Osteoporosis is characterized by low bone density, and osteopenia is responsible for 1.5 million fractures in the United States annually. 1 In order to identify regions of the genome which are likely to contain genes predisposing to osteopenia, we genotyped 149 members of seven large pedigrees having recurrence of low bone mineral density (BMD) with 330 DNA markers spread throughout the autosomal genome. Linkage analysis for this quantitative trait was carried out using spine and hip BMD values by the classical lod-score method using a genetic model with parameters estimated from the seven families. In addition, non-parametric analysis was performed using the traditional Haseman-Elston approach in 74 independent sib pairs from the same pedigrees. The maximum lod score obtained by parametric analysis in all families combined was + 2.08 (θ = 0.05) for the marker CD3D on chromosome 11q. All other combined lod scores from the parametric analysis were less than + 1.90, the threshold for suggestive linkage. Non-parametric analysis suggested linkage of low BMD to chromosomes 1p36 (Z max = + 3.51 for D1S450) and 2p23-24 (Z max = + 2.07 for D2S149). Maximum multi-point lod scores for these regions were + 2.29 and + 2.25, respectively. A third region with associated lod scores above the threshold of suggestive linkage in both singlepoint and multi-point non-parametric analysis was on chromosome 4qter (Z max = + 2.95 for D4S1539 and Z max = + 2.48 for D4S1554). Our data suggest the existence of multiple genes involved in controlling spine and hip BMD, and indicate several candidate regions for further screening in this and other independent samples.
Prostaglandin D synthase (PGDS) activity was detected in human seminal plasma (0.05-1.83 nmol/min per milligram protein). The enzyme was purified from human seminal plasma by immunoaffinity chromatography and found to be 27 kDa in size and N-glycosylated, similar to PGDS in the cerebrospinal fluid. The N-terminal amino acid sequence of 16 residues of the seminal enzyme, APEAQVSVQPNFQQDK, was identical to that of the cerebrospinal fluid PGDS. Although PGDS activity and the content determined by the immunoassay each highly varied in the seminal plasma, the concentration was significantly (p < 0.001) lower in the oligozoospermic group (2.47 +/- 0.51 microg/ml) than in the normozoospermic group (9.75 +/- 1.49 microg/ml). Prostaglandin (PG) D2 was detected in the seminal plasma (5.00 +/- 0.65 ng/ml) with a positive correlation to the PGDS concentration (p < 0.05). PGD2 was converted to the J series of PGs in the seminal plasma with a half-life of 6.5 h. Northern blot analysis revealed that mRNA for PGDS was expressed in the testis, prostate, and epididymis. Through immunohistochemistry, PGDS was localized in Leydig cells of the testis and in epithelial cells of the prostate and ductus epididymidis.
Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. SLPI transcripts in the cervical tissue were detected during the menstrual cycle by reverse transcription-polymerase chain reaction (RT-PCR). Western blot analysis revealed that the intensity of SLPI protein in cervical tissue in the ovulatory phase was stronger than in other phases. Immunohistochemistry using an anti-SLPI polyclonal antibody revealed positive staining in the epithelial cells of the endocervix. Western blot analysis also revealed that SLPI protein was present in the cervical mucus. Again the intensity of SLPI protein in the ovulatory phase was stronger than that in the follicular phase. The SLPI concentrations and SLPI/elastase ratios in the cervical mucus of women in the ovulatory phase were significantly higher than in the follicular and luteal phases. The SLPI and elastase concentrations in the cervical mucus were positively correlated. No significant difference was found in the SLPI serum concentrations of women during the menstrual cycle. These results suggest that production of SLPI from cervical epithelial cells during the ovulatory phase may be important for protection from the effects of elastase.
Uterine fundal pressure maneuver during the second stage of labor increased the risk of severe perineal laceration. The use of the maneuver must be cautioned and careful attention must be paid to its application.
We demonstrated that NBL was significantly shorter and BPD/NBL was significantly greater in the Japanese population than those in the white and black populations.
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