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Biomedical subjects

T Yoshikawa

Publications and source records attributed to T Yoshikawa.

At least 253 records · Page 14Linked to original sources

PSK and OK-432-induced immunomodulation of inducible nitric oxide (NO) synthase gene expression in mouse peritoneal polymorphonuclear leukocytes and NO-mediated cytotoxicity.

We investigated whether PSK (a polysaccharide from the mycelia of Coriolus versicolor) or OK-432 (a streptococcal preparation) can up-regulate inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production in mouse peritoneal polymorphonuclear leukocytes (PMNs). Six hrs after intraperitoneal injection of mice with PSK (2,500 microg/mouse) or OK-432 (100 microg/mouse), mouse peritoneal PMNs were restimulated with PSK (500 microg/ml) or OK-432 (10 microg/ml) plus 100 U/ml of mouse interferon-gamma (IFN-gamma) in vitro. Northern blot analysis showed strong synergism between both PSK and OK-432 and IFN-gamma for the induction of iNOS gene expression. NO production by PMNs was increased up to 20 microM (2 microM/10(6) PMNs/24 hrs) as measured by the Griess reagent method when PMNs were restimulated with PSK or OK-432 plus IFN-gamma for 24 hrs, although tumor cell killing was not detected. NO concentrations of more than 80 microM were required for P815 tumor cell killing. These results suggest that PMNs produce NO after stimulation with PSK or OK-432 in combination with IFN-gamma and may regulate the immune system in vivo, although the NO production induced by these agents is insufficient for tumor cell killing in vitro.

Adjuvants, Immunologic↗

Serotonin and pancreatic duct function.

1. 5-HT inhibits spontaneous fluid secretion as well as stimulated secretion with secretin (cAMP mediated) or ACh (Ca2+ mediated) in the isolated guinea pig pancreatic ducts. 2. The inhibitory effect of 5-HT is reversible and is dependent on the concentration in the range 0.01-0.1 microM, which is much lower than those that affect intestinal motility and secretion. 3. The 5-HT3 receptor in duct cells appears to mediate the inhibitory effect of 5-HT. 4. [Ca2+]i is unlikely to mediate the inhibitory effect of 5-HT.

5-Methoxytryptamine↗

[A case of advanced gastric cancer (type 3) with pyloric stenosis, multiple liver and lymph node metastases responding to UFT-E granules and lentinan].

The patient was a 80-year-old male with advanced gastric cancer (Type 3) accompanied by multiple liver and lymph node metastases. Histological findings in the stomach showed poorly differentiated adenocarcinoma. He had nausea, vomiting and anorexia due to pyloric stenosis, and was treated with 600 mg of UFT E granules/day orally for 5 consecutive days followed by 2 drug-free days (weekly-5 method), and 2 mg of lentinan intravenously twice a week. After 4 weeks of treatment, the primary tumor and metastatic lesions of the liver and lymph nodes were markedly reduced. His symptoms had completely disappeared along with lessening of the pyloric stenosis after 6 weeks of treatment. The patient survived for 7 months in a state of CR and PR. The adverse effects were very mild and negligible. A weekly-5 method of UFT, in comparison with conventional daily administration, may induce maximal antitumor effects with minimal adverse effects.

Adenocarcinoma↗

Endothelial cells exposed to anoxia/reoxygenation are hyperadhesive to T-lymphocytes: kinetics and molecular mechanisms.

OBJECTIVE: The objectives of this study were to 1) determine the time-course of T-lymphocyte adhesion to monolayers of human umbilical vein endothelial cell (HUVEC) that were exposed to 60 min of anoxia followed by 24 h of reoxygenation, and 2) define the mechanisms responsible for the hyperadhesivity of postanoxic HUVEC to human T-lymphocytes. METHODS: Human peripheral blood mononuclear leukocytes were isolated from heparinized peripheral blood. T-lymphocytes were obtained by negative selection using a MACS column. HUVEC monolayers were exposed to anoxia/reoxygenation (A/R), and then reacted with 51Cr -labeled T-lymphocytes in adhesion assays. RESULTS: A/R leads to an increased adhesion of T-lymphocytes to HUVEC monolayers, with peak responses occurring at 8 h after reoxygenation. This adhesion response was largely attributed to the CD4+ T-cell subset. The hyperadhesivity of A/R-exposed HUVEC was inhibited by monoclonal antibodies directed against either LFA-1, VLA-4, ICAM-1, or VCAM-1, indicating a contribution of these adhesion molecules and their ligands. Moreover, T-cell hyperadhesivity was attenuated by anti- IL-8. consistent with a role for this chemokine in the adhesion response. Protein synthesis inhibitors (actinomycin D and cycloheximide) as well as chemical inhibitors of (and binding ds-oligonucleotides to) NFkappaB and AP-1 significantly attenuated the A/R-induced T-lymphocyte adhesion responses. The kinetics of VCAM-1 on post-anoxic HUVEC correlated with the T-lymphocyte adhesion response. CONCLUSIONS: A/R elicits a T-lymphocyte-endothelial cell adhesion response that involves transcription-dependent surface expression of VCAM-1.

Antibodies, Monoclonal↗

[Intravenous sedation with target-controlled infusion (TCI) in patients with difficult airways].

Tracheal intubation was facilitated with an intubating laryngeal mask (ILM) in two patients with difficult airways. Target-controlled infusion (TCI) of propofol and fentanyl was used for sedation during placement of an ILM. An ILM was inserted smoothly. Spontaneous ventilation and oxygenation were well maintained throughout the induction. Both patients were satisfied with intravenous sedation using TCI for awake instrumentation of their airways.

Anesthetics, Intravenous↗

[The mechanisms for latency and reactivation of alpha herpesviridae].

Alpha herpesviridae (herpes simplex virus, HSV and varicella zoster virus, VZV) is a neurotropic phathogen of humans that establishes latent infection in the sensory ganglia, and periodically reactivates from latently infected neurons. Most of basic research for analyzing the mechanism of latency and reactivation of herpes viruses has been carried out in HSV. According to the results from the molecular analysis in the neurons latently infected with HSV, during latency, the virus genome is quiescent, except for the transcription of the latency associated transcripts (LATs). Thus, it has been considered that LATs play an important role for latency and reactivation of the virus. It has been shown that LATs are required for efficient reactivation from latency in vivo, and regulate the site specificity for reactivation of the virus. Recent studies demonstrated that the quantities of latent virus are correlated with the frequency of reactivation of the virus. Moreover, it was suggested that the latency-related gene of bovine herpesvirus 1 could inhibit the apoptosis of the several cells including neuronal cells.

Humans↗

[Balloon-occluded retrograde transvenous obliteration (B-RTO) for portal hypertension].

We reviewed the current techniques and published results of balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices (GV) and hepatic encephalopathy. The portal hemodynamics of gastric varices were classified into three types according to their feeding vessels, and the development of collateral veins under balloon occlusion of gastro-renal shunt was classified into five grades. The main draining veins of gastric varices were gastro-renal and gastro-inferior phrenic shunts. Preprocedural diagnosis of portal hemodynamics is important in selecting the technique for B-RTO. The rate of disappearance or marked reduction of GV was 98%, and the rate of recurrence of GV was 2%. Hepatic encephalopathy due to gastro-renal shunt improved markedly. In contrast, esophageal varices were aggravated at rates of 10% to 62.5% by the post-procedural elevation of portal pressure. Common adverse effects were hemoglobinuria, abdominal pain, and low-grade fever, but ascites and pleural effusion were also reported. Severe complications such as cardiogenic shock, atrial fibrillation, and pulmonary embolism were reported. We await technical improvements and further indications for this procedure.

Catheterization↗

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↗

Association study on the DUSP6 gene, an affective disorder candidate gene on 12q23, performed by using fluorescence resonance energy transfer-based melting curve analysis on the LightCycler.

We introduced a new genotyping method, fluorescence resonance energy transfer-based melting curve analysis on the LightCycler, for the analysis of the gene, DUSP6 (dual specificity MAP kinase phosphatase 6), in affective disorder patients. The DUSP6 gene is located on chromosome 12q22-23, which overlaps one of the reported bipolar disorder susceptibility loci. Because of its role in intracellular signalling pathways, the gene may be involved in the pathogenesis of affective disorders not only on the basis of its position but also of its function. We performed association analysis using a T>G polymorphism that gives rise to a missense mutation (Leu114Val). No evidence for a significant disease-causing effect was found in Japanese unipolars (n = 132) and bipolars (n = 122), when compared with controls (n = 299). More importantly, this study demonstrates that melting curve analysis on the LightCycler is an accurate, rapid and robust method for discriminating genotypes from biallelic markers. This strategy has the potential for use in high throughput scanning for and genotyping of single nucleotide polymorphisms (SNPs).

Adult↗

[Evaluation by FDG-PET of arterial infusion chemotherapy for unresectable metastatic liver tumor].

We evaluated arterial infusion chemotherapy for unresectable metastatic liver tumor using FDG-PET and CT. A 72-year-old female patient with multiple metastatic liver tumors of rectal cancer was treated by arterial infusion chemotherapy. The tumor size decreased by chemotherapy, but there was a high uptake lesion of FDG. Three months later, tumor ingrowth was detected. FDG produces images of regional glycolytic activity, and it is a useful method of assessment of tumor viability after chemotherapy in patients with cancer.

Aged↗

Manipulation of the L-arginine-nitric oxide pathway in airway inflammation induced by diesel exhaust particles in mice.

The role of the L-arginine-nitric oxide (NO) pathway in bronchial asthma that is characterized by eosinophilic airway inflammation has not yet been established. We investigated the effects of three different agents on eosinophilic airway inflammation induced by the intratracheal instillation of diesel exhaust particles (DEP) in mice: L-Arginine, the substrate for NO synthases; L-N(G)-nitro-L-arginine methyl ester (L-NAME), a relatively selective inhibitor of constitutive NO synthase; and aminoguanidine, a relatively selective inhibitor of inducible NO synthase. The mice received drinking water with or without added drug for a continuous period of 9 weeks plus 4 days. Lung histology showed that airway inflammation with goblet cell proliferation induced by DEP was aggravated by the administration of L-arginine or L-NAME, whereas it was reduced by aminoguanidine. The numbers of neutrophils around the airways in animals that received plain drinking water, L-arginine, L-NAME, and aminoguanidine were 0.98+/-0.26, 3.66+/-0.81, 1.64+/-0.31, and 0.12+/-0.04 (number/mm basement membrane), respectively. The numbers of eosinophils around the airways were 0.37+/-0.08, 16.1+/-6.47, 11.1+/-3.59, and 0.21+/-0.11, respectively. The numbers of goblet cells in the bronchial epithelium were 1.67+/-0.80, 16.5+/-7.33, 19.0+/-3.40, and 0.86+/-0.41, respectively. The cellular profiles of the bronchoalveolar lavage fluid also showed that airway inflammation induced by DEP was aggravated by the administration of L-arginine or L-NAME, whereas it was reduced by aminoguanidine. These results suggest that NO produced from inducible NO synthase may have a detrimental effect on the DEP-induced airway inflammation. A relatively selective inhibition of inducible NO synthase by aminoguanidine may have therapeutic value in the inhalant injury. NO derived from constitutive NO synthase may afford protection against the airway inflammation induced by DEP.

Animals↗

Tissue inhibitor of matrix metalloproteinase-1 in the plasma of patients with gastric carcinoma. A possible marker for serosal invasion and metastasis.

BACKGROUND: Expression of the tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in tumor tissue from patients with gastric carcinoma has been reported to be related to disease progression. However, to the authors' knowledge the clinical significance of plasma TIMP-1 concentrations in these patients has not been clarified. METHODS: Concentrations of TIMP-1 protein were examined by enzyme-linked immunoadsorbent assay in plasma samples from 149 patients who underwent resection of their primary tumors and from 18 patients with nonresected or recurrent disease. RESULTS: In the 149 patients whose primary tumors were resected, plasma TIMP-1 concentration was associated significantly with a variety of pathologic factors including macroscopic type, depth of invasion, lymph node and peritoneal metastases, vessel invasion, pattern of tumor infiltration into surround ing tissue, and disease stage. Plasma TIMP-1 concentration was significantly higher in patients with serosal invasion, lymph node metastasis, peritoneal dissemination, or liver metastasis than in those without these factors. Neither carcinoembryonic antigen (CEA) nor CA 19-9 concentrations appeared to be related to these measures of disease progression. In the 18 patients with nonresected or recurrent disease, TIMP-1, CEA, and CA 19-9 were similarly sensitive in predicting peritoneal, liver, and lymph node metastases. The combination of these three factors was able to detect 73.3% of patients with peritoneal metastasis, 83.3% of patients with liver metastasis, and 88.9% of patients with disease recurrence. CONCLUSIONS: In patients with gastric carcinoma, plasma concentration of TIMP-1 appears to correlate with both serosal invasion and metastasis.

CA-19-9 Antigen↗

Is the left atrium the only embolic source in ischemic stroke patients with nonvalvular atrial fibrillation?

Embolic sources were investigated in 74 ischemic stroke patients with nonvalvular atrial fibrillation using transesophageal echocardiography. In patients without left atrial spontaneous echo contrast, 78% had some embolic sources other than left atrial thrombus or spontaneous echo contrast, suggesting that these embolic sources play an important role in patients with nonvalvular atrial fibrillation.

Aged↗

Expression of nitric oxide synthase in gastric cancer.

The expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in samples of normal gastric mucosa and gastric cancer were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and semi-quantitative Western blot. In normal gastric mucosa, eNOS protein was found in all samples examined (mean, 70.2 +/- 60.1), relative to a standard protein. In gastric cancer specimens, eNOS protein was also detected in all samples, but the quantity (86.5 +/- 76.6) was not different from that found in samples of normal mucosa. The quantity of eNOS in gastric cancer tissues was negatively correlated with serosal invasion. iNbS mRNA, detected in nine of 18 cases, was slightly related to massive lymph node metastasis (n1-3 vs. n4). Neither tumor necrosis factor alpha (TNF-alpha) mRNA nor interleukin-6 (IL-6) mRNA was related to the expression of iNOS mRNA. These results suggest that iNOS not eNOS plays a role in gastric cancer tumor extension, but iNOS mRNA appears not to be induced by either TNF-alpha or IL-6.

Blotting, Western↗