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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 199 records · Page 11Linked to original sources
PubMed1999

The effects of circulating interleukin-8 and adhesion molecules on pulmonary dysfunction in pediatric orthotopic liver transplantation.

We investigated the effects of circulating inflammatory cytokines and adhesion molecules induced by ortho-topic liver transplantation (OLT) on pulmonary function. Although the plasma interleukin-8 (IL-8) levels increased gradually, peaking at the end of the operation, these increases were considered minimal. The baseline endothelial adhesion molecule (E-selectin) level was several times higher than the normal value, but after reperfusion of the new transplanted liver, the plasma E-selectin concentrations decreased to within the normal range and remained almost normal during the postoperative period. Similar changes were observed in the plasma levels of other types of adhesion molecules. Although PaO(2)/FIO(2) showed a significant inversed correlation with the peak IL-8 concentration, after the exclusion of two patients, one of whom died and one of whom rejected the transplanted liver, no correlation was able to be found between the PaO(2)/FIO(2) ratio and the maximum IL-8 concentration. Furthermore, there was no correlation between the adhesion moleclues and PaO(2)/FIO(2). These results suggest that IL-8 exerts only a slight effect on respiratory function following successful pediatric liver transplantation, and that circulating adhesion molecules do not affect perioperative lung function.

Adolescent↗
PubMed1999

Expression and localization of the Na+-H+ exchanger in the guinea pig cochlea.

Physiological studies have shown that the Na+-H+ exchanger (NHE) is a major carrier protein regulating the intracellular pH in the cells of the cochlea. The presence of multiple forms of the exchanger has been demonstrated by the recent cloning of four mammalian NHEs, NHE-1 to NHE-4. Despite the structural similarity, these NHE isoforms differ in their tissue distribution, kinetic characteristics, and responses to external stimuli. The present study was undertaken to examine the expression and distribution of four NHE isoforms in the guinea pig cochlea. We used reverse transcription-polymerase chain reaction to assess the expression of NHE-1-4 isoforms and non-radioactive in situ hybridization to examine their localization. Although NHE-2, -3 and -4 isoform mRNAs could be detected in the cochlear tissue, the NHE-1 message was predominant. Cloned guinea pig NHE-1-4 partial cDNA fragments were highly homologous to the corresponding rat NHE isoforms. NHE-1 isoform mRNA was distributed in the hair cells, marginal cells, spiral ligament fibrocytes, spiral prominence cells and spiral ganglion cells. NHE- localized in a variety of cochlear cells would contribute to their differential function.

Amino Acid Sequence↗
PubMed1999

Protective role of glutathione synthesis in response to oxidized low density lipoprotein in human vascular endothelial cells.

Impairment of endothelial cells by oxidized low density lipoprotein (OxLDL) is believed to be the first step in atherogenesis. It is also believed that oxidative stress/antioxidant imbalance is involved in the cell damage by OxLDL. However, little is known about the interaction between OxLDL and antioxidants. In this study, we show that treatment of human vascular endothelial cells with OxLDL caused a gradual increase of glutathione (gamma-glutamylcysteinyl glycine, GSH) levels in 24 h. OxLDL increased the intracellular levels of reactive oxygen species (ROS) and stimulated the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for the GSH synthesis, the mitogen-activated protein kinase (MAPK) activity, and the AP-1-DNA binding activity. The luciferase activity of gamma-GCS promoter containing AP-1 site was activated by OxLDL. Collectively, OxLDL induces gamma-GCS expression mediated by AP-1 resulting in an increase of GSH levels. The MAPK activity stimulated by ROS may be involved in the activation of AP-1. The increase in GSH by OxLDL may afford cellular protection against OxLDL-induced oxidative stress.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

The effect of exercise training on oxidative damage of lipids, proteins, and DNA in rat skeletal muscle: evidence for beneficial outcomes.

Moderate daily exercise is known to be beneficial to health, reducing risks of a number of age-related disorders. Molecular mechanisms that bring about these effects are not clear. In contrast, it has been claimed that some types of prolonged physical exertion are detrimental to health because active oxygen species are generated excessively by enhanced oxygen consumption. Using two age groups of rats, young (4 week) and middle aged (14 months), we investigated the effects of long-term swimming training on the oxidative status of phospholipids, proteins, and DNA. The concentration of thiobarbituric acid reactive substances and 4-hydroxynonenal protein adducts did not differ in the gastrocnemius muscle between exercised and nonexercised animals in the two age groups. The extent of carbonylation in a protein of molecular weight around 29 KDa and the amount of 8-hydroxydeoxyguanosine in nuclear DNA were smaller (p<.05) in the exercised rats than in the sedentary animals. Activities of DT-diaphorase (C1: 29.3+/-1.9; C2: 36.1+/-2.6; E1: 27.2+/-1.3; C2: 33.4+/-2.9 nmol/mg protein) and proteasome, a major proteolytic enzyme for oxidatively modified proteins were significantly higher in the exercised animals of both age groups (p<.05). The adaptive response against oxidative stress induced by moderate endurance exercise constitutes a beneficial effect of exercise.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells.

In the present study, we show that melatonin induces the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme of glutathione (GSH) synthesis, in ECV304 human vascular endothelial cells. One micromolar melatonin induced the expression of gamma-GCS mRNA followed by an increase in the concentration of GSH with a peak at 24 h. An electrophoretic mobility shift assay showed that melatonin stimulates the DNA-binding activity of activator protein-1 (AP-1) as well as retinoid Z receptor/retinoid receptor-related orphan receptor alpha (RZR/RORalpha). ECV304 cells transiently transfected with a plasmid containing the gamma-GCS promoter-luciferase construct showed increased luciferase activity when treated with melatonin. The melatonin-dependent luciferase activity was found in the gamma-GCS promoter containing AP-1 site. The luciferase activity mediated by AP-1 was repressed in the promoter containing RZR/RORalpha site. In addition, cell cycle analysis showed that melatonin increases the number of cells in the G0/G1 phase; however, treatment of the cells with buthionine sulfoximine, a specific inhibitor of gamma-GCS, abolished the effect of melatonin on the cell cycle, suggesting induction of cell arrest by melatonin requires GSH. As conclusion, induction of GSH synthesis by melatonin protects cells against oxidative stress and regulates cell proliferation.

Buthionine Sulfoximine↗
PubMed1999

IL-12 receptor beta2 and CD30 expression in paranasal sinus mucosa of patients with chronic sinusitis.

The aetiology of chronic sinusitis is still poorly understood. The expression of T-helper 1 (Th1) and T-helper 2 (Th2) cell markers, interleukin (IL)-12 receptor beta2 subunit (IL-12Rbeta2) messenger ribonucleic acid (mRNA) and CD30, respectively, were investigated in the paranasal sinus mucosa of patients with chronic sinusitis in an attempt to elucidate the involvement of Th1 and Th2 cells in this disease. Anterior ethmoidal mucosae were surgically obtained from two groups of patients with chronic sinusitis: those who had allergic rhinitis (allergic group, n=11) and those without allergy (nonallergic group, n=11). IL-12Rbeta2 mRNA was quantified by means of the reverse transcription polymerase chain reaction, and CD30-positive cells were examined immunohistochemically. Both IL-12Rbeta2 mRNA and CD30 were expressed in the sinus mucosa of the allergic and nonallergic groups. The proportion of mononuclear cells which were CD30-positive in the sinus mucosa was significantly greater in the allergic than in the nonallergic group. The expression levels of IL-12Rbeta2 mRNA were virtually equivalent in both groups. These results suggest a T-helper 2-dominated mucosal reaction in the allergic compared to the nonallergic group, and indicate T-helper 1 activity in the sinus mucosa of both groups. The ubiquity of T-helper 1 cells suggests that they play a role in maintaining local mucosal defences against foreign antigens, which continually enter the upper respiratory tract.

Chronic Disease↗
PubMed1999

The fas and fas ligand pathways in liver allograft tolerance.

The Fas and Fas ligand (Fas/FasL) pathways may play a central role in cytotoxicity or immunoregulation in liver transplantation. Here, in an attempt to examine the role of Fas/FasL on drug-free tolerance, we measured mRNA levels of Fas/FasL in livers by reverse transcriptase-polymerase chain reaction (RT-PCR), and also protein levels of Fas/FasL in livers by immunohistochemistry and in serum by dot blot assay. PVG recipients bearing DA livers showed serious rejection between post-operative (POD) days 7 and 14, but this rejection was naturally overcome without any immunosuppression. Fas gene and protein products were expressed on almost every cell in livers taken from naive rats, and at any time point in both syngeneic and allogeneic orthotopic liver transplantation (OLT) rats. In contrast, FasL mRNA in DA livers was detectable at POD 2, peaked at POD 14, and declined at POD 63 in allogeneic OLT (DA-PVG). Although the FasL gene was detectable in isografts at POD 14, its expression was much lower than in allografts. The time course and localization of FasL expression indicated that the expression of FasL gradually switched from infiltrating cells to hepatocytes when the rejection was naturally overcome and tolerance was induced in this OLT model. Soluble Fas could constitutively be detected at any time point in the serum of the tolerogenic OLT (DA-PVG) rats and was not diminished during the rejection phase. Soluble FasL peaked at POD 14 in allogeneic OLT, while sFasL was significantly lower in the serum of normal and syngeneic OLT rats. These findings suggest that the Fas and FasL pathways, including soluble forms, may contribute to the control of the immune response in this drug-free tolerance OLT model.

Animals↗
PubMed1999

Immunization with a synthetic peptide conjugate derived from the N-terminal sequence of either the beta-chain of haemoglobin or the immunosuppressive protein (reOLT 4) reduces the litter size of pregnant rats.

A synthetic peptide conjugate based on the N-terminal sequence of a 10 000 MW immunosuppressive serum protein (reOLT 4) was used to immunize female Lewis rats prior to mating, in order to determine whether blocking this protein had an effect on pregnancy. The N-terminal sequence of (reOLT 4) has close sequence homology to the beta-chain of rat haemoglobin so a peptide conjugate based on the N-terminal sequence of this protein was also used to immunize female Lewis rats. Controls included animals that were not immunized and animals that received the peptide carrier, diphtheria toxoid (DT). No statistical differences were found in gestation time or litter sizes in these groups. Differences were, however, evident between these groups and animals that received DT-(reOLT 4) (group 4) or the DT-beta-chain haemoglobin (group 5). There were no statistical differences in litter size or gestation time for group 4 when compared with group 5. Enzyme-linked immunosorbent assay and dot-blot analysis revealed that rats from both groups also had strong responses against DT, the peptide conjugate they were immunized with and the corresponding full-length protein. In both cases, animals from group 4 and group 5 had weak responses to the peptide that they did not receive, together with lower erythrocyte counts and haematocrits, and elevated heart to body weight ratios. Additionally, antibody purified on a (reOLT 4) immunoaffinity column was capable of binding to rat erythrocytes. A second investigation comparing anaemia prior to fertilization and maintained anaemia over the gestation period revealed that only the latter was capable of decreasing litter size to the same degree as obtained for groups 4 and 5. We conclude that for groups 4 and 5 it is the autoimmune effect of continual anaemia over the gestation period, mediated by autoantibodies, which results in the observed lower litter size.

Animals↗
PubMed1999

A lateral transzygomatic-transtemporal approach to the infratemporal fossa: technical note for mobilization of the second and third branches of the trigeminal nerve.

This report describes an alternative approach to the infratemporal fossa lesions through a lateral zygomato-temporal craniotemy, which modifies the extradural temporopolar technique for cavernous sinus surgery. First, an L-shaped osteotomy of the zygoma from the frontozygomatic suture attaching the zygomatre arch and low positioned temporal cramotomy are made. Through this zygomato-temporal craniotomy and orbitotemporal drilling, leaving the lateral orbital rim and orbital roof intact, skeletonization of the foramens rotundum and ovale are carried out. The key element of this infratemporal exposure is the dissection and mobilization of the trigeminal nerve, trigeminal second branch rostrally, and the third branch caudally, which facilitates a wide exposure of the infratemporal fossa with preserving trigeminal function. The corridor between the mobilized trigeminal branches provides direct access to the lateral and medial pterygoid plate, internal maxillary artery, sphenoid and maxillary sinuses, maxilla and, finally, the parapharyngeal area. Our experiences have demonstrated that this lateral transzygomatic-transtemporal exposure is satisfactory for use with infratemporal fossa tumors. This approach has an advantage for cranial-base exposure with decreased risks of cosmetic deformity and of trigeminal nerve dysfunction.

Journal Article↗
PubMed1999

Prevalence and prediction of allergic rhinitis using questionnaire and nasal smear examination in schoolchildren.

Allergic rhinitis is a common condition among schoolchildren. However, little is known about the prevalence of nasal eosinophilia. We investigated the prevalence of rhinitis via questionnaire and nasal smears for eosinophils. The questionnaire was administered in 1992 and 1995. Complete responses were obtained from 1044 and 431 schoolchildren, respectively, of whom 26.5% and 22.5% claimed to have nasal symptoms. Nasal smears were taken in 1992, 1993 and 1994, and 415, 285 and 384 samples were collected, respectively. Positive eosinophilia were seen in 39.8%, 35.1% and 35.9% children in 1992, 1993 and 1994, respectively. In 1992, we utilized both questionnaire and nasal smears simultaneously to evaluate 415 schoolchildren. Of 415 schoolchildren, 72 (17.3%) had both nasal symptoms and nasal eosinophilia. Interestingly, those who showed positive eosinophilia in 1992, especially those who had eosinophilia with nasal symptoms, had significantly higher incidence of nasal symptoms three years later in 1995 than those who showed negative eosinophilia in 1992. These results suggest that nasal eosinophilia in schoolchildren are associated with subsequent nasal symptoms, and that nasal smear examination may be a potentially valuable test to predict prolonged or recurrent allergic rhinitis.

Adolescent↗
PubMed1999

Regulation of gamma-glutamylcysteine synthetase expression in response to oxidative stress.

Glutathione (GSH) is synthesized by the activity of two ATP-requiring GSH synthesizing enzymes. Gamma-glutamylcysteine synthetase (gamma-GCS) is the rate limiting enzyme for the GSH synthesis. Gamma-GCS is a heterodimer of heavy, catalytic subunit and light, regulatory subunit and responsive to many stresses, such as heat shock, oxidative stress or cytokines. To know the regulation of the expression of gamma-GCS gene, in the present study, we show evidences that gamma-GCS heavy subunit is upregulated by oxidative stress by ionizing radiation and TNF-alpha mediated by nuclear factor-kappaB (NF-kappaB), and impairment of the expression of gamma-GCS by TNF-alpha in diabetic condition. Furthermore we describe the importance of GSH in the regulation of NF-kappaB subunits.

Animals↗
PubMed1999

Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells.

In this paper, we provide direct evidence that glutathione S-transferase pi (GSTpi) detoxifies cisplatin (CDDP). We used human colonic cancer HCT8 cells sensitive and resistant to CDDP, the level of cisplatin-glutathione adduct (DDP-GSH) being higher in the resistant cells. There was an overexpression of GSTpi mRNA in these CDDP-resistant cells. Incubation of the cells with CDDP resulted in the formation of DDP-GSH dependent on the CDDP concentration and the incubation time. The formation of DDP-GSH was abolished when the cells were pre-treated with ethacrynic acid or ketoprofen, inhibitors of GSTpi. Purified GSTpi also catalyzed the formation of DDP-GSH in vitro, with an apparent Km of 0.23 mM for CDDP and an apparent Vmax of 4.9 nmol/min/mg protein. The increase in DDP-GSH produced by GSTpi was linear with incubation time up to 3 h and optimal of pH 7.4. A GSTpi transfectant cell line was constructed in HCT8 cells using a pcDNA3.1 (-)/Myc-His B with an expression vector containing cDNA for GSTpi. Transfection of GSTpi cDNA into HCT8 cells resulted in an increase in the expression of GSTpi by 1.4-fold in parallel with an augmentation of the formation of DDP-GSH. These results suggest that GSTpi plays a role in the formation of DDP-GSH and the acquisition of resistance to CDDP in cancer cells.

Cisplatin↗
PubMed1999

[Efficacy of influenza vaccine among geriatric inpatients: effect of previous vaccination and antibody induction by single and twice injections].

To investigate the effect of previous influenza vaccination and the difference in antibody induction by single and twice injection of influenza vaccine in the elderly, hemagglutination inhibition (HI) antibody titers of the three types of influenza viruses were measured. Influenza vaccination was done for 217 inpatients. For the patients who had influenza vaccination in the year prior to the study, influenza vaccine was administered once to 77 patients and twice to another 70 patients. Influenza vaccine was injected twice to 70 patients who had not received influenza vaccine in the previous years. The influenza vaccine induced an increase in HI titer in almost all patients. The geometric mean of the HI titer and the frequency of patients with HI titers over 128x were similar after vaccination in the groups of patients who were injected twice, irrespective of whether or not influenza vaccination was given in the year prior to the study. The geometric means of the HI titers for influenzas A/H3N2 and B and the frequency of HI titers over 128x for influenza A/H3N2 after vaccination were lower in the patients who received vaccine once than in the patients vaccinated twice. These results suggest that prior vaccination does not diminish antibody response to influenza vaccine significantly in the elderly when influenza vaccine is injected twice. Although single injection is inferior to twice injection in antibody induction with some vaccine virus strains, induction of HI titers over 128x is found in more than 70% of elderly. Single injection of influenza vaccine may be practically effective and useful for protection of influenza infection in the elderly.

Aged↗
PubMed1999

Quantitative detection of hepatitis B virus by transcription-mediated amplification and hybridization protection assay.

We have developed a sensitive and quantitative assay using transcription-mediated amplification and hybridization protection assay for the detection of hepatitis B virus (HBV) DNA in serum. The transcription-mediated amplification was carried out in a single tube. The hybridization protection assay was carried out in a microtiter plate with two probes with different specific activities to obtain a broad detection range. As a result, the assay had a detection range of 5 x 10(3) to 5 x 10(8) genome equivalents (GE)/ml and good quantitative accuracy on a logarithmic scale. A moderately sized manual assay run can be completed within 5 h. Measurements of the amounts of HBV DNA in clinical samples by the assay showed the amounts under various disease conditions to be widely distributed (more than 5 logs, from approximately 5 x 10(3) to 5 x 10(8) GE/ml). It was also shown that the amount of HBV DNA in one chronic hepatitis patient varied widely, with a range of more than 5 logs during long-term monitoring. Our assay has the potential to be used to monitor and determine the prognosis of HBV patients and carriers, especially during interferon treatment.

Carcinoma, Hepatocellular↗
PubMed1999

p38 mitogen-activated protein kinase can be involved in transforming growth factor beta superfamily signal transduction in Drosophila wing morphogenesis.

p38 mitogen-activated protein kinase (p38) has been extensively studied as a stress-responsive kinase, but its role in development remains unknown. The fruit fly, Drosophila melanogaster, has two p38 genes, D-p38a and D-p38b. To elucidate the developmental function of the Drosophila p38's, we used various genetic and pharmacological manipulations to interfere with their functions: expression of a dominant-negative form of D-p38b, expression of antisense D-p38b RNA, reduction of the D-p38 gene dosage, and treatment with the p38 inhibitor SB203580. Expression of a dominant-negative D-p38b in the wing imaginal disc caused a decapentaplegic (dpp)-like phenotype and enhanced the phenotype of a dpp mutant. Dpp is a secretory ligand belonging to the transforming growth factor beta superfamily which triggers various morphogenetic processes through interaction with the receptor Thick veins (Tkv). Inhibition of D-p38b function also caused the suppression of the wing phenotype induced by constitutively active Tkv (TkvCA). Mosaic analysis revealed that D-p38b regulates the Tkv-dependent transcription of the optomotor-blind (omb) gene in non-Dpp-producing cells, indicating that the site of D-p38b action is downstream of Tkv. Furthermore, forced expression of TkvCA induced an increase in the phosphorylated active form(s) of D-p38(s). These results demonstrate that p38, in addition to its role as a transducer of emergency stress signaling, may function to modulate Dpp signaling.

Animals↗
PubMed1999

Proximal to distal cell communication in the Drosophila leg provides a basis for an intercalary mechanism of limb patterning.

Proximodistal patterning in the Drosophila leg is elaborated from the circular arrangement of the proximal domain expressing escargot and homothorax, and the distal domain expressing Distal-less that are allocated during embryogenesis. The distal domain differentiates multiply segmented distal appendages by activating additional genes such as dachshund. Secreted signaling molecules Wingless and Decapentaplegic, expressed along the anterior-posterior compartment boundary, are required for activation of Distal-less and dachshund and repression of homothorax in the distal domain. However, whether Wingless and Decapentaplegic are sufficient for the circular pattern of gene expression is not known. Here we show that a proximal gene escargot and its activator homothorax regulate proximodistal patterning in the distal domain. Clones of cells expressing escargot or homothorax placed in the distal domain induce intercalary expression of dachshund in surrounding cells and reorient planar cell polarity of those cells. Escargot and homothorax-expressing cells also sort out from other cells in the distal domain. We suggest that inductive cell communication between the proximodistal domains, which is maintained in part by a cell-sorting mechanism, is the cellular basis for an intercalary mechanism of the proximodistal axis patterning of the limb.

Animals↗
PubMed1999

Association between plasma homocysteine concentration and carotid atherosclerosis in hemodialysis patients.

Accelerated atherosclerosis is a major risk for uremic patients undergoing long-term hemodialysis. Because hyperhomocysteinemia may influence this condition, 168 such patients were examined for a possible association between plasma total homocysteine concentration (tHcy) and conventional cardiovascular risk factors. Generalized atherosclerosis was indicated by excessive intimal-medial wall thickness (IMT) of the extracranial carotid artery as measured by B-mode ultrasonography. The results documented tHcy in these patients of 33.0+/-16.9 micromol/L, a significantly higher amount than that of healthy subjects (11.0+/-3.1 micromol/L, p<0.0001). The patients' carotid maximum IMT was 1.79+/-1.16 mm. In multiple regression analyses with forward elimination procedure, carotid maximum IMT was clearly related to age (r = 0.417, p<0.0001), systolic blood pressure (r = 0.262, p = 0.0043), smoking (r = 0.177, p = 0.0076), duration of hemodialysis (r = 0.083, p = 0.0045), and tHcy (r = 0.195, p = 0.0021). These 5 factors accounted for 36.0% of the variation in carotid maximum IMT. Factors determined as unrelated were male gender, diastolic blood pressure, body mass index, total and HDL cholesterol, triglyceride, lipoprotein(a), uric acid, calcium, inorganic phosphate, and parathyroid hormone. Therefore hyperhomocysteinemia, along with advanced age, systolic hypertension and smoking aggravates atherosclerosis in chronic uremic patients.

Age Factors↗