Biomedical subjects
Publications and source records attributed to Y Umeda.
A pediatric patient with enteritis, which showed dramatically diffuse uptake of 99mTc pertechnetate in the intestine, is reported. Repeated study after medical treatment exhibited complete disappearance of the intestinal uptake. 99mTc pertechnetate scintigraphy has the potentiality for diagnosing and monitoring active enteritis.
This investigation was designed to evaluate the morphological changes of anterior spinal artery (ASA) and its reaction to prostaglandinE1 (PGE1) during aortic cross-clamping. ASA during 30 min cross-clamping was observed with charge-coupled device (CCD) and ASA diameter (ASAD) was measured. Group A: Infrarenal aorta was cross-clamped. Group B: Infrarenal aorta was cross-clamped and aorta above the bifurcation was snared. The aortic segment between clamp and snare was perfused with blood. Group C: PGE1 of 100 ng/kg/min was added to perfusate of Group B. The aortic segmental pressures in group B and C were about 30% of the proximal systolic arterial pressure and were significantly higher than distal pressure of group A. After cross-clamping, ASAD decreased about 80% of before cross-clamping in group A. By segmental perfusion of which pressure was about 30% of proximal systolic arterial pressure, ASAD remained almost 90% in group B. By administration of PGE1, ASAD was significantly increased in group C. The changes of ASAD were significantly different between group A and C, and between group B and C.
The aim of the present study was to clarify the differences in the progression and the characteristics of silent cerebral infarcts (SCI) between patients with coronary artery disease (CAD) and hypertensive patients. Silent cerebral infarcts, a powerful prognostic indicator for stroke, are frequently found in patients with CAD and in hypertensives. However, the differences in the characteristics of SCI and related risk factors between CAD and hypertensive patients have not been thoroughly investigated. We evaluated the number of SCI and their distribution using brain magnetic resonance imaging (T1- and T2-weighted images) in 107 patients with CAD (validated by coronary angiography) and 101 hypertensive patients without history of clinical stroke. The prevalence of multiple SCI (three or more infarcts per person) in patients with CAD and with hypertension was significantly higher than in hypertensives without CAD (46% v 21%; P = .001), whereas that of patients with CAD without hypertension was intermediate (31%). The patients with multi- (two- or three-vessel) vessel diseases (VD) had a significantly higher prevalence of multiple SCI than the hypertensives and the no-stenosis or 1-VD group (68.1% in the 3-VD group, 52.0% in the 2-VD group, 26.8% in the 1-VD group, and 21.0% in the no-stenosis group). Multiple logistic regression analysis revealed that in the CAD group, the number of involved coronary arteries was an independent determinant of SCI (P < .005), whereas in the hypertensive group, age was an independent determinant of SCI (P < .005). When we investigated the distribution of SCI, in the CAD group, SCI in the deep perforator territory (the basal ganglia and the thalamus) were independently associated with the number of involved coronary arteries (P < .005), whereas SCI in the white matter were independently associated with age only (P < .005). In conclusion, SCI were more advanced in the patients with multivessel CAD than in the hypertensive patients, and were more common in patients with CAD and hypertension than in those without hypertension. Coronary atherosclerosis was independently and specifically associated with SCI located in the deep perferator territory but not of SCI located in the white matter. The CAD-atherosclerosis and hypertension may be independently involved in the pathologic process of SCI.
In the present study, the low molecular-weight fraction of the culture supernatant of anti-Plasmodium falciparum antibody-producing hybridoma cells (HybSL) was used in synchronous culture with P. falciparum FVO strain. When synchronous cultures were treated with HybSL solution on day 5, gametocytogenesis was also induced. Gametocytes were consistently found from the third day after treatment and reached a peak on the fourth day. An increase in pH and hemoglobin concentrations and decrease in lactate concentrations were observed on the first day after treatment. These phenomena suggested that HybSL solution partially inhibited glycolysis of erythrocytes parasitized with schizonts and resulted in hemolysis of infected erythrocytes. On the other hand, the production of gametocytes did not increase in cultures treated with HybSL solution on day 4 of synchronous cultures in which ring forms were plentiful. Most ring forms were not killed by HybSL solution and quickly developed to trophozoites and schizonts rather than gametocytes. Consequently, it is assumed that ring forms on day 4 of synchronous cultures have finished differentiation into the asexual stage. The conversion of asexual parasites to gametocytes may be triggered only when late-stage trophozoites or early-stage schizonts are treated with HybSL solution.
Early-morning blood pressure is generally viewed as an important therapeutic target, for two reasons. First, for antihypertensive agents taken once daily in the morning, the timing of the trough plasma drug level, and thereby the lowest pharmacodynamic effect, often coincides with the early morning rise in blood pressure and heart rate. Evidence has been accumulated to suggest that blood pressure control throughout the 24 h period may be necessary to gain complete benefit from antihypertensive medication. In fact, in a longitudinal study, the regression of cardiac hypertrophy in patients with hypertension was more accurately predicted by treatment-induced changes in average 24 h ambulatory blood pressure than by clinic or home-monitored blood pressure readings. The other reason for the importance of morning blood pressure is that cardiovascular risk is heightened at this time of day. A morning surge in sympathetic activity alters haemodynamic forces and predisposes vulnerable coronary atherosclerotic plaques to rupture. At the same time as this risk of plaque rupture is greatest, circadian variations in haemostatic and fibrinolytic factors result in morning hypercoagulability and hypofibrinolysis, promoting the formation of intraluminal thrombi. We recently showed that, in older hypertensives, a greater morning blood pressure surge, mediated at least in part by an exaggerated alpha-sympathetic activity, is associated with more advanced silent cerebrovascular disease as well as a higher future incidence of stroke. The early morning surge in blood pressure could become a new therapeutic target for preventing target-organ damage and subsequent cardiovascular events in hypertension. Of greatest interest is the potential benefit of a chronotherapeutic approach, involving, for example, long-acting chronoformulations, which has not yet been extensively studied.
The generation mechanism of the screech tone in the helical oscillation mode is mainly investigated using a series of instantaneous schlieren photographs. From the photographs, five evanescent sound sources are observed as prominent points along the jet axis. The sound source for the dominant helical oscillation mode is found to be the second prominent point which moves along a circular orbit in a plane perpendicular to the jet axis and just downstream of the rear edge of the third shock cell. It is shown that the speed of a moving sound source is supersonic and that the Mach cone generated by the moving sound source forms the helical-shaped wave front of the screech tone for the helical oscillation mode of the jet. This idea of the moving sound source is well supported by a measured directionality of the screech tone. Sound sources of the other oscillation modes appearing in the other pressure ratio ranges are also described.
The oscillation modes of a supersonic circular twin jet and multijet with square configuration where the center-to-center spacing of nozzles was fixed to 1.4 times the nozzle diameter were investigated experimentally. It is found that the twin jet oscillates simultaneously in three different oscillation modes for the pressure ratios of about 4.1. From the acoustical observation, these oscillation modes are identified as one lateral oscillation mode perpendicular to a plane composed of the twin jet axes and two lateral oscillation modes parallel to this plane. For a multijet with a square configuration, only one lateral oscillation mode was observed. In this case, it is observed that when the spacing between two facing sides of the square formed by four jets is stretched, the spacing between the other two sides shrinks and vice versa.
This study was designed to determine whether gemfibrozil inhibits intestinal lipid absorption. Male Sprague-Dawley rats received an oral dose of 30 mg gemfibrozil/kg body weight for 14 days. Mesenteric lymph cannulation was performed, and a lipid infusion containing 40 micromol/h (35.4 mg/h) of radiolabeled triolein and 2.74 micromol/h (1.06 mg/h) of radiolabeled cholesterol with the addition of 1 mg/h of gemfibrozil was infused intraduodenally at a rate of 3 ml/h for 8 h. The lymph was collected, and the radioactivity levels of the lumen and gut mucosa were measured after the infusion. Lymph cholesterol transport was depressed in gemfibrozil-treated rats, in terms of mass measurements as well as radioactivity in a lesser degree. More radioactive cholesterol remained in the proximal portion of the intestinal lumen and mucosa in the treated rats than in the control rats. More radioactive triglycerides also remained in the proximal intestinal lumen of treated rats, although no difference in lymphatic triglyceride transport was observed between the groups. A significant portion of the radioactive cholesterol remained in the lumen in the gemfibrozil-treated rats. Gemfibrozil increased biliary cholesterol excretion. Thus, this study shows that gemfibrozil inhibits cholesterol absorption in rat intestine.
Two patients with a hyperkinetic syndrome contralateral to acute hemiplegia are presented. One patient showed a right-sided hemiplegia associated with abnormal movements of the left upper limb. In the other patient hemiplegia was localised on the left side while abnormal movements involved the right lower limb. Brain imaging showed acute infarctions (respectively left middle cerebral artery area and right lacunar infarctions) associated with a pre-existing contralateral infarction involving anterior non-primary motor areas. Hyperkinetic syndromes in stroke are mainly related to acute lesion of the contralateral subcortical areas. In our patients, the acute lesions were located ipsilateral to the hyperkinetic body part while the pre-existing lesions were located contralateral to the hyperkinetic side. We speculated that these pre-existing lesions might play a role in the pathophysiology of this clinical syndrome.
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A 75-year-old man was admitted due to nephrotic syndrome, purpura on the legs, which was associated with hepatitis C virus (HCV), and type II mixed cryoglobulinemia. Renal biopsy revealed features of cryoglobulinemic glomerulonephritis. Since the patient was elderly and the HCV genotype was Ib, interferon-alpha for reducing HCV was not indicated. Four sessions of cryofiltration and the administration of corticosteroids improved the proteinuria and renal function strikingly without adverse effects. This case demonstrates that an elderly patient who has nephrotic syndrome caused by cryoglobulinemic glomerulonephritis associated with HCV can be treated safely by cryofiltration with low doses of oral corticosteroids.
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One hundred and seven patients with prostate cancer were treated at Mie University Hospital during the past 12 years between 1988 and 1999. They were between 53 and 83 years old, with an average age of 70.8 years old. The clinical stage was defined as A, B, C and D in 3 (2.8%), 19 (17.8%), 50 (46.7%) and 35 (32.7%) patients, respectively. At initial diagnosis, the tumor was well, moderately and poorly differentiated adenocarcinoma in 26 (24.3%), 47 (43.9%) and 34 (31.8%) patients, respectively. The median follow-up period was 52.3 months. The overall 1, 3 and 5-year survival rates were 98.0%, 86.8% and 75.2%, respectively. The 5-year survival rates for stage A, B, C and D were 100%, 93.8%, 82.1% and 56.9%, respectively. A significant difference (p = 0.017) in 5-year survival rate was noted between stage C and D. The 5-year survival rate was 100% for well differentiated, 78.0% for moderately differentiated, and 53.2% for poorly differentiated adenocarcinoma. A significant difference (p = 0.0016) in the 5-year survival rate was noted between well differentiated and poorly differentiated adenocarcinoma. According to the therapy, the 5-year survival rate in stage C was 86.2% for the radical prostatectomy group and 84.0% for the endocrine therapy group. There was no significant difference between these 2 treatment groups. Endocrine therapies, classified into maximum androgen blockade (MAB) and endocrine therapy other than MAB were performed for stage D as an initial therapy. Although the prognosis in the patients treated with MAB was better than that with other endocrine therapies, there was no significant difference between these 2 endocrine treatment groups.
The induction of gene mutations was examined in MutaMouse after an intraperitoneal injection of 7, 8-dimethylbenz[a]anthracene (DMBA) at 20 mg/kg in a collaborative study participated by four laboratories. Although the DMBA dose used was lower than the level that has been reported to induce micronucleated erythrocytes maximally in several mouse strains, a killing effect appeared after day 9 of the post-treatment interval. Mutations in lacZ transgene were detected by the positive selection assay following in vitro packaging of phage lambda from the genomic DNA of the transgenic animals that survived. The mutant induction was evaluated in the bone marrow, liver, skin, colon, kidney, thymus, and testis 7 to 28 days after the treatment. In the bone marrow, the mutant frequency reached a maximum, approximately a 30-fold increase, 14 days after the treatment and the increased frequency persisted at least up to day 28 of the post-treatment. Induction of mutants was detected in the liver, colon, thymus, and skin to lesser extents. Marginal responses were obtained in the kidney and testis. The slight increases in the mutant frequencies in the kidney and testis observed in some laboratories were within laboratory-to-laboratory or animal-to-animal variations. In contrast to the gene mutation induction in the bone marrow, the frequency of micronucleated reticulocytes increased transiently 3 days after the treatment and returned to a control level before day 8 of the post-treatment. It was suggested that DMBA induced gene mutation is fixed in stem cells depending on cell proliferation while DNA damages responsible for chromosome breakage are not transmitted to progeny cells.
Three sets of cellulose synthase genes were cloned from a cellulose-producing bacterium Acetobacter xylinum JCM 7664. One set of genes (bcsAI/bcsBI/bcsCI/bcsDI) were highly conserved with the well-established type I genes in other strains of A. xylinum, while the other two (bcsABII-A, bcsABII-B) were homologous to the known type II (acsAII). Unexpectedly, they were immediately followed by a gene cluster of bcsX/bcsY/bcsCII/ORF569, likely forming an operon. Western blotting demonstrated that the BcsY protein accumulated in cells. Since BcsY showed striking similarities to a number of membrane-bound transacylases, it was hypothesized that the type II cellulose synthase produces acylated cellulose, which might be anchored on the cytoplasmic membrane. An insertion sequence of IS1380-type was found just upstream of the one type II gene (bcsABII-B), suggestive of nonfunctioning.
A rare case of myotonic dystrophy (MD) with congestive heart failure, associated with QT prolongation and torsade de pointes (TdP) is reported. A 53-year-old woman was admitted to the hospital because of congestive heart failure. Electrocardiograph (ECG) showed first-degree atrioventricular block and QT prolongation. During hospitalization, TdP appeared but returned to sinus rhythm spontaneously. As the patient had quadriplegia, a myopathic face, cataracts, diabetes mellitus, and an increased number of cytosine-thymineguanine (CTG) repeats (760 repeats), she was diagnosed as having MD. Electrocardiographic analysis of her family also revealed abnormal QT(U) prolongation in her daughter and brother who both had MD, while ECG findings of other family members without MD were normal. Thus, the presence of QT(U) prolongation was associated with MD in this family.
BACKGROUND AND PURPOSE: Silent cerebrovascular disease (CVD) has been proposed as a predisposing condition for clinically overt stroke and vascular dementia. Recently, we found increased thrombin generation in silent CVD patients. Here, we report the effect of thrombin inhibition using a potent selective thrombin inhibitor on the cerebral metabolism and function in peripheral arterial occlusive disease (PAOD) patients with or without silent CVD. METHODS: We examined 17 mild chronic PAOD patients, including 2 cases of vascular dementia. We divided the patients into 2 groups: 1 was the advanced CVD group with multiple lacunar infarction and/or advanced periventricular hyperintensity detected by brain MRI (n=12), and the other was the no CVD group that had none of these abnormalities (n=5). We assessed the cerebral biochemical compounds in the deep white matter area and cerebellar hemisphere (8 cm3) by proton MR spectroscopy before and after infusion of argatroban (10 mg/d IV) over 2 hours for 7 days. RESULTS: The ratio of N-acetylasparate (NAA) to total creatine (Cre) in the deep white matter area was significantly lower in the advanced CVD group than in the no CVD group, whereas there were no significant differences in this ratio in the cerebellar hemisphere between the 2 groups. In the former group, this decreased NAA/Cre ratio significantly increased after argatroban therapy, whereas there was no change in the latter group. The 2 patients with vascular dementia showed clinical improvement with marked increases in the NAA/Cre ratio and mini-mental score. CONCLUSIONS: These results suggest that increased thrombin generation may have some pathophysiological roles in developing vascular dementia and its chronic predisposing conditions. Thrombin inhibition may break this vicious cycle and lead to clinical improvement.
Dietary oxysterols can reach the circulation and this may contribute to atherosclerosis, where lipid oxidation is thought to be important. There is also evidence that, in rats, peroxidized lipids are absorbed and transported into lymph [Aw TY, Williams MW, Gray L. Absorption and lymphatic transport of peroxidized lipids by rat small intestine in vivo: role of mucosal GSH. Am J Physiol 1992; 262: G99-G106], although the method used to detect lipid peroxides lacked specificity. We tested whether intragastric administration of vegetable oils containing triglyceride hydroperoxides (TG-OOH) to rats resulted in detectable lipid hydroperoxides in mesenteric lymph. Using sensitive HPLC with postcolumn chemiluminescence detection, we were unable to detect hydroperoxides of triglycerides, cholesterylesters or phospholipids during the course of lipid absorption, and lymph levels of ascorbate, urate, alpha-tocopherol and ubiquinol-9 did not change significantly. By contrast, we observed a striking reducing activity judged by the efficient reduction of administered ubiquinones-9 and -10 to the corresponding ubiquinols. Exposure of rat lymph and isolated chylomicrons to aqueous peroxyl radicals revealed patterns of antioxidant consumption and lipid hydroperoxide formation similar to those described previously for human extravascular fluids and isolated lipoproteins, respectively. In particular, rates of TG-OOH formation in lymph and chylomicrons were very low to undetectable as long as ascorbate and/or ubiquinols were present, but subsequently proceeded in a chain reaction despite the presence of alpha-tocopherol. These studies demonstrate that rat intestine and mesenteric lymph possess efficient antioxidant defenses against preformed lipid hydroperoxides and (peroxyl) radical mediated lipid oxidation. We conclude that dietary lipid hydroperoxides or postprandial oxidation of lipids are not likely to contribute to these particular forms of oxidized lipids in circulation and aortic tissue.