Solution structure of a human calcitonin analog elucidated by NMR and distance geometry calculations

Three-dimensional structure of a human calcitonin analog (abbreviated as hCTa) in which the amino acids of the wild type are replaced at positions 12, 16 and 19 by leucine residues and further at position 22 by a tyrosine residue was studied in TFE solution by ¹H-NMR and distance geometry calculations. This analog has a 15-20 times activity as compared with the wild type. The amino acid replacements resulted in formation of an amphiphilic α-helix in the region between the residues 4-20. The overall three-dimensional structure is similar to that of the wild type. The conformational feature of hCTa with a hydrophobic face composed with a Met and four Leu residues may be related to its higher hypocalcemic potency.     

电刺激听神经诱发小鼠脑干神经元活动的光信号及GABA能的作用

目的　 使用光学记录的方法观察小鼠脑干听神经电刺激诱发冲动的时间 空间分布 ,及抑制性神经递质GABA和GABAA受体拮抗剂荷包牡丹碱 (BMI)对听觉诱发冲动的影响。 方法　 使用出生后早期的 (0～ 5d)ddy/ddy小鼠 ,在冷冻条件下制作有活性的脑干切片 ;用电压敏感染料 (NK 30 4 1)做脑片染色 ;16× 16像素的硅光电二极管阵列 (16× 16pixelsSiliconPhotodiodeArray)设备用来记录刺激听神经所诱发的光学信号 ;观察GABA及竞争性GABAA受体拮抗剂BMI对听神经诱发信号的作用。 结果　 刺激听神经诱发的光学信号以时间 空间分布的形式被记录。每一个光学信号分为两个成分 :快的峰电位样反应及慢的长时程反应。快电位的起始相具有突触前性质 ,晚期相具有突触后性质 ,慢的长时程反应可能与多突触传递有关。灌流液中使用 5 0 μmol/LGABA可最大限度地降低听神经诱发的脑干神经元信号的幅度 ,BMI可部分逆转GABA对此信号的作用。 结论　 多部位的光学系统可以记录电刺激听神经的诱发反应 ,光学信号显示了时间 空间分布的类型。应用药理学的方法可以分析诱发反应的性质。GABA对出生后早期小鼠的诱发反应有明显的抑制作用 ,其抑制作用部分是通过GABAA受体实现的。     

'Pseudo' systolic anterior motion in patients with hypertensive heart disease

The systolic motion of the mitral apparatus in patients withhypertensive heart disease and hypertrophic cardiomyopathy wasstudied in order to quantify the difference. Twelve out of 37patients with severe systemic hypertension were found to haveabnormal systolic anterior motion and had significantly smallerleft ventricular end-systolic dimension (P <0.05) and greaterejection fraction and mean velocity of circumferential fibreshortening (P <0.01 for each) than the other hypertensivepatients without abnormal systolic anterior motion. A comparisonbetween systolic anterior motion in 12 hypertensive patientsand mild or moderate systolic anterior motion in 28 patientswith hypertrophic cardiomyopathy showed a clear cut difference.‘Pseudo’ systolic anterior motion reached its peakat end-systole when the posterior wall had contracted fully.‘True’ systolic anterior motion, however, reachedits peak much earlier than maximum movement of the posteriorwall—approximately after two-thirds of systole had beencompleted. At the time of mitral valve opening, ‘pseudo’systolic anterior motion had not yet returned to this initiallevel, whereas ‘true’ systolic anterior motion returnedprior to the opening of the mitral valve. Anterior chordal motionin hyperdynamic ventricle appears to play a role in the productionof ‘pseudo’ systolic anterior motion.     

LONGITUDINAL STUDY OR SERUM THYROID HORMONES, CHORIONIC GONADOTROPHIN AND THYROTROPHIN DURING AND AFTER NORMAL PREGNANCY

Measurements of serum levels of thyroxine (T4), free T4, 3,5,3'-triiodothyronine (T3), free T3, 3,3',5'-triiodothyronine (reverse T3, rT3), thyroxine-binding globulin capacity (TBGcap), chorionic gonadotrophin (hCG) and thyrotrophin (TSH) were carried out prospectively in eight women with uncomplicated pregnancies, in order to examine interrelationships between the thyroid gland and thyroid stimulating hormones during pregnancy. During pregnancy the levels of T4, free T4, T3, rT3 and TBGcap were significantly elevated, and TSH was decreased. It was noted that the elevation of T4 was maintained from the 8th to the 27th week of gestation while the level of TBGcap progressively increased. The levels of free T4 and rT3 in the first and third trimesters were significantly higher than those of age-matched, non-pregnant women. The levels of hCG showed a biphasic variation, with a peak in the 8th to 15th weeks, followed by a decline in the second trimester and a small, secondary elevation in the 32nd to 39th weeks. This later elevation was positively correlated with changes in free T4 and free T3 levels. The increase of serum T4 accompanied by an increase of free T4 in the first trimester appeared due to augmented secretion of T4, rather than being secondary to the elevated levels of TBGcap.     

Expression of heat shock protein 47 is increased in remnant kidney and correlates with disease progression

Glomerulosclerosis is characterized by accumulation of the mesangial extracellular matrix, including type I and IV collagen. The processing for the collagens in the glomeruli may play a critical role for development of glomerulosclerosis. We examined the expression of heat shock protein 47 (HSP47), a collagen-binding molecular chaperone in the progresive glomerulosclerosis model. Subtotally nephrectomized rats, unlike sham-operated rats, developed focal and segmental glomerulosclerosis. Immunological staining demonstrated an increased expression of HSP47 which paralleled the expression of type I and IV collagen in the glomeruli of the nephrectomized rats as the glomerulosclerosis developed. The mRNA levels encoding type I and type IV collagen and HSP47 were increased 3.4 fold, 3.6 fold and 2.8 fold, respectively, at week 7 after nephrectomy. By in situ hybridization, the expression of HSP47 mRNA was determined to be localized to the glomeruli with segmental sclerosis. These results suggest that HSP47 may play a central role in the process of extracellular matrix accumulation during the development of glomerulosclerosis.     

Relation between distribution of viral RNA and development of histopathological changes in encephalomyocarditis virus-induced orchitis in mice

The relation between the distribution of viral RNA and the development of histopathological changes was investigated in the early stage of encephalomyocarditis (EMC) virus-induced orchitis in mice. Signals of viral RNA were first detected by in situ hybridization in a few Sertoli cells in almost intact germinal epithelia at 2 days post-inoculation (d.p.i.). The number of Sertoli cells bearing signals of viral RNA increased at 3 d.p.i. when mild degenerative changes were exceptionally found in germinal epithelia. Signals of viral RNA came to be detected not only in Sertoli cells but also in a small number of germinal cells and spermatogonia at 4 d.p.i. when mild to moderate degenerative changes developed in germinal epithelia, resulting in desquamation of degenerated cells. At the same time, virus-like particles were observed by electron-microscopy in the degenerated and desquamated germinal cells. At and after 5 d.p.i., luminal obstruction with cellular debris and inflammatory cells was generally found. These results suggest that EMC virus carried to seminiferous tubules via the blood first attacks Sertoli cells and then damages germinal cells and spermatogonia.