Near-fatal cerebral edema associated with adenovirus type 2 infection in a previously healthy infant

We report a near-fatal case of cerebral edema associated with adenovirus type 2 infection in a previously healthy 19-month-old boy. After 3 to 4 d of high fever and a series of seizures, he developed persistent loss of consciousness and irreversible respiratory arrest. Adenovirus type 2 infection was diagnosed by virus isolation from his stool and serology.     

Substance P containing nerve fibers in rectal mucosa of ulcerative colitis

BACKGROUND AND PURPOSE: The intestine is rich in peptidergic innervation, which modulates mucosal immune responses. Among neuropeptides, substance P (SubP) has received considerable attention for stimulatory effects on various immunocytes in inflammatory diseases. In our prior study, we demonstrated increased innervation of SubP containing nerve fibers (SubP fibers) in ulcerative colitis (UC) surgically resected colonic specimens. In the present study, we examined the alterations of SubP fibers among various subgroups of UC, divided according to clinicopathologic features. METHODS: Distribution of SubP fibers were examined immunohistochemically in the rectal biopsy specimens of UC. The UC group was further divided into subgroups according to six clinicopathologic parameters. The linear density of SubP fibers was measured by digitalized morphometry for quantitative analysis. RESULTS: Multivariate analysis revealed significant correlations between linear density of SubP fibers vs.activity of diseases and total dose of prednisolone. Linear density was significantly increased in active cases of UC (active UC, 22.6±1.6 μm/1,000 μm ²;vs.inactive UC, 12.2±0.8 μm/1,000 μm ²;P<0.01). Furthermore, the increase was pronounced in cases that showed persistent inflammation and, accordingly, needed a high dose or continuous administration of prednisolone. CONCLUSION: Alterations in SubP fibers appear to play an important role in the pathogenesis of UC.     

Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability

We demonstrated recently that chronic administration of aldosterone to rats induces glomerular mesangial injury and activates mitogen-activated protein kinases including extracellular signal-regulated kinases 1/2 (ERK1/2). We also observed that the aldosterone-induced mesangial injury and ERK1/2 activation were prevented by treatment with a selective mineralocorticoid receptor (MR) antagonist, eplerenone, suggesting that the glomerular mesangium is a potential target for injuries induced by aldosterone via activation of MR. In the present study, we investigated whether MR is expressed in cultured rat mesangial cells (RMCs) and involved in aldosterone-induced RMC injury. MR expression and localization were evaluated by Western blotting analysis and fluorolabeling methods. Cell proliferation and micromechanical properties were determined by [3H]-thymidine uptake measurements and a nanoindentation technique using an atomic force microscope cantilever, respectively. ERK1/2 activity was measured by Western blotting analysis with an anti-phospho-ERK1/2 antibody. Protein expression and immunostaining revealed that MR was abundant in the cytoplasm of RMCs. Aldosterone (1 to 100 nmol/L) dose-dependently activated ERK1/2 in RMCs with a peak at 10 minutes. Pretreatment with eplerenone (10 micromol/L) significantly attenuated aldosterone-induced ERK1/2 phosphorylation. Aldosterone (100 nmol/L) treatment for 30 hours increased [3H]-thymidine incorporation and decreased the elastic modulus, indicating cellular proliferative and deforming effects of aldosterone, respectively. These aldosterone-induced changes in cellular characteristics were prevented by pretreatment with eplerenone or an ERK (MEK) inhibitor, PD988059 (100 micromol/L). The results indicate that aldosterone directly induces RMC proliferation and deformability through MR and ERK1/2 activation, which may contribute to the pathogenesis of glomerular mesangial injury.     

Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones

In Japan the composition of gallstones is changing rapidly from the once-predominant brownpigment stones to cholesterol ones. The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol gallstones, 8 with black- or brown-pigment gallstones, 7 without gallstones) a liver biopsy and hepatic bile were surgically obtained under standardized conditions. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in gallstone-free controls (195 ±10 vs. 146 ±8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis, cholesterol 7 α-hydroxylase, the rate-limiting enzyme for bile acid synthesis, and 7 α-hydroxy-4-cholesten-3-one 12 α-hydroxylase (12 α-hydroxylase), the rate-limiting enzyme for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA reductase and cholesterol 7 α-hydroxylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 α-hydroxylase and 12 α-hydroxylase activities (Rs = 0.44, P < 0.05) in all subjects, irrespective of the existence of gallstones. The activities of the three rate-limiting enzymes did not differ significantly among the three groups (cholesterol stone, pigment stone and stone-free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients with cholesterol gallstones does not result from an increased hepatic cholesterol synthesis or a decreased bile acid synthesis. This study was supported in part by a Grant-in-Aid for Scientific Research (No. 02454226) from the Ministry of Education, Science and Culture of Japan, and a grant from University of Tsukuba Project Research.     

Aging,respiratory efforts during sleep,and pulsus paradoxus

Forty patients with either obstructive sleep apnea syndrome or a clinical complaint of daytime sleepiness with measured nocturnal increase in upper airway resistance and snoring were investigated during sleep for the presence of pulsus paradoxus, which is defined as a decrease in systolic blood pressure (SBP) of at least 10 mmHg during inspiration. Two thirds of the subjects presented pulsus paradoxus. Age, lowest oxygen saturation (SaO₂), and negative inspiratory esophageal pressure nadir (an index of inspiratory effort) were the only studied variables which could statistically dissociate patients presenting pulsus paradoxus. We then divided the patient population into three different subgroups of equal number based upon the degree of decrease in SBP (i.e., >20 mmHg, <20 but >10 mmHg, and <10 mmHg). In this second analysis, age was the only significant variable that separated the three groups. Lowest SaO₂ could not be used to statistically separate subjects with mild to moderate pulsus paradoxus from those without it; and negative inspiratory esophageal pressure measurements could only significantly identify subjects with severe pulsus paradoxus (i.e., >20 mmHg) from those without any pulsus paradoxus. The variable which correlated best with age was negative inspiratory esophageal pressure nadir (R = 0.83). Our interpretation is that as age increased, negative inspiratory esophagel pressure became less negative, due to the known impact of aging on muscles, and pulsus paradoxus was no longer observed. Offprint requests to: C. Guilleminault     

Microscopic observation of chemical modification in sections using scanning acoustic microscopy

A scanning acoustic microscope (SAM) calculates the speed of sound (SOS) through tissues and plots the data on the screen to form images. Hard tissues result in greater SOS; based on these differences in tissue properties regarding SOS, SAM can provide data on tissue elasticity. The present study evaluated whether tissue modifications, such as formalin fixation, periodic acid‐Schiff (PAS) reactions and protein degradation, changed the acoustic properties of the tissues and whether SAM could be a useful tool for following chemical changes in sections. The fixation process was observable by the increased SOS. During the PAS reaction, the glycosylation of tissues was characterized by an increased SOS. Mucous or glycogen distribution was visualized and was found to be statistically comparable among lesions and states. Protease digestion by pepsin led to a decreased SOS. Tissue sensitivity to proteases varied due to the stage, cause and duration of inflammation or ageing. Changes in acoustic properties were more sensitive than those in optical histology. SAM facilitates the visualisation of the time course or distribution of chemical modifications in tissue sections, thus aiding their comparison among tissues. SAM may be an effective tool for studying changes such as protein cross‐linkage, tissue repair and ageing.