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Biomedical subjects

K Yoshida

Publications and source records attributed to K Yoshida.

At least 109 records · Page 6Linked to original sources

Adenovirus-mediated gene transfer of interferon alpha improves dimethylnitrosamine-induced liver cirrhosis in rat model.

Several lines of evidence suggest that interferon (IFN)-alpha is effective in suppression of liver cirrhosis (LC) as well as hepatitis C virus (HCV) infection, which is a major cause of LC in Japan. However, IFN-alpha often causes systemic toxicity such as flu-like symptoms, which precludes the IFN-alpha dose escalation required for clinical efficacy. Since IFN-alpha is rapidly degraded in the blood circulation, only a small amount of subcutaneously injected IFN-alpha protein can reach the target organ, the liver. It is expected that on-site IFN-alpha production in the liver overcomes the limitation of the conventional parenteral IFN-alpha administration. An adenovirus vector expressing the rat IFN-alpha gene (AxCA-rIFN) was injected intravenously into rats with dimethylnitrosamine-induced LC. While the subcutaneous IFN-alpha protein injection led to a transient elevation of the cytokine both in the liver and serum, the vector-mediated IFN-alpha gene transduction induced a significant amount of IFN-alpha detected in the liver but not in the serum. The injection of AxCA-rIFN prevented the progression of the rat LC, and improved the survival rate of the treated rats. Although no significant toxicity was noted in the animals, we showed that IFN-alpha gene expression in the liver can be efficiently downregulated by the Cre/loxP-mediated shut-off system, in case the IFN-alpha overdose becomes a problem. The study suggested for the first time the advantage and feasibility of IFN-alpha gene therapy for LC.

Adenoviridae↗

Effects of pulmonary artery remodeling on pulmonary circulation after lung volume reduction surgery.

BACKGROUND: Significant pulmonary hypertension during exercise has been observed in patients with severe chronic obstructive pulmonary disease. Although favorable effects on pulmonary function and dyspnea symptoms have been demonstrated, the influence of lung volume reduction surgery (LVRS) on the pulmonary hypertension during exercise is still a controversial subject. METHODS: A pulmonary function test and 6-minute walking test were performed before and 3, 6, 12 and 24 months after LVRS (n = 12). Pulmonary hemodynamics at rest and during exercise was studied 6 months after operation. Morphology was examined in pulmonary arteries with external diameters of 100 - 200 micro m in the resected lung, and the wall thickness (defined as intima plus media) and percentage wall thickness (percentage wall thickness of the external diameter) of the pulmonary artery were calculated. RESULTS: LVRS improved early-phase pulmonary function and 6-minute walking distance. Although the increase in pulmonary capillary wedge pressure during exercise was significantly ameliorated, exercise pulmonary hypertension did not change after LVRS. The percent wall thickness was highly correlated with Delta Ppa (difference between mean pulmonary artery pressure at rest and mean pulmonary artery pressure during exercise) not only before, but also 6 months after LVRS. CONCLUSION: LVRS has no significant influence on exercise-induced pulmonary hypertension in patients with severe emphysema. From a histological analysis of the pulmonary artery in the resected lung, remodeling the pulmonary artery that may exist in the remaining lung is possibly one of the important factors preventing postoperative improvement in exercise pulmonary hypertension in patients with chronic obstructive pulmonary disease.

Aged↗

Inhibition of arthritis by systemic administration of endostatin in passive murine collagen induced arthritis.

OBJECTIVE: To investigate the arthritis inhibiting effect of endostatin, known to have potent antiangiogenic activity, systemically given to animal models of rheumatoid arthritis (RA). METHODS: Four kinds of monoclonal anti-type II collagen antibody followed by lipopolysaccharide (LPS) three days later were given to 6 week old, female Balb/c mice to induce arthritis. Three groups of mice received 0.2 mg/kg/day, 2 mg/kg/day, and 10 mg/kg/day of endostatin, respectively, whereas a control group received phosphate buffered saline (PBS). Endostatin or PBS was given for 13 days, starting before the development of arthritis. Arthritis was evaluated by arthritis scores and hind paw thicknesses. Mice were killed for histological examination on the 22nd day after the administration of monoclonal anti-type II collagen antibody. RESULTS: Arthritis developed within three days after LPS administration in both the control and endostatin treatment groups. No difference in the development rate of arthritis was noted between the control and endostatin treatment groups. Arthritis scores remained significantly lower in the endostatin 10 mg/kg/day group than in the control group. Hind paw thicknesses also remained significantly smaller in the endostatin 10 mg/kg/day group than in the control group. Histopathological examination showed that synovial thickening and subchondral bone erosion improved more in the endostatin treatment groups than in the control group. CONCLUSION: The systemic administration of endostatin had an arthritis inhibiting effect in RA animal models. Endostatin inhibited, in particular, pannus formation and bone destruction.

Analysis of Variance↗

Coronary flow velocity analysis during short term follow up after coronary reperfusion: use of transthoracic Doppler echocardiography to predict regional wall motion recovery in patients with acute myocardial infarction.

BACKGROUND: A recent study using a Doppler guide wire showed that coronary flow velocity measurements immediately after coronary reperfusion were useful in predicting recovery of regional left ventricular function. The value of coronary flow velocity analyses during follow up after reperfusion has not been established in the clinical setting. OBJECTIVE: To evaluate coronary flow velocity measurements in predicting recovery of regional left ventricular function during short term follow up after acute anterior myocardial infarction, using transthoracic Doppler echocardiography (TTDE). METHODS: 30 consecutive patients with anterior acute myocardial infarction were studied. They all underwent successful coronary angioplasty for lesions in the left anterior descending coronary artery (LAD). Using TTDE, coronary flow velocity in the LAD was recorded on days 1 and 3, and at one and two weeks after reperfusion. Regional wall motion was analysed by the wall motion score index (WMSI), calculated as an average of segmental scores in the LAD territory before reperfusion and one month after the infarction. RESULTS: Deceleration time of diastolic flow velocity (DDT) in patients with viable myocardium (WMSI in LAD territory at one month, < 2.0) was significantly longer after recanalisation than in patients without viable myocardium (WMSI in LAD territory at one month, > 2.0): 657 (226) v 271 (117) ms on day 1, p < 0.001; 732 (219) v 373 (217) ms on day 3, p < 0.01; and 903 (107) v 577 (300) ms at one week, p < 0.01. However, the difference at two weeks (991 (75) v 795 (281) ms) was not significant. For the prediction of viable myocardium, DDT > 600 ms had a sensitivity of 78% and a specificity of 92% on day 1, and a sensitivity of 78% and a specificity of 84% on day 3. At one and two weeks, DDT > 600 ms was sensitive (100% and 100%, respectively) but less specific (46% and 26%, respectively) for predicting viable myocardium. CONCLUSIONS: Non-invasive assessment of coronary flow velocity using TTDE within three days of successful coronary angioplasty in patients with anterior acute myocardial infarction is useful in predicting recovery of regional left ventricular function.

Blood Flow Velocity↗

A COX-2 inhibitor, nimesulide, inhibits chemically-induced rat tongue carcinogenesis through suppression of cell proliferation activity and COX-2 and iNOS expression.

The modifying effects of a cyclooxygenase (cox)-2 selective inhibitor nimesulide on tongue carcinogenesis were investigated in male F344 rats initiated with 4-nitroquinoline-1-oxide (4-NQO). The cell proliferation activity measured by proliferating cell nuclear antigen (PCNA)-positive index and apoptotic index, and the immunohistochemical expression of COX-2, and inducible nitric oxide synthase (iNOS) in the tongue mucosa or neoplasms were also examined for mechanistic analysis of modifying effects of nimesulide on tongue carcinogenesis. All animals except those treated with nimesulide alone and untreated rats were given 20 ppm 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 1 week after the cessation of 4-NQO exposure, rats given 4-NQO were fed the experimental diets containing nimesulide (100 and 400 ppm) for 22 weeks. At week 32, the incidence of tongue squamous cell carcinoma was significantly reduced by feeding of the diet containing 400 ppm nimesulide. Feeding of nimesulide significantly decreased polyamine content and PCNA-labeling index in tongue carcinoma. Apoptotic index in tongue carcinoma was increased by feeding of nimesulide. In addition, nimesulide feeding reduced COX-2 and iNOS expression in the tongue dysplasia and neoplasms. These results suggest that 400 ppm nimesulide in diet, when given during the promotion phase, exerts chemopreventive ability against 4-NQO-induced tongue tumorigenesis through inhibition of cell proliferation activity in conjunction with modification of COX-2 and iNOS expression of the target lesions.

4-Nitroquinoline-1-oxide↗

The present and future organisation of Veterinary Services in Asia: the examples of the Republic of Korea and Japan.

The Veterinary Services of the Republic of Korea and Japan are reviewed and summarised. To cope with ever-increasing demands on Veterinary Services, both countries have made continued efforts to expand the services, which currently only have a limited number of government personnel. To overcome some of the problems associated with international trade, e.g. outbreaks of foot and mouth disease and classical swine fever (hog cholera), the authorities of the Republic of Korea are considering strengthening quarantine services by combining the National Veterinary Research and Quarantine Service and the National Plant Quarantine Service of the Ministry of Agriculture and Forestry (MAF). In the field of veterinary public health services, the Republic of Korea and Japan have different organisational structures. All Veterinary Services, including veterinary public health, are kept within the MAF in the Republic of Korea, whereas in Japan, the Ministry of Agriculture, Forestry and Fisheries (MAFF) deals with general animal production and health services and the Ministry of Health, Labour and Welfare (MHLW) deals with the safety of animal products, food poisoning and the prevention/control of zoonoses, such as rabies and Q fever. In Japan, after the occurrence of bovine spongiform encephalopathy in 2001, the authorities undertook a thorough review of the Veterinary Services, focusing particularly on food safety. A reorganisation of the administrative structure was proposed, and will be completed by the end of 2003. Subject to the approval of the Diet (House of Councillors), an independent 'Food Safety Commission' will be created within the cabinet office which will undertake risk analyses related to foods, and risk management will be carried out by the relevant ministry, i.e. the MAFF or the MHLW. The Animal Health Division of the MAFF will also be moved from the Livestock Industry Department to a new 'Consumer Safety Department' of the MAFF, where additional responsibilities in fish health control and feed safety control will be assumed.

Commerce↗

Mental health and vitality among Canadian women with physical disabilities.

This study investigated scores for mental health and vitality in a large community-based sample of women with physical disabilities. The scores from two subscales of the SF-36 were collected from 1,096 women with physical disabilities through a mailed survey regarding health and well-being. These scores were compared to normative data using t tests. The mean scores of the vitality subscale were significantly lower than that of the normed sample when analyzed by age groups. The mental health scores were significantly lower as well, except for one age group (65-74 yr.). These results suggest that health care workers should address aspects of mental health and energy when caring for women with physical disabilities, as these areas are often overlooked in this population. Health promotion programs aimed at these topics should be designed specifically for this population as well.

Adolescent↗

Prediction of lymph node metastasis by p53, p21(Waf1), and PCNA expression in esophageal cancer patients.

Esophageal cancer is still one of the most widespread diseases, and surgery for esophageal carcinoma is very stressful for patients. Even though lymph node metastasis occurs more frequently in cases of early esophageal cancer than it does in cases of gastric cancer, surgeons prefer to avoid lymph node dissection if possible, thereby subjecting patients to less invasion. Thus, the aim of the present study was to examine the possibility of predicting lymph node metastasis on the basis of tumor location, quantification theory II analysis of tumor expression of genetic markers in primary esophageal cancer. Surgical specimens from 63 patients of esophageal cancer with submucosal invasion were examined for the relationship between tumor location and lymph node metastasis. In 19 of these 63 patients, p53, p21(Waf1, and proliferating cell nuclear antigen (PCNA) were examined immunohistologically, and to quantify the risk of lymph node metastasis, computer analysis was performed on the basis of quantification theory II, in which pathological lymph node metastasis (pN) was the objective variable and "high" or "low" expression of each of the three markers was the predictive variable. Tumors located in the lower third of the esophagus had no lymph node metastasis to the upper mediastinal region, and were thus indicated for trans-hiatal esophagectomy. A coefficient greater than 0.91 predicted node negative disease accurately without false-negative results; false-positive results were obtained for 54.5% of patients with a coefficient less than 0.064. Thus, we found that quantification theory II may be useful when considering indications for surgery without lymph node dissection in some cases of T1 esophageal carcinoma.

Carcinoma↗

Molecular biology and application of plant peroxidase genes.

Peroxidases are a family of isozymes found in all plants; they are heme-containing monomeric glycoproteins that utilize either H(2)O(2) or O(2) to oxidize a wide variety of molecules. These important enzymes are used in enzyme immunoassays, diagnostic assays and industrial enzymatic reactions. Peroxidase genes and their promoters can be used for molecular breeding of useful plants. Transgenic techniques have also been used to investigate the physiological and molecular functions of peroxidase genes in plants. Here, we review transgenic studies of peroxidase genes, including the functional analyses of the enzymes and their promoters. Regarding application of peroxidase genes, it has been reported that overexpression of the tomato TPX2 gene or the sweet potato swpa1 gene conferred increased salt-tolerance or oxidative-stress tolerance, respectively. The growth stimulation effect in transgenic tobacco and hybrid aspen upon overexpression of horseradish peroxidase gene is also discussed.

Enzyme Induction↗

Eclamptic encephalopathy: MRI, including diffusion-weighted images.

Eclampsia is a rare condition peculiar to pregnant and puerperal women. We analyse imaging features in five patients with eclampsia, and determine whether diffusion-weighted imaging (DWI) could differentiate cytotoxic and vasogenic oedema in four of them. All were imaged within 4 days of the onset of symptoms. We found lesions with a prolonged T2 in the brain of all five patients, in the basal ganglia in four, pons in three and posterior cerebral white matter in two. Isotropic DWI revealed variable intensity in these regions. The ADC was decreased in one, and increased in all the others. The lesion with reduced ADC progressed to infarction.

Adult↗

A variable number of tandem repeats in the serotonin transporter gene does not affect the antidepressant response to fluvoxamine.

A variable number of tandem repeats (VNTR) in the second intron of the serotonin transporter gene (STin2) has been studied in association with the susceptibility to affective disorders. Recently, it was reported that selective serotonin reuptake inhibitors were more effective in patients with major depressive disorder having the homozygous allele pair (12-copy/12-copy) of VNTR in the STin2 than in ones having other allele combinations. As the study had methodological problems, further studies are needed to confirm the above finding. Therefore, the authors investigated whether the allelic variation of VNTR in the STin2 was associated with the antidepressant response to fluvoxamine in 66 patients with major depressive disorder. Fluvoxamine was prescribed up to 200 mg/day in the dosing protocol for 6 weeks. The present study showed no significant association between the polymorphism of VNTR in the STin2 and the treatment response to fluvoxamine.

Adult↗

Phosphorylated tyrosine-containing proteins in primary lung cancer correlates with proliferation and prognosis.

To determine the usefulness of tyrosine phosphorylation in evaluating biological characteristics, we attempted to evaluate the relationship between the amount of phosphorylated tyrosine-containing proteins and clinicopathological factors, cell proliferation and outcome in non-small cell lung cancer. To evaluate phosphorylated tyrosine-containing proteins we used 96 surgically resected materials of non-small cell lung cancer and normal peripheral lung, while immunohistochemical evaluation was performed. Cell proliferating ability was evaluated using the labelling index of proliferating cell nuclear antigen-positive nuclear staining cells. There were statistically significant differences between the expression levels of phosphorylated tyrosine-containing proteins of normal and cancerous tissues (P<0.0001). Evaluations based on clinicopathological factors apart from histopathological differentiation, showed no statistically significant differences of phosphorylated tyrosine-containing proteins expression. However, phosphorylated tyrosine-containing proteins correlated with cell proliferation activity evaluated (P((Low, High))<0.0001; P((Low, Int)) <0.0001; P((Int, High))<0.0001). Furthermore, non-small cell lung cancer cases with high expression and intermediate expression of phosphorylated tyrosine-containing proteins had a significantly shorter disease-free postoperative survival than those with low expression of phosphorylated tyrosine-containing proteins using log-rank analysis (P((Low, Int)) <0.0028; P((Low, High))=0.0002). Furthermore, phosphorylated tyrosine-containing proteins expression level statistically contributed to disease-free survival in Cox's proportional hazard model. Therefore, phosphorylated tyrosine-containing proteins in non-small cell lung cancer tissues seem to reflect its biological malignancy, and this evaluation may be valuable for constructing the most appropriate therapeutic strategy.

Aged↗

A receptor-like protein kinase with a lectin-like domain from lombardy poplar: gene expression in response to wounding and characterization of phosphorylation activity.

Plant receptor-like protein kinases (RLKs) are thought to be involved in various cellular processes mediated via signal transduction pathways. To clarify the initial step in such a signal transduction pathway in woody plants, we cloned a cDNA encoding PnLPK (a P opulus n igra var. italica lectin-like protein kinase) from lombardy poplar. The C-terminal region of the predicted PnLPK protein includes a protein kinase catalytic domain consisting of the 12 subdomains typical of the eukaryotic protein kinase superfamily. Following the signal peptide at the N-terminus, a domain that shows homology to legume lectins retains the putative Mn(2+)- and Ca(2+)-binding amino acids, which are highly conserved among lectin-related proteins. Because a putative hydrophobic transmembrane domain was localized between the lectin-like domain and the protein kinase domain, PnLPK was determined to be a member of the plant RLK subfamily with a lectin-like domain. Transcripts of the PnLPK gene accumulate in roots, mature leaves and calli of lombardy poplar, whereas only trace amounts of the transcripts are detectable in stems, young leaves and apical buds. Wounding of the young leaves increased the amount of PnLPK mRNA, but none of several phytohormones tested had any effect on the transcription of PnLPK. When incubated in the presence of divalent metal cations such as Mn(2+), the C-terminal catalytic domain of PnLPK showed significantly higher autophosphorylation activity than the full-length PnLPK protein. The phosphorylation activity of PnLPK was also detected using beta-casein as substrate. Phosphoamino acid analysis indicated that PnLPK is a serine/threonine kinase.

Amino Acid Sequence↗

Concentric structure of thalamic lesions in acute necrotizing encephalopathy.

Acute necrotizing encephalopathy of childhood (ANE) is characterized by multiple, symmetrical brain lesions affecting the bilateral thalami, putamina and cerebral white matter, which often show a concentric structure on CT and MRI. To reveal the pathological substrate of this finding, comparison was made between CT and necropsy findings of three fatal cases of ANE. Cranial CT demonstrated a concentric structure of the thalamocerebral lesions in one patient who died 3.5 days after the onset of encephalopathy, but not in the other two patients who died within 30 h. Neuropathological examination of postmortem brains revealed laminar changes of vascular and parenchymal pathology in all the cases. Excessive permeability of blood vessels and resultant vasogenic edema became more prominent with increasing depth from the cerebral surface. The deep portion of the lesions showed severe perivascular hemorrhage, accounting for the central high density on the CT images of one patient.

Child Welfare↗

Serum thymidine kinase and soluble interleukin-2 receptor predict recurrence of malignant lymphoma.

Before and after therapy, serum thymidine kinase (TK) and soluble interleukin-2 receptor (sIL-2R) were serially determined in 28 patients with malignant lymphoma (ML). In 15 patients achieving and maintaining complete remission (CR) for more than 2 years, serum TK and sIL-2R were unchanged or decreased gradually. In contrast, logarithmic linear increases of TK and sIL-2R were observed in 13 relapsed patients. The increments of the serum markers occurred more than 10 months before the relapse. A significant positive correlation between the slope of the line for TK and that for sIL-2R was noted. The doubling time for TK estimated from the slope also showed a positive correlation with that for sIL-2R. Taken together, serum TK and sIL-2R were shown to be quite sensitive and interrelated serum markers for the recurrence of ML. Slopes of logarithmic linear increase, which are proper and specific for the individual patients, are inversely correlated with the doubling time and reflect proliferation of ML. We conclude that serum TK and sIL-2R are better predictors of relapse than LDH and the international prognostic index (IPI).

Adult↗