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Biomedical subjects

M Takei

Publications and source records attributed to M Takei.

At least 55 records · Page 3Linked to original sources

Successful methotrexate therapy for adult Still's disease with marked thrombocytopenia.

A 34-year-old Japanese woman developed spiking fever, splenomegaly, arthritis, neutrophilia, hyperferritinaemia (22517 ng/ml), elevated C-reactive protein (9.1 mg/ml) and severe thrombocytopenia (1.7 x 10(4)/microl). The patient had depressed antithrombin III activity and abnormally high concentrations of both fibrin degradation products and thrombin-antithrombin complexes. This condition was resistant to high-dose prednisolone therapy (120 mg/day) and non-steroidal anti-inflammatory drugs. We initiated oral methotrexate therapy (7.5 mg/week, orally) with a favourable outcome. The patient's spiking fever subsided on the first day of methotrexate administration. Elevated levels of ferritin and C-reactive protein in the sera rapidly normalised. Methotrexate rapidly improved the disease state which suggested that methotrexate act via modulation of cytokine production or secretion.

Administration, Oral↗

Predictability of conventional tests for the assessment of bladder outlet obstruction in benign prostatic hyperplasia.

BACKGROUND: The degree of bladder outlet obstruction (BOO) in benign prostatic hyperplasia (BPH) is most accurately quantified by pressure flow studies (PFS), although these studies are more invasive and complicated than conventional tests. We examined how precisely conventional tests predicted the PFS-assessed degree of BOO. METHODS: The study population consisted of 232 BPH patients who had undergone routine conventional tests and PFS. Correlation of the conventional test results with the degree of BOO assessed by PFS was examined by Spearman's correlation coefficients. Regression and subgroup analyses were performed to predict the degree of BOO using the conventional test results as the explanatory variables. RESULTS: The degree of BOO correlated with prostate volume, the degree of endoscopic obstruction, and to a lesser extent, with the maximum flow rate (Qmax) and age. The predictability of conventional tests alone, or in combination, for BOO, was approximately 60% to 70%, which is not acceptable for investigational use. However, almost all patients with a prostate volume larger than 30 mL, or with severe obstruction on urethroscopic findings, had an obstructed bladder outlet. CONCLUSION: PFS is mandatory when the precise evaluation of the degree of BOO is required, and patients are highly likely to have an outlet obstruction when they have a prostate larger than 30 mL, or severely obstructed posterior urethra on endoscopy.

Aged↗

Inhibitory activities of gatifloxacin (AM-1155), a newly developed fluoroquinolone, against bacterial and mammalian type II topoisomerases.

We determined the inhibitory activities of gatifloxacin against Staphylococcus aureus topoisomerase IV, Escherichia coli DNA gyrase, and HeLa cell topoisomerase II and compared them with those of several quinolones. The inhibitory activities of quinolones against these type II topoisomerases significantly correlated with their antibacterial activities or cytotoxicities (correlation coefficient [r] = 0.926 for S. aureus, r = 0.972 for E. coli, and r = 0.648 for HeLa cells). Gatifloxacin possessed potent inhibitory activities against bacterial type II topoisomerases (50% inhibitory concentration [IC50] = 13.8 microg/ml for S. aureus topoisomerase IV; IC50 = 0.109 microg/ml for E. coli DNA gyrase) but the lowest activity against HeLa cell topoisomerase II (IC50 = 265 microg/ml) among the quinolones tested. There was also a significant correlation between the inhibitory activities of quinolones against S. aureus topoisomerase IV and those against E. coli DNA gyrase (r = 0.969). However, the inhibitory activity against HeLa cell topoisomerase II did not correlate with that against either bacterial enzyme. The IC50 of gatifloxacin for HeLa cell topoisomerase II was 19 and was more than 2,400 times higher than that for S. aureus topoisomerase IV and that for E. coli DNA gyrase. These ratios were higher than those for other quinolones, indicating that gatifloxacin possesses a higher selectivity for bacterial type II topoisomerases.

Anti-Infective Agents↗

A case of mitochondrial cytopathy with a typical point mutation for MELAS, presenting with severe focal-segmental glomerulosclerosis as main clinical manifestation.

A 27-year-old female with short stature and mild hearing loss was diagnosed as having focal-segmental glomerulosclerosis by renal biopsy at our hospital. One year later she developed progressive renal dysfunction and cardiac failure and was admitted again to our hospital for evaluation. Though her only neurological disorder was mild hearing loss, her short stature and elevated lactate and pyruvate values in cerebrospinal fluid suggested mitochondrial cytopathy. A muscle biopsy specimen of the left biceps brachii, using modified Gomori trichrome stain, showed a typical image of ragged-red fibers, and an increased number of giant mitochondria with paracrystalline inclusions were visible by electron microscopy. Mitochondrial DNA from the skeletal muscle showed an A-to-G transition at 3243 of transfer RNALeu(UUR), the common point mutation for mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. These data confirmed the diagnosis of atypical mitochondrial cytopathy with renal and heart involvement. Mitochondrial cytopathies are often associated with hypertrophic cardiomyopathy but rarely with renal disease. Among the few reported cases with associated renal disease, most included renal tubular disorders; few cases with focal glomerular sclerosis are known. The present case of atypical mitochondrial cytopathy was characterized by a unique clinical course and rare complications with focal-segmental glomerulosclerosis.

Adult↗

Early and late events in Fc epsilon RI signal transduction in human cultured mast cells.

Protein tyrosine phosphorylation and other biochemical events have been shown to occur after cross-linking of Fc epsilonRI in rodent mast cells. To investigate the mechanism of Fc epsilonRI signal transduction in human mast cells, we used human cultured mast cells (HCMC) generated from cord blood cells in the presence of recombinant human stem cell factor and IL-6. We found that on cross-linking of Fc epsilonRI: 1) HCMC released histamine; 2) rapid tyrosine phosphorylation of multiple cellular substrates, including Syk, HS1, c-Cbl, ERK-1, and ERK-2, was observed; 3) intracellular Ca2+ and inositol phosphate production were increased within the first minute after Fc epsilonRI cross-linking; and 4) genistein, a tyrosine kinase inhibitor, inhibited both protein tyrosine phosphorylation and histamine release in a dose-dependent manner. These results were consistent with previous studies in rodent mast cells. In contrast, no tyrosine phosphorylation of phospholipase C gamma1 and Btk (Bruton's tyrosine kinase) were observed in our experimental conditions. These results suggest that the greater part of the early and late signaling events in HCMC is similar to those obtained with rodent mast cells and indicated that the requirement of tyrosine phosphorylation in the activation process of each of the signaling molecules might be different in HCMC and rodent mast cells. Our finding indicates that HCMC may be useful for analysis of Fc epsilonRI-mediated signal transduction in human mast cells.

Adaptor Proteins, Signal Transducing↗

Different sympathetic-parasympathetic interactions on sinus rate and atrioventricular conduction in dog hearts.

We investigated the sympathetic-parasympathetic interactions involved in SA nodal pacemaker activity and AV conductivity in the anesthetized dog heart. Stimulation of the intracardiac parasympathetic nerves to the SA nodal region (SAPS) and stimulation of the intracardiac parasympathetic nerves to the AV nodal region (AVPS) induced negative chronotropic and dromotropic responses, respectively. Cardiac sympathetic stimulation, aminophylline, 3-isobutyl-1-methylxanthine (IBMX, a relatively pure nonselective phosphodiesterase inhibitor) and methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-p iridine-5-carboxylate (Bay k 8644, a Ca2+ channel agonist) increased sinus rate and decreased AV conduction time. Sympathetic stimulation augmented the negative chronotropic response to SAPS but not the negative dromotropic response to AVPS, IBMX augmented both responses, Bay k 8644 augmented the chronotropic response and attenuated the dromotropic response, and aminophylline did not affect the chronotropic response to SAPS and inhibited the dromotropic response to AVPS. Additionally, when Bay k 8644 directly given via the AV node artery decreased AV conduction time, it attenuated the negative dromotropic response to AVPS and carbachol injected into the AV node artery. These results suggest that the differential sympathetic-parasympathetic interactions on sinus rate and AV conduction are at least partly induced by an interaction between changes in slow inward Ca2+ current or intracellular Ca2+ and the cardiac effects of acetylcholine in the heart in situ.

1-Methyl-3-isobutylxanthine↗

Elevation of soluble CD23 in sera from patients with infectious mononucleosis.

CD23 is induced in B cells upon infection by Epstein-Barr virus (EBV) and a soluble form (soluble CD23: sCD23) is found in culture supernatants from EBV-transformed B cell lines. Based on these observations, we measured serum sCD23 levels in patients with infectious mononucleosis (IM) caused by EBV infection. Sera from patients with IM at the time of diagnosis contained more sCD23 than sera from normal control subjects. Changes in serum sCD23 levels during the course of disease showed that serum sCD23 levels were elevated at the time of diagnosis and they decreased to the normal levels during the convalescent phase defined by the improvement of symptoms of IM. These results indicate that the elevated levels of sCD23 were observed at the acute phase of IM and may be useful in diagnosing IM.

Adolescent↗

Bladder neck support prosthesis: a nonoperative treatment for stress or mixed urinary incontinence.

PURPOSE: We evaluated the usefulness and safety of a bladder neck support prosthesis in patients with stress or mixed incontinence. MATERIALS AND METHODS: A total of 57 women with stress and 20 with mixed incontinence completed a 12-week prospective clinical trial of a bladder neck support prosthesis. While indexes of incontinence episodes, leakage amounts and urgency along with a bothersome index were subjectively evaluated, a 60-minute pad test and urinary flow parameters were objectively evaluated. Three patients scheduled to undergo surgery for stress incontinence voluntarily used the device, and provided urodynamic data and cystourethrograms. Two prongs at 1 end of the ring, a type of elastic vaginal pessary, elevate the bladder neck against the pubic bone and facilitate pressure transmission around the bladder neck, resulting in urinary continence. RESULTS: Four subjective indexes significantly improved. There was no urinary flow obstruction. Urine loss decreased from 20.6 to 4.8 gm. per hour (p < 0.001) on the 60-minute pad test. Of the patients 22 (29%) reported complete continence and 39 (51%) had decreased severity of incontinence by more than 50%. Minor adverse effects occurred in 26% of the patients. Taking subjective evaluation, changes in objective parameters and adverse effects into consideration, 62 patients (81%) had some or maximum benefit according to the global usefulness rating. CONCLUSIONS: The bladder neck support prosthesis is safe, well tolerated and clinically effective for the treatment of stress or mixed incontinence.

Adult↗

Detection of Epstein-Barr virus-encoded small RNA 1 and latent membrane protein 1 in synovial lining cells from rheumatoid arthritis patients.

Several investigators have demonstrated an association between Epstein-Barr virus (EBV) and the pathogenesis of rheumatoid arthritis (RA). However, there is no direct evidence that this virus exists in the synovial cells of patients with RA. We attempted to detect EBV in synovial cells from RA patients. Specimens of synovial tissues from 34 patients with RA and from 20 patients with osteoarthritis (OA), and from one patient with psoriatic arthritis as controls, were examined for evidence of the EBV by in situ hybridization. The specimens were also tested by immunoperoxidase staining for expression of the CD21 molecule (EBV receptor), EBV nuclear antigen (EBNA)-2 and latent membrane protein (LMP)-1. EBV-encoded small RNA-1 (EBER) was demonstrated in synovial lining cells from eight (23.5%) out of 34 RA patients but in none of 20 OA patients (P < 0.05) nor in the one psoriatic arthritis patient. Interestingly, EBER localized in synovial lining cells that were located at the apex of villus proliferating lesions. Furthermore, LMP-1 was also detected in synovial lining cells at the top of villus lesions. Nevertheless, CD19 and CD21 molecules, and EBNA-2 were not demonstrated in such lesions. The incidence of EBV-positive in synovial lining cells with severely infiltrated lymphocytes tended to be higher than that in moderately infiltrated ones. This is the first evidence that EBV exists in chronically inflamed synovial lining cells of human joints in RA.

Antigens, Viral↗

Effect of a chymotrypsin-like inhibitor, TPCK, on histamine release from cultured human mast cells.

The involvement of endogenous proteases in the secretory process from human mast cells remains to be clarified. A chymotrypsin-like protease inhibitor, N-tosyl-L-phenylalanylchloromethyl ketone (TPCK), blocked both FceRI- and A23187-mediated histamine release from cultured human mast cells at concentrations above 1 microM. At 10 microM, the concentration that completely inhibited FceRI-mediated histamine release, TPCK did not inhibit the chymase activity of the lysate or that in intact cells. The addition of TPCK to cells 30 min before challenge did not affect FceRI- or A23187-mediated Ca2+ mobilization. These findings suggest that a TPCK-sensitive molecule distinct from chymase is involved in a late stage of the process of histamine release from mast cells in man.

Calcimycin↗

Acetylcholine-induced relaxation of rat aorta is greatest during estrus in the sexual cycle.

Acetylcholine (ACh)-induced relaxation in the aortae precontracted with norepinephrine was significantly enhanced in the aortae from estrus (E) rats, compared with that in those from metestrus (D-1), diestrus (D-2) and proestrus (PE) rats. NG-Nitro-L-arginine methyl ester (L-NAME) inhibited the endothelium-dependent relaxation in E rats. These results suggest that there is a difference in ACh-induced relaxation of the thoracic aorta during the sexual cycle of rats, and the relaxation is greatest in E of the sexual cycle; this may be due to a difference in nitric oxide synthesis in the endothelium in the sexual cycle.

Acetylcholine↗

[Three cases of malignant lymphoma that developed from the chest wall].

Chronic tuberculous pyothrax and the development of non-Hodgkin's lymphoma (NHL) on the chest wall are believed to be closely related. We encountered three patients with NHL involving the chest wall in whom the tumor may have had a different origin Patient 1: A 65-year-old man with a history of pulmonary tuberculosis and right-sided pyothrax at the age of 28 years was found to have a tumor on the right sided of the chest wall, and NHL was diagnosed. Patient 2: A 65-year old woman with a history of right-sided tuberculous pyothrax at the age of 2 years had a left-sided chest-wall tumor, and NHL was diagnosed. Patient 3: A 78-year-old man with a history of tuberclous pleuritis on the left side at the age of 77 years was found to have a left-sided chest-wall tumor, and NHL was diagnosed. In patients 1 and 2, the Epstein-Barr virus was found in tissue specimens by in situ hybridization. These findings suggest that chronic tuberculous pyothrax and the development of NHL on the chest wall were not closely related in these patients, and that the Epstein-Barr virus may play an important role in the development of NHL on the chest wall after tuberculous pyothrax.

Aged↗

[Successful treatment with intermittent administration of etoposide for an adult case with recurrent hemophagocytic syndrome, developed in association with chronic EB virus infection related lymphoid hyperplasia in the small intestine].

A 28-year-old man complaining of melena accompanied by high grade fever was previously operated on for two small ulcerative, infiltrative lesions of the small bowel at another hospital in April, 1992. In the resected small intestines an immunohistochemical study was positive for EBV encoded RNA (EBER). It is assumed that Epstein-Barr (EB) virus infection has contributed to the small bowel lesions. In March, 1993, he was diagnosed as having chronic EB virus infection. In October, 1993, he was transferred to our hospital for further examination of high grade fever, rapidly worsening thrombocytemia and severe liver disfunction. Mature histiocytes with hemophagocytosis were detected in the bone marrow and he was diagnosed as having hemophagocytic syndrome (HPS) due to reactivation of chronic EB virus infection. Although treatment by corticosteroids, acyclovir and gamma globulin was not effective administration of etoposide induced remission of the disease. In December, 1993 and January, 1994 HPS recurred, but etoposide was again effective in alleviating the disease. To prevent recurrence of HPS after we discharge the patient, intermittent administration of small doses of etoposide was started. Since then HPS has not recurred, and the drug was eventually discontinued in November, 1995. Our case suggested that Etoposide could change the fulminant course of EB virus-associated HPS and that it is effective to sustained remission.

Adult↗

Lansoprazole elevates the ratio of serum pepsinogen I v.s. pepsinogen II.

In order to investigate the mechanism by which proton pump inhibitor increases serum pepsinogen levels, we evaluated the effects of ulcer location and IgG antibody against Helicobacter pylori on lansoprazole-induced elevations. Patients with endoscopically proven peptic ulcer received lansoprazole 30 mg/day for 6 or 8 weeks; pepsinogen I and II levels, along with antibody to H. pylori, were measured in fasting blood samples. We found that whether or not antibody to H. pylori was present, pepsinogen I and II levels and the I/II ratio rose significantly in lansoprazole-treated patients. Patients with stomach-body ulcers showed smaller increases in both pepsinogens than did those with ulcers in the gastric angle/antrum or in the duodenum. In conclusion, lansoprazole increases serum levels of both pepsinogens I and II, although a larger increase in pepsinogen I elevates the pepsinogen I/II ratio. The relatively small increases seen in patients with stomach-body ulcers suggest atrophic changes in the gastric mucosa in patients with stomach-body ulcer.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Patient with both lupus anticoagulant and acute disseminated encephalomyelitis.

We present the unusual case of 16-year-old girl who developed intractable convulsions five days after the onset of a cold. Meningeal signs, lymphopenia, proteinuria, and lupus anticoagulant were also present. Treatment with anticonvulsants, antituberculous agents, and adenine arabinoside were ineffective. The initiation of methylprednisolone pulse therapy immediately resolved convulsions and fever. The diagnosis, suggested by the clinical course and the marked improvement of the meningoencephalitis by pulse therapy, was an encephalitic form of acute disseminated encephalomyelitis. Clinical and laboratory findings indicated that an immune disorder may have triggered an abnormal response to a viral infection leading to this patient's neurologic disorder.

Acute Disease↗

Clinical significance of LEA-1 expression in adult acute myeloid leukemia.

In this study, we examined expressions of several adhesion molecules (AdMs), i.e. leukocyte function antigen-1 (LFA-1: CD11a/CD18), Hermes homing receptor (CD44) and intercellular adhesion molecule-1 (ICAM-1: CD54), on leukemia cells from 51 adult patients with newly diagnosed acute myeloid leukemias (AMLs) to elucidate clinical significance of these AdM expressions. Those expressions in lymphoid malignancies have been correlated with tumor evolutions, but CD44 was detected in all the AML cases examined and CD54 expression did not associate with their clinical characteristics or outcomes. However, we found that LFA-1 expressions significantly correlated with splenomegaly, resistance to induction chemotherapies and short survival periods in AML patients.

Acute Disease↗