三氧化二砷联合Ad-IκBαM诱导胃癌细胞凋亡的研究

目的研究三氧化二砷（As2O3）对胃癌SGC-7901细胞作用过程中细胞内核转录因子KB（NF-κB）的激活及重组腺病毒Ad—IκBαM通过抑制NF-κB的活化增强As2O3的诱导凋亡作用。方法培养胃癌SGC-7901细胞,以非感染组及感染Ad—IκBα组为对照,采用凝胶电泳迁移率实验（EMSA）及免疫组化法检测As2O3处理后细胞核内NF-κB的激活情况,以及感染Ad—IκBαM对NF-κB活性的影响;四甲基偶氮唑盐（MTT）法、Hoechest染色、原位末端标记（TUNEL）法分别检测感染Ad—IκBαM对As2O3诱导细胞凋亡的影响。结果EMSA及免疫组化法显示As2O3作用于胃癌细胞可使细胞内NF-κB激活,感染Ad—IκBαM使NF-κB活性受到明显抑制;MTT法证明,As2O3作用后,感染Ad—IκBαM细胞的凋亡率（59．2±2．5）％较感染Ad-IκBα组（47．5±2．3）％及未感染组（40．0±1．2）％明显升高,各组间比较P〈0．01;Hoechest法显示,感染Ad—IκBαM组的凋亡率为（27.7±2．6）％,明显高于感染Ad—IκBα组（18．3±1．5）％及未感染组（11.0±1．7）％（P〈0．05）。TUNEL法结果与Hoechest法一致,感染Ad—IκBαM组的凋亡率为（31．1±2．5）％,高于感染Ad-IκBα组（20.7±2．1）％及未感染组（13.0±1、7）％（P〈0．05）。可见,感染Ad—IκBαM可明显提高As2O3诱导的细胞凋亡。结论As2O3作用于胃癌细胞可使细胞内NF-κB激活,从而表明NF-κB激活可能为胃癌细胞抗诱导凋亡作用的重要机制;感染Ad．IKBctM可有效抑制NF-κB的活性,并增强As2O3的诱导凋亡作用。     

应用一氧化碳弥散功能检测结缔组织病患者肺间质病变的意义

目的　探讨对结缔组织病 (CTD)患者肺间质病变 (ILD)进行早期、安全、有效且可量化的诊断方法。方法　对 93例CTD患者 ,其中 4 8例系统性红斑狼疮 (SLE)、18例皮肌炎 (DM)、2 1例系统性硬皮病 (PSS)、6例干燥综合征 (SS)进行了一氧化碳弥散功能检测 ,并与X线胸片、肺部高分辨率CT(HRCT)结果相比较 ;同时测定了 5 0名正常人的X线胸片和一氧化碳弥散功能作为对照。结果　X线胸片、肺部HRCT和一氧化碳弥散功能检测 (以一氧化碳弥散吸收率 <80 %为标准 )在SLE中检测到ILD的比率分别是 15 %、36 %和 4 2 % ;在DM中的比率分别是 17%、36 %和 39% ;在PSS中的比率分别是 38%、4 2 %和 5 2 % ;SS的比率分别是 33%、6 7%和 5 0 %。而正常人的X线胸片均正常 ,一氧化碳弥散吸收率均≥ 80 %。结论　X线胸片在检测CTD患者ILD中敏感性最低 ,而HRCT和一氧化碳弥散功能是检测CTD患者ILD的敏感方法。尤其是后者 ,具有敏感性高、不受X线照射、易被患者接受和对其损害程度进行量化等优点 ,既可作为早期了解CTD患者ILD的检测方法 ,又可通过一氧化碳弥散功能的改变对治疗效果进行评价。     

Prognosis and follow-up of patients with ventricular tachycardias or ventricular fibrillation without coronary heart disease

We studied the follow-up of 49 patients (pts), mean age 34 +/- 9 years, without coronary artery disease who had sustained (duration greater than 30 s) monomorphic ventricular tachycardia (smvt) (n = 42) or ventricular fibrillation (vf) (n = 7). There were 9/49 pts (18%) with smvt who had right ventricular dysplasia (RVD) and 32/49 pts (65%) without structural heart disease ("idiopathic" ventricular arrhythmia) (26/32 pts with smvt and 6/32 pts with vf). There were 6/49 pts (12%) with congestive (COCM) and 2/49 pts (4%) with hypertrophic (HOCM) cardiomyopathy. Mean follow-up was 49 +/- 13 months. During the follow-up 1/9 pts (11%) with RVD died postoperatively from heart failure, 1/26 pts (4%) with idiopathic smvt from cancer and 2/6 pts (33%) with COCM from heart failure. There were no deaths in pts with idiopathic vf. Recurrent smvt occurred in 5/9 pts (56%) with RVD, in 10/26 pts (39%) with idiopathic smvt, in 2/6 pts (33%) with idiopathic vf, in 3/6 pts (50%) with COCM and in 1/2 pts (50%) with HOCM. Our data show that pts with smvt or vf without coronary artery disease have a good prognosis. However, there is a high incidence of recurrent ventricular arrhythmia in these patients.     

老年急性非ST段抬高型心肌梗死临床特点分析

目的：分析老年非ST段抬高型心肌梗死（NSTEMI）患者的临床特点。方法：回顾分析我院2008年1月至2010年12月43例急性NSTEMI患者的临床特点。结果：43例急性NSTEMI患者中,（1）危险因素及病史：38例（88．4％）患者伴有2～4个危险因素,40例（93．0％）有心绞痛病史,14例（32．6％）有陈旧性心肌梗死;（2）临床表现：36例有胸痛（83．7％）,35例（81．3％）NYHA心功能2—3级,40例（93．1％）心电图见ST—T段改变,43例（100．0％）心肌肌钙蛋白T水平升高,32例（74．4％）肌酸激酶-同工酶水平升高≥2倍;（3）冠脉造影检查,37例（100％）均有单支或多支病变,多支病变患者35例（94．6％）;（4）治疗、合并症及预后：在常规内科药物治疗基础上,31例（72．1％）行PCI治疗,3例（7．0％）行冠状动脉旁路移植术,合并急性左心衰竭13例（30．2％）,心源性休克5例（11．6％）,恶性心律失常5例（11．6％）,死亡6例（14．0％）。结论：老年非ST段抬高心肌梗死患者合并冠心病的危险因素多,多支病变常见,心功能不全多见,血运重建率高,远期预后较差。     

Relation of increased hemoglobin A(1c) levels to severity of peripheral arterial disease in patients with diabetes mellitus

The association between hemoglobin A(1c) levels and the severity of peripheral arterial disease (PAD) was investigated in 224 patients with diabetes mellitus and PAD. The mean hemoglobin A(1c) levels were 9.1 +/- 2.1% in patients with diabetes with ankle-brachial indexes (ABIs) <0.60 and 7.1 +/- 0.9% in those with ABIs of 0.60 to 0.89 (p <0.0001). Hemoglobin A(1c) levels <6.5% were present in 2 of 89 patients with diabetes (2%) with ABIs <0.60 and in 24 of 135 (18%) with ABIs of 0.60 to 0.89 (p = 0.0004). Hemoglobin A(1c) levels <7.0% were present in 24 of 89 patients with diabetes (27%) with ABIs <0.60 and in 63 of 135 (47%) with ABIs of 0.60 to 0.89 (p = 0.003). Hemoglobin A(1c) levels <7.5% were present in 30 of 89 patients with diabetes (34%) with ABIs <0.60 and in 92 of 135 (68%) with ABIs of 0.60 to 0.89 (p <0.0001). In conclusion, the higher the hemoglobin A(1c) levels in patients with diabetes with PAD, the higher the prevalence of severe PAD.     

Autoantibodies Against beta(1)-Adrenoreceptors in Patients With Cardiac Rhythm Disorders. Prevalence and Possible Role in Development of Arrhythmia

AIM: To assess prevalence of autoantibodies against beta(1)-adrenoreceptors (beta(1)-AR) in patients with arrhythmias of various etiology. MATERIAL: Patients with arrhythmias (n=110, including 59 patients with primary [idiopathic] electrical abnormalities, 33 - with chronic myocarditis and dilated cardiomyopathy [DCM]; 18 - with ischemic heart disease [IHD]) and healthy control subjects (n=20). METHODS: Antibodies against beta(1)-AR were measured in blood serum by direct immunoassay. Synthetic fragment containing 26 amino acids of beta(1)-AR second loop was used as antigen. RESULTS: Patients with primary electrical abnormalities and chronic myocarditis/DCM had similar prevalence of beta(1)-AR (49.1% and 54.5%, respectively), what was significantly higher than in controls (10%) and in patients with IHD (16.6%). These results provided evidence for the possible presence of an autoimmune process in the genesis of idiopathic arrhythmias. Among patients with idiopathic arrhythmias beta(1)-AR were found in 40% (10 of 25) of patients with ventricular tachycardia (VT), 63.6% (14 of 22) of patients with ventricular extrasystoles (VE), 41.6% (5 of 12) of patients with atrial fibrillation (AF). Among patients with chronic myocarditis and DCM beta(1)-AR were found in 72.2% (13 of 18) of patients with VT, 28.5% (2 of 7) of patients with VE, 37.5% (3 of 8) of patients with AF. Among patients with idiopathic arrhythmias female sex and frequent respiratory viral diseases were more common in beta(1)-AR-positive compared with beta(1)-AR-negative patients. VT and left ventricular ejection fraction <40% were more common in beta(1)-AR-positive than beta(1)-AR-negative patients among those with chronic myocarditis and DCM.     

Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes

The possible molecular basis for the previously described antagonistic interactions between adenosine A(1) receptors (A(1)R) and dopamine D(1) receptors (D(1)R) in the brain have been studied in mouse fibroblast Ltk(-) cells cotransfected with human A(1)R and D(1)R cDNAs or with human A(1)R and dopamine D(2) receptor (long-form) (D(2)R) cDNAs and in cortical neurons in culture. A(1)R and D(1)R, but not A(1)R and D(2)R, were found to coimmunoprecipitate in cotransfected fibroblasts. This selective A(1)R/D(1)R heteromerization disappeared after pretreatment with the D(1)R agonist, but not after combined pretreatment with D(1)R and A(1)R agonists. A high degree of A(1)R and D(1)R colocalization, demonstrated in double immunofluorescence experiments with confocal laser microscopy, was found in both cotransfected fibroblast cells and cortical neurons in culture. On the other hand, a low degree of A(1)R and D(2)R colocalization was observed in cotransfected fibroblasts. Pretreatment with the A(1)R agonist caused coclustering (coaggregation) of A(1)R and D(1)R, which was blocked by combined pretreatment with the D(1)R and A(1)R agonists in both fibroblast cells and in cortical neurons in culture. Combined pretreatment with D(1)R and A(1)R agonists, but not with either one alone, substantially reduced the D(1)R agonist-induced accumulation of cAMP. The A(1)R/D(1)R heteromerization may be one molecular basis for the demonstrated antagonistic modulation of A(1)R of D(1)R receptor signaling in the brain. The persistence of A(1)R/D(1)R heteromerization seems to be essential for the blockade of A(1)R agonist-induced A(1)R/D(1)R coclustering and for the desensitization of the D(1)R agonist-induced cAMP accumulation seen on combined pretreatment with D(1)R and A(1)R agonists, which indicates a potential role of A(1)R/D(1)R heteromers also in desensitization mechanisms and receptor trafficking.     

Thyroxine plus low-dose, slow-release triiodothyronine replacement in hypothyroidism: proof of principle.

Studies in hypothyroid rats show that, when infused with a combination of thyroxine (T4) plus triiodothyronine (T3) to normalize thyrotropin (TSH), euthyroidism in all organs is only ensured when T(4) and T(3) are administered in a ratio as normally secreted by the rat thyroid. As substitution with T(4)-only results in an abnormal serum T(4)/T(3) ratio, it is also possible that in humans, euthyroidism does not exist at the tissue level in many organs, considering that iodothyronine metabolism in the human and the rat share many similar mechanisms. Recent reports in which cognitive function and well-being are compared in patients with primary hypothyroidism substituted with T(4)-only versus substitution with T(4) plus T(3) result in controversial findings in that either positive or no effects were found. In all these studies T(3) was used in the plain form that results in nonphysiologic serum T(3) peaks. In these studies it is suggested that substitution with T(3 )should preferably be performed with a preparation that slowly releases T(3) to avoid these peaks. In the study reported here we show that treatment of hypothyroid subjects with a combination of T(4) plus slow-release T(3) leads to a considerable improvement of serum T(4) and T(3) values, the T(4)/T(3) ratio and serum TSH as compared to treatment with T(4)- only. Serum T(3) administration with slow-release T(3) did not show serum peaks, in contrast to plain T(3).     

Specificity analysis of blood group Lewis-y (Le(y)) antibodies generatedagainst synthetic and natural Le(y) determinants.

Le(y)-reactive monoclonal antibodies (mAbs) were generated in mice by immunization with synthetic Le(y) neoglycoproteins or with Le(y)-expressing cells. Serological analysis indicated that mAbs raised against synthetic Le(y) (i) reacted strongly with synthetic Le(y) but poorly with natural Le(y), (ii) cross-reacted with Le(x) or H-type 2 structures, and (iii) were IgG1, IgG2a, or IgG2b. mAbs raised against Le(y)-expressing cells (i) reacted with both synthetic Le(y) and natural Le(y), (ii) were of two types: cross-reactive with Le(x) or H-type 2 structures or specific for Le(y), and (iii) were IgM or IgG3. One of the mAbs raised against natural Le(y), mAb 3S193 (IgG3), showed high specificity for Le(y) in ELISA tests with synthetic Le(y) and Le(y) containing glycoproteins and glycolipids; it also reacted strongly in rosetting assays and cytotoxic tests with Le(y)-expressing cells. mAb 3S193 did not lyse O, A, AB, and B human erythrocytes in the presence of human complement. In flow cytometry, there was weak reactivity with granulocytes, a reactivity also observed with two previously described highly specific Le(y) mouse mAbs--BR55-2 (IgG3) and B3 (IgG1). A humanized version of mAb 3S193 has been constructed, and the specificity pattern and reactivity for Le(y) remain very similar to mouse mAb 3S193.     

Metastasis as the first sign of thyroid cancer

The aim of this paper is to review our experience with patients who presented with a metastatic tumor in the lymph nodes or other organs as the first sign of thyroid cancer. In 1974-1998, 18 602 patients were operated on due to goitre. There were 975 (5.2%) patients with thyroid malignant neoplasms. The group comprised 449 (46.1%) patients with papillary carcinoma, 309 (31.7%) with follicular carcinoma, 54 (5.5%) with medullary carcinoma, 106 (10.9%) with anaplastic carcinoma, and 57 (5.8%) with other types of thyroid malignant neoplasms. Out of these 975 patients, thyroid cancer was diagnosed on the basis of the detection of a metastatic tumor in 26 (2.7%) patients. In 16 (61.5%) of these patients the metastatic tumor was located in the regional lymph nodes. In 10 (38.5%) patients distant metastasis beyond the regional lymph nodes was the first sign of thyroid cancer. In (50%) patients metastasis was located in the bones, in 2 (20%) in the lung, in 1 (10%) in the heart, in 1 (10%) in the buttock, and in 1 (10%) in a central neck cyst. Metastasis was the initial manifestation of thyroid cancer in 18 (4%) of 449 papillary carcinoma patients, in 6 of 309 (1.9%) follicular carcinoma patients, and in 2 (3.7%) of 54 medullary carcinoma patients. Lymph node metastasis was the first sign of thyroid cancer in 13 (2.9%) patients with papillary carcinoma, 1 (0.3%) patients with follicular carcinoma and in 2 (3.7%) medullary carcinoma patients, and distant metastasis in 5 (1.1%) patients with papillary carcinoma and in 5 (1.6%) patients with follicular carcinoma. After the detection of the primary focus of thyroid cancer total thyroidectomy and modified neck dissection were performed in all patients. Differentiated thyroid carcinoma patients were treated complementarily with 131I and TSH suppressive doses of L-thyroxine, and medullary cancer patients with teleradiotherapy and substitutive doses of L-thyroxine.     

CD146在血管炎患者外周血白细胞表达的意义初探

目的探讨血管炎患者外周血白细胞CD146表达与临床活动性间的关系。方法流式细胞术检测39例活动期系统性血管炎患者[显微镜下多血管炎（MPA）13例,韦格纳肉芽肿（WG）9例,变应性肉芽肿性血管炎（CSS）2例,大动脉炎（TA）9例,白塞病（BD）4例,结节性多动脉炎（PAN）2例]及24例系统性红斑狼疮（SLE）患者外周血白细胞CD146表达,其中18例（MPA5例,WG4例,CSS2例,SLE4例,PAN2例,TA1例）患者经糖皮质激素和环磷酰胺治疗后于病情好转时再次检测。结果（1）与健康者相比,血管炎患者活动期中性粒细胞、淋巴细胞CD146表达增多,尤以中性粒细胞最多,差异均有统计学意义（P〈0．05）。（2）中性粒细胞CD146表达与淋巴细胞、单核细胞CD146表达相关（r值分别为0．66、0．853,P=0．000）,与病程、年龄、血沉、C反应蛋白、抗中性粒细胞胞浆抗体（ANCA）、PR3-ANCA、MPO-ANCA、血肌酐、伯明翰血管炎活动指数（BVAS）、系统性红斑狼疮疾病活动指数（SLEDAI）等无明显相关（r值分别为-0．108、-0．059、-0．073、-0．103、0．012、-0．5、-0．232、0．001、-0．08、0．089,P〉0．5）。（3）18例患者经治疗后好转期中性粒细胞、淋巴细胞CD146表达多数呈逐渐减少的趋势（P〈0．05）。结论CD 146在血管炎患者活动期外周血白细胞尤其是中性粒细胞中表达明显升高,随着糖皮质激素和免疫抑制剂治疗病情好转后呈下降或转阴趋势,其在血管炎发病机制中的意义有待深入研究。     

Lipoprotein (a) and ischemic heart disease in patients with hypertensive disease

Relationship between level of lipoprotein (a) and presence of ischemic heart disease (IHD) was studied in 191 patients with hypertensive disease (essential hypertension) (112 men, 79 women, age 56.9-/+10.6 years) and 33 patients with normal blood pressure (23 men, 10 women, age 50.8-/+11.0 years). Concentration of lipoprotein (a) in men with hypertension and IHD (n=62) was significantly higher than in men with hypertension without IHD (n=50) (median 19 and 9 mg/dl, respectively, p=0.02). Women with hypertension and with (n=23) and without (n=56) IHD had similar blood levels of lipoprotein (a) (median 13 and 15 mg/dl, respectively, p=0.89). Difference in lipoprotein (a) levels between patients with hypertensive disease and those with normal blood pressure was not significant (median 14 and 10 mg/dl, respectively, p=0.50).     

A Galphas mutation (D229S) differentially effects gonadotropin-releasing hormone receptor regulation by RGS10, RGS3 and RGS3T

Regulators of G protein signaling (RGS) act as GTPase-activating proteins for Galpha(i) and for Galpha(q/11). There is recent evidence for interaction of RGS proteins with Galpha(s), and substitution of Ser for Asp(229) in RGS proteins enhances interactions with G proteins. Site-directed mutagenesis of Asp(229) was used to assess the effect of this site on the gonadotropin-releasing hormone receptor (GnRHR)-Galpha(s) mediated signaling in the absence or presence of over-expressed RGS3, RGS10 or a truncated form of RGS3 (RGS3T). We observed increased cAMP release with the mutant Galpha(s)(D(229)S) compared to wt Galpha(s) when GGH(3) cells (GH(3) cells stably expressing the GnRH receptor) were stimulated with a GnRH agonist. In the presence of RGS3, we did not observe any difference in cAMP release with wt Galpha(s) or with Galpha(s)(D(229)S) compared to control values; in the presence of RGS3T there was an increase of cAMP release with wt Galpha(s) compared to the control but there was no difference between the Galpha(s)(D(229)S) and the control values. When cells co-expressed wt Galpha(s) and RGS10, there was a significant increase of cAMP release compared with cells co-expressing wt Galpha(s) and Lac Z. Cells co-expressing Galpha(s)(D(229)S) and RGS10 showed a significant increase of cAMP release compared to control cells. These results indicate differential regulation of the GnRHR-Galpha(s) mediated signaling by a single mutation in Galpha(s) in the presence of RGS10 and RGS3T, but not with RGS3. This is the first report of an effect of the Galpha(s)(D(229)S) mutation on G protein-coupled receptor-mediated activation.     

Valine/valine genotype at position 247 of the beta2-glycoprotein I gene in Mexican patients with primary antiphospholipid syndrome: association with anti-beta2-glycoprotein I antibodies

OBJECTIVE: To determine the polymorphism at position 247 of the beta(2)-glycoprotein I (beta(2)GPI) gene in Mexican patients with antiphospholipid syndrome (APS) and to compare these data in patients with or without antibodies to beta(2)GPI and with the clinical manifestations of APS. METHODS: We studied 39 patients with primary APS and compared them with 106 clinically healthy subjects. Polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. The presence of "true" anticardiolipin (aCL) antibodies, beta(2)GPI-dependent aCL antibodies (IgG and IgM), and phospholipid-free anti-beta(2)GPI antibodies (IgG isotype) were detected by enzyme-linked immunosorbent assay (ELISA) utilizing nonirradiated ELISA plates. Clinical manifestations associated with antiphospholipid antibodies were also evaluated. RESULTS: We found no significant differences in the genotype expression between the control group and the primary APS patients (13% with VV, 52% with VL, and 35% with LL versus 23% with VV, 51% with VL, and 26% with LL, respectively). In contrast, anti-beta(2)GPI-positive patients had significantly higher frequencies of the VV genotype and V allele expression than the control subjects and the anti-beta(2)GPI-negative patients. These genotype and allele frequencies were also significantly higher in patients with arterial thrombosis than in patients without it. Anti-beta(2)GPI-negative patients without arterial thrombosis did not express the VV genotype. We found no differences in the Val/Leu(247) polymorphism of the beta(2)GPI gene in primary APS patients with or without "true" aCL antibodies or in primary APS patients with or without beta(2)GPI-dependent aCL antibodies. CONCLUSION: Our results suggest that the VV genotype at position 247 of the beta(2)GPI gene may play a role in the generation of anti-beta(2)GPI antibodies and perhaps in the expression of arterial thrombosis in primary APS.     

Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn's disease

BACKGROUND: Crohn's disease (CD) can commonly involve the terminal ileum, which is the site of B(12) absorption. The aim of this study was to define the prevalence of vitamin B(12) abnormalities in a population with CD and to identify risk factors associated with B(12) abnormalities in CD. METHODS: The medical records of 201 patients with CD evaluated at a tertiary care center were retrospectively reviewed to determine the prevalence of B(12) deficiency and to evaluate factors associated with B(12) deficiency. The prevalence of B(12) deficiency in a control population of 40 patients with ulcerative colitis was also assessed. RESULTS: The prevalence of an abnormal serum B(12) concentration in patients with CD was 18.4% (95% confidence interval [CI] 13.1-23.8%) compared with 5% (95% CI, 0-11.8%) (P = 0.035) in ulcerative colitis controls. Risk factors for B(12) deficiency in patients with CD included prior ileal (odds ratio [OR], 7.22; 95% CI, 1.97-26.51) or ileocolonic (OR, 5.81; 95% CI, 2.09-16.12) resection and the need for ongoing medical therapy (OR, 2.59; 95% CI, 1.03-6.47). Neither disease location nor duration was independently associated with the risk of B(12) deficiency. CONCLUSIONS: Vitamin B(12) abnormalities are common in patients with CD and patients with a prior ileal or ileocolonic resection are at particular risk. Routine screening for B(12) deficiency in patients with CD is warranted.     

Mechanisms involved in the effects of TRH on GHRH-stimulated growth hormone release from ovine and bovine pituitary cells

Incubation of cultured ovine pituitary cells with growth hormone-releasing hormone (GHRH) (10(-12)-10(-7) M) stimulated growth hormone secretion up to 3-fold. At a maximal stimulatory concentration of GHRH (10(-10) M), thyrotropin-releasing hormone (TRH) (10(-7) M) caused an inhibition of growth hormone release to approx. 50% of the response obtained with GHRH alone (during a 15 min incubation period). TRH also caused a small inhibition of the GHRH-stimulated cellular cyclic AMP level but this effect was only significant at a relatively high concentration of GHRH (10(-9) M). Incubation of cultured bovine pituitary cells with GHRH (10(-11)-10(-8) M) plus TRH (10(-7) M) caused a significant stimulation of growth hormone release by up to 40%, compared with the response obtained with GHRH alone (at all concentrations of GHRH). TRH (10(-7) M) had no effect on GHRH (10(-8) M)-stimulated cellular cyclic AMP levels in a partially purified bovine pituitary cell preparation. The effects of varying extracellular [Ca2+] (0.1-10 mM) on intracellular [Ca2+] and on the responsiveness to releasing hormones were also determined using ovine pituitary cells. GHRH (10(-10) M)-stimulated growth hormone release was inhibited when cells were incubated at both high (10 mM) and low (0.1 mM) [Ca2+] (compared with 1 mM or 3 mM Ca2+) with or without TRH (10(-7) M). At 1 mM Ca2+, TRH produced a synergistic effect with GHRH to stimulate growth hormone release. However, at 3 mM Ca2+ TRH inhibited GHRH-stimulated growth hormone release.(ABSTRACT TRUNCATED AT 250 WORDS)     

非ST段抬高心肌梗死临床及冠状动脉病变特点

目的　探讨非ST段抬高心肌梗死 (NSTEMI)患者的临床及冠状动脉 (冠脉 )病变特点 ,提高其诊治水平。方法　对 73例NSTEMI病人的临床及冠脉造影结果进行分析。结果　冠心病危险因素 :合并高血压者 5 0例 (6 8% ) ,糖尿病者 2 6例 (35 % ) ,高血脂者 34例 (4 6 % ) ,有吸烟史 2 8例 (38% )。既往有冠心病心绞痛者 5 2例(71% ) ,住院期间发生心肌梗死后心绞痛 2 2例 (30 6 % )、严重心律失常 15例 (2 0 4 % ) ,心源性休克者 7例(10 2 % )、死亡 3例 (4 % )。心电图ST -T下移 5 2例 (71% ) ,大致正常 2 1例 (2 9% )。冠脉造影显示 :≥ 2支血管病变 5 4例 (74 % ) ,单支血管病变 19例 (2 6 % ) ,两者有显著性差异 (P <0 0 1)。阻塞程度为 95 %～ 99%狭窄者最多 ,占 6 5 8% (4 8/ 73) ,侧支循环形成者占 2 6 5 % (19/ 73)。在 2～ 3支血管病变的 5 4例中 4 9例 (90 7% )血管狭窄部位相互对应。结论　NSTEMI病人临床症状往往较轻 ,住院并发症较低 ,但其基础病变较重 ,预后较差 ,需及时进行冠脉血运重建。     

Del (9q) AML: clinical and cytological characteristics and prognostic implications

Del (9q) is a recurrent cytogenetic abnormality in acute myeloid leukaemia (AML). We report an analysis of 81 patients with del(9q) as a diagnostic karyotypic abnormality entered into the Medical Research Council AML trials 10, 11 and 12. Patients were divided into three groups: (i) Sole del (9q), 21 patients; (ii) Del(9q) in association with t(8;21), 29 patients; (iii) Del(9q) in association with other cytogenetic abnormalities, 31 patients. Sole del(9q) was associated with a characteristic bone marrow phenotype at diagnosis: a single Auer rod was found in all cases examined. There was also an association with erythroid dysplasia (74%) and granylocytic lineage vacuolation (90%). The incidence of all three of these features was significantly higher (P < 0.05) in the sole del(9q) group compared with control cases lacking del(9q). The overall survival (OS) of all 81 patients was compared with a control group of 1738 patients with normal cytogenetics entered in the same trials over the period of investigation. The 5-year OS for patients with del(9q) was 45%, compared with 35% for the control group (P = 0.09). Patients with del(9q) in association with t(8;21) had a 5-year OS of 75%, which was significantly better than the groups with either sole del(9q) (40%) and del(9q) with other abnormalities (26%; P = 0.008). Karyotyping indicated a common area of deletion in the region 9q21-22, which was present in 94% of cases. It is likely that the deletion of single or multiple tumour suppressor genes located in this region may underlie the pathogenesis of del (9q) AML.     

Mechanics of the ventilatory system in sedated infants: forced oscillations versus single-breath method

The real--Re(Z)--and imaginary--Im(Z)--parts of the ventilatory system impedance were measured between 6 and 30 Hz in 18 normal infants and in 19 with airway obstruction. The intercept (R0) and slope (S) of the Re(Z)-frequency function, as well as inertance (I) and compliance (C) estimated from Im(Z), were compared with ventilatory system resistance (Rrs) and compliance (Crs) (single-breath method). R0 correlated significantly with Rrs (r = 0.86), although the slope of the regression equation was significantly lower than 1 (P less than 0.01). Negative frequency dependence of Re(Z) was observed in all subjects and a significant correlation was found between S and Rrs (r = -0.80). "Inertance" was negative in 20 subjects and correlated negatively with Rrs (r = -0.61). C correlated with Crs (r = 0.64) and with 1/Rrs (r = 0.85). The ratio of C to Crs (mean +/- SD = 0.168 +/- 0.082) also correlated with 1/Rrs (r = 0.51). The main characteristics of the total impedance/frequency function could be simulated with a model featuring the upper airway wall (Zuaw) in parallel with the ventilatory system (Zrs). It is suggested that the differential change in Zuaw and Zrs with growth accounts for the marked frequency dependence of Re(Z) as well as the inaccurate estimation of both I and C in this population.     

Ventricular tachycardia and ventricular fibrillation following myocardial infarct: determinants of prognosis and disease course

To assess the risk of sudden death 79 patients (pts) with sustained monomorphic ventricular tachycardia (SMVT) and 37 patients with ventricular fibrillation (VF) after myocardial infarction (MI) were studied by coronary angiography, ambulatory monitoring, and programmed electrical stimulation. Mean follow-up was 28 +/- 12 months. Total mortality was significantly higher in pts with VF (13/37, 35%) than in pts with SMVT (15/79, 19%) (p less than 0.05), whereas there were no significant differences in the incidence of sudden death between pts with VF (6/37, 16%) and those with SMVT (5/79, 6%) (p = 0.09). Patients with VF had more frequent anterior and multiple MI's (33/37, 89%) than pts with SMVT (42/79, 53%) (p less than 0.05) and more often presented their arrhythmia earlier (within 2 months) after MI (23/37, 62%) than SMVT pts (28/79, 36%) (p less than 0.05). In addition, there were significant differences in mean left-ventricular ejection fraction between pts with VF (30 +/- 8%) and those with SMVT (35 +/- 12%) (p less than 0.05). Our data show that pts with VF after myocardial infarction have more severe left ventricular dysfunction and more extensive coronary disease and a somewhat higher risk of sudden death than pts with SMVT.