Electrical behaviour in a line of anterior pituitary cells (GH cells) and the influence of the hypothalamic peptide, thyrotrophin releasing factor

Anterior pituitary cells of the GH line, which secrete prolactin spontaneously, showed spontaneous action potential activity. Thyrotrophin releasing factor, which increases secretion in these cells, caused a prompt increase of action potential frequency. Potassium, another secretagogue, depolarized the cells and sometimes initiated a burst of action potentials at the onset of this effect. The action potentials persisted in tetrodotoxin-containing and Na-free media, but were suppressed by the Ca-channel blocker, methoxyverapamil. Moreover, elevating the extracellular Ca²⁺ concentration increased the amplitude of the action potentials. These action potentials therefore have a prominent Ca component. This endows them with a particular interest since secretory activity of these cells is known to be dependent on extracellular Ca²⁺. Ba²⁺, which can substitute for Ca²⁺ in maintaining secretion, also substituted for Ca²⁺ in the maintenance of the action potentials. In addition, Ba²⁺ prolonged action potentials remarkably: tetraethylammonium was less effective in this regard.The several parallels between known secretory behaviour and electrical phenomena encourage the view that analysis of electrical activity in anterior pituitary cells may provide useful clues to events involved in stimulus-secretion coupling and in the secretory control exerted by the brain.     

Deacetylation of 4-(5-acetylamino-2-furyl)thiazole and formation of 1-(4-thiazolyl)-3-cyano-1-propanone by rat liver tissues

The reductive metabolism of the rat carcinogen 4-(5-nitro-2furyl)thiazole (NFT) to 1-4-thiazolyl)-3-cyano-1-propanone (TCP) is reported. Formation of TCP from NFT involved furan ring fission. This could have occurred through involvement of either aminofuran or N-hydroxylaminofuran as precursors. To examine if 4-(5-amino-2-furyl)thiazole is a precursor for TCP, a stable model compound, 4-(5-acetylamino-2-furyl)thiazole (AAFT), was prepared and subjected to enzymatic deacetylation, using rat liver tissue homogenates. AAFT was synthesized by catalytic hydrogenation of NFT with 5% palladium on activated carbon, followed by acetylation with acetic anhydride. AAFT, a white crystalline powder, melted at 168–170°, had an extinction coefficient of 17.9 mM^?1 cm^?1 at 293 nm in ethyl acetate, and exhibited spectroscopic and mass spectral characteristics consistent with the assigned structure. Incubation with rat liver 10,000 g supernatant preparations resulted in the biotransformation of AAFT as evidenced by a decrease in absorption at 290 nm. Incubation of ¹⁴C-labeled AAFT followed by extraction with chloroform-diethyl ether (1:1) resulted in the recovery of a major portion (56%) of the radioactivity in the organic phase when the label was at the 2-position of the thiazole ring, while the major amount (82%) of radioactivity was recovered in the aqueous phase when the 1-¹⁴C-acetyl group was labeled. The radioactivity from the aqueous phase was extractable into the organic phase following acidification to pH 1, an observation consistent with deacetylation. Furthermore, the deacetylation product exhibited a mass spectrum, and retention times in gas and high pressure liquid chromatography, similar to those of synthetic TCP. These data establish 4-(5-amino-2-furyl)thiazole, derived from AAFT by deacetylation, as a precursor for TCP.     

The Role of American Thyroid Association Pediatric Thyroid Cancer Risk Stratification and BRAFV600E Mutation in Predicting the Response to Treatment in Papillary Thyroid Cancer Patients ≤18 Years Old

Objective:This study aimed to evaluate the role of risk stratification by the American Thyroid Association (ATA) pediatric thyroid cancer risk levels and BRAF^V600E mutation to predict the response to treatment in papillary thyroid cancer (PTC) patients ≤18 years old.Methods:Clinical outcomes during a median period of 6 (2-21.8) years were assessed in 70 patients, according to ATA pediatric risk stratification, BRAF^V600E mutation status, and dynamic risk stratification (DRS) at final follow-up.Results:Of 70 patients, 44 (63%), 14 (20%), and 12 (17%) were classified initially as low-, intermediate-, and high-risk, respectively. BRAF^V600E mutation analysis data was available in 55 (78.6%) patients, of whom 18 (32.7%) had the BRAF^V600E mutation. According to the final DRS, 61 (87%), two (3%), six (9%), and one (1%) patients were classified as an excellent, incomplete biochemical, incomplete structural, and indeterminate response, respectively. All ATA low-risk patients showed excellent response to treatment, whereas the rate of excellent response was 65.4% in intermediate- and high-risk levels (p<0.001). The rates of excellent response in BRAF^V600E positive and negative patients were 83% and 92%, respectively (p=0.339). The rate of locoregional recurrence was significantly higher in BRAF^V600E positive vs negative patients (33.3% vs 2.7% respectively, p=0.001).Conclusion:ATA pediatric risk stratification is effective in predicting response to treatment in PTC patients ≤18 years old. The presence of BRAF^V600E mutation was highly predictive for recurrence but had no significant impact on the rate of excellent response to treatment at final follow-up.     

Regional wall motion improvement after coronary thrombolysis with recombinant tissue plasminogen activator: importance of coronary angioplasty

To evaluate functional recovery in 20 consecutive patients with acute myocardial infarction who received recombinant tissue-type plasminogen activator, serial two-dimensional echocardiograms were performed before and immediately after tissue plasminogen activator administration and at 1 and 10 days postinfarction. Tissue plasminogen activator was administered intravenously (17 patients) or by intracoronary infusion (3 patients) after angiographic confirmation of total occlusion. Reperfusion, documented by angiography, occurred in 13 of the 20 patients. The mean time from onset of chest pain to thrombolysis was 5.1 +/- 1.1 hours. Echocardiograms were evaluated for regional function with a visual semiquantitative scoring system by two independent observers who had no knowledge of patient identity, temporal sequence, therapy or effect of therapy. There was no immediate or 24 hour improvement in wall motion. At day 10 compared with pretreatment, 28 of 33 reperfused infarct zone segments versus 6 of 20 nonreperfused infarct segments demonstrated improved wall motion (p = 0.01). This improvement did not relate to time from onset of chest pain to successful thrombolysis. Of reperfused infarct zone segments in the distribution of coronary artery balloon dilation, 19 of 23 segments exhibited improvement versus 7 of 17 (reperfused, no angioplasty) and 6 of 20 (nonreperfused, no angioplasty) segments (p = 0.001). Infarct zone segments reperfused at the time of ongoing chest pain demonstrated functional recovery compared with segments reperfused in the absence of chest pain (18 of 23 versus 10 of 20, respectively; p = 0.05). Thus, in this uncontrolled series, there was echocardiographically detectable improvement in function of reperfused infarct segments 10 days after coronary thrombolysis with recombinant tissue plasminogen activator.     

A case of an epithelioid glioblastoma with the BRAF V600E mutation colocalized with BRAF intact low‐grade diffuse astrocytoma

Epithelioid glioblastomas are one of the rarest histological variants of glioblastomas, which are not formally recognized by the World Health Organization (WHO) classification. Epithelioid glioblastomas usually occur as primary lesions, but there have been several reports of secondary epithelioid glioblastomas or epithelioid glioblastomas with pre‐ or co‐existing lesions to date. The serine/threonine‐protein kinase B‐Raf (BRAF) V600E mutation has been found at a high frequency of 54% in epithelioid glioblastomas. We present a case of a 26‐year‐old female patient with an epithelioid glioblastoma with the BRAF V600E mutation in her right frontal lobe. In the present case, a low‐grade diffuse astrocytoma component had colocalized with the epithelioid glioblastoma. The component presented prominent calcification on neuroimages as well as by histology, and low‐grade diffuse astrocytoma was considered to be a precursor lesion of an epithelioid glioblastoma. However, the BRAF V600E mutation was detected only in epithelioid glioblastoma but not in low‐grade diffuse astrocytoma. To the best of our knowledge, this is the first report demonstrating a discrepancy in the BRAF V600E mutation states between epithelioid glioblastoma and colocalized low‐grade astrocytoma.     

基于固体培养基的金黄色葡萄球菌计数方法的相关性研究

目的 基于固体培养条件下对金黄色葡萄球菌传统计数方法 的比较研究,并探讨A600值和金黄色葡萄球菌活菌数二者之间的关系.方法金黄色葡萄球菌在固体条件下培养至对数生长期,无菌生理盐水制成菌悬液,采用平板计数法、麦氏比浊法、显微计数法检测菌悬液,同时记录3种方法计数结果 ;在相同培养条件下初步稀释后检测菌液的吸光度(A600)值,取A600值在0.2～1间的菌液进一步稀释并检测A600,同时对各个稀释度的菌液进行平板菌落计数.结果在固体培养条件下,传统细菌计数方法计数结果:显微计数法>平板计数法>比浊法;同时A600值和金黄色葡萄球菌活菌数二者之间呈线性相关,线性回归方程为Y=28.98601X-0.17331,A600值(X),菌液浓度(Y×107cfu/mL).结论 基于固体培养条件下,3种传统计数方法之间存在各自的特点.同时,金葡菌菌液的吸光度与金黄色葡萄球菌活菌数之间呈良好的相关性,适用于金黄色葡萄球菌浓度的测定.     

细针穿刺检测BRAFV600E突变丰度与甲状腺乳头状癌临床病理特征的相关性

目的：探讨术前细针穿刺基因检测BRAF^V600E突变丰度与甲状腺乳头状癌(papillary thyroid cancer,PTC)临床病理特征的关系。方法：回顾性统计2021年1月30日至2022年2月28日就诊于南京中医药大学附属中西医结合医院的301例患者临床资料,术前细针穿刺基因检测示BRAF^V600E突变(含突变丰度检测),所有患者完成甲状腺癌根治术,术后病理证实为甲状腺乳头状癌,分析BRAF^V600E基因突变丰度与临床病理特征的关系。结果：纳入301例患者,男91例,女210例,年龄42(33～51)岁,范围18～69岁。肿瘤直径>1 cm的患者BRAF^V600E基因突变丰度高于肿瘤直径≤1 cm者[29.05(18.03～37.56) vs.18.35(6.74～29.61),P<0.001],颈部淋巴结转移患者BRAF^V600E基因突变丰度高于无颈部淋巴结转移者[24.72(8.08～34.32) vs.18(8.68～28.54),P=0.040]...     

C-TIRADS及BRAFV600E基因检测对细针穿刺细胞学难以定性的甲状腺结节的诊断价值

目的 探讨中国版甲状腺影像数据与报告系统（C-TIRADS）、BRAFV600E 基因检测及二者联合对细针穿刺细胞学难以定性的甲状腺结节的诊断价值。方法 纳入我院2020年1月—2021年4月的甲状腺手术患者53例行回顾性分析,术前完成超声、细针穿刺抽吸及BRAFV600E基因检测,选取细针穿刺细胞学难以定性的患者作为研究对象,53例患者共62个结节。以手术病理结果作为金标准,比较C-TIRADS、BRAFV600E基因检测及二者联合诊断对甲状腺结节的诊断效能。结果 C-TIRADS诊断甲状腺癌的敏感性、特异性、阳性预测值、阴性预测值及准确性分别为92.50%、50.00%、77.08%、78.57%、77.42%。BRAFV600E基因诊断甲状腺癌的敏感性、特异性、阳性预测值、阴性预测值及准确性分别为55.00%、100.00%、100.00%、55.00%、70.97%。C-TIRADS联合BRAFV600E基因诊断甲状腺癌的敏感性、特异性、阳性预测值、阴性预测值及准确性分别为95.00%、50.00%、77.55%、84.62%、79.03%。C-TIRADS及联合诊断对甲状腺癌诊断的敏感性高于BRAFV600E基因检测（P<0.001）,BRAFV600E基因检测特异性及阳性预测值高于C-TIRADS及联合诊断（P<0.05）。C-TIRADS、BRAFV600E基因检测及联合诊断对甲状腺癌诊断的阴性预测值和准确性差异无统计学意义（P>0.05）。结论 C-TIRADS及BRAFV600E基因检测对于细胞学难以定性的甲状腺结节均有良好的诊断效能,术前联合应用可以更好地评估甲状腺结节     

Inheritance of the mitral valve prolapse syndrome. Discussion of a three-dimensional penetrance model

The families of 12 probands with classic mitral valve prolapse were studied for evidence of mitral valve prolapse. Seventy parents, sibs, and progeny were included in the analysis. Forty-seven percent (16 of 34) of progeny were affected compared with 30 percent (3 of 10) of parents. Thirty-eight percent (10 of 26) of sibs were affected. A three-compartmental penetrance model was devised to account for the variation in expression with age. This includes a latent stage (time before onset of signs), an affected stage, and a stage in which the subjects are withdrawn (because of treatment, regression, or death). The implications of this model are discussed.