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Biomedical subjects

M Seki

Publications and source records attributed to M Seki.

At least 91 records · Page 5Linked to original sources

Monosynaptic inputs from the nucleus tractus solitarii to the laryngeal motoneurons in the nucleus ambiguus of the rat.

The cricothyroid (CT) and the posterior cricoarytenoid (PCA) muscles in the larynx are activated by the laryngeal motoneurons located within the nucleus ambiguus; these motoneurons receive the laryngeal sensory information from the nucleus tractus solitarii (NTS) during respiration and swallowing. We investigated whether the neurons in the NTS projected directly to the laryngeal motoneurons, and what is the synaptic organization of their nerve terminals on the laryngeal motoneurons using the electron microscope. When wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin subunit B-conjugated HRP (CT-HRP) was injected into the CT muscle or the PCA muscle, the anterogradely WGA-HRP-labeled terminals from the NTS were found to directly contact the retrogradely CT-HRP-labeled dendrites and soma of both the CT and the PCA motoneurons. The labeled NTS terminals comprised about 4% of the axosomatic terminals in a section through the CT motoneurons, and about 9% on both the small (PCA-A) and the large (PCA-B) PCA motoneurons. The number of labeled axosomatic terminals containing round vesicles and making asymmetric synaptic contacts (Gray's type I) was almost equal to that of the labeled terminals containing pleomorphic vesicles and making symmetric synaptic contacts (Gray's type II) on the CT motoneurons. The labeled axosomatic terminals were mostly Gray's type II on the PCA-A motoneurons, while the majority of them were Gray's type I on the PCA-B motoneurons. These results indicate that the laryngeal CT and PCA motoneurons receive a few direct excitatory and inhibitory inputs from the neurons in the NTS.

Animals↗

Hepatic parenchymal transection using ultrasonic coagulating shears: a preliminary report.

Ultrasonically activated coagulating shears (CS) can coagulate and divide blood vessels of up to medium size by a tissue-welding technique. We present an application of CS in hepatic parenchymal transection during liver surgery. Intrahepatic vessels are uncovered by the so-called forceps fracture method, and they are coagulated and divided by CS. Larger vessels are tied only on the preserving side before the application of CS. Although further refinement of the CS tip is needed, this method has the potential to significantly simplify and improve surgical procedures for hepatic parenchymal transection.

Adult↗

Jejunal limb obstruction caused by a cholesterol stone 15 years after a total gastrectomy and 20 years after a cholecystectomy: report of a case.

We present herein the rare case of a 74-year-old woman found to have jejunal limb obstruction caused by a cholesterol stone 15 years after a total gastrectomy with Roux-en-Y anastomosis, and 20 years after a cholecystectomy. The patient complained of repeated episodes of upper abdominal distress on three separate occasions over a period of 20 months, and jejunal limb obstruction was diagnosed by abdominal computed tomography scanning and (99m)Tc scintigraphy. Surgery revealed a stone incarcerated in the jejunal limb, where the anastomosis had become slightly stenotic. The removed stone was 3.5 cm in diameter and was subsequently demonstrated to be a cholesterol stone by chemical analysis. This report is thought to be the first to describe jejunal limb obstruction caused by a gallstone incarcerated in the jejunal limb after a total gastrectomy in a patient with a history of cholecystectomy.

Acute Disease↗

Organization and expression of two Arabidopsis DREB2 genes encoding DRE-binding proteins involved in dehydration- and high-salinity-responsive gene expression.

In plants, a cis-acting element, DRE/CRT, is involved in ABA-independent gene expression in response to dehydration and low-temperature stress. To understand signal transduction pathways from perception of the dehydration stress signal to gene expression, we characterized a gene family for DRE/CRT-binding proteins DREB2A and DREB2B in Arabidopsis thaliana. Northern analysis showed that both genes are induced by dehydration and high-salt stress. Organ-specific northern analysis with gene-specific probes showed that these genes are strongly induced in roots by high-salt stress and in stems and roots by dehydration stress. The DREB2A gene is located on chromosome 5, and DREB2B on chromosome 3. We screened an Arabidopsis genomic DNA library with cDNA fragments of DREB2A and DREB2B as probes, and isolated DNA fragments that contained 5'-flanking regions of these genes. Sequence analysis showed that both genes are interrupted by a single intron at identical positions in their leader sequence. Several conserved sequences were found in the promoter regions of both genes. The beta-glucuronidase (GUS) reporter gene driven by the DREB2 promoters was induced by dehydration and high-salt stress in transgenic Arabidopsis plants.

Arabidopsis↗

Effects of macrophage colony-stimulating factor (M-CSF) on anti-fungal activity of mononuclear phagocytes against Trichosporon asahii.

Trichosporon asahii is an emerging opportunistic pathogen in immunocompromised patients. Little is known about the mechanisms of host defence against T. asahii. We investigated the fungicidal activity of human peripheral blood monocytes and murine peritoneal macrophages against T. asahii isolates, and the effects of M-CSF on the anti-fungal activity of mononuclear phagocytes. We also established a neutropenic mouse model of disseminated trichosporonosis with T. asahii. M-CSF enhanced the phagocytic fungicidal activity of mononuclear cells, and infected mice treated with human M-CSF at 10 x 106 U/kg showed a significant improvement in survival rate, with fewer fungal colony counts in the lung compared with control mice. Mice treated with human M-CSF showed higher concentrations of tumour necrosis factor-alpha (TNF-alpha) in the lung and plasma compared with control mice. The survival rate was significantly reduced in mice treated with anti-mouse TNF-alpha. Our results showed that M-CSF enhanced the fungicidal activity of mononuclear phagocytes partly by production of TNF-alpha, and suggest that the administration of M-CSF to patients with disseminated trichosporonosis may be a useful adjunct to conventional anti-microbial therapy and prophylaxis.

Animals↗

Up-regulation of human T lymphotropic virus type 1 (HTLV-1) tax/rex mRNA in infected lung tissues.

HTLV-1 has been implicated in certain pulmonary diseases. We previously demonstrated that expression of HTLV-1 tax/rex mRNA, encoding the transcriptional transactivator Tax, was closely associated with infiltration of activated T lymphocytes into lung tissue. To explore mechanisms of tax/rex expression in the lung, tax/rex mRNA expression and proviral DNA load were compared between peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage cells (BALC) from four patients with HTLV-1-associated myelopathy (HAM/TSP) and 13 carriers with various pulmonary symptoms. Semiquantitative detection of tax/rex mRNA strongly suggested that the lung was a preferential site for its expression. Proviral DNA loads in non-HAM/TSP carriers were variable but correlated well between PBMC and BALC in each individual, and revealed no relationship with tax/rex mRNA expression. In contrast, both cell groups from four HAM/TSP patients expressed detectable tax/rex mRNA accompanied by high proviral DNA load. The ratio of tax/rex mRNA expression to proviral DNA load was higher in BALC than in PBMC in three of four carriers and in three of four HAM/TSP patients, suggesting up-regulation of tax/rex mRNA in infected lung tissue. To analyse differences in distribution of HTLV-1 quasispecies between the two tissues, phylogenetic analysis was performed for sequence sets of the proviral tax open reading frame (ORF: 1059 bp) derived from PBMC and BALC of two infected individuals. Sequences derived from the two tissues distributed similarly to branches of phylogenetic trees, and there was no evidence of selective distribution of certain quasispecies in the lung. Our results suggest the presence of tissue-specific conditions that activate viral expression in infected cells in the lung. Constitutive exposure of this tissue to foreign antigens leading to up-regulation of basal viral promoter activity is likely to be one such mechanism.

Adolescent↗

Significance of percutaneous cardiopulmonary bypass support for volume reduction surgery with severe hypercapnia.

In patients with reduced respiratory function, lung resection is associated with high risk because separate ventilation is generally needed for safe management. For patients with end-stage emphysema, intraoperative respiratory management is important and particularly difficult because neither incomplete oxygenation nor selective ventilation can be performed, so the operation may be interrupted. In this study, we assess the effectiveness of the percutaneous cardiopulmonary support (PCPS) system for lung volume reduction surgery in patients with severe hypercapnia (arterial carbon dioxide tension >50 mm Hg) and discuss the significance of PCPS for patients who are beyond the standard criteria for lung volume reduction surgery (LVRS). We studied 3 patients with severe hypercapnia due to emphysema who underwent volume reduction surgery. One patient was previously treated surgically for contralateral pneumothorax. All patients had a severe smoking history and were suspected to have fragile lungs. During the operation. PCPS provided sufficient support flow. Intraoperative management using PCPS was easy, and no severe complications were observed. One patient exhibited severe hemodynamic deterioration on postoperative Day 15. Other patients' PaCO2 improved postoperatively. One had a calcification of a femoral artery, but there was no trouble inserting a cannula. Bilateral or unilateral volume reduction surgery was performed under PCPS in patients with end-stage emphysema. We conclude that PCPS is an adjunct to LVRS, useful for intraoperative management of some patients with severe hypercapnea, and the LVRS indications can be extended.

Aged↗

K-ras gene mutations and loss of heterozygosity at the p53 gene locus relative to histological characteristics of mucin-producing tumors of the pancreas.

Mucin-producing tumors (MPTs) of the pancreas accompanied by carcinomas usually include various grades of dysplasia in the ductal epithelium, and invasive areas are histologically similar to those of common invasive ductal carcinomas, suggesting that MPTs provide a good tool to investigate early stages of pancreatic carcinogenesis. Thus, to clarify genetic alterations in the early stage of pancreatic carcinogenesis, we analyzed K-ras gene mutations and loss of heterozygosity (LOH) at the p53 gene locus using 37 cases of MPTs harboring dysplastic epithelium. Further, we conducted an extended, multifocal microdissection analysis focusing on the histological features of ductal epithelium and the distribution of genetic alterations for 3 cases of MPT positive for LOH of the p53 gene to determine the relation to tumor progression. K-ras gene mutations were detected with high frequency in 50% or more cases of the adenomas (14 of 19), borderline tumors (4 of 7), and carcinomas (8 of 11), whereas LOH of the p53 gene was limited to carcinomas (3 of 5 informative cases, 60%) and always accompanied by K-ras gene mutation. Investigation of a total of 126 microdissection sites from 3 cases showed the presence of K-ras gene mutations in mild dysplasia and all (100%) regions of moderate or more marked dysplasia, whereas LOH of the p53 gene showed more gradual tendency to increase with grade from moderate dysplasia. In addition, the multifocal genetic analysis showed K-ras gene mutations to be widely distributed throughout tumors, whereas LOH of the p53 gene was localized to 1 or a few areas. Further, topographically delimited areas with the same histology in the same tumor did not always show the same genetic alteration. In conclusion, we could confirm that both the K-ras and p53 gene alterations occur in the intraductal stage of MPT, and the latter is superimposed on the former during the course of tumor progression. However, the pattern of association of histological features with genetic alteration differs from tumor to tumor.

Adult↗

Production of interferon-gamma by tonsillar mononuclear cells in IgA nephropathy patients.

Much evidence, both in vivo and in vitro, suggests that patients with IgA nephropathy (IgAN) have enhanced IgA production. We hypothesized that Haemophilus parainfluenzae (HP) in the tonsil plays an important role in the IgA production of IgAN patients. In this study, we focused on interferon-gamma (IFN-gamma) and IgA production by tonsillar mononuclear cells (TMC) in patients with IgAN. Tonsillectomies were performed in patients with IgAN and chronic tonsillitis (CT). The induction of IFN-gamma and IgA in vitro by TMC from IgAN patients was compared with that from CT patients. In addition, we investigated whether stimulation with the outer membranes of HP (OMHP) enhanced IFN-gamma and IgA induction by TMC from patients with IgAN. Spontaneous IFN-gamma production and spontaneous total IgA production by TMC were higher in IgAN patients than in those patients with CT (p < 0.05). IFN-gamma induction by OMHP stimulation was also higher in IgAN patients than in CT patients. The stimulation of OMHP enhanced HP-specific IgA in IgAN but had no influence on the production of IFN-gamma in patients with either IgAN or CT compared with spontaneous IFN-gamma production. IFN-gamma production was positively correlated with total IgA values in both IgAN and CT patients, but not with HP-specific IgA. These results suggest that increased IFN-gamma production in patients with IgAN is not associated with HP infection but may play a role in the pathogenesis of IgAN.

Adenoids↗

T(h)1 transmigration anergy: a new concept of endothelial cell-T cell regulatory interaction.

Stimulation of endothelial cells (EC) with IFN-gamma generates selective enhancement of T(h)1 cell transmigration and induction of MHC class II expression on EC. In the present study, we tested whether antigen presentation by EC could influence transmigrating T cells in an in vitro system. Bacterial antigen presentation by EC from primary culture and after cloning induced antigen-specific anergy of transmigrating T(h)1 clone cells in a MHC class II-dependent manner as characterized by non-responsiveness to subsequent antigen presentation and inability to produce IL-2. This T cell transmigration anergy induced by EC was abrogated by anti-rat CD28 mAb, suggesting that lack of B7 co-stimulatory signals by EC might be related to the induction of anergy. While MHC class II expression on primary and cloned EC was observed after IFN-gamma stimulation, these cells never expressed B7. B7-1 gene-transfected endothelial clone cells (ECC/B7-1) were developed to elucidate the influence of B7 co-stimulation by EC. ECC/B7-1 induced proliferation of T(h)1 clone cells, whereas ECC did not induce proliferation in co-culture of T(h)1 clone cells and EC stimulated with IFN-gamma and antigen. In the transmigration assay, ECC/B7-1 did not induce transmigration anergy of T(h)1 clones or T(h)1 lines unless anti-rat B7-1 blocking mAb was added. Therefore, in rats, the T cell anergy induced during transmigration across a layer of EC seemed to be due to antigen presentation in the absence of B7 on the EC. We introduce the concept of transmigration anergy in this manuscript. Thus, EC can play a critical immune regulatory role in the context of antigen presentation by MHC class II to transmigrating T cells.

Animals↗

Effect of olprinone, phosphodiesterase III inhibitor, on cerebral blood flow assessed with technetium-99m-ECD SPECT.

Few clinical reports exist regarding the effects of phosphodiesterase III inhibitors on cerebral arteries. Therefore we used a [99mTc]-ECD brain SPECT and an ultrasound method to quantitatively evaluate cerebral and systemic flow dynamics after the administration of olprinone, a phosphodiesterase III inhibitor. In 15 patients (65 +/- 8 years, M/F = 13/2) with no abnormalities on a brain computed tomography (CT), cerebral blood flow and cardiac output were measured using [99mTc]-ECD brain SPECT and Doppler echocardiography, respectively. Measurements were repeated at baseline and after the administration of olprinone. Significant increases in cerebral blood flow (p = 0.0007) and cardiac output (p = 0.001) were observed, and systolic blood pressure (p = 0.02) and systemic vascular resistance (p = 0.002) significantly decreased. No significant correlation between the increase in cerebral blood flow and the increase in cardiac output was observed. The data indicate that olprinone has a direct vasodilator effect on the cerebral artery, which was little related to the increase in cardiac output in patients who had not experienced stroke.

Aged↗

Sgs1 helicase activity is required for mitotic but apparently not for meiotic functions.

The SGS1 gene of Saccharomyces cerevisiae is a homologue for the Bloom's syndrome and Werner's syndrome genes. The disruption of the SGS1 gene resulted in very poor sporulation, and the majority of the cells were arrested at the mononucleated stage. The recombination frequency measured by a return-to-growth assay was reduced considerably in sgs1 disruptants. However, double-strand break formation, which is a key event in the initiation of meiotic DNA recombination, occurred; crossover and noncrossover products were observed in the disruptants, although the amounts of these products were slightly decreased compared with those in wild-type cells. The spores produced by sgs1 disruptants showed relatively high viability. The sgs1 spo13 double disruptants sporulated poorly, like the sgs1 disruptants, but spore viability was reduced much more than with either sgs1 or spo13 single disruptants. Disruption of the RED1 or RAD17 gene partially alleviated the poor-sporulation phenotype of sgs1 disruptants, indicating that portions of the population of sgs1 disruptants are blocked by the meiotic checkpoint. The poor sporulation of sgs1 disruptants was complemented with a mutated SGS1 gene encoding a protein lacking DNA helicase activity; however, the mutated gene could suppress neither the sensitivity of sgs1 disruptants to methyl methanesulfonate and hydroxyurea nor the mitotic hyperrecombination phenotype of sgs1 disruptants.

Adenosine Triphosphatases↗

Sensitive detection of myocardial contraction abnormality in chronic hemodialysis patients by ultrasonic tissue characterization with integrated backscatter.

Since acoustic properties of the myocardium are sensitive to the myocardial structure and the contractile conditions of myocyte, the authors evaluated cardiac dysfunction based on the integrated ultrasonic backscatter in 18 hemodialysis (HD) patients (duration: 102 +/- 84 months, mean age: 57.6 +/- 9.7 years) and 11 age-matched normals. The cyclic variation of integrated backscatter (CV-IB) at interventricular septum (IVS) and left ventricular posterior wall (PW) was measured and compared with percent fractional shortening (%FS) and percent wall thickening (%Th). The CV-IB of HD patients was smaller than that of control subjects (IVS: 6.2 +/- 1.1 dB vs 8.2 +/- 1.1 dB, p = 0.0003 and PW: 8.4 +/- 2.2 vs 10.3 +/- 1.3, p= 0.025). No significant difference was observed in %FS and %Th between HD patients and control subjects. In HD, the ratio of velocities of early diastolic inflow (E) to late atrial inflow was decreased (0.7 +/- 0.2 vs 1.1 +/- 0.7, p = 0.049) and deceleration time of E was prolonged significantly (200 +/- 28 msec vs 159 +/- 30 msec, p = 0.0082). In the absence of overt cardiac systolic dysfunction, myocardial damage indicated as a decrease in CV-IB and diastolic dysfunction identified on transmitral velocity waveform were detected, which may reflect from the myocardial fibrosis. As a mechanism, pressure overload, hyperparathyroidism, and anemia were neglected, and the other humoral factors may contribute to the myocardial damage in chronic renal failure.

Aged↗

Different domains of Sgs1 are required for mitotic and meiotic functions.

The SGS1 of Saccharomyces cerevisiae is a homologue for human Bloom's syndrome, Werner's syndrome, and Rothmund-Thomson's syndrome causative genes. Disruptants of SGS1 show high sensitivity to methyl methanesulfonate (MMS) and hydroxyurea, and hyper recombination phenotypes including interchromosomal homologous recombination in mitotic growth. In addition, sgs1 disruptants show poor sporulation and a reduced level of meiotic recombination as assayed by return-to-growth. We examined domains of Sgs1 required for mitotic and meiotic functions of Sgs1 by transfecting variously mutated SGS1 into sgs1 disruptants. The N-terminal 1-401 amino acid region was required for complementation of MMS sensitivity and suppression of hyper heteroallelic recombinations of sgs1 disruptants in mitotic growth and for complementation of poor sporulation and of reduced meiotic recombination. Although the N-terminal 1-125 amino acid region was absolutely required for the complementation of MMS sensitivity and suppression of hyper heteroallelic recombinations in mitotic growth, it was dispensable for the meiotic functions. In contrast, the highly acidic region (400-596 amino acid) was dispensable for the mitotic functions but a deletion of this region affected the meiotic functions. The C-terminal 1271-1350 amino acid region containing a HRDC (helicase and RNaseD C-terminal) domain was dispensable for the mitotic and meiotic functions. Although DNA helicase activity of Sgs1 was not required for Sgs1 to complement the meiotic functions, a deletion of helicase motifs III-IV (842-1046 amino acid) abolished the complementing activity of Sgs1, indicating that a structurally intact helicase domain is necessary for Sgs1 to fulfill its meiotic functions.

Alleles↗

Elevated levels of soluble adhesion molecules in sera and BAL fluid of individuals infected with human T-cell lymphotropic virus type 1.

STUDY OBJECTIVE: T-lymphocytic alveolitis and increased levels of interleukin-2 receptor-alpha (CD25)-bearing T cells in the BAL fluid (BALF) of human T-cell lymphotropic virus type 1 (HTLV-1) carriers have been reported. Several chemokines and adhesion molecules may contribute to the accumulation of T lymphocytes in the lungs of HTLV-1 carriers. To clarify the correlation between adhesion molecules and HTLV-1-associated pulmonary disorders, we compared the distribution of T-lymphocyte subsets and soluble adhesion molecules, including soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble L-selectin (sL-selectin), soluble E-selectin (sE-selectin), and soluble P-selectin (sP-selectin), in BALF and peripheral blood, between HTLV-1 carriers and noninfected healthy subjects. DESIGN: Flow cytometric analysis with monoclonal antibodies to cell-surface antigens was used to identify T-lymphocyte subsets in BALF samples from HTLV-1 carriers (n = 13) and noninfected healthy control subjects (n = 10). The levels of various soluble adhesion molecules in serum and in BALF were estimated by enzyme-linked immunosorbent assay. RESULTS: Higher percentages of CD3+ cells, CD3-expressing human leukocyte antigen-DR antigen, and CD3+CD25+ cells were detected in the BALF of HTLV-1 carriers than in that of noninfected control subjects. The concentrations of sICAM-1, sVCAM-1, sL-selectin, SE- selectin, and sP-selectin in the sera of patients were significantly higher than those in noninfected healthy control subjects. The concentration of sICAM-1 in the BALF of patients was significantly higher than that in noninfected healthy control subjects, and the concentration of sICAM-1 correlated well with the percentage of CD3+CD25+ cells. CONCLUSION: The concentrations of adhesion molecules in the sera of and sICAM-1 in the BALF of HTLV-1 carriers were significantly higher than those in noninfected individuals, and the concentration of sICAM-1 correlated well with the percentage of CD3+CD25+ cells in BALF. Our results suggest a possible interaction between activated T cells bearing CD25 and soluble adhesion molecules, especially sICAM-1, which may contribute to the pulmonary involvement in HTLV-1 carriers.

Adult↗

Effect of food restriction on hepatotoxicity of carbon tetrachloride in rats.

Five-week-old Sprague-Dawley rats of both sexes were assigned to two types of feeding condition. One was fed ad libitum (AL) on commercial chow and another was fed a restricted amount of the chow (FR), approximately 75% of that fed in the AL condition. In each feeding condition, animals were orally administered carbon tetrachloride (CCl4) at levels of 0 (control), 0.1 or 0.2 ml/kg 6 days a week for 8 weeks. Lesions of the liver (hepatic cellular degeneration and fibrosis) and of the kidney (proximal tubular vacuolation and glomerular sclerosis) induced by CCl4 were aggravated in the FR group. The FR-control showed a higher metabolic activity of aniline in the liver than the AL-control group. Plasma lipid-peroxide (LPO) level was higher in the AL-control group than in the FR-control group. With CCl4 0.2 ml/kg treatment, however, the plasma LPO level was reversed between the AL and the FR groups. Taking together these somewhat unexpected results, it was concluded that (1) 25% food restriction increases toxicity of repeatedly administered CCl4 in rats, and (2) aggravation of CCl4 toxicity may be partly due to enhanced metabolic activation of CCl4 resulting from food restriction.

Animals↗

Aspergillus fumigatus isolated from blood samples of a patient with pulmonary aspergilloma after embolization.

Aspergillus DNA was detected by PCR in the serum sample of a 78-year-old man and galactomannan antigen of Aspergillus by sandwich ELISA was found. However, the infiltrative hyphae were not detected by the histopathologic examination of the lung. He developed hemoptysis, which required embolization of bronchial arteries. Aspergillus fumigatus was isolated from blood samples after embolization by the lysis centrifugation method. To our knowledge, this is probably the first case in which Aspergillus spp. has been isolated from the systemic circulatory blood in a patient with pulmonary aspergilloma after embolization.

Aged↗