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Biomedical subjects

T Tsuda

Publications and source records attributed to T Tsuda.

At least 181 records · Page 10Linked to original sources

Pyomyositis associated with Bacteroides fragilis in a patient with multiple myeloma.

Pyomyositis is an infection of the skeletal muscle that is usually caused by Staphylococcus aureus. We report a 68-year-old Japanese woman who developed pyomyositis caused by Bacteroides fragilis following treatment for multiple myeloma. There are only two cases of pyomyositis associated with multiple myeloma in the literature. After receiving melphalan and prednisolone for five days, she developed multiple abscesses in the muscles of the right arm and thigh. Purulent exudate was aspirated from the abscess, and B. fragilis was identified. This is the first case of B. fragilis pyomyositis. Magnetic resonance imaging aided the diagnosis. Treatment consisted of surgical incision and drainage, with antibiotic administration. The immunosuppression caused by the myeloma and/or the chemotherapy presented a risk factor for the unusual infection observed in this patient.

Abscess↗

[A case of chronic progressive external ophthalmoplegia presenting as inflammatory myopathy].

A 64-year-old female had slowly progressive bilateral external ophthalmoplegia, blepharoptosis and muscle weakness of the extremities since age 30. Laboratory examination showed an elevation of serum CK level. Biopsied specimens from the left biceps and the left orbicularis oculi muscles revealed myopathic change with infiltration of mononuclear cells. In addition, some ragged-red fibers and a few cytochrome c oxidase-negative fibers, which are characteristic of mitochondrial myopathy, were observed. Polymerase chain reaction analysis of mtDNA in the muscles showed multiple mtDNA deletions. On administration of prednisolone (initial dose, 60 mg/day), blepharoptosis and muscular strength improved transiently and serum CK level was normalized but external ophthalmoplegia was not improved. We diagnosed our case as chronic progressive external ophthalmoplegia (CPEO). This is the first report of CPEO presenting as inflammatory myopathy.

DNA, Mitochondrial↗

[Drug-induced pneumonitis with eosinophilic infiltration due to tosufloxacin tosilate].

A 74-year-old man had been given tosufloxacin tosilate for the treatment of acute bronchitis on December 6,1996. Seven days after initiating tosufloxacin tosilate treatment, the patient developed headache and a high fever. He was admitted for dyspnea and generalized erythema. Chest X-ray and chest CT revealed multiple patchy infiltrates in both lung fields and minimal pleural effusion. Bronchoalveolar lavage fluid showed a marked increase in total cell number, and in the percentages of lymphocytes, neutrophils and eosinophils. Transbronchial lung biopsy specimens demonstrated prominent eosinophilic infiltration of the alveolar walls and spaces with fibrin formation. With the tentative diagnosis of drug-induced pneumonitis, all drug administration was discontinued and the patient was treated with corticosteroid. Following the initiation of corticosteroid treatment, dyspnea and erythema improved quick and chest X-rays became clear. The challenge test for tosufloxacin tosilate obtained positive results. Based on these findings, a diagnosis of eosinophilic pneumonia due to tosufloxacin tosilate was made. To our knowledge, no previous cases of pulmonary hypersensitivity to tosufloxacin tosilate have been reported.

Aged↗

[Pulmonary edema associated with the Chinese medicine shosaikoto].

A 45-year-old Japanese woman presented with a high fever, a nonproductive coughing, and severe dyspnea, and was admitted to another hospital. During the week prior to hospitalization, she had been given Shosaikoto for treatment of liver dysfunction of unknown etiology. Mycoplasma pneumonitis was initially suspected, so she was treated with antibiotics (clindamycin and minocycline) and received oxygen therapy. Pulmonary insufficiency worsened rapidly, and she was transferred to our hospital. On admission, a chest roentgenogram revealed bilateral alveolar infiltrates predominantly in the medial lung fields. Furosemide and high-dose methylprednisolone were immediately administered, but hypoxemia increased. When the PaO2 was 55.7 Torr while the patient breathed 100% oxygen, mechanical ventilation with positive end-expiratory pressure (PEEP) was started. Arterial blood-gas values improved dramatically, and the chest roentgenogram became clear. Our diagnosis of noncardiogenic pulmonary edema is based on the chest-roentgenographic findings, infiltration of inflammatory cells as seen in two lung-biopsy specimens and bronchoalveolar lavage fluid, the lack of findings of heart failure on physical examination and electrocardiography, and the good clinical response to PEEP. A positive lymphocyte stimulation test in response to Shosaikoto implicated this non-traditional herbal medicine as an etiologic factor in the non-cardiogenic pulmonary edema. Shosaikoto has been identified as the cause of interstitial pneumonia or eosinophilic pneumonia, but pulmonary edema associated with Shosaikoto has not been previously described. This case suggests that methylprednisolone treatment may be insufficient for Shosaikoto-induced pulmonary edema, and that mechanical ventilation with PEEP is very effective.

Drugs, Chinese Herbal↗

Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.

Recent studies show that tyrosine phosphorylation by a number of neuropeptides may be an important intracellular pathway in mediating changes in cell function, particularly related to growth. Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action. In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides. NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells. NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP). The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells. TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB. A23187 potentiated the effect of TPA. Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation. Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X. The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%. However, tyrphostin A25 did not inhibit NMB-stimulated increases in [3H]inositol phosphates. Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely. In contrast, colchicine, an agent which disrupts microtubules, had no effect. Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%. These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK). NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC. The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK). The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK). These results suggest that similar to some other neuropeptides, activation of this pathway may be an important mechanism in mediating cellular changes by this receptor such as growth.

ADP Ribose Transferases↗

Are pyridoxal and fluorescein probes in lysine residues of alpha-chain in Na+,K(+)-ATPase sensing ATP binding?

Na+,K(+)-ATPase preparations from pig kidneys were treated with 50 microM pyridoxal 5'-diphospho-5'-adenosine (AP2PL) in the presence of NaCl. The resulting preparations contained 0.5 mol of the AP2PL probe at the Lys-480/mol alpha-chain. This modification reduced both Na+,K(+)-ATPase activity and the amount of Na(+)-dependent phosphoenzyme from ATP to around 50% but not that from acetyl phosphate (AcP). The addition of 1 mM AcP to the modified enzyme in the presence of Mg2+ and Na+ induced phosphorylation (3.0/s) followed by an AP2PL fluorescence increase (1.2/s). The addition of 10 microM ATP instead of AcP induced rapid phosphorylation (28/s) followed by a slow increase in fluorescence (1.0/s). When modified enzyme preparations were treated with fluorescein 5'-isothiocyanate (FITC), the phosphorylation capacity from ATP was reduced to around 5% with little influence on either the AP2PL fluorescence change by ATP or phosphorylation from AcP. The addition of increasing concentrations of ATP with 160 mM NaCl to the K(+)-bound AP2PL-FITC-labeled enzyme showed different rates for each fluorescence change and different affinities for ATP of the changes. These data and others indicate that the AP2PL probe at Lys-480 can monitor ATP binding to high- and low-affinity sites and suggest the simultaneous presence of two different low-affinity sites for ATP detected by an AP2PL probe at Lys-480 and an FITC probe at Lys-501.

Adenosine Diphosphate↗

CCK causes rapid tyrosine phosphorylation of p125FAK focal adhesion kinase and paxillin in rat pancreatic acini.

Recent studies show CCK stimulates tyrosine phosphorylation (TYR PHOSP) of a number of proteins and evidence from the pancreas and other cellular systems suggest this could be important in mediating some of CCK's growth and secretory effects. In other tissues various neuropeptides such as bombesin can cause tyrosine phosphorylation of p125 focal adhesion kinase (p125FAK) and paxillin which are important in mediating their growth effects. The purpose of the present study was to determine the effects of CCK in rat pancreatic acini on the TYR PHOSP of these latter proteins. In dispersed rat pancreatic acini, cell lysates were incubated with an anti-phosphotyrosine mAb (PY20) which was immunoprecipitated and then analyzed by Western blotting with anti-phosphotyrosine mAb (4G10), anti-p125FAK mAb or anti-paxillin mAb. CCK-8 at 5 min increased TYR PHOSP of five proteins of molecular weight > 60,000 including a broad M(r) 110-130,000 and M(r) 70-80,000. An increase in TYR PHOSP of both p125FAK and paxillin was detected within 1 min of adding CCK and reached a maximum at 2.5 min with a 9.1 +/- 1.9-fold increase for p125FAK and 3.6 +/- 0.6-fold for paxillin. CCK-8 caused a half-maximal increase in TYR PHOSP of p125FAK at 0.1 nM and paxillin at 0.03 nM. CCK-JMV also stimulated an increase in TYR PHOSP of both proteins, but was only 50% as efficacious as CCK-8. CCK-JMV caused a half-maximal increase at 10 nM and maximal at 1 microM for both proteins. To investigate whether the low affinity CCK receptor state also caused TYR PHOSP of both proteins, increasing concentrations of CCK-JMV were added to a maximally effective CCK-8 concentration (1 nM). Detectable inhibition of CCK-8-stimulated TYR PHOSP occurred with 1 microM CCK-JMV and with 3 microM CCK-JMV the CCK-8-stimulated response was inhibited 50% and was the same as that seen with CCK-JMV alone. These studies demonstrate that in rat pancreatic acini, CCK causes rapid TYR PHOSP of both p125FAK and paxillin. This stimulation is mediated by both the high affinity and low affinity CCK receptor states. This phosphorylation of these proteins could be important in mediating CCK's effect on the cytoskeleton or growth effects as shown for a number of other agents (oncogenes, neuropeptides, integrins).

Animals↗

Expressed emotion among families and course of schizophrenia in Japan: a 2-year cohort study.

A 2-year cohort study was conducted to determine whether expressed emotion (EE) in families is associated with relapse of schizophrenia in Japan. Key relatives of 52 schizophrenic patients were interviewed using the Camberwell Family Interview (CFI) and the patients were classified into high and low EE groups. The 2-year relapse risks were 71% (17/24) in the high EE group and 37% (10/27) in the low EE group. The risk ratio was 1.9 and the 95% confidence interval (CI) ranged from 1.1 to 3.3. In the multiple logistic regression analysis, the odds ratio between families' EE and schizophrenic relapse was 4.6, controlling for other potential confounding factors. It was concluded that, in Japan, the families' EE is a good predictor for schizophrenic relapse within 2 years. This association between EE and relapse could be due to the strong difference in the first 9 months. The period during which EE's predictive validity for schizophrenic relapse is applicable may vary according to the society to which the patients and their families belong.

Adolescent↗

Protective effects of peony root extract and its components on neuron damage in the hippocampus induced by the cobalt focus epilepsy model.

Protective effects of peony root extract and its components on neuron damage in the CA1 area of the hippocampus induced by the cobalt focus epilepsy model were examined. Neuron damage in the CA1 area of the hippocampus and frequent spike discharges induced by application of metallic cobalt to the cerebral cortex of rats were completely prevented when peony root extract was continuously administered orally at 1 g/kg/day for 30 days prior to cobalt application. Component crude gallotannin fraction showed marked but incomplete protective action. A combination of crude gallotannin fraction and paeoniflorin showed complete protective action in the same way as peony root extract against neuron damage although use of paeoniflorin alone had no effect. These findings together with our previous reports indicate that peony root extract and its component, gallotannin, have excellent protective effects on neuron damage in addition to anticonvulsant action by prior oral administration.

Animals↗

Compartmental analysis of asialoglycoprotein receptor scintigraphy for quantitative measurement of liver function: a multicentre study.

A multicentre study on multicompartmental analysis of hepatic scintigraphy using technetium-99m labelled galactosyl serum albumin (GSA), which binds to the asialoglycoprotein receptor, was carried out at seven institutions in Japan. Seventy-four patients with liver disease received 3 mg (185 MBq) of 99mTc-GSA by intravenous injection. Sequential scanning was performed 30 min after injection to obtain anterior images of the heart and liver, followed by single-photon emission tomography (SPET). The indices included in this analysis were hepatic blood flow (Q) and maximal receptor binding rate (Rmax), which showed a good correlation with semiquantitative ratio indices for 99mTc-GSA, namely the retention rate in blood (HH15) and the hepatic uptake rate (LHL15). Q and Rmax also showed a significant correlation with other measures of hepatic function. When patients were grouped according to the severity of chronic liver damage (hepatocellular functional damage), Q was reduced in the moderate and severe groups, while Rmax was reduced in proportion to the functional stage. Both parameters showed no inter-institution difference using analysis of co-variance with the functional stage as a co-variant. With regard to the hepatic uptake rate, anterior planar images and SPET images gave similar results for Q and Rmax. Acquisition times of 15 or 30 min provided the same results. The multicompartmental model analysis permitted comparable results to be obtained at institutions using different gamma cameras, and is therefore considered a universally applicable method. These results indicate that Q and Rmax are useful general indices for evaluating the functional reserve capacity of the liver.

Asialoglycoprotein Receptor↗

Micrometastatic tumor cells in the bone marrow of patients with non-small cell lung cancer.

BACKGROUND: This study was designed to evaluate the incidence and clinical implications of detection of micrometastatic cancer cells in bone marrow aspirates of patients with operable non-small cell lung cancer. The relationship between micrometastatic cells and p53 overexpression in the primary tumor was also assessed. METHODS: Thirty-nine patients with stages I through III non-small cell lung cancer who underwent curative resection were entered into this study. Immunohistochemistry with monoclonal antibody to cytokeratin 18 was used to detect tumor cells in bone marrow. Immunostaining of p53 protein in the corresponding primary tumors was also done. RESULTS: Cytokeratin 18-positive cells were detected in 15 (39%) of the 39 patients. Overexpression of p53 was associated with positivity of the tumor cells in the bone marrow at borderline significance (14/29 versus 1/10; p = 0.0574). The patients with cytokeratin 18-positive cells in bone marrow demonstrated a significantly earlier recurrence than those without such cells (p = 0.0083, log-rank test). CONCLUSIONS: Micrometastatic cancer cells were frequently present in bone marrow of patients with operable non-small cell lung cancer and may be a significant predictor of early recurrence. Further evaluation of this method may be useful in identifying patients with non-small cell lung cancer who are most likely to benefit from adjuvant chemotherapy.

Aged↗

LpA-I levels do not reflect pre beta1-HDL levels in human plasma.

High-density lipoprotein (HDL) containing apo A-I but no apo A-II (LpA-I) can promote cholesterol efflux from cells, while HDL containing apo A-I and apo A-II can not. Pre beta1-HDL, a minor fraction of LpA-I, is the initial acceptor of cellular cholesterol. To determine whether the pre beta1-HDL:LpA-I ratio is constant in human plasma, we measured LpA-I levels by differential electroimmunoassay, and HDL subfraction levels by nondenaturing 2-dimensional gel electrophoresis in 26 subjects. We found that the pre beta1-HDL:LpA-I ratio was higher in hypercholesterolemia (0.21+/-0.09; n = 11, P < 0.05), coronary artery disease (0.26+/-0.13; n = 5, P = 0.08) and hypertriglyceridemia (0.39+/-0.22; n = 3, P = 0.16) than in normolipidemia (0.11+/-0.03, n = 5). LpA-I levels were significantly correlated with HDL2b (r = 0.771, P=0.000001), HDL2a (r = 0.438, P < 0.01), and pre beta2-HDL levels (r = 0.496, P < 0.005) but not with pre beta1-HDL or HDL3 levels. In conclusion, the pre beta1-HDL:LpA-I ratio is not constant in human plasma. These findings strongly suggest that size distribution of LpA-I may change in various disorders.

Adult↗

Acute toxicity, accumulation and excretion of organophosphorous insecticides and their oxidation products in killifish.

Acute toxicity, accumulation and excretion of four organophosphorous insecticides (diazinon, malathion, fenitrothion and EPN) and their oxidation products (diazinon oxon, malaoxon, fenitrothion oxon and EPN oxon) were studied for killifish (Oryzias latipes). The 48-hr LC50 was 4.4 mg l-1 for diazinon, 1.8 mg l-1 for malathion, 3.5 mg l-1 for fenitrothion, 0.58 mg l-1 for EPN, 0.22 mg l-1 for diazinon oxon, 0.28 mg l-1 for malaoxon, 6.8 mg l-1 for fenitrothion oxon, and 0.16 mg l-1 for EPN oxon. The bioconcentration factors (BCF) of diazinon oxon 0.5, malaoxon 1.1, fenitrothion oxon 2.3 and EPN oxon 11 in the whole body of the fish were much lower than those of diazinon 49, malathion 11, fenitrothion 122 and EPN 1124. As reference data, partition coefficients between n-octanol and water (Pow) were measured for these chemicals. The BCF values of each pesticide and its oxidation product were consistent with the Pow values. The excretion rate constants (k) from the whole body of the fish were 0.12 hr-1 for diazinon, 0.27 hr-1 for malathion, 0.11 hr-1 for fenitrothion, 0.02 hr-1 for EPN, 0.30 hr-1 for fenitrothion oxon and 0.59 hr-1 for EPN oxon. The rates of diazinon oxon and malaoxon could not be measured, but were presumed to be as rapid as or more rapid than those of fenitrothion oxon and EPN oxon. The results suggest that the contamination of fish and other aquatic organisms by the oxidation products in the environment is very low.

1-Octanol↗

Molecular mechanism of regulation of pentylenetetrazol-induced calcium entry by 3'-untranslated region of a seizure-related cDNA, PTZ-17, in Xenopus oocytes.

To determine the molecular mechanism of regulation of pentylenetetrazol (PTZ)-induced calcium entry by the seizure-related gene, PTZ-17, the role of the 3'-untranslated region (3'UTR) and also interaction between 3'UTR and intracellular factors were investigated. PTZ-induced calcium inward current in Xenopus oocytes injected with PTZ-17 RNA varied in magnitude among strains of mice: RNA derived from the DBA/2 mouse, which has a high susceptibility to convulsions, showed the largest current and that from the BALB/c mouse with a low susceptibility to convulsions showed no PTZ response. The sequence of 3'UTR showed alterations among mouse strains: 3'UTR of BALB/c showed a sequence alteration from T to G and that of DBA/2 showed a GTG insertion compared with that of B6. The 3'UTR also regulated the translation of chloramphenicol acetyltransferase (CAT) RNA depending on its sequence. A particular region within the 3'UTR demonstrated interaction with 60- and 47-kDa proteins. Sequence alterations in this region corresponded to disappearance or increase in PTZ-induced calcium entry. These findings suggest that a particular region within 3'UTR of the seizure-related gene, PTZ-17, is involved in PTZ-induced calcium entry via interaction between mRNA and specific RNA-binding proteins.

Animals↗

Nervous diseases and Kampo (Japanese herbal) medicine: a new paradigm of therapy against intractable nervous diseases.

Doctors who learned exclusively western medicine probably understand a priori Kampo (Japanese herbal) medicine merely as a kind of folk medicine which is not so effective and only a supplementary therapy to western medicine. We have been performing experiments on the mechanism of epileptogenesis mainly at the cellular level for a long time. During the research process, we unexpectedly encountered Kampo (Japanese herbal) medicine, and also performed research on the mechanism of action of a herbal mixture prescription, saiko-keishi-to-ka-shakuyaku (SK, TJ-960). Recently we discovered that SK acts to induce the best functional state of neurons and consequently intractable nervous symptoms disappear. SK has protective effects against neuron damage, normalizing effects on developmental defects of El mouse neurons, complete preventive effects on stress-induced increased c-fos and HSP 72 expression, complete suppression effects on the Reilly syndrome, complete normalizing effects on expression of the seizure-related gene, PTZ-17, and also, surprisingly, complete suppression effects on amyloid beta protein-induced neuron death. Such wide ranging effects which are preferable to functional maintenance and development of neurons can not be obtained by pure chemical drugs. These findings suggest that we should effectively use such ancient herbal prescriptions which show excellent preventive effects against neuron damage, enforcing action on natural healing forces and even regulatory action against adverse expression of genes, at least to prevent intractable nervous diseases, such as epilepsy, Alzheimer's disease and developmental defects of neurons during pregnancy and after birth. We should also create a future medicine, the 'third medicine', which is situated in a higher dimension than that of contemporary oriental and western medicines. For this purpose, it is necessary to perform research on the mechanism of action of Kampo (Japanese herbal) medicine.

Animals↗

Instrumentation of a handy microscopic probe for concurrent observation and measurement of active sweat secretion, and its applications.

Instrumentation for the concurrent, dynamic monitoring of active sweat glands and perspiration volume is described. A device for the measurement of the rate of sweat secretion was installed on the head part of a microscope. The combined apparatus (microscopic probe) is handy for use and its weight is very light (ca. 300 g). The microscopic probe is easily attached to the surface of human skin. The dynamic activities of the sweat glands on the forehead and nose and under the nose were observed and measurement when thermal, mental and physical stimuli were applied. The activities of individuals sweat glands were asynchronous when observed in units of a few seconds or less; however, they worked synchronously in a unit period of several seconds. The latter were recorded as fine peaks by a strip chart recorder. The proposed system may be useful for the study of the sympathetic nervous system, the skin sympathetic reflex and the working of sudomotor nerves.

Adult↗