Cooling enhances alpha2-adrenoceptor-mediated vasoconstriction in human hand veins

The contribution of different receptor subtypes in the contractile response during cooling in human hand vessels is of considerable interest in the understanding of cold-induced peripheral vasospasm as it appears in Raynaud's phenomenon. Subcutaneous vein segments from 50 patients undergoing hand operations not related to vascular disorders were examined in vitro. The temperature in the organ bath was initially 37 °C and was either continuously lowered to 10 °C or kept constant at 37 °C, 29 °C or 20 °C. The characteristics of the α-adrenoceptor-mediated motor response were elucidated with the use of the α₁-antagonist, prazosin, and the α₂-antagonist, yohimbine. A great variability between individuals in the proportions of α₁- and α₂-adrenoceptors was found. In the majority of the vessels continuous cooling to 25 °C augmented a noradrenaline-induced contraction. This augmentation was unaltered in the presence of prazosin but abolished by yohimbine, suggesting that it was mediated via the α₂-adrenoceptor. In the remaining vessels with a predominating α₁-adrenoceptor-mediated response a cold-induced relaxation was registered. This could be the result of a reduced α₁-adrenoceptor-mediated contraction at this low temperature. These varying reactions to cooling were unaffected by the β-antagonist, propranolol, and by endothelial denudation. The results obtained in corresponding experiments with the α₁-agonist methoxamine and α₂-agonist, oxymetazoline, were conflicting, probably due to the poor selectivity of these agonists in human tissues. The results suggest that in patients with peripheral cold-induced vasospasm administration of an α₂-adrenoceptor antagonist might be of therapeutic interest in order to relieve vasospasm in the hand vessels.     

Identifying leucocytes and leucocyte subpopulations in semen using monoclonal antibody probes

An indirect immunoperoxidase technique employing specific monoclonal antibodies has been used to identify leucocyte subpopulations in cytocentrifuge smears of washed human ejaculate. Cells reacting with the pan antihuman leucocyte monoclonal antibody (HLe-1) were demonstrated in 63/67 specimens from subfertile patients with a mean count of 14.5 +/- 17.1 leucocytes per HPF (X 320). Cells with similar reactivity were observed in all specimens examined from 10 fertile men with a mean count of 41.6 +/- 26.3 leucocytes per HPF (X 320). Leu-T4+ cells (T-lymphocytes) were demonstrated in only 13/63 of the subfertile group with a mean count of 4.46 +/- 3.3 T-lymphocytes per HPF (X 320). Studies with the anti-leu 2a antibody revealed that these leu-4+ cells were mainly of the suppressor/cytotoxic phenotype. In contrast, no leu-4+ cells were detected in the control group. No leu-12+ cells (B-lymphocytes) were detected in any of the 80 specimens examined.     

竹叶椒化学成分的研究

自芸香科花椒属植物竹叶椒Zanthoxylum planispinum Sieb. et Zucc根的石油醚提取物中分离得到三种结晶。经物理常数测定,光谱(IR.NMR和MS)及X-射线单晶衍射分析,确定了化合物Ⅲ的绝对构型为(1R,2R,5R,6S)-2-(3′,4′-二甲氧基苯基)-6-(3″,4″-亚甲二氧苯基)双骈四氢呋喃,是一个新化合物,命名为竹叶椒脂素(L-planinin)。化合物Ⅰ为β-香木脂醇(β-amyrin),化合物Ⅱ为L-细辛脂素(L-asarinin),这三种化合物均系首次从本植物中分离得到。     

Human red blood cell Wright antigens: a genetic and evolutionary perspective on glycophorin A-band 3 interaction

The Wright (Wra/Wrb) blood group polymorphism is defined by an allelic change (Lys658Glu) in the band 3 protein; nevertheless, the Wrb antigen apparently requires glycophorin A (GPA) for surface presentation. To gain insight into the structural basis for this protein-protein interaction and delineate its relationship with Wrb antigen expression, we investigated GPA and band 3 sequence polymorphisms occurring in rare humans and nonhuman primates. The lack of GPA or amino acid residues 59 through 71 of GPA results in the absence of Wrb from human red blood cells (RBCs) exhibiting the MkMk, En(a-), or MiV phenotype. However, the SAT homozygous cells carried a Glu658 form of band 3 and a hybrid glycophorin with the entire GPA extramembrane domain from residues 1 through 71, yet expressed no Wrb antigen. This finding suggests that formation of the Wrb antigenic structure is dependent on protein folding and that the transmembrane junction of GPA is important in maintaining the required conformation. Comparative analyses of GPA and band 3 homologues led to the identification in the interacting regions of conserved and dispensable amino acid residues that correlated with the Wrb positive or negative status on nonhuman primates. In particular, the chimpanzee RBCs cells expressed Wrb and the Glu658 form of band 3, which is identical to humans, but their GPA contained the Gly rather than Arg residue at position 61. Taken together, the results suggest that (1) Arg61 of GPA and the proposed Arg61-Glu658 charge pair are not crucial for Wrb antigen exhibition and (2) the role of GPA for interaction with band 3, including Glu658, probably involves a number of amino acid residues located in the alpha-helical region and transmembrane junction.     

Amino-sugars enhance recognition and phagocytosis of particles by human neutrophils

Neutrophils were examined for their ability to recognize and ingest beads coated with amino-derivatives of glucose, mannose, and galactose. Radioactive or fluorescent beads coated with any of the three sugars were ingested to an extent three times that observed with albumin- coated beads. Enhancement of ingestion of sugar-coated beads was much more evident when examined by electron micrographic studies. Inclusion of glucose or mannose in the medium with glucose- or mannose-coated beads caused a dose-dependent reduction of ingestion to control levels, but ingestion of galactose-coated beads was poorly inhibited. Similarly, galactose or fucose (6-deoxy-galactose) markedly inhibited ingestion of galactose-coated beads, but caused only a slight decrease in ingestion of glucose- or mannose-coated beads. Thus, neutrophils possess carbohydrate-binding membrane structures that can mediate recognition and ingestion of sugar-coated beads. Such carbohydrate recognition systems may underlie certain interactions of neutrophils and other surfaces.     

MITOCHONDRIAL FUNCTION IN RAT RENAL CORTEX IN RESPONSE TO PROTEINURIA AND IRON

1. Proximal tubular cell dysfunction in chronic glomerular disease (CGD) has been ascribed, in part, to reabsorption of transferrin-iron from tubular fluid and subsequent cytosolic peroxidative injury. To investigate a possible role for altered mitochondrial function in tubular cell injury in CGD, renal cortical mitochondrial respiratory function was examined in rats with adriamycin nephrosis. 2. State 4 (resting) respiration was increased in adriamycin nephrosis in comparison with control (51±2 vs 43±2ng atoms oxygen (0)/min per mg protein, respectively; P < 0.02). 3. Mitochondrial iron concentration was increased in nephrotic rats compared with contro. (9.52±0.70 vs 5.97±0.26 nmol Fe/mg protein, respectively; P < 0.001) and rates of state 3, state 4 and uncoupled respiration and the severity of proteinuria correlated with mitochondrial iron concentration. 4. To further define the relationship between mitochondrial iron accumulation and altered respiratory function, rats were loaded wit. iron. 5. In comparison with control, acute iron loading of normal rats impaired creatinine clearanc. (1.48±0.02 vs 0.40±0.29 mL/min), increased kidney weight (1.33±0.07 vs 1.74±0.14g) and impaired mitochondrial enzyme activity (e.g. cytochrome oxidase 185.0±46.6 vs 362.0±32.8Alog [cytochrome C]/min per mg protein; P < 0.05), but had no significant effect on rates of mitochondrial respiration or on mitochondrial fragility. 6. Mitochondrial iron concentration was not increased by iron loading, despite a similar increment in cytoplasmic iron to that seen in rats with adriamyci. nephrosis. 7. In summary, resting mitochondrial respiration is increased in nephrotic rats in proportion to mitochondrial iron accumulation. Changes in mitochondrial oxygen consumption do not appear to be a primary event in the tubular cell injury of iron loading.     

Serum albumin and survival in CAPD patients: the implications of concentration trends over time

HYPOTHESIS: Trends in serum albumin concentration over time provide a better prediction of clinical outcome in CAPD patients than a single mean value. METHODS: This was a retrospective review of outcome at 36 months in 225 adult CAPD patients. Mean serum albumin was determined for the first (SA1) and second (SA2) 6 months of treatment and patients grouped according to SA1 (group I, > 37; group II, 34-37; group III, < 34 g/l) and according to the change in serum albumin (delta SA) between the first and second 6 months (increased/static or decreased). Patient (PS) and technique (TS) survival were determined by Kaplan-Meier survival analysis. The effect of SA1 and delta SA on survival were determined in a multivariate Cox regression analysis model that included age and presence or absence of a systemic disease. RESULTS: By SA1 group, PS and TS survival at 36 months were 94 and 76% (group I), 64 and 53% (group II) and 70 and 52% (group III). If delta SA increased/remained static, then SA1 did not predict PS (group I, 100%; group II, 96%; group III, 74%; P = n.s.) or TS (group I, 72%; group II, 63%; group III, 65%; P = n.s.). If delta SA decreased, PS was worse in groups II and III, both as compared to group I (PS group I, 88%; group II, 52%; group III, 34%; P = 0.02) and as compared to the groups II and III when delta SA increased (PS group II, 74 vs 52%, P = 0.05; group III, 82 vs 34%, P = 0.005) The same trend was seen for TS. In the multivariate Cox regression model, age, direction of change in serum albumin, and presence of a multisystem disease were significant predictors of survival, whereas SA1 was not. CONCLUSION: Early hypoalbuminaemia in CAPD only predicts a worse patient and technique survival if mean serum albumin decreases further from the first to second 6 months of dialysis therapy. Change in serum albumin between the first and second 6 months of CAPD and the mean serum albumin over the first 6 months together offer better discrimination of outcome than either alone.      

Juxta-articular fibrotic nodules in Borrelia infection-ultrastructural details of therapy-induced regression

Juxta-articular fibrotic nodules in chronic Borrelia burgdorferi infection commonly regress rapidly under antibiotic therapy. They may therefore serve as a good invivo model for studying the development and regression of cutaneous fibrotic processes. As shown in a typical case of acrodermatitis chronica atrophicans, this spirochete-induced fibrosis in the upper subcutis of the elbow region is histologically characterized by broad hyalinized collagen tracts interspersed with prominent perivascular lymphocytes and plasma cells. These immune cells vanish completely after 5 days of antibiotic treatment, while fibroblasts discharge matrix vesicles and form elastic fibres.     

Neurodevelopment of surviving infants at age two years, with a birthweight less than 2000 g and cared for in neonatal intensive care units (NICU)-results from a population based longitudinal study in Taiwan

All surviving infants from nine neonatal intensive care units (NICU) in a southern city and county of Taiwan were followed up and assessed at 2 y of age if they had a birthweight of less than 2000 g and were born between February 1, 1993 and January 31, 1994. The assessments included: neurological, growth and general health. A comparison group of normal birthweight and full-term infants without congenital anomalies, matched by birth month and sex to the NICU survivors was also studied with respect to the same outcome measures. A developmental delay (either a severe neurological deficit or Mental Development Index <68 or Psychomotor Development Index <68) was present in 21 (15.4%) of the cases, compared to 3 (2.5%) of the controls (P < 0.0004). Significant correlates of developmental outcome for the cases were birthweight, gestational age, and maternal education. The very low birthweight (VLBW) children (<1500 g) in our study cohort had a comparatively higher incidence of severe neurological deficits (and cerebral palsy) than that reported by other similar studies in developed countries. The incidence of abnormal neurodevelopmental outcome remained high in the graduates of NICU at 2 y of age, compared to that in normal controls. The findings have important implications in future health policy making regarding postnatal management of the surviving infants of NICU in developing countries such as Taiwan.