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Biomedical subjects

T Nishikawa

Publications and source records attributed to T Nishikawa.

At least 253 records · Page 14Linked to original sources
PubMed1999

Effect of fleroxacin on mouse bladder carcinogenesis with N-butyl-N- (4-hydroxybutyl) nitrosamine.

We recently reported fleroxacin significantly affected cell proliferation in a dose-dependent manner in transitional cell carcinoma cell lines. In this study, we investigated the effect of fleroxacin on mouse bladder carcinogenesis with N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN). Five-week-old C57BL/6 female mice were divided into three groups. The forced oral administrations of fleroxacin (10 or 50 mg/kg/day) were done for 1 week, then the 0.05% BHBN was given for 8 or 12 weeks. Fleroxacin treatments were continued until sacrifice. The mice were sacrificed at 4 weeks or 8 weeks latent period after BHBN administration, and the histological changes in the bladder were examined. Our study suggested that fleroxacin tended to suppress the development of bladder carcinoma or the malignant changes induced by a shorter period of BHBN administration (8 weeks) in mice. However, in the group of the BHBN administration for 12 weeks, there were no significant effects on the prevention of bladder carcinoma in both of the treatment groups with fleroxacin (10 or 50 mg/kg/day). This study did not make it clear that oral administration of fleroxacin suppressed the development of bladder carcinoma induced by BHBN in mice. However, it is very preliminary data and further experiments need to be done with a much higher dose of the fleroxacin or with other kinds of fluoroquinolone antibiotics.

Animals↗
PubMed1999

[The ameliorating effects of a novel NC-1900 on impairments of learning/memory caused by glutamic acid].

The effects of a novel vasopressin fragment analog NC-1900 (pGlu-Asn-Ser-Pro-Arg-Gly-NH2 acetate) were studied on learning and/or memory impairment in passive avoidance task and on cell damage of cultured cerebro-cortical neurocytes induced by glutamic acid. A small dose of NC-1900 (1 ng/kg, s.c.) ameliorated impairments of learning and/or memory induced by intracisternal injection of 467.6 micrograms of 10 microliters glutamic acid. NC-1900 also ameliorated the impairments induced by intracisternal NMDA, AMPA-antagonist CNQX and by metabotropic receptor (mGluR1) agonist 3,5-dihydroxyphenylglycine but not by kainate agonist domoic acid nor MK-801 in mice. NC-1900 (100 pM, 1nM) ameliorated the cell damage of cultured rat cerebro-cortical neurocytes induced by 100 and 1000 microM of glutamic acid. These results suggest that NC-1900 may serve as a remedies in various patients with certain brain disorders induced by excess glutamic acid.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1999

Diminished facial expression despite the existence of pleasant emotional experience in schizophrenia.

In order to investigate the relationship between pleasant emotional experience and facial expression (i.e., laughter), mood before and after watching comic film clips, self-rated pleasant emotional experience for each film clip and electromyographic activities of facial muscles involved in laughter while watching film clips were measured for 25 patients with schizophrenia and 20 normal controls. Patients with schizophrenia who showed a significant correlation between self-rated emotional experience and major zygomatic activity were equivalent to normal controls in self-rated emotional experience and in mood after film clips; they had a significant increase in mood scores related with pleasure. Although these patients were thought to have sufficient pleasant emotional experience, they showed significantly low major zygomatic activity as compared to normal controls. It is suggested that these patients have a disturbance in the process of emotional expression rather than emotional experience.

Adult↗
PubMed1999

A patient with preclinical Cushing's syndrome and excessive DHEA-S secretion having unilateral adrenal carcinoma and contralateral adenoma.

We report a case of preclinical Cushing's syndrome in a 54-year-old male associated with bilateral adrenocortical tumours. Physical findings and general laboratory data were unremarkable except for mild hypertension (158/90 mmHg) and impaired glucose tolerance. Endocrinological evaluation revealed the presence of autonomous cortisol secretion including unsuppressible serum cortisol by 8 mg dexamethasone test (11 microg/dl), high serum DHEA-S (3580 ng/ml, normal: 400-3500) and increased urinary 17-KS excretion (31.0-35.8 mg/day, normal: 5.8-21.3). CT scan demonstrated the presence of tumours in both adrenals and bilateral adrenalectomy was subsequently performed. Histological examination of the resected specimens revealed an adrenocortical carcinoma on the right side and an adenoma on the left side with noticeable cortical atrophy in non-neoplastic adrenals. Immunohistochemical study of steroidogenic enzymes demonstrated that all the steroidogenic enzymes involved in cortisol biosynthesis were expressed in both right and left adrenal tumours. Enzymatic activities of 21, 17alpha, 18, 11beta-hydroxylases were detected in both right and left adrenals except for the absence of 11beta-hydroxylase activity in the left adrenal adenoma. Results of in vitro tissue steroidogenesis examined in short-term tissue culture of the specimens revealed no significant differences between carcinoma and adenoma in cortisol production, but the production of adrenal androgens in carcinoma was significantly higher than that in adenoma, which may indicate the importance of evaluating adrenal androgen levels in patients with adrenocortical neoplasms.

17-Ketosteroids↗
PubMed1999

Changes in c-Fos expression induced by noxious stimulation in the trigeminal spinal nucleus caudalis and C1 spinal neurons of rats after hyperbaric exposure.

The present study aims to test the hypothesis that hyperbaric exposure inhibits nociceptive processing in the trigeminal spinal nucleus caudalis and C1 spinal neurons. We investigated the c-Fos-like immunoreactivity of the brainstem and upper cervical spinal cord (C1 region) following an injection of mustard oil (15 microliters of 20%) into the nasal mucosa of pentobarbital anesthetized rats after exposure to hyperbaric (2-atmospheres, 1 h) and normobaric pressures. After the hyperbaric exposure, the mean number of Fos-immunoreactive neurons in the ipsilateral laminae I-II and III-IV of the trigeminal spinal nucleus caudalis were significantly lower than those in the normobaric condition. Similarly, the mean number of c-Fos positive neurons in the superficial layer (I-II) of the ipsilateral C1 segment were significantly reduced as compared with that in the normobaric condition. When treated with the vehicle alone, no significant difference was detected in the numbers of c-Fos positive neurons in the trigeminal spinal nucleus caudalis and C1 regions between hyperbaric and normobaric conditions. These results suggest that hyperbaric exposure may attenuate nociceptive signals from the area innervated by the trigeminal nerves at the level of both the trigeminal spinal nucleus caudalis and C1 dorsal horn.

Animals↗
PubMed1999

Peroneal motoneuron excitability increases immediately following application of a semirigid ankle brace.

STUDY DESIGN: Within-session, within-subject comparison of 2 conditions. OBJECTIVES: To determine the influence of application of a semirigid ankle brace on the excitability of the peroneus longus muscle motoneuron pool as measured by the H-reflex. BACKGROUND: The literature suggests that cutaneous mechanoreceptors can contribute to proprioception, especially during conditions in which skin experiences displacement. Further, skin displacement and stimulation of cutaneous mechanoreptors have been shown to increase motoneuron excitability. METHODS AND MEASURES: H-reflexes and M-waves of the peroneus longus muscle were acquired by stimulating the common peroneal nerve of 11 uninjured subjects during 2 randomly ordered conditions, with and without application of an Aircast Air-Stirrup. Five reflexes were collected at each of 12 stimulation voltages. The peak-to-peak amplitudes of the M-wave and H-reflex from each subject's ensemble-averaged data at each stimulation voltage was used to generate H-reflex and M-wave recruitment curves. The H-reflex amplitude was subsequently expressed as a percentage of the maximum M-wave amplitude. RESULTS: The normalized H-reflex amplitude increased by approximately 10% during the braced condition compared to the nonbraced condition. The peroneus longus H-reflex latency and M-wave amplitude were not affected by the bracing condition. CONCLUSIONS: Application of the ankle brace excited afferents possibly arising from a number of candidate mechanoreceptors, 1 of which is likely cutaneous. The findings raise questions as to whether the increased motorneuron excitability can be used for the purposes of rehabilitation from ankle injury.

Adult↗
PubMed1999

A case of melanonychia caused by Exophiala dermatitidis.

We report a case of a healthy 61-year-old woman with discoloration of the nail on her right big toe. We first treated her with topical steroid and urea under suspected diagnosis of nail eczema, but the lesion remained. In culture, black, shiny, pasty and yeast-like colonies grew repeatedly. Examination of debris from her nail showed dematiaceous spherical cells and hyphal elements. Microscopically, annelloconidia were produced at the apical ends of anellidic conidiogenous cells. This colony grew at 40C. Mitochondrial DNA restriction fragment length polymorphism was analysed in this strain and its restriction pattern confirmed the isolate to be Exophiala dermatitidis. Based on these findings, we diagnosed this nail deformity as fungal melanonychia due to Exophiala dermatitidis. This is the third reported case of this disease.

Exophiala↗
PubMed1999

[A case of pure agraphia with a deficit of drawing].

We examined a drawing ability in a case with pure agraphia. The patient, having lesions in the left middle frontal gyrus and inferior parietal lobule, could not write in both dictation and spontaneous writing tasks, with the ability to copy letters being well spared. Correspondingly, he showed a deficit of spontaneous drawing, with the ability to copy complex figures being well spared. These findings suggest that he could have an impairment of retrieving visual image, not restricted to letter image. Although some previous cases with pure agraphia were attributed to an impairment of retrieving visual letter image, drawing ability which seemed to be related to retrieving visual image had not been investigated. In the present case, disability of both writing and drawing could be attributed to a common mechanism, that was an impairment of retrieving visual image. In addition, the patient did not show a significant difference between the performance on Kana writing and on Kanji writing. But it has been said that an impairment of retrieving visual letter image could be related to a deficit of Kanji writing more than of Kana writing. Then, it could be assumed that the mechanism of Kana writing involved not only the pathway depending on graphical motor pattern but one depending on visual image.

Agraphia↗
PubMed1999

[A study on the efficacy of combination chemoendocrine therapy consisting of cyclophosphamide, adriamycin, UFT, and tamoxifen for advanced or recurrent breast cancer].

The efficacy of the combination chemoendocrine therapy CAUT against advanced and recurrent breast cancer was examined. One course of this therapy lasted 3 weeks and consisted of adriamycin (i.v.) at 30 mg/m2 on day 1, cyclophosphamide (p.o.) at 65 mg/m2 and UFT (p.o.) at 300 mg/m2 on days 1-14, and tamoxifen (p.o.) at 20 mg/body on days 1-21. Twenty patients were enrolled, of whom 19 were eligible including seven with advanced cancer and 12 with recurrent cancer. One patient achieved CR, ten PR, three NC, and five PD, for a response rate of 58% (95% CI: 29-87%). The response rates according to type of lesion were 73% (8/11) for the soft tissue, 38% (3/8) for the bone, 20% (1/5) for the lungs and pleura, and 50% (2/4) for the liver. Adverse events with a severity of grade 3 or more included a reduction in WBC in six patients (31.6%), a reduction in RBC in one (5.3%), alopecia in four (21.1%), and severe general fatigue in one (5.3%). One patient experiencing a grade 4 reduction in WBC, and one of five patients experiencing a grade 3 reduction with a fever, recovered after treatment with G-CSF. The other four patients recovered following suspension of administration. This therapy is considered useful, exhibiting a high response rate and relatively slight adverse effects.

Adult↗
PubMed1999

Combination therapy for advanced breast cancer: cyclophosphamide, doxorubicin, UFT, and tamoxifen.

We evaluated combination therapy for advanced and recurrent breast cancer with cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), UFT (uracil and tegafur), and tamoxifen (Nolvadex) (CAUT), designed as chemoendocrine therapy with a high antitumor effect and less severe adverse reactions. In this therapy, one 3-week cycle consisted of doxorubicin 30 mg/m2 intravenously on day 1, cyclophosphamide 65 mg/m2 orally (po) and UFT 300 mg/m2 po on days 1 to 14, and tamoxifen at 20 mg/day po on days 1 to 21. Twenty patients were registered and 19 were eligible, including seven with advanced breast cancer and 12 with recurrent disease. Six patients had received previous treatment. The comprehensive evaluation for objective response revealed one patient with a complete response and 10 patients with partial responses, producing an overall response rate of 58% (95% confidence interval, 29% to 87%). Three patients experienced no change, and five patients had progressive disease. Adverse events > or = grade 3 were leukopenia in six patients, erythropenia in one patient, alopecia in four, and severe generalized malaise in one. One patient who developed grade 4 leukopenia and one of five patients who developed grade 3 leukopenia recovered after receiving granulocyte colony-stimulating factor. CAUT therapy produced high response rates and relatively mild adverse reactions and is considered useful for the treatment of advanced and recurrent breast cancer.

Adult↗
PubMed1999

Perception and conception: separate memory systems in the medial temporal lobe.

The purpose of the present study was to investigate, by using positron emission tomography, whether the functionally different types of information are subserved by different memory systems in human medial temporal lobe structures. Before explicit retrieval tests during scans, subjects studied words in perceptually and conceptually processed manners separately. It was found that different parts of the medial temporal lobe structures were involved in each of the different conditions. These results indicated that perceptually and conceptually processed types of information were subserved by at least two partially segregated memory systems in human medial temporal lobe structures.

Adult↗
PubMed1999

[Diaminodiphenyl sulfone therapy for refractory idiopathic thrombocytopenic purpura--long-term effectiveness and possible mechanisms].

Eight patients with idiopathic thrombocytopenic purpura (ITP) refractory to corticosteroids were given oral diaminodiphenyl sulfone (DDS) (75 mg to 150 mg/day). Responses to DDS were observed in 5 patients, and their platelet counts significantly increased to more than 10 x 10(4)/microliter. The duration of treatment required to obtain platelet counts of more than 10 x 10(4)/microliter ranged from 35 to 64 days. In 3 of the 5 responsive patients, platelet counts stabilized at over 10 x 10(4)/microliter during DDS therapy for 3 to 6 years. Although adverse effects including local skin rash and itching were observed in 3 patients, they disappeared after suspension of DDS or in response to medication with antihistamines. Although the exact mechanism by which it increases the platelet counts in ITP patients is still obscure, DDS may inhibit the reticuloendothelial system by excessive red blood cell destruction. We concluded that DDS therapy is well-tolerated and seems to be an effective alternative treatment for patients with ITP that is refractory to other conventional therapies.

Administration, Oral↗
PubMed1998

The Fas/Fas ligand system is involved in the pathogenesis of autoimmune myocarditis in rats.

The mechanisms responsible for myocardial injury and cell death in myocarditis are still unclear. We examined whether myocardial cell death occurs via apoptosis in myosin-induced autoimmune myocarditis in rats and whether the Fas/Fas ligand (FasL) system plays a role in this apoptosis. On days 14, 17, 21, and 35 after immunization with porcine heart myosin, some cardiomyocytes and infiltrating lymphocytes were found to be apoptotic on in situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay, but none was on day 60 and in control rats. Apoptotic indices peaked at day 17, and laddering of genomic DNA from the affected myocardium was observed on days 17 and 21 on agarose gel electrophoresis. The expression of Fas mRNA and protein was detected on days 17 and 21 in some cardiomyocytes and infiltrating lymphocytes by Northern blot analysis and immunohistochemistry, respectively. In addition, FasL was detected in some infiltrating lymphocytes on days 14, 17, and 21 by both in situ hybridization and immunostaining, and FasL-positive lymphocytes were mainly CD4+ cells. Some rats were injected with anti-Fas Ab (0.1 mg/kg) or anti-FasL Ab (0.1 mg/kg), and subsequently, inflammatory lesions exhibited less severe than did untreated rats with myocarditis. These findings suggest that cell death via apoptosis of cardiomyocytes and lymphocytes is one of the mechanisms of myocardial injury in autoimmune myocarditis, and that the Fas/FasL system might play a role in the induction of this apoptosis.

Acute Disease↗
PubMed1998

The stereo-specific effect of D-serine ethylester and the D-cycloserine in ataxic mutant mice.

Spinocerebellar ataxia is one of the most common neurological disorders. However, few therapeutics are effective for the treatment of this disorder. In the present study, we investigated the efficacy of d-serine ethylester and a related substance, d-cycloserine, as therapeutic agents for ataxia in a murine model. Both compounds are known to stereospecific modulate N-methyl-d-aspartate type glutamate receptors, and impaired glutamate-mediated signaling has been implicated in spinocerebellar ataxia. Using a microdialysis method, we found that intraperitoneal administration of d-serine ethylester increases the extracellular content of endogenous d-serine in the mouse cerebellum for at least 3 h. Maximum elevation of the extracellular d-serine was observed at 40 min after injection. An open-field study was used to assay the effect of the d-serine derivatives on movement and ataxia. In mice exhibiting cytosine arabinoside-induced ataxia, d-serine ethylester reduced the falling index in a dose-dependent manner. The effect of d-serine ethylester was stereo-specific in that l-serine ethylester had no effect on the falling index at the maximum doses tested, and was partially inhibited by 5,7-dichlorokynurenate, an antagonist that binds to the glycine-binding site. Locomotor activity was not changed by the d-serine ethylester treatment. d-cycloserine also significantly reduced the falling index of the mice. Both d-serine ethylester and d-cycloserine had longer lasting effects than other potential therapeutic reagents for ataxia. Growing evidence suggests the essential involvement of endogenous d-serine in mammalian brain function, and our results suggest that d-serine derivatives may represent an effective new therapeutic for the treatment of spinocerebellar ataxia.

Animals↗
PubMed1998

An early stage mechanism of the age-associated mitochondrial dysfunction in the brain of SAMP8 mice; an age-associated neurodegeneration animal model.

In order to characterize the early stage of mitochondrial dysfunction, we investigated the redox state and oxidative phosphorylation of the brain mitochondria from 2-month-old Senescence-accelerated mouse (SAM)P8 and SAMR1 mice; SAMP8 mice exhibit various signs of age-associated neurodegeneration and rapid mitochondrial dysfunction, although SAMR1 mice do not. The redox state was estimated as the reduction rate of Cu-pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM), the reduction of which is closely related to the electron leakage from the mitochondrial electron transport system in the brain, using electron spin resonance spectrometry (ESRS). The oxidative phosphorylation was measured polarographically. The SAMP8 mouse brain mitochondria demonstrated higher redox state and a higher activity of mitochondrial respiration with lower respiration control ratio than the mitochondria of SAMR1 mouse brains. This indicates that an inefficient hyperactive state can exist in the mitochondrial electron transport system before the age-associated mitochondrial dysfunction develops.

Aging↗
PubMed1998

Production of parathyroid hormone-related peptide by synovial fibroblasts in human osteoarthritis.

Synovial fibroblasts from patients with osteoarthritis in culture produced parathyroid hormone-related peptide (PTHrP) on treatment with phorbol ester (TPA) in a dose- and time-dependent manner. The levels of PTHrP immunoreactivity in the conditioned medium of synovial fibroblast cultures were measured using specific PTHrP antibody. The maximum production was obtained at a concentration of 10(-8) M and 24 h after TPA treatment. But sensitivity to TPA of synovial fibroblasts differed among four patients from slight to marked. PTHrP production was also induced with inflammatory cytokines, such as 1 ng/ml of IL-1alpha, IL-1beta, IL-6 and TNF-alpha, and 10(-6) M prostaglandin E2, after 24 h treatment. The expression of PTHrP was confirmed by reverse-transcriptase polymerase chain reaction. Since the synovial fibroblasts isolated from osteoarthritic patients produce high levels of IL-6 and IL-8, typical cytokines produced in synovial fibroblasts, production of PTHrP may provide new insight into the pathophysiology of joint disorder.

Cells, Cultured↗
PubMed1998

Solution structure of the DNA-binding domain of human telomeric protein, hTRF1.

BACKGROUND: Mammalian telomeres consist of long tandem arrays of the double-stranded TTAGGG sequence motif packaged by a telomere repeat binding factor, TRF1. The DNA-binding domain of TRF1 shows sequence homology to each of three tandem repeats of the DNA-binding domain of the transcriptional activator c-Myb. The isolated c-Myb-like domain of human TRF1 (hTRF1) binds specifically to telomeric DNA as a monomer, in a similar manner to that of homeodomains. So far, the only three-dimensional structure of a telomeric protein to be determined is that of a yeast telomeric protein, Rap 1p. The DNA-binding domain of Rap 1p contains two subdomains that are structurally closely related to c-Myb repeats. We set out to determine the solution structure of the DNA-binding domain of hTRF1 in order to establish its mode of DNA binding. RESULTS: The solution structure of the DNA-binding domain of hTRF1 has been determined and shown to comprise three helices. The architecture of the three helices is very similar to that of each Rap 1p subdomain and also to that of each c-Myb repeat. The second and third helix form a helix-turn-helix (HTH) variant. The length of the third helix of hTRF1 is similar to that of the second subdomain of Rap 1p. CONCLUSIONS: The hTRF1 DNA-binding domain is likely to bind to DNA in a similar manner to that of the second subdomain of Rap 1p. On the basis of the Rap 1p-DNA complex, a model of the hTRF1 DNA-binding domain in complex with human telomeric DNA was constructed. In addition to DNA recognition by the HTH variant, a flexible N-terminal arm of hTRF1 is likely to interact with DNA.

Amino Acid Sequence↗