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Biomedical subjects

S Suga

Publications and source records attributed to S Suga.

At least 73 records · Page 4Linked to original sources
PubMed2000

Clinical characteristics of febrile convulsions during primary HHV-6 infection.

OBJECTIVE: To clarify clinical characteristics of children with febrile convulsions during primary human herpesvirus 6 (HHV-6) infection. SUBJECTS AND METHODS: The clinical characteristics of first febrile convulsion were compared between those with and without primary HHV-6 infection in 105 children. HHV-6 infection was verified by culture or acute/convalescent anti-HHV-6 antibody titres. RESULTS: Primary infection with HHV-6 was seen in 21 of 105 patients with febrile convulsions (3 upper respiratory infection, 1 lower respiratory infection, and 17 exanthem subitum). 13 of 23 patients < 1 year, 19 of 79 patients with first febrile convulsion, and 2 of 15 with second convulsion were infected with HHV-6. The median age of patients with first febrile convulsion and HHV-6 was significantly lower than those without infection. The frequency of clustering seizures, long lasting seizures, partial seizures, and postictal paralysis was significantly higher among those with primary HHV-6 infection than among those without. The frequency of atypical seizures in 19 patients with first febrile convulsion associated with primary infection was significantly higher than in 60 patients without primary infection. The frequency in infants younger than 1 year of age was also significantly higher than that in 10 age matched infants without primary infection. CONCLUSIONS: These findings suggest that primary infection with HHV-6 is frequently associated with febrile convulsions in infants and young children and that it often results in the development of a more severe form of convulsions, such as partial seizures, prolonged seizures, and repeated seizures, and might be a risk factor for subsequent development of epilepsy.

Age Distribution↗
PubMed2000

Invasion by human herpesvirus 6 and human herpesvirus 7 of the central nervous system in patients with neurological signs and symptoms.

METHODS: A total of 43 children with neurological signs and symptoms were enrolled in the study. All children were suspected of having meningitis, and lumbar punctures were performed. Human herpesvirus 6 (HHV-6) and HHV-7 DNA was detected in cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) by nested polymerase chain reaction. RESULTS: Most patients had detectable serum antibody to both HHV6 and 7. HHV6 DNA was detected in PBMC of 15 patients and in CSF cell pellet of seven. Corresponding figures for HHV7 were 28 and 6.2/7, and 5/6 with CSF viral DNA also had it in PBMC, respectively. No viral DNA was detected in CSF supernatants. The seven HHV6 CSF viruses were all variant B. CONCLUSION: These data suggest that HHV-7 may invade the CNS.

Child↗
PubMed2000

Immune response to gangliosides in a case of Guillain-Barré syndrome after varicella.

An 8 year old girl was admitted to hospital with the typical clinical features of Guillain-Barré syndrome (GBS) after recovering from varicella. Onset of the disease was just two weeks after the onset of varicella in her young sister. Examination of cerebrospinal fluid and nerve conduction studies showed typical findings of GBS. Although serum from both the patient and sister were analysed for autoantibodies to gangliosides and myelin P0 protein, IgM anti-GM1 antibody and anti-GD1b antibody were only detected in the patient. HLA DR haplotypes were quite different between the two subjects. This suggests that these autoantibodies may play an important role in the pathogenesis of GBS after varicella zoster virus infection.

Autoantibodies↗
PubMed2000

Protein kinase C-dependent inhibition of K+ currents in noradrenaline-induced depolarization of smooth muscle of guinea-pig vas deferens.

Ionic mechanisms and signal transduction underlying noradrenaline (NA)-induced depolarization in single smooth muscle cells of guinea-pig vas deferens were studied. NA caused depolarization followed by action potentials through activation of 1-adrenoceptors. In the presence of nifedipine, no action potential was generated, and the magnitude of the depolarization depended on the concentration of NA (0.1-100 micrometer). NA, through 1-adrenoceptor activation, reduced the magnitude of membrane currents in response to voltage ramp pulses from -90 to -30 mV in a concentration-dependent manner. The reversal potential of the current inhibited by NA changed proportionally to the change in the equilibrium potential of K+, suggesting that NA inhibited K+ channel activity. Treatment of cells with GDPS, an inhibitor of G proteins, or bisindolylmaleimide (BIM), a selective protein kinase C (PKC) inhibitor, prevented the NA inhibition of the currents. Application of 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of PKC, mimicked the effect of NA. It is suggested that in the smooth muscle of guinea-pig vas deferens, activation of 1-adrenoceptors and the subsequent activation of PKC led to inhibition of K+ currents, which is responsible for the depolarization induced by NA.

Adrenergic alpha-Agonists↗
PubMed2000

[Clinical manifestations of the subfamily alpha-herpesvirinae in childhood].

Herpes simplex virus(HSV) and varicella-zoster virus(VZV) belonging to the subfamily of alpha-herpesvirinae have the capacity to establish latent infection in neural tissues and to reactivate from these sites. HSV infection is characterized by a vesicular eruption, fever, and other constitutional symptoms but frequently inapparent both in primary and recurrent infections. However, the infection produces a wide spectrum of illness ranging from the trivial fever blisters to the most severe fatal sporadic encephalitis and neonatal infection. In contrast, VZV develops varicella, a common contagious disease of childhood during primary infection and zoster by reactivation of latent virus acquired during varicella. In normal children, the systemic symptoms of both diseases are mild, whereas serious complications are often observed in children with deficiencies in cell-mediated immunity. Acyclovir has been the drug of choice for treatment of severe infection with HSV and VZV for approximately 2 decades. Now, two new agents, valacyclovir and famciclovir will supplant acyclovir for certain indications.

Alphaherpesvirinae↗
PubMed2000

[Evaluation of cerebral metabolism by multi-voxel proton magnetic resonance spectroscopy imaging in chronic unilateral internal carotid artery occlusion].

Proton magnetic resonance spectroscopy(1H-MRS) has less been used to analyze cerebral metabolism in ischemic lesions compared to single photon emission computed tomography or positron emission computed tomography. Recent advances in magnetic resonance imaging apparatus and the related software have made possible obtaining multi-voxel 1H-MRS in a single study. We examined multi-voxel 1H-MRS in patients with unilateral internal carotid artery(ICA) occlusion to study the relationship between cerebral metabolism and cerebral blood flow. Fifteen patients(male 11; female 4, 47-76; average 67.1 year-old) with chronic unilateral ICA occlusion and without any marked infarction were studied. 1H-MRS was obtained using a 1.5 T Siemens Magnetom Vision scanner. Multi-voxel spectra were recorded using a SE-2 D-CSI sequence(TR/TE = 1500/135 ms). The volume of interest was 90 x 90 x 20 mm3, placed axially above the lateral ventricle. The single voxel size was 10 x 10 x 20 mm3. N-acetyl aspartate/creatine ratios(NAA/Cr) were calculated on each voxel and were averaged in view of the cortex and the white matter. The regional cerebral blood flow(CBF) was measured by Xenon-CT method. Eight patients were also examined by acetazolamide challenge to evaluate the cerebrovascular reserve capacity. NAA/Cr ratios in normal subjects were 1.905 +/- 0.090(mean +/- standard deviation) in the cortex and 2.183 +/- 0.258 in the white matter in 40's(n = 6), 2.046 +/- 0.166 in the cortex and 2.039 +/- 0.288 in the white matter in 60's(n = 5). The study revealed 7 patients with normal NAA/Cr ratio and CBF, 5 with reduced NAA/Cr ratio and normal CBF, and 3 with reduced NAA/Cr ratio and CBF in the affected cortex. A low correlation coefficient of 0.46 was noted between NAA/Cr ratio and the cerebrovascular reserve capacity calculated by acetazolamide challenge in the affected cortex. In the range of less than +10%(lower limit) in percentile change of regional CBF after acetazolamide injection, NAA/Cr ratio was distributed between 1.600 and 2.044, which were normal or slightly under the lower limit(mean-2 x standard deviation). Multi-voxel 1H-MRS is useful for the evaluation of cerebral metabolism, because it enables to quantify different chemicals in many fields at one time and to compare its distribution with regional CBF. In patients with unilateral ICA occlusion, NAA/Cr ratio of the affected cortex varies depending on the collateral circulation and the contralateral ICA lesions. The Extracranial-Intracranial Bypass should be considered if the case with unilateral ICA occlusion reveals reduced CBF and normal or slightly decreased NAA/Cr ratio in the affected cortex.

Aged↗
PubMed2000

Human herpesvirus 6 infection after living related liver transplantation.

The aim of the study was to investigate human herpesvirus-6 (HHV-6) infection after liver transplantation from living related donors, and to evaluate the reliability of the presence of HHV-6 DNA in plasma by the polymerase chain reaction (PCR) for monitoring active HHV-6 infection. EDTA peripheral blood was collected from 47 donor and recipient (16 males and 31 females, age 1-320 months) pairs at the time of transplantation and biweekly from these recipients after transplantation until 2 months after operation. Isolation of HHV-6 and serological assays were carried out to evaluate active HHV-6 infection in this study. The presence of the viral DNA in plasma was tested by nested PCR. Four clinical events, such as unexplained fever, thrombocytopenia, rejection, and central nervous system (CNS) involvement, were evaluated for clinical features of the virus infection. Risk factors for the virus activity after liver transplantation were also examined. HHV-6 activity was detected in 23 (49%) of the 47 recipients approximately 2-4 weeks after transplantation. All 9 isolates were HHV-6 variant B. The presence of the viral DNA in plasma correlated well with virus isolation and serology (P < 0.01). Only unexplained fever was associated statistically with HHV-6 activity after liver transplantation (P < 0. 01). If the recipient was seronegative to HHV-6 before transplantation, the recipient was more likely to develop the active virus infection after liver transplantation (P = 0.11). HHV-6 activity occurred in one-half of the recipients approximately 2-4 weeks after liver transplantation, and there was a close association between HHV-6 activity and unexplained fever following transplantation. Detection of the viral DNA in plasma by PCR is useful for monitoring active HHV-6 infection in these patients. Seronegative recipients were more likely to have evidence of active HHV-6 infection after liver transplantation.

Adolescent↗
PubMed2000

[Changes in proton magnetic resonance spectroscopy and Wechsler adult intelligence scale revised after clipping of unruptured aneurysms].

The purpose of this study is to evaluate the influence of surgery for unruptured aneurysms on neuropsychological status and cerebral metabolism. We studied 21 patients with unruptured aneurysms treated with direct surgery accompanied by craniotomy, rather than by the endovascular method. Patients were evaluated before and after surgery, using the Wechsler adult intelligence scale revised (WAIS-R) and proton magnetic resonance spectroscopy which measured the ratio of N-acetyl-aspartate to creatine (NAA/Cr). Although the results of WAIS-R (total IQ, verbal IQ and performance IQ) was not significantly different after surgery in any of the patients, the total IQ of the patients with anterior communicating artery aneurysms (AcoA) showed a significant decline compared with patients with other aneurysms after surgery. Five of eight AcoA patients showed a specific reduction in verbal IQ, suggesting deterioration of recent memory. The NAA/Cr remained within the normal range and was not significantly different before and after surgery. However, the NAA/Cr in the white matter of the frontal lobe of AcoA patients showed a significant reduction compared with that of non-AcoA patients. All three elderly patients older than 70 showed a reduction in NAA/Cr of more than one standard deviation from normal subjects in their frontal or parietal lobes. These results indicated that operation for unruptured aneurysms is reliable and well established but they also show that careful consideration should be given to possible deterioration in neuropsychological status and cerebral metabolism after operation in AcoA and elderly patients.

Age Factors↗
PubMed2000

A 35-year-old man with cerebral hemorrhage and pheochromocytoma: the second brain-dead organ donor in Japan.

A 35-year-old man was brought into the emergency room of Keio University Hospital by ambulance because of a sudden onset of coma. His Glasgow Coma Scale was 3 and his blood pressure 150/100 mmHg. CT scanning revealed a subcortical hemorrhage 8 cm in diameter. His respiration deteriorated rapidly, and an emergency craniotomy was performed for hematoma removal and cerebral decompression. Postoperatively the patient remained in a deep coma (GCS = 3) requiring respiratory support. The family presented an organ donor card previously signed by the patient, and brain death was confirmed in accordance with Japan's transplant law. As a result of two tests conducted six hours apart brain death was confirmed on the 5th postoperative day. With the family's consent, the donor's heart, kidneys and skin were removed for organ transplantation to be performed in other institutions. An autopsy was performed after the removal of the organs and skin. An extensive subgaleal hemorrhage was found in the left cerebral hemisphere, and microscopic examination revealed extensive necrosis with karyolysis of neuronal cells, but no viable neuronal cells were found in the cerebrum. The brain stem was marked by edema, hemorrhage, infarction necrosis and neuronal cell loss. The cerebellum was swollen and congested and showed autolysis of the granular layer. These findings suggested brain death syndrome with respirator brain. Other autopsy findings included a huge pheochromocytoma in the right adrenal gland, bilateral bronchopneumonia, liver congestion and fatty metamorphosis with four cavernous hemangiomas, and mild chronic lymphocytic thyroiditis. This patient was the second brain-dead organ donor and the first brain-dead patient to undergo postmortem examination in Japan.

Adrenal Gland Neoplasms↗
PubMed2000

Involvement of macrophage migration inhibitory factor (MIF) in experimental uric acid nephropathy.

BACKGROUND: Deposition of uric acid in the kidney can lead to progressive tubulointerstitial injury with granuloma formation. We hypothesized that uric acid crystal deposition may induce granuloma formation by stimulating local expression of macrophage migration inhibitory factor (MIF), which is a known mediator of delayed type hypersensitivity (DTH). MATERIALS AND METHODS: A model of acute uric acid nephropathy was induced in rats by the administration of oxonic acid (an inhibitor of uricase), together with uric acid supplements. MIF expression and local cellular response were examined by in situ hybridization and immunohistochemistry. RESULTS: Kidney tissue examined at 35 days posttreatment showed widespread tubulointerstitial damage with intratubular uric acid crystal deposition and granuloma formation. Tubules within the areas of granuloma showed a six-fold increase in MIF mRNA, compared with uninvolved areas by in situ hybridization. Moreover, the areas of increased MIF mRNA expression correlated with sites of dense accumulation of macrophages and T cells, and these cells were activated when assessed by the expression of interleukin-2R (IL-2R) and (MHC) class II. Interestingly, cytoplasmic staining for MIF protein in the uric acid (UA) crystal-associated granulomatous lesions was reduced, indicating a rapid MIF secretion by damaged tubules and macrophages secondary to uric acid crystal stimulation. This was confirmed by the demonstration of a marked increase in urinary MIF protein by Western blot analysis. Control rats fed either a normal diet or only oxonic acid had no discernible evidence of renal disease by routine light microscopy and minimal tubular expression of MIF mRNA and protein. CONCLUSIONS: These data suggest that intrarenal granulomas in urate nephropathy may be the consequence of a crystal induced DTH reaction mediated by MIF.

Animals↗
PubMed1999

NADH shuttle system regulates K(ATP) channel-dependent pathway and steps distal to cytosolic Ca(2+) concentration elevation in glucose-induced insulin secretion.

The NADH shuttle system is composed of the glycerol phosphate and malate-aspartate shuttles. We generated mice that lack mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH), a rate-limiting enzyme of the glycerol phosphate shuttle. Application of aminooxyacetate, an inhibitor of the malate-aspartate shuttle, to mGPDH-deficient islets demonstrated that the NADH shuttle system was essential for coupling glycolysis with activation of mitochondrial ATP generation to trigger glucose-induced insulin secretion. The present study revealed that blocking the NADH shuttle system severely suppressed closure of the ATP-sensitive potassium (K(ATP)) channel and depolarization of the plasma membrane in response to glucose in beta cells, although properties of the K(ATP) channel on the excised beta cell membrane were unaffected. In mGPDH-deficient islets treated with aminooxyacetate, Ca(2+) influx through the plasma membrane induced by a depolarizing concentration of KCl in the presence of the K(ATP) channel opener diazoxide restored insulin secretion. However, the level of the secretion was only approximately 40% of wild-type controls. Thus, glucose metabolism through the NADH shuttle system leading to efficient ATP generation is pivotal to activation of both the K(ATP) channel-dependent pathway and steps distal to an elevation of cytosolic Ca(2+) concentration in glucose-induced insulin secretion.

Animals↗
PubMed1999

Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease.

An elevated uric acid level is associated with cardiovascular disease. Hyperuricemia is predictive for the development of both hypertension and coronary artery disease; it is increased in patients with hypertension, and, when present in hypertension, an elevated uric acid level is associated with increased cardiovascular morbidity and mortality. Serum uric acid level should be measured in patients at risk for coronary artery disease because it carries prognostic information. Hyperuricemia is caused by decreased renal excretion. In this article, we suggest that this may be mediated by intrarenal ischemia with lactate generation and the inhibition of the secretion of urate by the anion-exchange transport system. The possibility that hyperuricemia directly contributes to cardiovascular or renal disease needs to be reconsidered. Although hyperuricemia is associated with a number of cardiovascular or renal risk factors, several studies have found uric acid level to be independently associated with increased mortality by multivariate analysis. If hyperuricemia is directly toxic, the most likely site is the kidney. Chronic hyperuricemia is strongly associated with chronic tubulointerstitial disease, and many of these patients have decreased renal function. Although it is possible that the hyperuricemia could simply be the consequence of the renal disease, further studies are necessary to rule out a pathogenic role for uric acid in the development of renal disease and salt-dependent hypertension.

Cardiovascular Diseases↗
PubMed1999

Human herpesvirus 6 latently infects mononuclear cells but not liver tissue.

AIM: To investigate whether human herpesvirus 6 (HHV-6) can cause latent infection of liver tissue. METHODS: Peripheral blood and liver tissue were collected from 25 living related liver transplant recipients at the time of transplantation. An avidin-biotin complex peroxidase method was used to identify HHV-6 antigen in the liver tissue. A nested polymerase chain reaction (PCR) was used to detect HHV-6 DNA in the liver tissue and mononuclear cells. Variant of HHV-6 was determined by the presence of the Hind III site in a second PCR product. RESULTS: Immunohistochemical analysis for HHV-6 antigen was negative in all the liver specimens. HHV-6 DNA was not detected in liver tissue. Virus DNA was detected in peripheral blood mononuclear cells in nine of 25 recipients. All nine HHV-6 identified in the mononuclear cells were variant B. CONCLUSIONS: HHV-6 variant B latently infects mononuclear cells but not liver tissue.

Adolescent↗
PubMed1999

Salt-sensitive hypertension develops after short-term exposure to Angiotensin II.

We hypothesized that short-term exposure to angiotensin II (Ang II) could result in structural and functional changes in the kidney that would favor sodium retention and the development of sustained hypertension. To test this hypothesis, rats were exposed to pressor doses (435 ng. kg-1. min-1) of Ang II for 2 weeks. The infusion of Ang II was associated with acute hypertension, renal dysfunction, proteinuria, and focal tubulointerstitial and vascular damage. At sites of the tubulointerstitial damage, there was a reduction in peritubular capillary endothelial cell staining. By use of immunostaining, we found focal loss of endothelial nitric oxide synthase (eNOS) in the peritubular capillaries at sites of injury and a generalized reduction in eNOS in collecting ducts, thin loops of Henle, and vascular bundles in the medulla. When the Ang II infusion ended, the rats became normotensive and renal function returned toward normal. However, exposure of the rats to high salt diet (4% NaCl) resulted in the redevelopment of hypertension after 3 to 4 weeks. Rats maintained on a high salt diet with no prior exposure to Ang II and rats placed on low salt diet (0.1% NaCl) after exposure to Ang II remained normotensive. Thus, we report a new model of salt-sensitive hypertension induced by transient exposure to pressor doses of Ang II. The mechanism may relate to microvascular injury with peritubular capillary loss coupled with functional changes, such as a loss in intrarenal nitric oxide formation, that could alter the ability of the kidney to excrete a salt load.

Angiotensin II↗
PubMed1999

Renal injury and salt-sensitive hypertension after exposure to catecholamines.

We investigated whether chronic infusion of phenylephrine could induce structural and functional changes in the kidney of rats with the subsequent development of salt-sensitive hypertension. Rats were infused with phenylephrine (0.15 mmol/kg per day) by minipump, resulting in a moderate increase in systolic blood pressure (BP) (17 to 25 mm Hg) and a marked increase in BP variability as measured by an internal telemetry device. After 8 weeks, the phenylephrine infusion was stopped with the return of BP to normal, and a nephrectomy was performed for histological studies. Glomeruli were largely spared, but focal tubulointerstitial fibrosis was present, with the de novo expression of osteopontin by injured tubules, macrophage and "myofibroblast" accumulation, and focal increases in mRNA for transforming growth factor beta by in situ hybridization. Peritubular capillaries at sites of injury had distorted morphology with shrinkage, rounding, and focal rarefaction, and endothelial cell proliferation was also identified. Rats were randomized to a high (8% NaCl or 1.36 mol/kg) or low (0.1% NaCl or 17 mmol/kg) salt diet. After 4 to 8 weeks, phenylephrine-treated rats on a high salt diet developed marked hypertension, which was in contrast with phenylephrine-treated rats placed on a low salt diet or vehicle-treated rats given a high salt diet. Hypertension after phenylephrine exposure correlated with the initial mean systolic BP (r(2)=0.99) and the degree of BP lability (r(2)=0.99) during the phenylephrine infusion, the amount of osteopontin expressed in the initial biopsy/nephrectomy (r(2)=0.74), and the final glomerular filtration rate (r(2)=0.58). These studies provide a mechanism by which a markedly elevated sympathetic nervous system can induce salt-dependent hypertension even when the hyperactive sympathetic state is no longer engaged.

Adrenergic alpha-Agonists↗
PubMed1999

Neutron generator (HIRRAC) and dosimetry study.

Dosimetry studies have been made for neutrons from a neutron generator at Hiroshima University (HIRRAC) which is designed for radiobiological research. Neutrons in an energy range from 0.07 to 2.7 MeV are available for biological irradiations. The produced neutron energies were measured and evaluated by a 3He-gas proportional counter. Energy spread was made certain to be small enough for radiobiological studies. Dose evaluations were performed by two different methods, namely use of tissue equivalent paired ionization chambers and activation of method with indium foils. Moreover, energy deposition spectra in small targets of tissue equivalent materials, so-called lineal energy spectrum, were also measured and are discussed. Specifications for biological irradiation are presented in terms of monoenergetic beam conditions, dose rates and deposited energy spectra.

Dose-Response Relationship, Radiation↗