An investigation of the interaction between isoniazid and the contraceptive steroid norethindrone in vivo

Summary Isonicotinic acid hydrazide (isoniazid) was shown to react readily with 17-ethinyl-17-hydroxyestr-4-en-3-one (norethindrone) to form the isonicotinyl hydrazone of the steroid under conditions likely to exist in the stomach. The hydrazone was detected in guinea-pig, but not rat, plasma following its oral administration. Rat liver tissue metabolized the compound more rapidly than guinea-pig liver in vitro which probably accounts for the failure to detect the hydrazone in rat plasma.     

仓鼠妊娠期瘦素分泌及其调节机制

对妊娠期瘦素的分泌及其调节机制进行探讨. 将100只3月龄雌性金黄仓鼠分成16组, 每组6~7只, 每天采血样用于测定其妊娠期的瘦素分泌. 实验结果表明, 瘦素于妊娠第9天开始显著升高, 于妊娠第12天达到高峰. 为验证不同生殖阶段的血清是否对瘦素分泌有不同影响, 将不同生殖阶段抽提与未抽提类固醇激素的血清加入培养液中进行培养, 发现动情期及妊娠期的血清均可刺激体外培养的脂肪细胞瘦素分泌, 动情期抽提与未抽提类固醇激素的血清对脂肪细胞瘦素分泌的刺激作用没有显著差异(P > 0.05). 与动情期血清相比, 妊娠中后期未抽提类固醇激素的血清显著刺激脂肪细胞瘦素分泌(P < 0.01). 但妊娠中后期的血清在抽提类固醇激素后对瘦素分泌的刺激作用显著下降, 与动情期的血清对瘦素分泌的刺激作用已没有显著差异(P > 0.05). 妊娠不同阶段未抽提类固醇激素的血清对瘦素分泌的刺激作用有很大差异, 妊娠第15天的血清对瘦素分泌的刺激作用显著高于妊娠第8天(P < 0.0001)和妊娠第12天(P < 0.001)的血清. 体外研究进一步表明, 肾上腺皮质素、孕酮以及胰岛素均能刺激瘦素分泌, 而雌激素却能抑制体外瘦素分泌. 研究结果提示, 妊娠期血液类固醇激素水平的上升是引起妊娠期瘦素峰出现的重要因素.     

A high-resolution environmental change record since 19 cal ka BP in Pumoyum Co,southern Tibet

A 380-cm-long sediment core was acquired from the deep water area of Pumoyum Co, southern Tibet. Twenty-five plant residue samples were selected, and organic carbon stable isotopes were obtained using the AMS ¹⁴C chronological method. The ¹⁴C age and carbon reservoir effect were calibrated with surface sedimentation rate measurements using ²¹⁰Pb dating. Results showed that the core sediment deposited over 19 cal ka BP. Based on a multi-proxy analysis of TOC and IC contents, grain size and pollen assemblage data, the palaeoclimatic evolution of Pumoyum Co was reconstructed since the last glacial. Pumoyum Co was a shallow lake prior to 16.2 cal ka BP; although the glacier around the lake began to melt due to increasing temperatures, climate was still cold and dry. In the interval of 16.2–11.8 cal ka BP, the sedimentary environment fluctuated drastically and frequently. Two cold-events occurred at 14.2 and 11.8 cal ka BP, and these may correspond to the Older Dryas and the Younger Dryas events, respectively. After 11.8 cal ka BP, Pumoyun Co developed into the deep lake as it is now. The lake water temperature was relatively lower at that time because of influx of cold water from glacial meltwater entering the lake. As a result, the multi-proxy indicators showed no sign of warm conditions. Comparisons between the sedimentary record of Pumoyum Co with that of other lakes of the same age in southern Tibet indicate a warmer climate following the last deglaciation influenced the southeastern Tibetan Plateau. These results imply that the southwest Asian monsoon gradually became stronger since the deglaciation during its expansion to the inner plateau. The glacial-supplied water of the lake responded sensitively to cold-events. The entire southern Tibet region was dominantly influenced climatically by the southwest Asian monsoon during the Holocene.     

A morphometric study of spermatogenesis in the testes of mice of a senescence accelerated strain

The morphometric parameters of spermatogenic cells in a mouse strain prone to accelerated senescence (SAM-P), a novel murine model of spontaneously promoted aging, were compared with those of a SAM resistant strain (SAM-R) after birth until 40 weeks (mean life span of SAM-P). A mixture of gonocytes and spermatogonia were present in the testis in 1-week-old mice, and no gonocytes were observed in 2-week-old mice. At 6 weeks of age, the absolute number of spermatogonia in SAM-P was 27% greater than that in SAM-R, whereas the cell number in 40-week-old SAM-P was 17% less than in SAM-R. Primary spermatocytes were first observed in 3-week-old animals, and the cell numbers in SAM-P at 3, 5 and 6 weeks were 78%, 31% and 25%, respectively, greater than in SAM-R, whereas the cell number in SAM-P at 40 weeks was 30% less than SAM-R. Round spermatids were first observed in all SAM-P at 4 weeks old, but 20% of SAM-r had no spermatids and the rest had only a few. At 5 and 6 weeks old, the absolute numbers of round spermatids in SAM-P was about 34% and 41%, respectively, greater than in SAM-R, whereas the cell number in 40-week-old SAM-P was about 34% less than SAM-R. These results indicate that testicular maturation begins at an earlier age in SAM-P than SAM-R. Furthermore, at the age of 40 weeks signs of testicular deterioration are evident in SAM-P mice only     

Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin

When stimulated with antigen, B cells are influenced by T cells to proliferate and differentiate into antibody-forming cells. Since it was reported that soluble factors could replace certain functions of helper T cells in the antibody response, several different kinds of lymphokines and monokines have been reported in B-cell growth and differentiation. Among these, human B-cell differentiation factor (BCDF or BSF-2) has been shown to induce the final maturation of B cells into immunoglobulin-secreting cells. BSF-2 was purified to homogeneity and its partial NH2-terminal amino-acid sequence was determined. These studies indicated that BSF-2 is functionally and structurally unlike other known proteins. Here, we report the molecular cloning, structural analysis and functional expression of the cDNA encoding human BSF-2. The primary sequence of BSF-2 deduced from the cDNA reveals that BSF-2 is a novel interleukin consisting of 184 amino acids.     

Bottom water warming in the North Pacific Ocean

Observations of changes in the properties of ocean waters have been restricted to surface or intermediate-depth waters, because the detection of change in bottom water is extremely difficult owing to the small magnitude of the expected signals. Nevertheless, temporal changes in the properties of such deep waters across an ocean basin are of particular interest, as they can be used to constrain the transport of water at the bottom of the ocean and to detect changes in the global thermohaline circulation. Here we present a comparison of a trans-Pacific survey completed in 1985 (refs 4, 5) and its repetition in 1999 (ref. 6). We find that the deepest waters of the North Pacific Ocean have warmed significantly across the entire width of the ocean basin. Our observations imply that changes in water properties are now detectable in water masses that have long been insulated from heat exchange with the atmosphere.     

Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity

Elucidating the signalling mechanisms by which obesity leads to impaired insulin action is critical in the development of therapeutic strategies for the treatment of diabetes. Recently, mice deficient for S6 Kinase 1 (S6K1), an effector of the mammalian target of rapamycin (mTOR) that acts to integrate nutrient and insulin signals, were shown to be hypoinsulinaemic, glucose intolerant and have reduced beta-cell mass. However, S6K1-deficient mice maintain normal glucose levels during fasting, suggesting hypersensitivity to insulin, raising the question of their metabolic fate as a function of age and diet. Here, we report that S6K1-deficient mice are protected against obesity owing to enhanced beta-oxidation. However on a high fat diet, levels of glucose and free fatty acids still rise in S6K1-deficient mice, resulting in insulin receptor desensitization. Nevertheless, S6K1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from S6K1 to insulin receptor substrate 1 (IRS1), which blunts S307 and S636/S639 phosphorylation; sites involved in insulin resistance. Moreover, wild-type mice on a high fat diet as well as K/K A(y) and ob/ob (also known as Lep/Lep) mice-two genetic models of obesity-have markedly elevated S6K1 activity and, unlike S6K1-deficient mice, increased phosphorylation of IRS1 S307 and S636/S639. Thus under conditions of nutrient satiation S6K1 negatively regulates insulin signalling.     

A neural correlate of response bias in monkey caudate nucleus

Primates are equipped with neural circuits in the prefrontal cortex, the parietal cortex and the basal ganglia that predict the availability of reward during the performance of behavioural tasks. It is not known, however, how reward value is incorporated in the control of action. Here we identify neurons in the monkey caudate nucleus that create a spatially selective response bias depending on the expected gain. In behavioural tasks, the monkey had to make a visually guided eye movement in every trial, but was rewarded for a correct response in only half of the trials. Reward availability was predictable on the basis of the spatial position of the visual target. We found that caudate neurons change their discharge rate systematically, even before the appearance of the visual target, and usually fire more when the contralateral position is associated with reward. Strong anticipatory activity of neurons with a contralateral preference is associated with decreased latency for eye movements in the contralateral direction. We conclude that this neuronal mechanism creates an advance bias that favours a spatial response when it is associated with a high reward value.