Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 271 records · Page 15Linked to original sources

PubMed1997

Characterization of CD4+CD8+ thymocytes observed in SCID-bg mice.

Previously, we reported that a strain of severe combined immunodeficient (SCID) mice, namely SCID-bg, spontaneously develop CD4+CD8+ double positive (DP) thymocytes despite their scid mutation. In the present study, we intend to further characterize the DP thymocyte population in SCID-bg mice with Southern hybridization and flow cytometry. Southern hybridization analyses of sorted DP thymocytes in SCID-bg mice showed rearrangement of T cell receptor (TCR) beta and TCR gamma gene segments, although the expression of TCR beta and gamma delta TCR molecules was absent. The phenotype of the DP thymocytes in SCID-bg mice was CD44- heat-stable antigen (HSA)+CD25-, and they did not express CD69. Interestingly, the expression of thymus leukaemia (TL) antigen was observed in the DP thymocytes of SCID-bg mice but not in their CD4-CD8- double negative (DN) fraction. Fas expression was higher and bcl-2 expression was down-regulated in the DP thymocytes as compared to the DN thymocytes in SCID-bg mice, suggesting that they are not immortalized cells having escaped from apoptosis. Taken together, these results show that the phenotype of the DP thymocytes in SCID-bg mice is similar to that of the earliest phase of the DP thymocytes in normal mice, although the expression of the molecules in the pre-TCR complex is absent.

Animals↗

PubMed1997

Criteria of normal blood pressure and hypertension in Japanese preschool children.

The blood pressure (BP) of 5332 Japanese preschool children from 2 to 6 years of age was measured using an automated BP recorder (Dinamap Model 8104). The third reading of the consecutive measurement of BP was used for analysis. This study adopted a definition of hypertension developed by The Task Force conducted in the United States in 1987, which showed the 95th percentiles of systolic and diastolic BP for age and sex. Stepwise regression analysis revealed that body height, weight and heart rate had significant effects on both systolic and diastolic BP, whereas age had an effect on diastolic BP only, while sex and area where the subjects lived did not affect either BP. The 95th percentiles of systolic/diastolic BP at 2, 3, 4, 5, and 6 years of age were 115/69, 113/68, 114/65, 118/67 and 116/69 mm Hg in boys, and 121/70, 114/69, 115/67, 118/68 and 120/69 mm Hg in girls, respectively. The BP of Japanese preschool children can be evaluated using the data shown in this study.

Age Factors↗

PubMed1997

Isolation of a differentiation-defective myoblastic cell line, INC-2, expressing muscle LIM protein under differentiation-inducing conditions.

A non-differentiating myoblastic cell line, INC2, and a differentiating cell line, COM3, were established from the mouse myoblastic cell line C2C12. Under differentiation conditions, both COM3 and INC2 cells stopped proliferation in a similar manner. The COM3 cells then differentiated into myotubes during the 4-day differentiation culture. In contrast, almost none of the INC2 cells differentiated into myotubes even in differentiation medium. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analyses showed that the levels of myogenin and MyoD proteins were significantly decreased in INC2 cells. The differentiation marker sarcomeric myosin heavy chain (MHC) was expressed in COM3 but not in INC2 cells. In contrast, both INC2 and COM3 cells expressed another myogenic regulatory factor, muscle LIM protein (MLP), in a differentiation condition-dependent manner. These results suggest that MLP gene expression is regulated in a myogenin/MyoD-independent manner. Enforced expression of the myogenin gene induced MHC expression in INC2 cells. Thus, the signaling pathway situated downstream is assumed to be intact in INC2 cells and suppression of myogenin, gene expression may be a primary defect in INC2 cells.

Animals↗

PubMed1997

Early diagnosis of vertical HIV infection in infants by rapid detection of immune complex-dissociated HIV p24 antigen.

Conventional HIV antibody detection was problematic for diagnosis of HIV infection in young infants < 18 months of age who were born to HIV-infected mothers. The HIV p24 antigen (Ag) is mainly bound to the antibody as an immune complex which causes underdetection by conventional methods. Attempts were made to dissociate these immune complexes to release free p24 Ag for detection. The current study's objective was to evaluate the rapid assays for detection of immune complex-dissociated p24 Ag (ICD p24 Ag) for early identification of HIV-infected infants as compared to the detection of HIV RNA by polymerase chain reaction (PCR) assay. The ICD was performed by acid dissociation and heat-denatured dissociation, and then the released ICD p24 Ag were detected. Tested were 41 HIV-infected children who acquired the infection perinatally and who had positive PCR and 30 HIV noninfected children with negative PCR. The overall sensitivity of the ICD p24 Ag detection after acid- and heat-denatured dissociation in the infected children was 85.4% and 87.8%, respectively, compared to 34.2% of p24 Ag without pretreatment for dissociation of the serum samples. The specificity of nonimmune complex dissociation and both methods of immune complex dissociation test were 100%. The sensitivity of ICD-p24 Ag test using these two methods showed excellent agreement (K = 0.893). Besides the relatively high sensitivity and specificity of the ICD p24 Ag test, its advantages include simplicity, rapidity, and relatively low cost--indicating ICD p24 Ag detection as a promising method for early diagnosis of vertical HIV infection in infants.

Antibodies, Viral↗

PubMed1997

Positron emission tomography for quantitative determination of glucose metabolism in normal and ischemic brains in rats: an insoluble problem by the Harderian glands.

To examine the reliability of quantitative positron emission tomography studies in the rat (Rat-PET), we assessed the influence of radioactivity accumulated in the Harderian glands on PET CMRglc determination. We measured CMRglc by PET and ex vivo dissection methods by using 2-[18F]fluoro-2-deoxy-D-glucose in rats with and without focal brain ischemia. The CMRglc values obtained by PET, after correcting with recovery coefficients, were higher than those measured by the ex vivo method at rostral slices, and reduction of the CMRglc in the ischemic brain was not demonstrated by PET in the frontal cortex. The radioactivity accumulated in the Harderian glands prevents the quantitative determination of CMRglc using Rat-PET.

Animals↗

PubMed1997

Platelet-derived growth factor-BB, but not -AA, prevents delayed neuronal death after forebrain ischemia in rats.

Our previous studies demonstrated coordinate expression of platelet-derived growth factor (PDGF) -B chain and beta-receptor in neurons at risk in the rat brain with focal ischemia. To clarify a role of the -B chain in the brain further, we examined whether PDGF-A or -B chain protects CA1 pyramidal neurons from delayed neuronal death after forebrain ischemia in rats. Pretreatment with PDGF-BB, but not -AA, at 120 ng/d for 2 days until forebrain ischemia was performed markedly ameliorated delayed neuronal death in CA1 pyramidal neurons on day 7 after ischemia. This neuroprotective effect of PDGF-BB was dose-dependent, and pretreatment with PDGF-BB at 240 ng/d showed almost complete inhibition of delayed neuronal death. In contrast, posttreatment with PDGF-BB at 120 ng/d starting 20 minutes after ischemia demonstrated no significant neuroprotective effect. The current study established marked neuroprotective actions of PDGF-BB in ischemic neuronal damage.

Animals↗

PubMed1997

The relationship between fatty liver and hyperinsulinemia in obese Japanese children.

BACKGROUND: Previous reports have revealed that fatty liver involving obesity is closely related to insulin resistance or hyperinsulinemia in adulthood. This study investigates the importance of hyperinsulinemia in obese children with fatty liver. METHODS: The subjects were 228 obese children 6 to 15 years old in Niigata Prefecture, Japan. The serum level of glutamic pyruvic transaminase (GPT) was evaluated as an indicator of fatty liver. The effects of their percent obesity (percent over ideal body weight), Rohrer index (g/cm3), skinfold thickness, percent body fat measured by bioelectrical impedance analysis, total cholesterol (TC), high-density lipoprotein cholesterol, triglyceride (TG), blood glucose, and immuno-reactive insulin (IRI) on GPT were evaluated using regression analyses. RESULTS: The incidence of fatty liver (GPT over 35 IU/I) was 24.1% in this study. In simple regression analyses, percent obesity, Rohrer index, skinfold thickness, TC, TG, blood glucose, and IRI correlated positively with GPT (p < 0.05). In stepwise regression analysis including these seven variables, the predictive equation for GPT as a function of IRI alone accounted for 24.2% of the total variance of GPT. The addition of TC alone, and TC and percent obesity together increased the coefficients of determination to 28.4% and 29.9%, respectively. Rohrer index, skinfold thickness, Tg, and blood glucose were not taken as related variables with GPT. CONCLUSION: Hyperinsulinemia is an important contributor to the development of fatty liver, apparently more than anthropometric data, blood glucose, or serum lipids in childhood obesity.

Adolescent↗

PubMed1997

Predictability of extracranial/intracranial bypass function: a retrospective study of patients with occlusive cerebrovascular disease.

OBJECTIVE: When the efficacy of extracranial/intracranial bypass surgery is discussed, can we include the patients with extensive collateral circulation through the bypass and those with poor collateral circulation in the same group? The bypass function should be determined not by the patency of the bypass but by the extent of collateral circulation through the bypass. We retrospectively analyzed our patients to determine whether the extent of bypass flow can be predicted from the results of preoperative studies. METHODS: In 51 hemispheres of 44 consecutive patients who underwent extracranial/intracranial bypass surgery, correlation between the extent of bypass flow and the preoperative results of angiographic and stimulated cerebral blood flow studies were investigated. RESULTS: The bypass function is highly predictable with the aid of preoperative studies. In 11 hemispheres that showed both retrograde spontaneous circulation via leptomeningeal anastomoses and decreased reactivity to acetazolamide of cerebral blood flow in an area distal to the arterial lesion, collateral circulation through the bypass developed well and reactivity to acetazolamide improved. In all of 13 hemispheres that showed normal reactivity to acetazolamide, the bypass was patent but the collateral circulation did not develop well. In only 4 of 24 hemispheres with spontaneous antegrade circulation distal to the lesion was there satisfactory collateral circulation through the bypass. CONCLUSION: Our results indicate that improvement of the hemodynamic status by bypass surgery should be expected only in patients with both spontaneously developed leptomeningeal anastomoses and decreased reactivity to acetazolamide.

Acetazolamide↗

PubMed1997

Serum level and gene polymorphism of angiotensin I converting enzyme in Japanese children.

The aim of the present study was to determine the distribution of the insertion/deletion polymorphism of angiotensin I converting enzyme (ACE) gene in Japanese children. In addition, the relationship between this polymorphism and serum ACE levels in the same population were analyzed. Insertion/deletion polymorphism located in intron 16 of the ACE gene was examined by polymerase chain reaction in Japanese children aged 10-15 years. Allele frequencies were 0.64 for the insertion allele and 0.36 for the deletion allele in 122 subjects. No association was found between genotypes in this polymorphism and the level of systolic or diastolic blood pressure. A significant relationship between this polymorphism and serum ACE activity was observed. These results suggest that interindividual variability of serum ACE level is strongly influenced by the ACE genotype as early as in childhood.

Adolescent↗

PubMed1997

A case of tick-borne encephalitis in Japan and isolation of the the virus.

A case of tick-borne encephalitis (TBE) has not been reported for many years in Japan, although a serological survey of sera from domestic animals suggested the presence of TBE foci in Hokkaido, the northern island of Japan. Studies were conducted to prove the presence of an endemic focus of TBE virus in Japan by means of serology and virus isolation. In October 1993 in Hokkaido, a severe case of encephalitis in a dairy farmer's wife was diagnosed as TBE. Serological examination of paired serum specimens showed a rise in the neutralization antibody titer to Russian spring summer encephalitis virus. A seroepizootiological survey of dogs showed that the TBE-related virus was prevalent in the area. Three virus isolates were obtained from the blood of sentinel dogs, and antigenic analysis grouped the isolates into TBE-related viruses. Sequence analysis of the envelope protein gene identified one of the isolates as being of the same subtype as the Russian spring summer encephalitis (Far Eastern TBE) virus. The results provide evidence that TBE is endemic in a certain area of Japan.

Animals↗

PubMed1997

Prostaglandins induce proliferation of rat hepatocytes through a prostaglandin E2 receptor EP3 subtype.

We characterized the proliferative action of prostaglandins (PGs) in relation to their membrane receptors on rat hepatocytes in primary culture. PGs in the order 16,16-dimethyl PGE2 > PGE2 > PGF2alpha >> PGD2 augmented epidermal growth factor (EGF)/insulin-induced DNA synthesis, assessed by [(3)H]thymidine incorporation, in a concentration-dependent manner, whereas PGs alone did not stimulate basal DNA synthesis without EGF and insulin. The cells exhibited [(3)H]PGE2 binding sites that were displaced by unlabeled PGs in the order PGE1 = PGE2 > PGF2alpha > PGD2. PGE2 inhibited glucagon-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation concentration dependently. The mean effective concentration for DNA synthesis, median inhibitory concentration for cAMP accumulation, and dissociation constant for [(3)H]PGE2 binding at 25 degrees C were almost identical (approximately 70 nM). Treatment of the cells with pertussis toxin (100 ng/ml), which ADP-ribosylated most of the 41-kDa substrate, abolished the proliferative effects of PGs. We detected the expression of mRNA of the EP3 subtype PGE2 receptor using reverse transcription-polymerase chain reaction. Moreover, an EP3 agonist, enprostil, but not the EP1 agonist 17-phenyl-trinor-PGE2 or the EP2/EP4 agonist 11-deoxy-PGE1, stimulated EGF/insulin-induced DNA synthesis. These results indicate that PGs act as comitogenic growth factors through the EP3 subtype PGE2 receptor coupled with G(i) protein in cultured rat hepatocytes.

Animals↗

PubMed1997

Cerebral aneurysms arising at nonbranching sites. An experimental Study.

BACKGROUND AND PURPOSE: The origin and pathogenesis of cerebral aneurysms arising at nonbranching sites are not clear. Using our animal model to induce cerebral aneurysms in rats, we examined induced aneurysms that developed at nonbranching sites. METHODS: In 35 Sprague-Dawley rats, the left common carotid artery was ligated and renal hypertension was produced to induce cerebral aneurysms. Twelve months later, the circle of Willis was carefully examined under a dissecting microscope. RESULTS: Other than cerebral aneurysms at branching sites of the circle of Willis, aneurysmal bulges developing at nonbranching sites were found in the proximal portion of the posteriorice rebral artery (P1) on the side of carotid ligation, which supposedly acted as a major collateral pathway after the ligation, in 19 of 35 treated rats. A total of 30 lesions were found in these 19 rats, and they were classified into fusiform aneurysms (22 lesions) involving the entire vessel wall for a short distance and saccular aneurysms (8 lesions) involving only a part of the wall and expanding laterally from the vessel wall. These P1s became larger in caliber and more tortuous after ligation. Aneurysms developed more frequently in proportion to these changes in these vessels. Moreover, most aneurysms in these vessels developed at or near the curvatures. All of the lateral aneurysms were found on the lateral wall of the curvatures of the vessels. CONCLUSIONS: The present findings indicate that cerebral aneurysms at nonbranching sites and saccular aneurysms at branching sites can occur under the same etiologic conditions. The site of origin is strongly related to hemodynamic stress.

Animals↗

PubMed1997

SCID-bg mice as xenograft recipients.

SCID-bg (scid/scid, beige/beige) is a strain of double-mutant mice with impaired lymphoid development and reduced natural killer (NK) cell activity. The present study was undertaken to evaluate the usefulness of SCID-bg mice as xenograft recipients. Fetal guinea pig tissues (liver, thymus, spleen) were transplanted under the kidney capsule of the mice and their serum guinea pig IgG levels were measured weekly thereafter, C.B.-17-scid and anti-asialo GM1 antiserum-treated (NK-depleted) C.B.-17-scid (C.B.-17-scid-AGM1) mice that received the identical transplants were used as controls. Throughout the experimental period (1, 2, and 3 weeks after transplantation), the average serum guinea pig IgG concentrations was highest in C.B.-17-scid-AGM1 mice followed by SCID-bg mice and lowest in C.B.-17-scid mice without antiserum treatment, though we could not find any statistical significance among these groups. However, SCID-bg mice always showed the smallest within-group variance (individual difference) in the serum guinea pig IgG concentrations (P < 0.05, versus C.B.-17-scid-AGM1 mice at 1, 2, and 3 weeks and versus C.B.-17-scid mice at 2 weeks). The graft size was not significantly different among these three groups, but the spleen grafts in C.B.-17-scid mice contained fewer nucleate cells than the other two groups. These results indicate that the reduced NK cell activity by beige mutation is not crucial for the success of xenogenic transplantation, though SCID-bg mice may be useful as xenograft recipients with a consistent potential to retain the viability and function of engrafted tissues.

Animals↗

PubMed1997

A case of nonfunctioning pituitary adenoma resembling so-called silent corticotroph adenoma.

It has been indicated that some subsets of clinically nonfunctioning pituitary adenoma exhibit immunohistochemical and ultrastructural features of somatotroph or corticotroph cells, which are described as silent somatotroph and corticotroph adenomas, respectively. We here describe a 70-year-old woman with nonfunctioning pituitary adenoma presenting with visual disturbance. None of the pituitary hormones show abnormal finding. Magnetic resonance imaging study revealed a pituitary tumor which developed inferiorly into the sphenoidal sinus. Tumor resection was performed by a transsphenoidal approach, and resulted in a partial resection of the tumor. The specimen indicated chromophobic adenoma. Immunohistochemical examination revealed a characteristic distribution pattern of cytokeratin staining for ACTH cell adenoma, although immunostaining for ACTH was only weakly positive. After the operation, only ACTH secretion was impaired, requiring replacement therapy with glucocorticoid. Bromocriptine was administered in order to prevent the recurrence of the tumor. It remains to be elucidated whether the present case could be classified as silent corticotroph adenoma, which was originally indicated to have aggressive characteristics, i.e., progressive visual defect, high incidence of infarction and frequent recurrence.

Adenoma, Chromophobe↗

PubMed1997

Hemodynamic and metabolic disturbances in patients with intracranial dural arteriovenous fistulas: positron emission tomography evaluation before and after treatment.

In patients with intracranial dural arteriovenous fistulas (AVFs), clinical symptoms and angiographic findings vary. The relevance of disturbed venous drainage to clinical symptoms and prognosis has been recognized. However, the roles of cerebral hemodynamics and metabolism, which are impaired by shunt flow or disturbed venous drainage, have not been fully evaluated. The authors studied the cerebral hemodynamic and metabolic status in 10 patients with intracranial dural AVFs using positron emission tomography (PET) scanning. Ten patients with dural AVFs underwent a PET study before treatment. The regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF), regional cerebral metabolic rate of oxygen (rCMRO2), and regional cerebral blood volume (rCBV) were measured using the 15O-labeled gas inhalation steady-state method The PET parameters that were obtained were analyzed and compared with the patients' neurological and angiographic findings. In six of the 10 patients, a PET study was also performed after treatment. Before treatments, all four patients with cerebral symptoms showed a severe reduction in rCBF and a mild elevation in the rOEF. The areas showing reduced rCBF corresponded with areas in which retrograde venous drainage into the cortical veins and delayed parenchymal circulation were seen on angiograms. In another two patients with occlusion of the affected sinus and/or retrograde drainage into the cortical veins, mild abnormalities were demonstrated in rCBF mapping. In the remaining four patients, all PET parameters except rCBV were within normal limits and venous flow was not impaired on the angiograms. In four patients who underwent surgical excision or transvenous embolization of the affected sinus, the cerebral hemodynamics and metabolism were improved, as were the clinical symptoms. In two patients who underwent transarterial embolization of the feeding vessels only or craniotomy, no hemodynamic improvement was achieved. Our results indicate that hemodynamic insufficiency detected by the PET study corresponded well with cerebral symptoms and angiographic findings of retrograde venous drainage into the cortical veins and delayed parenchymal circulation, but not with sinus occlusion or arterial blood supply. Eradication or prevention of retrograde venous drainage from the affected sinus into the cortical veins should be a treatment goal in patients with dural AVFs.

Aged↗

PubMed1997

Resection of a large, high-flow arteriovenous malformation during hypotension and hypothermia induced by a percutaneous cardiopulmonary support system. Case report.

The key to successful surgical resection of cerebral arteriovenous malformations (AVMs) is control of bleeding and cerebral swelling. Induced hypotension is one of the most valuable means of achieving this control. The authors introduced induced hypotension with mild hypothermia by using a percutaneous cardiopulmonary support system (PCPS) to resect a large, high-flow AVM. The efficacy and technical points of this method are discussed. The PCPS, whose entire intraluminal surface was coated with heparin, was established through a transfemoral route. During resection of the AVM, a mean arterial blood pressure of 60 mm Hg and a mean body temperature of 30 degrees C were easily maintained by regulating the flow rate of the PCPS and by blood cooling. The activated coagulation time was maintained at approximately 250 seconds with a minimum systemic administration of heparin. The authors report the case of a 30-year-old woman who presented with intraventricular hemorrhage and was diagnosed as having a large, high-flow AVM located in the left sylvian fissure. The AVM was fed by the left middle, posterior, and anterior cerebral arteries and drained by the many cortical ascending veins and the basal vein. The patient underwent surgery after hypotension and hypothermia had been induced via the PCPS method. Induced hypotension decreased the tension of the nidus and made its dissection easier. The AVM was totally resected and no hemostatic difficulties were encountered. On the basis of the authors' experience, they suggest that hypotension and hypothermia induced by using the PCPS is a powerful tool for the successful resection of large, high-flow AVMs.

Adult↗

PubMed1997

[Detection of microemboli in patients with extracranial carotid artery stenosis by transcranial Doppler sonography].

Embolism from a stenotic lesion of the extracranial internal carotid artery (ICS) is considered to be an important pathomechanism of cerebral infarction. The purpose of this study is to estimate the risk of cerebral infarction associated with microembolism in patients with ICS and thereby to determine the importance of TCD-detected microemboli in this condition. Seventy-one cases with more than 30% ICS and 10 cases without ICS were studied. TCD monitoring was carried out for an hour at the ipsilateral middle cerebral artery of each case using a 2-MHz pulse-wave transcranial Doppler device. High intensity transient signals were counted as microemboli. Microemboli were detected in 27 of 71 cases with ICS, but not in cases without ICS. Microemboli were detected more frequently in cases with 70% to 99% ICS (53.3%) compared with in cases with 30% to 69% ICS (12.5%). Cerebral infarctions were recognized in the ipsilateral hemisphere in 23 of 27 cases with microemboli (85.2%) by means of MRI. In contrast, cerebral infarctions were recognized only in 21 of 45 cases without microemboli (47.7%). These results suggest that a stenotic lesion of the extracranial internal carotid artery, especially high-grade stenosis, is a major source of cerebral embolism and that detection of microemboli by TCD is a useful tool capable of reliably assessing the risk of cerebral infarction due to ICS.

Aged↗

PubMed1997

Thyroxine-binding globulin and thyroid hormones after resection of hepatocellular carcinoma.

OBJECTIVES: Some human hepatocellular carcinomas (HCCs) produce thyroxine-binding globulin (TBG). High serum TBG levels in such patients may be associated with increased thyroxine (T4) levels. This study aimed to elucidate the serum TBG and thyroid hormone profile in Japanese patients with HCC, to compare the difference between TBG-producing and -nonproducing HCCs, and to investigate the changes in serum TBG level and the thyroid hormone profile after removal of the tumor. METHODS: The 40 subjects included 20 patients with HCC, 10 healthy controls, and 10 operative controls. Serum TBG, 3,5,3'-triiodothyronine (T3), T4, and free T4 were measured serially for 4 wk after resection of HCC in 16 patients and after control operations in 10 patients. Assay methods were a radioimmunoassay for TBG and enzyme immunoassays for T3, T4, and free T4. RESULTS: Values higher than the mean +/- 2 SD of controls were considered abnormally high. Of patients with HCC, 60% had abnormally high TBG values, 65% had abnormally high T3 values, 39% had abnormally high T4 values, and 6% had abnormally high free T4 values. The mean levels of TBG and T3 were significantly higher than those in healthy controls, but no difference was found for T4 and free T4 levels. There were no significant differences in various clinicopathological factors between patients with high TBG levels and those with normal TBG levels. After resection of HCC, serum TBG decreased significantly in patients with high TBG levels but not in those with normal TBG levels. CONCLUSIONS: This study shows that >50% of HCCs in Japanese patients produce TBG; removal of the tumor reduces serum TBG in such cases.

Adult↗