Glial-vascular reactions to angiotensin II in the rat brain

Reactions of the glia and blood vessels in the sensomotor cortex of adult rats to intraperitoneal injection of angiotensin II were studied electron-microscopically. Repeated injections of the hormone led to edema of increasing severity of the astrocytes, constriction of the lumen of the capillaries, and changes in the structure of their endothelium. It is suggested that these disturbances may be the cause of the cerebrovascular insufficiency and of functional changes in the CNS.Laboratory of Morphology of the Central Nervous System and Laboratory of Experimental Pathology and Therapy of Higher Nervous Activity, Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. S. Rusinov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 615–617, November, 1979.     

Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material

The expression and cellular localization of angiotensin II (Ang II) and AT(1) receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT(1) receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.4+/-0.2%, n=5 vs. BPH: 22.7+/-1.9%, n=5, p<0.001). However, AT(1) receptor immunoreactivity was significantly decreased in BPH compared with the normal prostate [normal: 16.4+/-2.2%, n=4 vs. BPH: 9.4+/-1.3%, n=5, p<0.05 (p=0.025)]. The present study demonstrates the presence of Ang II peptide in the basal layer of the epithelium and AT(1) receptors on stromal smooth muscle, suggesting that Ang II may mediate paracrine functions on cellular growth and smooth muscle tone in the human prostate. Furthermore, AT(1) receptor down-regulation in BPH may be due to receptor hyperstimulation by increased local levels of Ang II in BPH. These data extend previous findings in support of the novel concept that overactivity of the renin-angiotensin system (RAS) may be involved in the pathophysiology of BPH.     

尾加压素II与糖尿病

尾加压素II(urotensin II，UII)最早是从鱼尾部下垂体中分离出的调节肽，近来已从人体中克隆出来，并发现体内一种孤立的G蛋白偶联受体GPR14是其特异性受体。UII与GPR14结合后，参与许多生物学效应，如调节内分泌，调节渗透压平衡，调节胃肠道平滑肌及心血管收缩功能等，是迄今体内最强的缩血管活性肽。UII不仅与许多人类心血管疾病如高血压，充血性心力衰竭（CHF），冠心病和动脉粥样硬化有关，而且研究发现，糖尿病患者血液中UII含量升高。初步研究表明,UII的基因多态性和2型糖尿病的发生有关；尾加压素II还可抑制胰岛素的释放。     

Mucopolysaccharidosis type II (Hunter disease): Identification and characterization of eight point mutations in the iduronate-2-sulfatase gene in Japanese patients

Mucopolysaccharidosis type II (Hunter disease) is a lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. Varied clinical phenotypes of this disease have been described. To identify mutations in individual patients and to examine possible correlations between mutations and clinical phenotypes, we analyzed the iduronate-2-sulfatase gene in Japanese patients with different clinical phenotypes. Five missense mutations, S333L (severe), R468Q (severe), R468L (severe), W337R (intermediate), R48P (mild), and three nonsense mutations, W345X (severe), R443X (intermediate), Q531X (mild), were identified by the RT-PCR method. Transient expression in the enzyme-deficient fibroblasts revealed that all five missense mutant enzymes were synthesized as the normal-size precursor (73 kD), and the nonsense mutant enzymes were synthesized as truncated ones (W345X:54 kD, R443X:59 kD, and Q531X:69 kD), although stable mature enzymes (45–56 kD) were not detected by Western blot analysis. Further more, expression of the eight mutant cDNAs resulted in severe reductions of iduronate-2-sulfatase enzyme activity in comparison with a normal cDNA. © 1995 Wiley-Liss, Inc.     

Body fluid changes, thirst and drinking in man during free access to water

To investigate whether human thirst and drinking during ad lib access to water occur in response to body fluid deficits, we obtained blood samples and visual analog scale thirst ratings from five healthy, volunteer, young men at hourly intervals and when they were thirsty during a normal working day. Although there were significant increases in ratings of thirst, pleasantness of drinking water, mouth dryness and unpleasantness of the taste in the mouth when subjects were thirsty enough to drink compared with intervening intervals, there were no concomitant changes in body fluid variables (microhematocrit, plasma osmolality and plasma sodium, potassium, protein and angiotensin II concentrations). Subjects drank mainly in association with eating and were not overhydrated as indicated by constantly hypertonic urine and significant tubular reabsorption of free water over the experimental period. The results indicate that during free access to water humans become thirsty and drink before body fluid deficits develop, perhaps in response to subtle oropharyngeal cues, and so provide evidence for anticipatory thirst and drinking in man.     

Use of class II tetramers for identification of CD4+ T cells

Multivalent MHC class II molecules containing peptide antigens are useful tools for the detection of antigen specific human CD4+ T cells. Tetramers produced by exogenous peptide loading onto empty class II molecules are comparable to tetramers with peptide tethered to the class II chain covalently, but have many practical advantages. Conditions for optimal peptide loading to generate tetramers are discussed and optimal conditions of using tetramers for staining T cells are examined. As the frequency of antigen specific CD4+ T cells in peripheral blood is low, we demonstrate that an in vitro expansion step is effective in detecting low frequency T cells. Two new applications with tetramers, their uses for mapping T cell epitopes and for the detection of low affinity T cells are described. In a clinical setting, potential applications include using these reagents for monitoring disease progression during clinical intervention.     

High frequencies of human T-lymphotropic virus type I (HTLV-I) infection and presence of HTLV-II proviral DNA in blood donors with anti-thyroid antibodies

To investigate the relationship between human T-lymphotropic virus (HTLV) types I and II and the pathogenesis of autoimmune thyroid diseases, we examined serum anti-thyroid antibodies in 1019 blood donors with or without serum anti-HTLV-I antibody as well as proviral DNA for HTLV-II in leukocyte DNA by the polymerase chain reaction in 395 blood donors with or without anti-thyroid antibodies. The frequency of donors with anti-HTLV-I antibody who also showed anti-thyroid antibodies (7.9%) tended to be higher than that (6.3%) among donors who did not have the anti-HTLV-I antibody. The frequency of anti-thyroid antibodies in 125 young male donors aged 16–39 years with anti-HTLV-I antibody (4.8%) was significantly higher (P<0.05) than that (0.6%) in 164 control donors without the antibody. In blood donors with anti-thyroid antibody, 25.0% of those with anti-HTLV-I antibody and 14.3% of those without the antibody had HTLV-II proviral DNA. In contrast, in donors without anti-thyroid antibody HTLV-II proviral DNA was detected in 2.3% of those with anti-HTLV-I antibody and in 0.6% of those without the anti body. Thus the detection rates in donors with anti-thyroid antibody were significantly higher (P<0.001) than those in donors without the antibody, regardless of HTLV-I infection. These results suggest that HTLV-I infection and the presence of HTLV-II proviral DNA may be independently related to the pathogenesis of autoimmune thyroid diseases.Abbreviations HTLV Human T-lymphotropic virus - PCR Polymerase chain reaction     

Effects of ageing on the alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells in monkey lungs

The effects of ageing on the numbers of alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells were studied in monkey lungs by scanning and transmission electron microscopy. Lung tissue from 26 female and three male pigtail macaques whose ages ranged from 1 month to 31 years (life span is 35 years) was analysed. From the age of 1 month to 10 years there was a significant increase in the number of alveolar pores (r = 0.85, p less than 0. 001); however, between the ages of 14 years to 31 years there was no significant change. In seven animals ranging in age from 1 month to 4 years (mean 2.4 years) the number of pores was 5.8 +/- 3.9 (mean +/- S.D.), whereas in 10 animals aged 16 to 31 years (mean 20.3 years) the number of pores was 32.7 +/- 17.5 (mean +/- S.D.) per alveolar profile, a significant difference (p less than 0.002). In older animals (15-20 years) there was a significant decrease, both in the number of lamellar bodies per alveolar type II cell (p less than 0.01) and in the volume density of lamellar bodies to cytoplasmic volume (p less than 0.05) compared with young animals (1 month to 4.8 years). In older animals, there was also a significant increase in the volume density of a vacuole-like dilatation of the endoplasmic reticulum in alveolar type II cells (p less than 0.05) compared with young animals. These findings suggest impaired pulmonary surfactant production with aging. Both the increased number of alveolar pores and the postulated decrease of surfactant production could play a role in the pathogenesis of pulmonary emphysema.     

Masking,De Lange curves and integration time as revealed by the electroretinogram of a tree shrew (Tupaia chinensis)

In order to elucidate the effects of angiotensin II on renal function, angiotensin II (AII; 1 ng/kg per min) and the AII antagonist 1-sar-8-ala-angiotensin II (AIIA; 200 ng/kg per min) were infused into the renal artery of anesthetized dogs (pentobarbital), on either a high (8 mmol/kg per day for seven days) or a low sodium intake (0.5 mmol/kg). In sodium replete dogs AII produced renal vasoconstriction with decreased RBF (–28%;P<0.001), but with less decrease of GFR (–14%;P<0.001), leading to an increase of FF (+19%;P<0.01),andantidiuresis(–39%;P<0.001); the antinatriuresis (–58%;P<0.001) exceeded the antidiuresis (P<0.001). RBF (–10%;P<0.001) was less pronounced (P<0.001) during AII in sodium deplete dogs, GFR remained unchanged, but FF increased to the same extent (+16%;P<0.05); diuresis and urinary electrolyte excretion were however not affected. AIIA did not affect RBF, GFR, FF, nor diuresis in sodium replete dogs suggesting that endogenous AII has no tonic influence on renal function in these conditions. In sodium deplete animals AIIA produced an 11% (P<0.001) increase of RBF, without changes of GFR; FF decreased by 12% (P<0.01), but diuresis, natriuresis and kaliuresis were not affected.