Effects of renin-angiotensin system blockade on macrophage infiltration in patients with hypertensive nephrosclerosis.

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.     

Transient Brain Ischaemia Provokes Ca2+, PIP2 and Calpain Responses Prior to Delayed Neuronal Death in Monkeys

To clarify the mechanism of postischaemic delayed cornu Ammonis (CA)-1 neuronal death, we studied correlations among calpain activation and its subcellular localization, the immunoreactivity of phosphatidylinositol 4,5-bisphosphate (PIP₂) and Ca²⁺ mobilization in the monkey hippocampus by two independent experimental approaches: in vivo transient brain ischaemia and in vitro hypoxia-hypoglycaemia of hippocampal acute slices. The CA-1 sector undergoing 20 min of ischaemia in vivo showed microscopically a small number of neuronal deaths on day 1 and almost global neuronal loss on day 5 after ischaemia. Immediately after ischaemia, CA-1 neurons ultrastructurally showed vacuolation and/or disruption of the lysosomes. Western blotting using antibodies against inactivated or activated μ-calpain demonstrated μ-calpain activation specifically in the CA-1 sector immediately after ischaemia. This finding was confirmed in the perikarya of CA-1 neurons by immunohistochemistry. CA-1 neurons on day 1 showed sustained activation of μ-calpain, and increased immunostaining for inactivated and activated forms of μ- and m-calpains and for PIP₂. Activated μ-calpain and PIP₂ were found to be localized at the vacuolated lysosomal membrane or endoplasmic reticulum and mitochondrial membrane respectively, by immunoelectron microscopy. Calcium imaging data using hippocampal acute slices showed that hypoxia-hypoglycaemia in vitro provoked intense Ca²⁺ mobilization with increased PIP₂ immunostaining specifically in CA-1 neurons. These data suggest that transient brain ischaemia increases intracellular Ca²⁺ and PIP₂ breakdown, which will activate calpain proteolytic activity. Therefore, we suggest that activated calpain at the lysosomal membrane, with the possible release of biodegrading enzyme, will cause postischaemic CA-1 neuronal death.     

Hydrolysis of phenyl esters in cyclodextrin-polymer systems

The catalytic hydrolysis of phenyl esters in systems containing ß-cyclodextrin (ß-CD) and polyelectrolytes was investigated. Poly(methacrylic acid) was found to exhibit an inhibition effect on the hydrolysis, while poly(sodium styrenesulfonate) (NaPSS) shows a pronounced acceleration effect on the hydrolysis: the larger the molecular weight and the lower the degree of substitution, the greater is the acceleration effect. On the other hand, sodium ethylbenzenesulfonate and sodium dodecylbenzenesulfonate inhibit the reaction. The acceleration of the reaction in presence of NaPSS is attributed to the concentration of ß-CD and the substrate esters near to the chain of the macromolecule, through inclusion effects and hydrophobic interactions.     

Neuronal responses in monkey anterior putamen during operant bar-press behavior

Single neuron activity was recorded in the monkey anterior putamen to compare visuomotor-related responses during operant bar-press behavior with visual discrimination of objects. Of 615 neurons recorded 9.8% ( ) responded to the presentation of food during forced delay of access to the bar. Of these 60 neurons, 38 were also tested with nonfood, and 19 of these responded to the nonfood objects regardless of the following movement. The amplitude of the visual-related responses of some differential neurons was graded for different objects to reflect the relative degree of preference for the food presented. However, these responses disappeared in reaction time tasks in which the bar could be accessed for pressing immediately upon presentation of an object. The visual response latency of differential neurons ranged from 50 to 700 ms (mean ± SD, 386 ±211 ms), which was longer than that of the nondifferential responses (207 ± 204 ms). These results suggest that anterior putamen neurons might participate in estimation of visual information that could be related to forecasting movement.     

Generators of visual evoked potentials for faces and eyes in the human brain as determined by dipole localization

Human visual evoked potentials were recorded during presentation of photos of human and animal faces and various face features. Negative waves with approximate peak latencies of 165 msec (N170) were bilaterally recorded from the occipito-temporal regions. Mean peak latencies of the N170 were shorter for faces than eyes only. Analyses of amplitudes of evoked potentials indicated that the N170 elicited by faces reflected activity of a specific neural system which was insensitive to detailed differences among individual faces regardless of species, and consequently suggest that this system might function to detect existence of faces in general. On the other hand, the mean amplitude of the N170 elicited by human eyes was significantly larger than those by animal eyes. These differences in response latencies and amplitudes of the N170 suggest existence of at least 2 different visual evoked potentials with similar latencies (i.e., N170) which are sensitive to faces in general and human eyes, respectively. Dipole source localization analysis indicated that dipoles for the N170 elicited by eyes were located in the posterior inferior temporal gyrus, and those for faces, located initially in the same region, but moved toward the fusiform and lingual gyri at the late phase of the N170. The results indicated that information processing of faces and eyes separated at least as early as the latency of the N170 at the posterior inferior temporal gyrus as well as the fusiform and lingual gyri, and might provide neurophysiological and anatomical bases to an initial structural encoding stage of human faces.     

猴脑杏仁体的认知功能

认知是脑的高级功能，其产生机制是脑科学的研究前沿之一。脑的认知功能涉及大脑皮质和皮质下的广泛脑区，不同部位涉及不同的认知类型。杏仁体（amygdala）是参与情绪性学习认知的重要结构。作者工作过的日本富山医科药科大学（现为富山大学医学部）研究生院系统情绪科学研究室长期从事杏仁体的认知功能研究，成绩卓著。本文综述了该研究室对猴脑杏仁体社会认知功能以及相关的最新研究成果，以飨读者。     

Effect of aerobic capacity on sweat rate and fluid intake during outdoor exercise in the heat

We measured the aerobic capacity, sweat rate and fluid intake of trained athletes during outdoor exercise and examined the relationship between aerobic capacity and thermoregulatory responses at high ambient temperatures. The maximal aerobic capacity ( ) of the subjects, nine male baseball players of college age, was determined by maximal exercise tests on a cycle ergometer. The subjects practised baseball regularly without drinking fluids from 1330 to 1530 hours. After 30 min rest, they played a baseball game with free access to a sports drink at 15°C from 1600 to 1830 hours. At a mean ambient temperature of 36.7 (SEM 0.2)°C, the mean percentage of body mass loss (m _b) and increase of oral temperature (T _o) from 1330 to 1530 hours was 3.47 (SEM 0.12)% and 0.81 (SEM 0.14)°C, respectively. The sweat loss from 1330 to 1830 hours was 56.53 (SEM 1.56)ml · kg^–1 of body mass (M _b) while the mean fluid consumption was 44.78 (SEM 2.39)ml · kg^–1 ofm _b, with recovery of 76.08 (SEM 2.81)% of sweat loss. The was significantly inversely correlated withm _b, fluid intake and rehydration amount, but showed no correlation withT _o. These results would suggest that at a given exercise intensity in subjects with a higher aerobic capacity body temperature is maintained with a lower sweating rate than that in subjects with a lower aerobic capacity.     

Mixed connective tissue disease with fatal pulmonary hypertension and a review of literature

Summary The paper presents an autopsy case of mixed connective tissue disease (MCTD) with pulmonary hypertension (PH) and a review of literature. A 33-year-old woman with Raynaud's phenomenon and dyspnea of one year duration was diagnosed as having MCTD on the basis of a higher titer (1:163,840) of serum antibodies to the ribonucleoprotein (RNP). Cardiac catheterization showed complicating PH, confirmed an autopsy by the findings of concentric intimal cellular proliferation and typical plexiform lesions in the small arteries and arterioles of the lung, suggesting primary PH. Fatal PH with MCTD has been reported only 6 cases in literature including our case. All were young females, with histopathological findings consistent with plexogenic pulmonary arteriopathy in 5 cases and with recurrent pulmonary thromboembolism in the other. The aetiology of PH is still unknown, but it may be due to vasoconstriction evoked by the hyper-reactivity of the vessels.     

Prediction of hepatic graft viability before reperfusion: an analysis of effluent from porcine allografts

Rapid and reliable assessment of hepatic graft viability is important for successful orthotopic liver transplantation (OLTx). OLTx was performed in 11 pairs of pigs via a venovenous bypass. Six of these grafts were transplanted immediately (group A), while the other five were preserved in University of Wisconsin (UW) solution for 24 h and then transplanted (group B). All grafts were flushed with 300 ml of chilled (4°C) Ringer's lactate solution before reperfusion of the graft, when 20 ml of effluent from the graft was collected and the concentrations of ammonia, lactic acid, GOT, and LDH were measured. Four of the six pigs in group A survived longer than 3 days, while the other two pigs died of causes other than graft dysfunction. All five pigs in group B died either of hemoperitoneum or hemodynamic instability due to liver failure. The histology of postperfusion biopsies in group A showed minimal pathological changes, while the grafts in group B revealed moderate to severe ischemic injuries. Ammonia and lactic acid in the effluent of group B were significantly higher than those of group A (1511±216 vs 417±333 g/dl and 114.1±12.2 vs 91.4±12.2 mg/dl, respectively; P<0.05 in both cases). Before reperfusion, the rate of total adenine nucleotides in all of the substances in the graft, which were measured using high performance liquid chromatography (HPLC), inversely correlated with the ammonia levels in the effluent. We conclude that an analysis of the effluent, (i.e. the levels of ammonia and lactic acid), flushed from a hepatic graft before reperfusion could serve as a predictor of hepatic graft viability.     

Immunocytochemical evaluation abl-Gene products in Leukemic Cell Lines

We raised monoclonal antibody (MAb) against a synthetic oligopeptide corresponding to a portion of the predictedv-abl protein sequence (379–390). This MAb reacted with all of theabl-gene products (pl45^c-abl, pl50^c-abl and 210^bcr-abl fused protein) and was not specific for any one of them. Immunocytochemically, we investigated the expression and localization of theabl-gene products in various leukemic cell lines. Positive immunoreactions were observed in Ph¹ positive leukemic cell lines (K562 and KU-812) and erythro-leukemic cell lines (HEL and K3D) and were located on the cell membrane. Electron microscopically, a different distribution pattern was observed among the cell lines: linear and almost even in Ph¹ positive leukemic cell lines, whereas spotted or budding-like in erythroleukemic cell lines. Ph¹ translocation produces p210^nbcr-abl fused protein with not only altered autophosphorylation activities but also altered subcellular distribution patterns.