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Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 325 records · Page 18Linked to original sources

Modes of Seoul virus infections: persistency in newborn rats and transiency in adult rats.

To understand the mode of persistent infection of Seoul virus in rodents, we examined the distribution of the virus genome and antibody production in infected rats. When 1-day-old rats were inoculated with the KI-83-262 strain, the S segment of viral genome was detected in sera, clots, lungs and kidneys from 3 to 184 days post inoculation (d.p.i.) by nested reverse transcriptase PCR. On the other hand, when 7-week-old rats were infected with this virus, viral genome was detected only in the lungs from 3 to 50 d.p.i. The neutralizing antibody titers of rats inoculated at 1-day of age were higher than those of rats inoculated at 7 weeks of age. In both age groups, however, the IgG avidity of antibody increased along with the course of infection. We found that urban rats (Rattus norvegicus) infected early in life harbored the virus for more than 6 months.

Animals↗

Role of platelet-activating factor in pathogenesis of galactosamine-lipopolysaccharide-induced liver injury.

In an attempt to clarify the role of platelet-activating factor (PAF) in the pathogenesis of hepatic injury induced by galactosamine (GalN) plus lipopolysaccharide (LPS), effects of WEB 2086 (PAF receptor antagonist) on hepatic injury in vivo as well as on neutrophil adherence to hepatic endothelial cells in vitro have been investigated, as we have recently clarified the role of neutrophils in this experimental model of hepatic injury. Although an enhanced serum TNF-alpha level after GalN-LPS administration was not reduced by WEB 2086, hepatic injury and hepatic neutrophil accumulation in the liver after GalN-LPS administration were attenuated by WEB 2086. An in vitro study revealed that an enhanced neutrophil adhesion to hepatic endothelial cells by stimulation with the sera that were collected from the GalN-LPS-treated rats, was reduced in the presence of WEB 2086 in a dose-dependent manner. In addition, LPS, TNF-alpha, and PAF were found to enhance the neutrophil adherence to hepatic endothelial cells, which was reduced in the presence of WEB 2086. These results suggest that PAF play an important role in the GalN-LPS induced hepatic injury and that PAF receptor antagonist reduces the neutrophil adherence to hepatic endothelial cells in the liver.

Animals↗

Large spleno-caval shunt not accompanied by cirrhosis or encephalopathy.

A 40-year-old man with a large spleno-caval shunt through the azygos vein is described. This was considered a rare case, because the patient had no accompanying advanced liver disease, or episodes of hepatic encephalopathy. During checks after abnormal liver function test results, a shunt vessel was detected incidentally by ultrasonography. Computed tomography, magnetic resonance imaging, and angiography demonstrated that it was a large shunt between the splenic vein and superior vena cava through the coronary and azygos veins. The patient was a hepatitis B virus carrier and was positive for anti-HBe, and had a history of heavy drinking. However, on laparoscopic examination, the liver was not cirrhotic and the biopsy revealed only mild chronic hepatitis without bridging fibrosis. There were no esophageal varices or hepatosplenomegaly. On hemodynamic evaluation, the wedge hepatic vein pressure was slightly elevated and hepatic blood flow was reduced to half the normal value. Despite the large portal-systemic shunt, the patient had no history or signs of hepatic encephalopathy. The clinical features of this rare case are discussed.

Adult↗

ETA receptor-mediated role of endothelin in the kidney of DOCA-salt hypertensive rats.

Renal effects of FR139317, an endothelin ETA receptor antagonist, were examined using anesthetized normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The intravenous bolus injection of FR139317 (10 mg/kg) produced a slight decrease in mean blood pressure (MAP; -13%) in the control rats and this hypotension was accompanied by a moderate renal vasodilation (renal vascular resistance: RVR; -12%). In the DOCA-salt hypertensive rat, FR139317 had a more pronounced hypotensive effect (MAP; -26%) accompanied by a potent renal vasodilation (RVR; -33%). FR139317 significantly increased renal blood flow only in the DOCA-salt rats. In contrast, FR139317 produced a significant decrease in urine flow and urinary sodium excretion only in control rats. Northern blot analysis revealed that the renal prepro endothelin-1 (ET-1) mRNA level was significantly increased in DOCA-salt hypertensive rats. Thus, it seems likely that endogenous ET-1 is responsible for the maintenance of DOCA-salt-induced hypertension. We also suggest that at least in part, ET-1 and ETA receptors are involved in renal hemodynamic abnormalities in DOCA-salt-induced hypertension. The augmentation of renal ET-1 production may possibly have a function in the development and maintenance of DOCA-salt-induced hypertension.

Animals↗

Detection of an amino acid polymorphism in hormone-sensitive lipase in Japanese subjects.

Hormone-sensitive lipase (HSL) plays an important role in energy metabolism by controlling the hydrolysis of triglycerides stored in adipose tissue. To investigate whether mutations in the HSL gene are associated with non-insulin-dependent diabetes mellitus (NIDDM), we screened for mutations of this gene using single-stranded conformation polymorphism (SSCP) in 35 Japanese subjects with NIDDM. SSCP analysis identified a variant pattern in axon 4, and the sequence showed that this variant pattern resulted from amino acid polymorphism (Arg309Cys). Subsequent study showed that this polymorphism was found in 18 of 151 NIDDM patients and 10 of 97 nondiabetic subjects, but allele frequency was not significantly different between the two groups (P = .7). Body mass index, serum triglyceride, and high-density lipoprotein (HDL) cholesterol were not different in subjects with and without the polymorphism. But serum total cholesterol was higher in subjects with the polymorphism than in subjects without it (P = .0005). These data indicate that this HSL polymorphism is not associated with NIDDM, obesity, and serum triglyceride level. However, an effect of the polymorphism to elevate serum total cholesterol has not been excluded, although further study is necessary to resolve its association with cholesterol metabolism.

Alleles↗

Hypoglossal premotor neurons in the rostral medullary parvocellular reticular formation participate in cortically-induced rhythmical tongue movements.

Premotor neurons projecting to the hypoglossal (XII) nucleus and participating in cortically-induced rhythmical tongue movements were defined by extracellular recording in the cat. Two thirds (37/57) of antidromically identified XII premotor neurons sampled in the rostral medullary parvocellular reticular formation showed changes in their firing pattern during cortically-induced rhythmical activity of XII motoneurons. Fifteen of the 37 neurons showed a firing in phase with rhythmical activity of either the medial or lateral branch of the XII nerve (phasic-type). The remaining 22 neurons showed an increase in discharge with no apparent correlation with cortically-induced rhythmical activity of the XII nerve (non-phasic-type). Among the phasic- and non-phasic-type neurons, 30 neurons received inputs from the cortical masticatory area, and 14 neurons received further excitatory inputs from the inferior alveolar nerve. By systematic mapping of the stimulation sites effective for antidromic activation, four phasic-type neurons were confirmed to project to either tongue-protruding or -retracting XII motoneuron pools in accordance with their burst firing, suggesting that the phasic-type premotor neurons contribute to excitation of XII motoneurons during cortically-induced rhythmical activity. It is concluded that there are the XII premotor neurons driving cortically-induced rhythmical activity of XII motoneurons in the rostral medullary parvocellular reticular formation.

Animals↗

[1-11C]octanoate as a potential PET tracer for studying glial functions: PET evaluation in rats and cats.

To evaluate the ability of [1-11C]octanoate as a PET tracer for imaging the brain, we examined its distribution in the brain and surrounding tissues in rats and cats with PET. In rats, owing to the accumulated radioactivity in the harderian glands, clear brain images were not obtained at rostral levels. In cats, the brain was imaged clearly at every level of the coronal brain slices, suggesting the potential of [1-11C]octanoate for imaging the brain.

Animals↗

Second transplantation with CD34+ bone marrow cells selected from a two-loci HLA-mismatched sibling for a patient with chronic myeloid leukaemia.

A 43-year-old man with chronic myeloid leukaemia underwent a second transplant with CD34+ bone marrow cells selected from his two-loci HLA-mismatched sibling after rejection of the first graft from an HLA-matched unrelated donor. By immunomagnetic positive selection, CD34+ marrow cells at 0.95 x 10(6)/kg with 97% purity and CD3+ T lymphocytes at 1.3 x 10(4)/kg were collected and transplanted. Engraftment was confirmed to be of CD34+ cell-donor origin. The patient developed only grade I acute graft-versus-host disease (GVHD) and no chronic GVHD to date. These observations suggest that allogeneic CD34+ bone marrow cells are capable of reconstituting haemopoiesis and that CD34+ selection could be applicable to T-cell depletion.

Adult↗

The relationship of neuropsychological status and productive outcomes following traumatic brain injury.

Neuropsychological assessment is a standard component of traumatic brain injury rehabilitation programmes; however, the relationship between neuropsychological test scores and functional abilities is not clear. The current study compared serial neuropsychological test data with functional outcomes for 152 subjects. Outcome was operationally defined for three activity settings (home, school, work) with six levels of productivity for each. Productivity was defined as one's ability to function at increasing levels of independence. Demographic and caseload variables were analysed utilizing correlation and stepwise multiple regression analyses. Significant relationships to outcome were found between certain neuropsychological test scores, and certain demographic variables. Positive outcomes were related in part to patient's speed of information processing, memory skills, and simultaneous processing abilities. Also related to positive outcomes were mechanism of injury, level of insurance funding, premorbid educational level, and negative history of substance abuse. The activity setting influenced outcome such that it appeared to be most difficult to return to work, suggesting the necessity of adequate vocational assistance. However, cognitive and demographic variables accounted for less than 30% of the total variance in outcome. Therefore, brain injury rehabilitation must be multifaceted.

Activities of Daily Living↗

Life span and tumours in the first-generation offspring of the gamma-irradiated male mouse.

C57BL/6 male mice were exposed to 3 Gy 60Co gamma-rays and mated with unirradiated females after 15 days to produce F1 progeny produced following irradiation of the spermatids. After weaning the offsprings were allowed to live their normal life span. The mean litter size of the irradiated group significantly decreased from 7.1 to 4.9 (p < 0.01), but the sex ratio was not altered by the irradiation. No significant differences in the survival curve and mean life-span between the irradiated and control groups were noted. The only radiation effect in tumour incidence was a decrease of histiocytic sarcoma in female offspring of irradiated males. Except for this, there were no significant differences between the irradiated group and the control group in the incidence or age distribution of tumours.

Animals↗

Individual expression of Candida tropicalis peroxisomal and mitochondrial carnitine acetyltransferase-encoding genes and subcellular localization of the products in Saccharomyces cerevisiae.

In an n-alkane assimilating yeast, Candida tropicalis, carnitine acetyltransferase (CAT; EC 2.3.1.7) was localized in both peroxisomes and mitochondria. Both CATs were encoded by one gene, CT-CAT, although the initiation sites of translation were suggested to be different. In the present study, the genes corresponding to the supposed C. tropicalis peroxisomal and mitochondrial CATs, which were truncated from the CT-CAT gene, were individually expressed in Saccharomyces cerevisiae, using the C. tropicalis isocitrate lyase promoter (UPR-ICL), which is inducible by oleic acid in concert with proliferation of peroxisomes in S. cerevisiae [Umemura, K., Atomi, H., Kanai, T., Teranishi, Y., Ueda, M., and Tanaka, A. (1995) Appl. Microbiol. Biotechnol. 43, 489-492]. The 71 kDa precursor of mitochondrial CAT, initiating at the first Met, was found to be processed to the mature size (66 kDa) in S. cerevisiae and immunoelectronmicroscopical observation revealed that this enzyme was localized in mitochondria. On the other hand, 68 kDa CAT, initiating at the second Met (residue No. 19), had no cleavable signal and was translocated into peroxisomes and cytosol, but not into mitochondria. The amino-terminal amino acid sequences of individually expressed CATs were identical to those of CATs isolated from alkane-grown C. tropicalis cells, respectively. These results demonstrated that only the 71 kDa protein yielded the 66 kDa protein and that peroxisomal and mitochondrial CATs arose from the difference in the initiation sites of translation.

Amino Acid Sequence↗

Induction of platelet-derived growth factor beta-receptor in focal ischemia of rat brain.

Our previous study on the ischemia-induced expression of platelet-derived growth factor (PDGF)-B chain in the rat brain prompted us to examine expression of PDGF beta-receptor in the ischemic brain. Focal ischemia was induced by permanent tandem occlusion of middle cerebral and common carotid arteries in spontaneously hypertensive rats. Northern analysis revealed that ischemia significantly increased expression of the receptor in the ischemic neocortex at 4 and 7 days (328 +/- 109%; 323 +/- 119%, respectively, over control: n = 4, p < 0.05 versus sham). Neurons in infarct transiently showed increased immunostaining for the receptor at 1 day, whereas neurons in periinfarct area showed sustained and increased immunoreactivity from 1 to 14 days post-ischemia. Reactive glial cells in the external capsule and in molecular layer of the neocortex adjacent to infarct possessed enhanced immunoreactivity from 1 to 21 days. Furthermore, marked immunoreactivity was observed on brain macrophages in infarct and on the abluminal side of capillaries surrounding infarct from 4 to 7 days. These results demonstrated that ischemic insult increases expression of the PDGF beta-receptor at both the mRNA and protein level in the brain, suggesting its important role in cellular cascade of the ischemic brain.

Animals↗

The relevance of hemodynamic factors to perioperative ischemic complications in childhood moyamoya disease.

Of 124 children younger than 15 years who underwent surgery for moyamoya disease, 21 (16.9%) experienced perioperative ischemic complications that could not be unequivocally attributed to the surgery. Eleven of the 21 patients experienced infarctions, and 10 experienced reversible ischemic neurological deficits without new lesions, as revealed by computed tomographic scans. An examination of the patients' perioperative clinical and laboratory data revealed that the mean values of intra- and postoperative minimum arterial carbon dioxide pressure, maximum arterial carbon dioxide pressure, and mean arterial pressure were similar in patients with and without ischemic complications. However, in patients with perioperative complications, the incidence of preoperative transient ischemic attacks (TIAs) and intra- and postoperative hypercapnia (maximum arterial carbon dioxide pressure > 45 mm Hg) was significantly higher. In addition, 7 of the 11 perioperative infarctions occurred in patients with frequent preoperative TIAs and intra- and postoperative hypercapnia. Cerebral blood flow studies with preoperative acetazolamide loading showed that the new infarctions were located in areas in which the cerebral blood flow had been compromised. Our results suggest that the occurrence of frequent preoperative TIA is an important indicator of the instability of the cerebral hemodynamics and of the risk of perioperative ischemic complications. To prevent these complications, preoperative management aimed at stabilizing the hemodynamic status is very important. Children who have moyamoya disease and who experience frequent preoperative TIAs are at risk for ischemic brain damage caused by hypercapnia as well as hypocapnia and hypotension. The establishment and maintenance of normocapnia with normotension are highly desirable for the perioperative management of moyamoya disease in children.

Adolescent↗

Polymerase chain reaction for the detection of Chlamydia psittaci in the feces of budgerigars.

The polymerase chain reaction (PCR) targeting the ompA gene of Chlamydia psittaci was evaluated for its ability to detect chlamydiae in fecal specimens of budgerigars as compared with isolation procedures using cell culture and embryonated egg inoculations. Several procedures for PCR template DNA preparation were compared so as to determine their detection levels for chlamydiae propagated in cell culture in the presence of fecal materials. Tween-20 and proteinase K treatments followed by centrifugation of the template DNA were found to be an appropriate procedure for DNA preparation for primary PCR. Subsequent nested PCR was shown to detect 4.8 IFU/ml or 84 particles/ml of chlamydiae. Chlamydiae in 50 fecal specimens from apparently healthy budgerigars were examined by nested PCR and several other methods. Nested PCR detected chlamydiae at a higher rate (12/50, 24%) than the isolation procedure in embryonated eggs (6/50, 12%). Primary PCR combined with the isolation procedure in cell culture gave a detection rate (5/50, 10%) similar to that of isolation from embryonated eggs. Detection rates by primary PCR (1/50, 2%) and in cell culture (0%) were inferior to the other procedures.

Animals↗

Experimental Chlamydia psittaci infection of Japanese quail.

Japanese quail were used for the infection model of avian chlamydiosis. One-day-old Japanese quail were highly susceptible to lethal infection by a Chlamydia psittaci strain of budgerigar origin upon inoculation via the air sac route with 10(4.1) FFU of the organism, showing an acute and lethal course with chlamydial propagation. In contrast, 7-day-old quail developed resistance to the infection as shown by the lack of lethal effect with the same dose. The resistance of 7-day-old birds was abolished by immunosuppressive treatment with cyclophosphamide. Upon inoculation with a sublethal dose of 10(2.1) FFU, latent infection was established in 1-day-old birds with a minimum number of the organism. The latent infection in the birds was converted to the lethal form by treatment with cyclophosphamide along with chlamydial propagation and suppression of antibody production.

Aging↗

Multiple primary cancers with microsatellite instability: report of a case.

We report here a patient who developed a variety of tumors both synchronously and metachronously over a 2-year period. The involved organs were the uterus, ureter, and small and large intestines. The patient underwent open surgery 3 times and polypectomies 6 times. Postoperative histopathologic analysis showed 2 adenomas and 8 carcinomas. Genetic analysis revealed microsatellite instabilities at the tested loci in all 10 tumors, indicating that replication errors played an essential role in the tumorigenesis. Early identification of microsatellite instability could be useful for predicting development of additional primary cancers.

DNA, Neoplasm↗

Analysis of Met235 to Thr variant of the angiotensinogen gene in relation to the blood pressure and family history of essential hypertension in Japanese children.

A recent study reported a significant relationship between a T704-->C (Met235-->Thr) variant in exon 2 of the angiotensinogen gene in adults and essential hypertension. In the present study, this variant was detected in 131 Japanese children using a polymerase chain reaction. The allele frequency of the variant was 0.76. The genotype frequency of the homozygote for the allele was 0.59, and children who were homozygous had higher systolic blood pressure than those with the other two genotypes. No relationship was found between children's polymorphism and a family history of essential hypertension. These findings suggest that this molecular variant of the angiotensinogen gene may play some role in the regulation of blood pressure in Japanese children.

Angiotensinogen↗

The usefulness of measuring body fat deposition for detecting obesity and atherogenesity in Japanese school children.

Body fat deposition was measured in overweight and non-overweight children using a bioelectrical impedance method, and its relationship with serum lipids and apolipoproteins was investigated in 90 overweight children (over 120% of their ideal weight) and 241 non-overweight children aged 10-15 years in Niigata Prefecture. The results were as follows. Overweight boys had significantly higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), atherogenic index (AI), RLP-cholesterol (RLP-C), apoA1, apoA2, apoB, apoC2, apoC3, apoE and the ratio of apoB to apoA1 than non-overweight boys. Overweight girls had significantly higher levels of TC, LDL-C, AI, remnant-like lopoprotein cholesterol (RLP-C), apoA2, apoB, apoC2, apoC3, apoE and the ratio of apoB to apoA1 than non-overweight girls. It has been reported that of all children studied 2.1% had higher levels of RLP-C than its upper limit known for adults (12 mg/dL). Of the overweight children in the present study, 4.4% had a high level of RLP-C whereas only 1.2% of non-overweight children had a high RLP-C level. No difference in the lipoprotein levels was found between overweight and non-overweight children. In both boys and girls, relative weight, body fat, skinfold thickness and body mass index (BMI) were correlated with the lipoprotein levels. Non-overweight boys whose body fat was over 20% had significantly higher levels of TC, LDL-C, apoA2, apoB, apoC2, apoE and apoB/A1 than those whose body fat was less than 20%. It was concluded that the measurement of body fat deposition, together with relative weight, was useful for detecting obesity and atherogenesity in Japanese school children.

Adolescent↗