Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states

Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant trait characterized by tumors of the parathyroids, gastro- intestinal endocrine tissue, anterior pituitary and other tissues. We recently cloned the MEN1 gene and confirmed its identity by finding mutations in FMEN1. We have now extended our mutation analysis to 34 more unrelated FMEN1 probands and to two related states, sporadic MEN1 and familial hyperparathyroidism. There was a high prevalence of heterozygous germline MEN1 mutations in sporadic MEN1 (8/11 cases) and in FMEN1 (47/50 probands). One case of sporadic MEN1 was proven to be a new MEN1 mutation. Eight different mutations were observed more than once in FMEN1. Forty different mutations (32 FMEN1 and eight sporadic MEN1) were distributed across the MEN1 gene. Most predicted loss of function of the encoded menin protein, supporting the prediction that MEN1 is a tumor suppressor gene. No MEN1 germline mutation was found in five probands with familial hyperparathyroidism, suggesting that familial hyperparathyroidism often is caused by mutation in another gene or gene(s).      

手术治疗颅咽管瘤75例

0　引言　 1998～ 2 / 2 0 0 0～ 8我们手术治疗颅咽管瘤 75例 ,取得了满意效果 ,报告如下 .1　对象和方法1.1　对象　本组 75 (男 5 1,女 2 4)例 ,年龄 4～ 6 3岁 ,其中 4～15岁 31例 (占 41.3% ) .病程 2 mo～ 3a.有 5 7例共 93只眼视力下降 ,其中 2只眼失明 ,5 4例共 90只眼视野缺损 ,多为双颞侧偏盲 ,或左右不对称的视野缩小 .异常泌乳 11例 ,第二性征发育迟缓 6例 ,性欲低下 4例 ,多饮多尿 12例 ,月经失调5例 . 5 4例有头痛、呕吐症状 .记忆力下降 3例 ,嗜睡 2例 ,抑郁 3例 . X线平片示 17例有蝶鞍扩大 ,33例鞍上或鞍内钙化斑 ;CT上…     

女性假两性畸形1例

0　引言　女性假两性畸形是性别异常中常见的类型之一 ,多由先天性肾上腺皮质增生引起 ,少数由妊娠早期母体内雄激素过多或孕母患肾上腺男性化肿瘤所致 .1　病例报告　患者 ,女 ,6 mo.其母发现其无阴道 ,阴蒂如小阴茎畸形前来就诊 .外阴检查 :外阴女性型 ,大阴唇正常 ,无小阴唇和阴道前庭 .阴蒂肥大似小阴茎 .阴蒂下方见尿道口 ,无阴道口 .B超检查 :子宫及卵巢正常 .细胞遗传学检查 :外周淋巴细胞培养 ,常规制片 ,G显带 ,染色体核型为 46 ,XX.诊断为 :女性假两性畸形 .该患儿可行阴道成形术及阴蒂矫形术2　讨论　性腺分化包括许多受遗传调…     

The commissuro-mamillary plane in MRI of the brain (preliminary communication)

Summary MRI sections of the brain in the coronal plane through the line joining the anterior commissure and the mamillary bodies display the constituent parts of the basal forebrain. The visualisation of the septal nuclei and the anterior columns of the fornix show the importance of this plane in the study of behaviour disorders and amnesic syndromes.This work was carried out under CNAM/INSERM contract N^o 86 3 36E     

Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations

Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.     

Immunologic analysis of the cloned platelet thrombin receptor activation mechanism: evidence supporting receptor cleavage, release of the N-terminal peptide, and insertion of the tethered ligand into a protected environment

The recently cloned functional thrombin receptor is thought to be activated by thrombin cleavage of the bond between R41 and S42, followed by the insertion of the new N-terminal region ("tethered ligand") into an unknown site in the receptor. Antibodies to peptides at or near the cleavage site have been reported to inhibit thrombin- induced platelet activation to varying extents, but the precise mechanism(s) of their inhibition is unknown. We have produced: (1) a polyclonal antibody in rabbits to a peptide containing amino acids 34 to 52 (anti-TR34-52); enzyme-linked immunosorbent assays (ELISA) indicate that anti-TR34-52 contains antibodies to regions on both sides of the thrombin cleavage site; (2) two murine monoclonal antibodies (MoAbs) to a peptide containing amino acids 29 to 68; one antibody reacts primarily with residues N-terminal to the thrombin cleavage site, and the other reacts primarily with residues C-terminal to the cleavage site; and (3) a polyclonal rabbit antibody to a peptide containing amino acids 83 to 94 (anti-TR83-94). Anti-TR34-52 binds to platelets as judged by flow cytometry, and pretreating platelets with a thrombin receptor peptide ligand does not lead to loss of antibody reactivity, suggesting that platelet activation does not initiate redistribution or internalization of surface thrombin receptors. In contrast, pretreating platelets with thrombin leads to complete loss of anti-TR34-52 binding. Similarly, the binding of both MoAbs to platelets is dramatically reduced by pretreatment with thrombin. However, the binding of anti-TR83-94 is not decreased by thrombin activation, confirming that the receptor is not internalized. Anti-TR34-52 profoundly inhibits low dose thrombin-induced platelet shape change and aggregation, but the inhibition can be overcome with higher thrombin doses. However, anti-TR34-52 does not inhibit platelet aggregation induced by tethered ligand peptides. The TR34-52 peptide is a thrombin substrate, with cleavage occurring at the R41-S42 bond as judged by high performance liquid chromatography (HPLC) and platelet aggregation analysis. Anti-TR34-52 prevented cleavage of the TR34-52 peptide, suggesting that the antibody prevents platelet activation, at least in part, by preventing cleavage of the thrombin receptor. These data, although indirect, provide additional support for a thrombin activation mechanism involving thrombin cleavage of the receptor; in addition, they provide new evidence indicating that receptor cleavage is followed by loss of the N-terminal peptide, and insertion of the tethered ligand into a protected domain.     

Continuous multi-channel intravascular monitoring of the effects of dopamine and dobutamine on plasma potassium in dogs

The effects of dopamine and dobutamine on plasma potassium were investigated in dogs using continuous, multi-channel, intravascular ion-selective potassium electrodes situated in the aorta and abdominal and thoracic inferior vena cavae. Doses of 10 and 30 g kg^-1 min^-1 of each drug were used, and the effects on potassium compared with isoprenaline 0.07 and 0.2 g kg^-1 min^-1. Both the drugs caused a biphasic pattern of potassium change consisting of an initial small rise in the potassium level, followed by a sustained period of hypokalaemia. The changes were greater with the higher dose of each drug compared with the lower dose, but there were no significant differences between the drugs. Comparison of the potassium changes between the three vascular sites studied suggested that the rise in potassium may be a result of release of the ion from the liver, and that the liver may also be the principle site of potassium uptake during the hypokalaemic phase.