Fabry''s disease

Fifteen hemizygotes and 30 heterozygotes have been diagnosed since our investigations of Fabry's disease were started 10 years ago. They belong mainly to three Danish families. Genetic counseling and prenatal diagnoses have been performed, and in vitro studies of cultured fibroblasts and endothelial cells have been made with special reference to enzyme therapy.     

Patterns of spontaneous unitary discharge in thalamic ventro-basal complex during wakefulness and sleep

Summary Influences of the wake-sleep states on spontaneous activity of thalamic ventro-basal neurons have been studied in the chronic cat using the following analyses for cell discharges: mean firing rate, interspike histogram and joint interval histogram (J.I.H.). While slow wave sleep is accompagnied by a characteristic firing pattern it is more difficult to compare spontaneous unit activity during wakefulness (W) and desynchronised sleep (D).A detailed analysis (especially of the J.I.H.) of the same neuron during the three states indicates marked differences between W and D; on the contrary, the intraburst pattern shows definite similarities between D and S. The greatest stability in the firing pattern of a given neuron is found during S on long recording. During D the variability in the firing pattern is mainly due to phasic activity but may also be related to tonic changes.     

Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice

Neuromedin B (NMB) is a mammalian bombesin (BN)-like peptide that exerts its function via the neuromedin B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced by elevated blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhibited a marked reduction in memory performance. NMB-R-deficient mice exhibited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also observed between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced by electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.     

序列解剖层片的全局和局部色彩校正

本研究提出了一种全局和局部相结合的序列解剖层片的色彩校正算法。利用数字人层片（中国女婴一号）上提供的彩色灰度卡对相邻层片间各颜色通道的色彩差异进行全局校正，以消除解剖数据集沿垂直方向的光照变化；再利用线性校正模型和差值图像各通道（R、G、B）的灰度局部直方图，对解剖数据集进行局部色彩差异校正。重建结果表明，经过全局和局部色彩校正后，重建视图中的明暗条纹基本消失，说明层片间颜色的不连续现象得到了校正。     

Spontaneous reanastomosis between lymphatic vessels following syngeneic transplantation of the small intestine in the rat

Abstract Spontaneous lymphvascular reanastomosis (SLR) following small bowel transplantation in rats is of clinical relevance for the resorption of long chain fatty acids. Detailed morphological and molecular data concerning the process of lymphvascular reanastomosis are not available in the literature. In this study SLR was investigated using microradiology and scanning electron microscopy. Between the 8^th and 21^st postoperative days following transplantation SLR does not occur between the intestinal trunk of the transplant and the thoracic duct of the recipient. Instead, an indirect connection was observed between the inserted advential lymphatic vessels of the mesenteric artery and lymphatic vessels of the aorta or ductus deferens, which are connected with the thoracic duct.     

自发性高血压大鼠的微血管改变及其与血管内皮细胞损伤的关系

目的：探讨自发性高血压大鼠（SHR）的微血管改变与血管内皮细胞（VEC）损伤的关系。方法：以10只成年Wistar－Kyoto大鼠（WKY）为正常对照组（WKY组）。观察、计数10只成年SHR的肠壁微动脉管径和分支数，同时测定血浆亚硝酸根（NO2－）和内皮素（ET）并与WKY组对照。结果：SHR组的肠壁各级微动脉管径较WKY组变细（P＜0．01～0．001）、各级微动脉总条数较WKY组减少（P＜0．001～0．0001）；SHR组的血浆NO2-水平和K值［10g（NO2－／ET）」较WKY组低（P＜0．05～0．001），而ET较WKY组高（P＜0．05）。血压和K值分别与肠壁微动脉管径和条数呈负相关和正相关（P＜0．005～0．001）。结论：高血压的微血管结构异常与VEC损伤有密切的关系。     

Suppressed Cell-Mediated Immunity and Monocyte and Natural Killer Cell Activity Following Allogeneic Immunization of Women with Spontaneous Recurrent Abortion

Spontaneous recurrent abortion (SRA) has been treated by means of immunization with paternal or third-party white blood cells, yet the immunological basis for SRA and for the role of immunization protocols in pregnancy outcome remains controversial. To elucidate this question, nine women with SRA were immunized with paternal mononuclear cells and studied before and 2 weeks after immunization. Seven women who became pregnant gave birth to live newborns. Secretion of the T helper 1 cytokines IL-2 and interferon- by patients' mononuclear cells decreased, while production of IL-10 increased. The levels of natural killer and lymphokine-activated killer cell-mediated cytotoxicity were markedly decreased. Monocyte functions such as secretion of IL-l, tumor necrosis factor a, IL-6, and cytotoxic activity decreased concurrently with elevations in IL-10 and transforming growth factor secretion. Production of IL-12, a pivotal regulatory cytokine, decreased. Furthermore, B7/1 expression on patients' mononuclear cells was downregulated. This resulted in a decrease in monocyte costimulatory activity of purified T cells with soluble anti-CD3, paralleled by a decline in allogeneic proliferative responses. These results suggest that the improved pregnancy success rate in women with SRA following immunization may be partly related to suppression of cell-mediated immunity and monocyte and natural killer cell activity.     

Spontaneous transient inward currents and rhythmicity in canine and guinea-pig tracheal smooth muscle cells

Spontaneous transient inward currents (STICs) were recorded in canine and guinea-pig tracheal myocytes held at negative membrane potentials. STICs were Cl^– selective since their reversal potential was dependent on the Cl^– gradient and they were blocked by the Cl^– channel blocker niflumic acid. STICs were insensitive to Cs⁺, charybdotoxin, and nifedipine. Ca²⁺-activated K⁺ currents often preceded STICs, suggesting that the STICs are Ca²⁺ dependent. In support of this suggestion, we found the Cl^– currents were: (1) abolished by depleting intracellular Ca²⁺ stores using caffeine, acetylcholine, histamine, or substance P; (2) enhanced by increasing external concentrations of Ca²⁺; (3) evoked by voltage-dependent Ca²⁺ influx. The channels responsible for this Cl^– current are of small unitary conductance (<20 pS). Decay of the STICs was described by a single exponential with a time constant of 94±9 ms at –70 mV; the time constant increased considerably at more positive potentials. Using Ca²⁺-dependent Cl^– currents and contractions as indices of internal levels of Ca²⁺, we found that isolated tracheal cells are capable of exhibiting rhythmic behaviour: bursts of currents and contractions with a periodicity of less than 0.1 Hz and which continued for more than 20 min. These rhythmic events were recorded at negative membrane potentials, suggesting that cyclical release of internally sequestered Ca²⁺ is responsible. We conclude that spontaneous release of Ca²⁺ from intracellular stores in tracheal muscle cells leads to transient currents in some cases accompanied by rhythmic contractions. Our studies provide evidence for a cellular mechanism that could underly myogenic oscillations of membrane potential in smooth muscle.     

Distribution of cardiac output in different models of hypertension in the conscious rat

The distribution of cardiac output was determined by 15 m radioactive microspheres in all the major organs of spontaneous, DOCA/NaCl and one kidney Goldblatt hypertensive rats and compared to normotensive Wistar rats. Although there were alterations in cardiac output distribution which were characteristic of each model of hypertension significant changes were common to all three were an increased distribution to skeletal muscle with decreases to the lungs, spleen and hepatosplanchnic tissues. The results suggest that alterations in peripheral resistance induced by hypertension are of unequal importance in the different vascular beds with certain vascular resistance changes occurring irrespective of the origin of the hypertension.Abbreviations used in this paper SHR spontaneously hypertensive rats - DOCA deoxycorticosterone acetate Supported by I.C.I. Pharmaceutical Ldt and the Mersey Regional Health Authority (Research Schemes No. 338).     

Spontaneous tension oscillation in skinned bovine cardiac muscle

 Skinned fibres from bovine ventricles exhibited spontaneous tension oscillations when MgADP and inorganic phosphate (Pi) were added to the solution bathing fibres in the relaxed state (ADP-SPOC). A similar type of oscillation was observed at intermediate concentrations of free Ca²⁺ in the absence of MgADP and Pi (Ca-SPOC). To investigate the correlation between ADP-SPOC and Ca-SPOC, we constructed two-dimensional state diagrams of cardiac muscle using different concentrations of Pi (0–20 mM) and free Ca²⁺ [pCa=around 5 (+Ca²⁺), pCa=5.15–6.9 and +EGTA (–Ca²⁺)], with varying concentrations of MgADP (0–10 mM), with 2 mM MgATP and 2 mM free Mg²⁺ maintaining ionic strength at 0.15±0.01 M, pH 7.0, 25 °C. The three-dimensional (pCa-Pi-MgADP) state diagram thus obtained was divided into three regions, i.e. the contraction region in which tension oscillation was undetectable, the spontaneous tension oscillation (SPOC) region and the relaxation region. We found that the regions of ADP-SPOC and Ca-SPOC were continuously connected by a single oscillation region sandwiched between the contraction and relaxation regions. The state diagram, which encompasses physiological conditions, shows that the probability of SPOC is higher in cardiac muscle than in skeletal muscle. From these results, we suggest that, despite distinct ionic conditions, the molecular state of cross-bridges during SPOC is common to both ADP-SPOC and Ca-SPOC. Received 19 February 1996 / Received after revision: 16 July 1996 / Accepted: 14 August 1996