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Biomedical subjects

S Suga

Publications and source records attributed to S Suga.

At least 91 records · Page 5Linked to original sources

Spread of varicella-zoster virus DNA to family members and environments from siblings with varicella in a household.

OBJECTIVE: To elucidate virus spread from siblings with varicella to other family members and environmental objects in a family setting before and after onset of the disease. MATERIALS AND METHODS: Among a family consisting of five members, a boy developed varicella and the remaining two siblings developed the disease 17 and 18 days after onset of the index case. Swab samples from throats and hands of parents and three siblings and samples from several sources in the environment of the house were collected frequently before and/or after onset of the disease. Varicella-zoster virus (VZV) DNA in the samples was examined by a sensitive polymerase chain reaction amplification assay. RESULTS: In total, 108 samples from the throats and hands of the three children with varicella, 72 such samples from parents, and 72 samples from the surfaces of several sources in the house were collected. Eight days after onset of the index case (the older boy), VZV DNA was detected in both samples from the index case and on the surfaces of four sources (air conditioner filter, table, television channel push-buttons, and door handle), but not from the two other siblings or parents. Then, it was detected once on the mother's hand and the air conditioner filter and three times on the television channel push-buttons by January 30, 1998, when the girl developed varicella, 17 days after onset of the index case. The younger brother developed the disease on January 31. Viral DNA could not be detected in any samples obtained on January 30; however, it was detected on the hands of the older boy and the father and in samples from the hand and throat of the girl on January 31. Thereafter, virus DNA was detected three times intermittently by February 13 on the hand and three times persistently in the throat of the girl. The virus DNA was detected three times between February 1 and 3 on the hand and three times between February 1 and 4 in the throat of the younger boy. It was detected occasionally on the hands of the older boy and the parents, and occasionally or intermittently on surfaces of four environmental sources between February 2 and 13. CONCLUSIONS: The present study showed the rapid and broad contamination of the environment with the VZV DNA when the varicella patient appeared in a family, although it does not directly mean infectivity.

Adult↗

Corticotropin-releasing factor modulation of Ca2+ influx in rat pancreatic beta-cells.

The effects of corticotropin-releasing factor (CRF) on the intracellular concentration of Ca2+ were studied in isolated single beta-cells of the rat islet. Immunohistochemical staining using CRF-receptor antibodies revealed the presence of both type 1 (CRF-R1) and type 2 (CRF-R2) receptors for CRF in the majority of islet cells. CRF (2 nmol/l) increased cytosolic Ca2+ concentration under 2.8 mmol/l glucose, dependent upon extracellular Ca2+. CRF caused depolarization of the cell membrane, which was followed by action potentials under 2.8 mmol/l glucose. The dose-response relationships of CRF-induced depolarization in the presence of 1 micromol/l nifedipine produced a bell-shaped curve, showing the peak response at 2 nmol/l. In the whole-cell patch-clamp recording, CRF enhanced Ca2+ currents through L-type Ca2+ channels in a dose-dependent manner similar to that for depolarization. In cells pretreated with Rp-deastereomer of adenosine cyclic 3',5'-phosphorothiolate (100 micromol/l), neither depolarization nor an increase in the Ca2+ current was caused by CRF at concentrations <2 nmol/l. In these cells, CRF at 20 nmol/l reduced the Ca2+ current. These results suggest that in single beta-cells of rat islets, CRF, through its own receptor, potentiates Ca2+ influx through the L-type Ca2+ channel by activation of the cAMP/protein kinase A signaling pathway. CRF at a high concentration also shows an inhibitory effect on the Ca2+ current through an unknown signaling pathway.

Animals↗

Four cases of human herpesvirus 6 variant B infection after pediatric liver transplantation.

BACKGROUND: Little is known about human herpesvirus (HHV)-6 infection after liver transplantation. We present our experiences with four cases of HHV-6 infection after liver transplantation from living related donors. METHODS: Peripheral blood was collected from four donor and recipient pairs at the time of transplantation and biweekly from the recipients after transplantation. We attempted to isolate HHV-6 and measure antibody titers to HHV-6 and HHV-7. RESULTS: HHV-6 was isolated from four recipients approximately 2 weeks after transplantation. A significant rise in HHV-6 antibody titers was observed in four recipients at some point in their course, whereas HHV-7 antibody titers were increased in one recipient. Four isolates were variant B. When HHV-6 was isolated, all recipients had an unexplained fever. CONCLUSIONS: HHV-6 variant B infection after pediatric liver transplantation was confirmed. HHV-6 infection occurred approximately 2 weeks after transplantation. Moreover, there appears to be an association between HHV-6 infection and unexplained fever.

Antibodies, Viral↗

Twin helical undulator beamline for soft X-ray spectroscopy at SPring-8.

A very high resolution soft X-ray beamline, BL25SU, has been designed and is under construction at SPring-8. Completely right or left circularly polarized light is supplied on a common axis of a newly designed twin helical undulator. A helicity modulation up to 10 Hz can be performed using five kicker magnets. The fundamental radiation covers the region 0.5-3 keV. Higher-order radiation is rather weak on the axis. A monochromator with varied-line-spacing plane gratings is installed to cover the region below 1.5 keV. A very high resolution beyond 10(4) is expected for the whole energy region.

Journal Article↗

Postischemic hyperthermia increases expression of hsp72 mRNA after brief ischemia in the gerbil.

Brain temperature during ischemia critically determines insult severity, and temperature changes during recirculation may also affect subsequent injury. We have examined the impact of postischemic temperature on induction of the 70 kDa stress protein, hsp72, after brief ischemia in the gerbil. Animals were subjected to 2 min ischemia after which they were maintained under continuous halothane anesthesia during 3 h recirculation, and were either kept normothermic or subjected to hyperthermia comparable to that which occurs spontaneously in gerbils released from anesthesia immediately after the occlusion. Quantitative in situ hybridization showed striking dependence of hsp72 induction on postischemic hyperthermia. This result establishes that delayed temperature-sensitive signals mediate this injury-associated transcriptional response, and demonstrates that postischemic temperature must be carefully monitored in studies of gene expression and induced tolerance employing brief ischemic insults.

Animals↗

Kinetics of Ca2+ release evoked by photolysis of caged InsP3 in rat submandibular cells.

Quantitative time-resolved measurements of cytosolic Ca2+ release by photolysis of caged InsP3 have been made in single rat submandibular cells using patch clamp whole-cell recording to measure the Ca2+-activated Cl- and K+ currents. Photolytic release of InsP3 from caged InsP3 at 100 Joules caused transient inward (V(H) = 60 mV) and outward (V(H) = 0 mV) currents, which were nearly symmetric in their time course. The inward current was reduced when pipette Cl- concentration was decreased, and the outward current was suppressed by K+ channel blockers, indicating that they were carried by Cl- and K+, respectively. Intracellular pre-loading of the InsP3 receptor antagonist heparin or the Ca2+ chelator EGTA clearly prevented both inward and outward currents, indicating that activation of Ca2+-dependent Cl- and K+ currents underlies the inward and the outward currents. At low flash intensities, InsP3 caused Ca2+ release which normally activated the K+ and Cl- currents in a mono-transient manner. At higher intensities, however, InsP3 induced an additional delayed outward K+ current (I[K,(delay)]). I[K(delay)] was independent of the initial K+ current, independent of extracellular Ca2+, inhibited by TEA, and gradually prolongated by repeated flashes. The photolytic release of Ca2+ from caged Ca2+ did not mimic the I[K(delay)]. It is suggested that Ca2+ releases from the InsP3-sensitive pools in an InsP3 concentration-dependent manner. Low concentrations of InsP3 induce the transient Ca2+-dependent Cl- and K+ currents, which reflects the local Ca2+ release, whereas high concentrations of InsP3 induce a delayed Ca2+-dependent K+ current, which may reflect the Ca2+ wave propagation.

Animals↗

Intracellular cAMP potentiates voltage-dependent activation of L-type Ca2+ channels in rat islet beta-cells.

Intracellular cAMP-dependent modulation of L-type Ca2+ channel activation in cultured rat islet beta-cells has been investigated using the patch-clamp whole-cell current recording mode. The L-type voltage-dependent Ca2+ current (ICa) showed a fast activation followed by a slow inactivation, and was sensitive to Ca2+ channel blockers, for example nifedipine. Application of a cAMP analogue, dibutyryl cyclic AMP (db-cAMP), increased the magnitude of the peak ICa in a concentration-dependent manner. Values of the half-activation potentials (V1/2), taken from activation curves for ICa, were -16.7 +/- 1.8 and -21.9 +/- 3.4 mV (P < 0.05) before and after application of db-cAMP, respectively, with no change of the slope factor (k) or the reversal potential. Pretreatment with a specific protein kinase A antagonist, Rp-cAMP, prevented the potentiating effect of db-cAMP. These results indicate that in rat islet beta-cells, phosphorylation of cAMP-dependent kinase potentiates the voltage-dependent activation of L-type Ca2+ channels.

Animals↗

Effect of hyperosmotic solutions on human brain tumour vasculature.

Reversible opening of the blood-brain barrier (BBB) has been used to increase delivery of chemotherapeutic agents into brain tumours, but it is complicated and requires general anaesthesia. Without affecting the normal BBB, and avoiding the complications of BBB modification by hyperosmotic solution, we tried an adequate minimal BBB disruption in brain tumours. Although the effect of BBB disruption on normal brain has been described, there are no reports of the effect of an impaired BBB on microcirculation. In this study, four patients underwent surgical resection of a glioblastoma multiforme (GM; n = 1), astrocytoma (n = 2), or metastatic brain tumour (n = 1). Epicerebral microcirculation was observed in the operative field. Serial fluorescein microangiograms of the tumour and peritumoural area were obtained before and after BBB disruption was introduced intra-operatively by retrograde infusion of mannitol introducing a catheter via the temporal superficial artery back to the carotid bifurcation. On the initial microangiogram, staining by the fluorescein dye was observed in the GM and metastatic tumour but not in the astrocytoma; no extravasation of fluorescein dye was observed in the peritumoural areas. After BBB disruption, fluorescein perfusion increased and extravasation of fluorescein dye from the venules was observed in the GM and the metastatic tumour and in the peritumoural area of both lesions; BBB disruption started from venules in the peritumoural area without affecting the normal brain. However, such effects were not observed in the astrocytomas after BBB disruption nor in normal brain tissue in any patient. It appears that the integrity of the BBB is less stable in the peritumoural area of GM and metastatic brain tumours than it is in astrocytomas or normal brain. Osmotic BBB disruption may offer a method for achieving global delivery of therapeutic agents to brain tumours and peritumoural areas.

Astrocytoma↗

Identification of homozygous lipoprotein lipase gene mutation in a woman with recurrent aggravation of hypertriglyceridaemia induced by pregnancy.

We herein report a case of a 40-year-old Japanese woman (patient IT) with a history of recurrent aggravation of hypertriglyceridaemia, pancreatitis and miscarriages in three previous pregnancies. However, strict dietary intervention was applied during a fourth pregnancy. As a result, acute pancreatitis was avoided, and the patient gave birth to a healthy infant. In patient IT, the underlying etiology of the recurrent aggravation of hypertriglyceridaemia during pregnancy was a lipoprotein lipase (LPL) gene aberration. She was homozygous for LPL deficiency due to a nonsense mutation (TGG1401 --> TGA/Trp382 --> Stop) in exon 8 of the LPL gene, which resulted in the absence of LPL activity and immunoreactive LPL mass. Our findings indicate that, in LPL deficiency, pregnancy seriously exacerbates hypertriglyceridaemia and increases the risk of acute pancreatitis, which endangers both the mother and fetus. Early diagnosis of LPL deficiency and appropriate management thereof are essential for normal childbirth.

Abortion, Habitual↗

Molecular cloning, water channel activity and tissue specific expression of two isoforms of radish vacuolar aquaporin.

A major membrane intrinsic protein (VM23) in vacuoles of radish (Raphanus) tap root was investigated. The cDNAs for two isoforms of VM23, gamma- and delta-VM23, encode polypeptides of 253 and 248 amino acids, respectively. gamma- and delta-VM23 correspond to the gamma- and delta-TIP (tonoplast intrinsic protein) of Arabidopsis. The deduced amino acid sequences of the two VM23 isoforms were 60% identical. The amino-terminal sequence of gamma-VM23 showed agreement with the direct sequence of the purified VM23, suggesting that gamma-VM23 is the most abundant molecule among the VM23 isoforms. When mRNAs of gamma- and delta-VM23 were injected into Xenopus oocytes, the osmotic water permeability of oocytes increased 6-fold (60 to 200 microns s-1) of the control oocytes. The transcripts of both isoforms were detected in a high level in growing hypocotyls and young leaves, but delta-VM23 was not detected in seedling roots. Light illumination enhanced the transcription of two genes of VM23 in cotyledons and roots but suppressed their expression in hypocotyls the growth of which was inhibited by light. These findings suggest that the expression of VM23 is tightly related to cell elongation.

Amino Acid Sequence↗

Five cases of thrombocytopenia induced by primary human herpesvirus 6 infection.

Five patients suffering from exanthem subitum with thrombocytopenia were confirmed as primary human herpesvirus 6 (HHV-6) infection by serological test. All cases had thrombocytopenia during the acute phase of exanthem subitum. The clinical features of these cases were benign, and all recovered without any specific treatment. Moreover, 4 of the 5 cases showed a mild elevation of hepatic transaminase during the same period, and other viral infections including cytomegalovirus, Epstein-Barr virus, and human herpesvirus 7 were ruled out in these patients. It was speculated that direct inhibition of platelet production by the virus or cytokine induced by the virus-infected cells was the mechanism of the thrombocytopenia induced by primary HHV-6 infection.

Acute Disease↗

Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells.

Adrenomedullin (AM), a potent vasorelaxant and natriuretic peptide isolated from human pheochromocytoma, is present in the kidney and secreted from endothelial cells (EC) and vascular smooth muscle cells (VSMC), but the functional role of AM is still unclear. To clarify the significance of AM as a local regulator, we investigated its secretion and action in cultured cells, and examined the effects of neutralization using a specific monoclonal antibody against AM. The prepared antibody directed against the ring structure showed a high affinity for human and rat AM. Using radioimmunoassay with this antibody, we found significant secretion from cultured rat mesangial cells (MC) of a 6-kDa mature form of AM as seen from EC and VSMC. The addition of AM into cultured cells dose-dependently increased cAMP production and potently inhibited PDGF-stimulated thymidine incorporation. Pretreatment with the monoclonal antibody completely abolished cAMP increase induced by exogenous AM. Moreover, antibody neutralization of endogenously secreted AM in cultured EC, but not in MC or VSMC, markedly (by approximately 70%) reduced basal cAMP production and significantly (1.7-fold) enhanced DNA synthesis. These results indicate that AM, acting as an autocrine/paracrine regulator, exerts an antiproliferative action on EC and MC, and suggest its role as a local modulator of endothelial and mesangial function.

Adrenomedullin↗

Regulation of spontaneous rhythmic contractions in rat pregnant myometrium by corticotrophin-releasing factor.

To elucidate the role of corticotrophin-releasing factor (CRF) in the spontaneous rhythmic contractions of pregnant myometrium, isometric contractions of longitudinal myometrial preparations taken from Sprague-Dawley rats (18-21 days gestation) were measured. CRF (0.03-30 nM) significantly increased the amplitude (117 +/- 4% of control at 30 nM, mean +/- S.E.M.) and significantly decreased the frequency (74 +/- 5%) in a concentration-dependent manner. The area under the tension curve did not increase (89 +/- 8%). Such effects of CRF were not observed in preparations pretreated with the RP diastereomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS, 10 microM), an inhibitor of protein kinase A. In preparations pretreated with indomethacin (1 microM), CRF caused little change in the amplitude but significantly decreased the frequency of the contractions. Intracellular cAMP levels in the preparations, measured by enzyme immunoassay, rose when CRF was applied at 30 nM. These results suggest that the slight positive inotropic action of CRF is due to activation of both cAMP and prostaglandin pathways, whereas the negative chronotropic action is due solely to the cAMP signalling pathway.

Animals↗

Persistence of protective immunity after postexposure prophylaxis of varicella with oral aciclovir in the family setting.

The persistence of protective immunity after postexposure prophylaxis against varicella using oral aciclovir was evaluated in the family setting. Sixty one of 78 recipients of oral aciclovir were assessed by questionnaire, and 13 of 61 were evaluated for serum antibody to varicella zoster virus (VZV) using the fluorescent antibody to membrane antigen method. The observation period ranged from 33 to 50 months. None of those (n = 44) who had initially seroconverted to VZV after aciclovir prophylaxis developed breakthrough varicella. All 13 who had serology repeated still had titres > or = 4. Antibody titres in those who had histories of re-exposure to the virus were significantly higher than in those who had not (p < 0.01).

Acyclovir↗