Human chorionic gonadotrophin-beta gene sequences in women with disorders of HCG production

Women with recurrent abortion, primary unexplained infertility, and gestational trophoblastic neoplasia (GTN) manifest disordered human chorionic gonadotrophin (HCG) secretion. Mutations in the HCG beta/luteinizing hormone (LH) beta gene complex could cause aberrant HCG production in these disorders. The purpose of this study was to determine whether HCG beta gene deletions occur in women with recurrent abortion or primary unexplained infertility, and whether HCG beta gene duplications are present in women with GTN. DNA was extracted from 10 patients with unexplained recurrent abortion, 10 patients with unexplained primary infertility, 12 patients with GTN, three partners of women with GTN, and 30 controls. Southern blots were constructed and hybridized with DNA probes for HCG beta-5 and the LH beta gene. No gene deletions were identified in patients with recurrent abortion or primary unexplained infertility. Likewise, no gene duplications were identified in women with GTN. A previously described Mbol restriction fragment length polymorphism (RFLP) was identified in both patients and controls. A new Pstl RFLP was also characterized, but was present in patients and controls. Deletion/duplication mutations in the HCG beta/LH beta gene complex do not appear to be common causes of aberrant HCG production in humans with these disorders.      

Trisomy 16鼠结肠和人先天性巨结肠蛋白基因产物9.5的表达

目的：研究Ｄｏｗｎ’ｓ 综合征动物模型ｔｒｉｓｏｍｙ １６ 结肠神经系发育和先天性巨结肠（ＨＤ） 病变肠管蛋白基因产物９－５（ｐｒｏｔｅｉｎ ｇｅｎｅ ｐｒｏｄｕｃｔ９ ．５ ,ＰＧＰ９－５） 的神经表达。方法：Ｔｒｉｓｏｍｙ １６ 鼠培育;细胞遗传学分析;Ｔｒｉｓｏｍｙ １６ 鼠结肠和ＨＤＰＧＰ９－５ 免疫组织化学。结果：（１）Ｔｒｉｓｏｍｙ １６ 鼠结肠神经系发育异常,肌间神经丛发育迟缓,粘膜下神经丛缺失,结肠末端有５ ｍｍ 的无神经节区,但结肠系膜神经发育良好;（２）ＨＤ狭窄段肠管ＰＧＰ９－５ 阳性神经纤维大量增生,神经节细胞缺如。结论：（１）Ｔｒｉｓｏｍｙ １６ 鼠具有稳定的遗传学特征,可能伴先天性巨结肠。（２） 由于ＨＤ 狭窄段肠管神经节细胞缺失,增生的ＰＧＰ９－５ 阳性神经纤维是肠道外源性神经的代偿,对其神经元的性质尚有待确定。（３）ＨＤ有遗传倾向     

Comparative immunolocalization studies of collagenase 1 and collagenase 3 production in the rheumatoid lesion, and by human chondrocytes and synoviocytes in vitro

The degradation of fibrillar type II collagen is a major feature of cartilage destruction in rheumatoid arthritis (RA). Since collagenase 3 is produced by chondrocytes and preferentially degrades type II cartilage collagen, it seemed likely that this enzyme would have a prominent role in the destruction of rheumatoid joints. Using immunolocalization techniques, we have examined and compared the production and distributions of collagenase 1 and collagenase 3 in cells and tissues derived from rheumatoid knee arthroplasties. Primary cultures of chondrocytes stimulated with interleukin-1 beta showed that most of the cells produced collagenase 1, whereas only a minority (approximately 5-10%) produced collagenase 3; a few chondrocytes demonstrated the co-ordinate production of both enzymes. Primary cultures of rheumatoid synoviocytes produced collagenase 1, but not collagenase 3. Both enzymes were demonstrated in the rheumatoid lesion. Collagenase 1 was more commonly observed in both synovium and cartilage (22 of the 28 specimens), was especially prominent at cartilage erosion sites, and most of the positive specimens demonstrated extracellular enzyme. By contrast, collagenase 3 was observed less frequently (7/28 specimens) and was produced by relatively few chondrocytes and synovial cells, this usually being much less than that observed for chondrocytes of osteoarthritic cartilage. These observations suggest different regulatory mechanisms for the production of collagenases 1 and 3 in the rheumatoid lesion, and demonstrate that the distribution and production of collagenase 1 are far more prevalent than those for collagenase 3.      

Hereditary hemolytic anemia caused by diverse point mutations of pyruvate kinase gene found in Japan and Hong Kong

We identified four distinct point mutations in homozygous pyruvate kinase (PK) variants in Japanese and Chinese patients with chronic nonspherocytic hemolytic anemia. All gene abnormalities were missense mutations that caused single amino acid substitutions. 1261A (Q421K) and 1436A (R436H), which were identified in PK Sendai and PK Shinshu, had been found in unrelated Japanese and Amish PK variants, respectively. The clinical severity and extremely low residual erythrocyte PK activity of PK Shinshu as well as of the Amish PK might be caused partly by aberrant splicing, because the 1436A mutation changes a nucleotide at the last nucleotide in the exon 10. Recently, we diagnosed a 42-year-old Japanese woman with chronic nonspherocytic hemolytic anemia as having a homozygous PK deficiency. DNA sequencing of the variant PK gene showed a homozygous missense mutation at 1403GCT- ->GTT, resulting in a single amino acid substitution from 468la-->Val. The gene mutation is likely to impair the allostericity of this enzyme, speculated from the tertiary structure. A homozygous missense mutation in PK Hong Kong, a boy of a non-Han southern Chinese minority group, was identified in exon 7 of the human L-PK gene, 941ATT-->ACT, resulting in a single amino acid substitution from 314lle-->Thr. The R- PK activity is expected to be severely affected, because the mutated amino acid residue is located between the 313 Lys and the 315 Glu, which are very important for acid-base catalysis and magnesium binding, respectively. Both the R- and M2-type PK were shown by polyacrylamide gel electrophoresis of the PK Hong Kong erythrocyte lysate, and this is the first report of a homozygous individual whose erythrocytes contain the immature (M2)-type isozyme.     

Patients’ preference for radiotherapy fractionation schedule in the palliation of symptomatic unresectable lung cancer†

The palliative radiotherapeutic management of unresectable non‐small‐cell lung cancer is controversial, with various fractionation (Fx) schedules available. We aimed to determine patient’s choice of Fx schedule after involvement in a decision‐making process using a decision board. A decision board outlining the various advantages and disadvantages apparent in the Medical Research Council study of Fx schedules (17 Gy in two fractions vs 39 Gy in 13 fractions) was discussed with patients who met Medical Research Council eligibility criteria. Patients were then asked to indicate their preferred Fx schedules, reasons and their level of satisfaction with being involved in the decision‐making process. Radiation oncologists (RO) could prescribe radiotherapy schedules irrespective of patients’ preferences. Of 92 patients enrolled, 55% chose the longer schedule. English‐speaking patients were significantly more likely to choose the longer schedule (P = 0.02, 95% confidence interval: 1.2–7.6). Longer Fx was chosen because of longer survival (90%) and better local control (12%). Shorter Fx was chosen for shorter overall treatment duration (80%), cost (61%) and better symptom control (20%). In all, 56% of patients choosing the shorter schedule had their treatment altered by the treating RO, whereas only 4% of patients choosing longer Fx had their treatment altered (P < 0.001). Despite this, all (100%) patients were satisfied with being involved in the decision‐making process. The decision board was useful in aiding decision‐making, with both Fx schedules being acceptable to patients. Interestingly, despite the longer average survival associated with longer Fx, nearly half of the patients believed that this was not as important as a shorter duration of treatment and lower cost. Despite patients’ preferences, there were significant alterations of preferred schedules because of RO’s own biases.     

Humoral immune response to an allogenic foetus in normal fertile women and recurrent aborters

Background  

Several humoral immune factors are responsible for a successful pregnancy. There are a few studies, which demonstrate the role of antipaternal cytotoxic antibodies (APCA) and mixed lymphocyte reaction blocking factor (MLR-Bf) in the maintenance of pregnancy. However, these factors have not been studied in women with history of recurrent spontaneous abortion (RSA). We designed this study to review the role of APCA and MLR-Bf in normal pregnancy as well as in women with a history of RSA.     

氯屈膦酸二钠合成工艺改进

目的：对氯屈膦酸二钠的合成工艺进行了研究。方法：以二溴甲烷和亚膦酸三异丙酯为原料,经缩合,氯化,热裂解和成盐反应得到氯屈膦酸二钠。结果：合成产物的化学结构经元素分析,红外光谱,质谱和核磁共振谱确证,总收率为60．3％。结论：此合成路线是完全可行的。