Treatment of mandibular prognathism.

Mandibular prognathism (MP) or skeletal Class III malocclusion with a prognathic mandible is one of the most severe maxillofacial deformities. Facial growth modification can be an effective method of resolving skeletal Class III jaw discrepancies in growing children with dentofacial orthopedic appliances including the chincup, face mask, maxillary protraction combined with chincup traction and the Fr?nkel functional regulator III appliance. Orthognathic surgery in conjunction with orthodontic treatment is required for the correction of adult MP. The two most commonly applied surgical procedures to correct MP are sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy. Both procedures are suitable for patients in whom a desirable occlusal relationship can be obtained with a setback of the mandible, and each has its own advantages and disadvantages. In bilateral SSRO, the intentional ostectomy of the posterior part of the distal segment can offer long-term positioned stability. This may be attributable to reduction of tension in the pterygomasseteric sling that applies force in the posterior mandible. While various environmental factors have been found to contribute to the development of MP, heredity plays a substantial role. The relative contributions of genetic and environmental components in the etiology of MP are unclear. The recent identification of the genetic susceptibilities to MP constitutes the first step toward understanding the molecular pathogenesis of MP. Further studies in molecular biology are needed to identify the gene-environment interactions associated with the phenotypic diversity of MP and the heterogenic developmental mechanisms thought to be responsible for them.     

Identifying Risk Drinking in Expectant Fathers

Abstract: Background: Identification of risk drinking in expectant fathers may be helpful as an important part of efforts to minimize maternal alcohol use, and as an opportunity to inform them about a problematic practice during a critical developmental stage for the couple. The purpose of this study was to evaluate the T‐ACE screening questionnaire, which asks about t olerance to alcohol, being a nnoyed by other's comments about drinking, attempts to c ut down, and having a drink first thing in the morning (“ e ye‐opener”), in the male partners of pregnant women who themselves were T‐ACE positive. Methods: Two hundred fifty‐four male partners were asked to complete the T‐ACE embedded in a health survey, the Alcohol Use Disorders Identification Test (AUDIT), and other questions about their alcohol use in the past 30 days when their pregnant partners had a median gestation of 11.5 weeks (T₁). After delivery, male partners again completed the T‐ACE and quantity‐frequency questions (T₂). The predictive ability of the T‐ACE and AUDIT was compared, using risk drinking (>4 drinks/day or >14 drinks/week) as the criterion standard. Results: A substantial minority of male partners had risk drinking, 31 percent at T₁ and 25 percent at T₂. Although the AUDIT was better than the T‐ACE as an independent predictor of risk drinking, the latter was most accurate when the tolerance threshold exceeded 2 drinks, the same established for pregnant women. The sensitivity (T₁ = 84.6%, T₂ = 82.8%) and specificity (T₁ = 43.8%, T₂ = 51.1%) of the T‐ACE at this threshold compared favorably with those of the AUDIT at the standard cut point of 8. Conclusions: The T‐ACE may be a practical way for clinicians to identify risk drinking in both pregnant women and expectant fathers. (BIRTH 33:2 June 2006)     

nm23-H1基因转染对人胆管癌细胞系QBC939体外浸润能力的影响

目的：探讨nm23-H1基因转染对人胆管癌细胞系QBC939体外浸润能力的影响。方法：将含有全长nm23-H1 cDNA的真核表达载体通过脂腩体法转染人胆管癌细胞系。结果：转染成功的QBC939细胞，其nm23-Hl基因的mRNA、蛋白表达明显增加，转染nm23-H1基因的胆管癌细胞体外浸润能力下降，穿越matrigel的细胞数明显低于亲本QBC939细胞，代表浸润能力的IV型胶原酶（MMP-9）分泌量下降。结论：nm23-Hl基因可以抑制胆管癌细胞的体外浸润能力。     

Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease

Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic GnRHa administration results in apparently complete persistent suppression of ovarian steroid secretion; 2) adrenal steroid secretion is not influenced directly or indirectly; and 3) its use may be helpful in the treatment of endometrial hyperplasia and ovarian androgen excess in women with PCO.     

No impact of repeated endoscopic screens on gastric cancer mortality in a prospectively followed Chinese population at high risk.

BACKGROUND: Gastric cancer (GC) is the leading cause of cancer deaths in China. Our study prospectively evaluated the impact of repeated endoscopic screens on GC mortality in a high-risk population in China. METHODS: Between 1989 and 1999, a population-based gastroscopic screening was conducted in 4,394 residents of Linqu County, China, a region with the highest rates of GC worldwide. Residents ages 35 to 64 years received initial gastroscopies with biopsies in 1989. Repeated endoscopies were performed in 1994 and 1999. Cancer occurrences and deaths were actively monitored throughout the entire period until July 2000. Mortality from GC was compared with expected values based on mortality rates obtained for Linqu in the 1990-1992 Chinese Cancer Mortality Survey. RESULTS: Between March 1989 and July 2000, 39,303 person-years were accumulated; 85 new GCs occurred, 29 (34.5%) were in early stage. Fifty-eight cases (68%) were identified at one of the screens. The number of observed deaths from GC (37) was close to the expected (36.8). The standardized mortality ratio was 1.01 (95% CI 0.72-1.37) for the entire cohort, 1.13 (95% CI 0.77-1.57) for males, and 0.65 (95% CI 0.26-1.32) for females. CONCLUSIONS: Despite high population coverage with repeated screens, no reduction in GC mortality was observed in this high-risk population in China.     

Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases.

Serine hydroxymethyltransferase (SHMT) provides activated one-carbon units required for the biosynthesis of nucleotides, protein, and methyl group by converting serine and tetrahydrofolate to glycine and N(5),N(10)-methylenetetrahydrofolate. It is postulated that SHMT activity is associated with the development of methotrexate resistance and the in vivo activity of SHMT is regulated by the binding of N(5)-CHO-THF, the rescue agent in high-dose methotrexate chemotherapy. The aim of this study is to advance our understanding of the folate-mediated one-carbon metabolism in zebrafish by characterizing zebrafish mitochondrial SHMT. The cDNA encoding zebrafish mitochondrial SHMT was cloned, overexpressed in Escherichia coli, and purified with a three-step purification protocol. Similarities in structural, physical, and kinetic properties were revealed between the recombinant zebrafish mitochondrial SHMT and its mammalian orthologs. Surprisingly, leucovorin significantly inhibits the aldol cleavage of serine catalyzed by zebrafish cytosolic SHMT but inhibits to a lesser extent the reaction catalyzed by the mitochondrial isozyme. This is, to our knowledge, the first report on zebrafish mitochondrial folate enzyme as well as the differential inhibition of leucovorin on these two SHMT isoforms. Western blot analysis revealed tissue-specific distribution with the highest enrichment present in liver for both cytosolic and mitochondrial SHMTs. Intracellular localization was confirmed by confocal microscopy for both mitochondrial and cytosolic SHMTs. Unexpectedly, the cytosolic isoform was observed in both nucleus and cytosol. Together with the previous report on zebrafish cytosolic SHMT, we suggest that zSHMTs can be used in in vitro assays for folate-related investigation and antifolate drug discovery.