-6/ω-3 ratio in tumors from LA diet-fed mice and a 4.2-fold decrease in the ratio in tumors from the SDA diet-fed mice. There was an increased Δ-6-desaturase and Δ-9 desaturase enzyme activities and reduced estimated Δ-5-desaturase activity in tumors from mice fed the SDA diet. Opposite effects were observed in tumors from mice fed the LA diet. Together, these observations provide mechanistic roles of ω-3 fatty acids in slowing prostate cancer growth by altering ω-6/ω-3 ratios through diet and by promoting apoptosis and inhibiting proliferation in tumors by directly competing with ω-6 fatty acids for 15-LO-1 and COX-2 activities.     

Blood lead concentrations in children and method of water fluoridation in the United States, 1988-1994

Some have hypothesized that community water containing sodium silicofluoride and hydrofluosilicic acid may increase blood lead (PbB) concentrations in children by leaching of lead from water conduits and by increasing absorption of lead from water. Our analysis aimed to evaluate the relation between water fluoridation method and PbB concentrations in children. We used PbB concentration data (n=9,477) from the Third National Health and Nutrition Examination Survey (1988-1994) for children 1-16 years of age, merged with water fluoridation data from the 1992 Fluoridation Census. The main outcome measure was geometric mean PbB concentration, and covariates included age, sex, race/ethnicity, poverty status, urbanicity, and length of time living in residence. Geometric mean PbB concentrations for each water fluoridation method were 2.40 microg/dL (sodium silicofluoride), 2.34 microg/dL (hydrofluosilicic acid), 1.78 microg/dL (sodium fluoride), 2.24 microg/dL (natural fluoride and no fluoride), and 2.14 microg/dL (unknown/mixed status). In multiple linear and logistic regression, there was a statistical interaction between water fluoridation method and year in which dwelling was built. Controlling for covariates, water fluoridation method was significant only in the models that included dwellings built before 1946 and dwellings of unknown age. Across stratum-specific models for dwellings of known age, neither hydrofluosilicic acid nor sodium silicofluoride were associated with higher geometric mean PbB concentrations or prevalence values. Given these findings, our analyses, though not definitive, do not support concerns that silicofluorides in community water systems cause higher PbB concentrations in children. Current evidence does not provide a basis for changing water fluoridation practices, which have a clear public health benefit.