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Biomedical subjects

H Matsuda

Publications and source records attributed to H Matsuda.

At least 919 records · Page 51Linked to original sources
PubMed1995

Further metabolism of FK506 (tacrolimus). Identification and biological activities of the metabolites oxidized at multiple sites of FK506.

To characterize the metabolic pathway of FK506 (tacrolimus), FK506 or its 31-O-desmethyl metabolite was incubated with liver microsomes prepared from dexamethasone-treated rats in the presence of a NADPH-generating system under aerobic conditions. Besides the four oxidized metabolites already reported, four new metabolites were isolated and identified by HPLC, mass spectrometry, and NMR spectroscopy, and their biological activities were examined. The di-demethylated metabolites at the 15- and 31-, 13- and 31-, and 13- and 15-methoxy groups of FK506, were designated respectively as M-V, M-VI, and M-VII. The fourth, M-VIII, was the metabolite produced after O-demethylation at the 31-methoxy group and formation of a fused 10-membered ring structure through the 19- to 22-carbon of the macrolide ring after oxidation of the 19-methyl group, and of the 36- and 37-vinyl group of FK506. The immunosuppressive activity of the isolated metabolites was estimated in a mouse mixed lymphocyte reaction system and the IC50 values for M-V, M-VI, M-VII, M-VIII, and FK506 were > 1000, 8.78, > 1000, 15.27, and 0.11 ng/ml, respectively. Reactivity of the metabolites with mouse anti-FK506 monoclonal antibody was studied and immunocrossreactivity of M-V was 92.3% of FK506, but no reactivity was observed for M-VI, M-VII, and M-VIII. FK506 thus was metabolized at multiple sites by rat hepatic microsomes and the metabolites formed (M-V) - (M-VIII) exhibited weak or negligible immunosuppressive activity.

Animals↗
PubMed1995

Intratumor cellular heterogeneity and alterations in ras oncogene and p53 tumor suppressor gene in human prostate carcinoma.

To assess the potential role of ras oncogene activation and p53 tumor suppressor gene mutations in the development of human prostate carcinoma, nine cases of histologically heterogeneous prostate tumors obtained from total prostatectomies were probed for these specific events. Each tumor was divided into 5 to 10 areas according to different growth or histological patterns. Targeted DNA sequences coding for ras and p53 were amplified by the polymerase chain reaction, analyzed by single-strand conformational polymorphisms, and confirmed by direct DNA sequencing. Point mutations of the ras gene were found in three of the nine tumors. Two contained K-ras codon 13 and H-ras codon 61 mutations, found in only one and three areas of each lesion, respectively. The third tumor contained two different point mutations in K-ras codons 13 and 61 in different foci of the sample. Loss of heterozygosity at the polymorphic codon 72 in the p53 gene was detected in two of four informative cases (50%) showing fragment cleavage by restriction fragment length polymorphism analysis. Mutations in p53, missense transversions, single base insertions, and two base deletions were also detected in three tumors. The present results reveal mutated ras and p53 occasionally occurring in small foci of the tumor and that genetic mutations in p53, as opposed to those in ras, are more closely associated with invasive growth of heterogeneous prostate carcinoma.

Carcinoma↗
PubMed1995

[Brain MRI and single photon emission computed tomography in severe athetotic cerebral palsy: a comparative study with mental and motor disorders].

Single photon emission computed tomography (SPECT) using N-isopropyl-p-[123I]-iodoamphetamine(123I-IMP) was performed in twelve patients with severe athetotic cerebral palsy (Ath; 5 males and 7 females) who had both motor delay (unable to move) and mental retardation (I.Q, or D.Q, below 30). The neuroimaging findings of those patients were compared with those of patients mental and motor disorders. In five cases suffering from neonatal asphyxia, SPECT demonstrated a decreased regional cerebral blood flow (rCBF) in corpus striatum, thalamus, orbitofrontal areas, pericentral gyrus areas, prefrontal areas and medial temporal areas. In seven cases suffering from neonatal jaundice, SPECT demonstrated a decreased rCBF in orbito-frontal areas, prefrontal areas and medial temporal areas. SPECT showed hypoperfusion of peri-central gyrus areas in cases with complications of spastic palsy. The decreased rCBF in medial temporal areas mostly corresponded to an alteration in hippocampal formation as assessed by magnetic resonance imaging (MRI). Cases with hypoperfusion of bilateral medial temporal areas showed a lower score of language understanding than those with the unilateral damage. In cases with hypofusion of bilateral prefrontal areas and bilateral medial temporal areas, the grade of understanding of language was almost below 12 months. In cases with hypoperfusion of orbitofrontal areas, psychomotor hypersensitivity had been observed. Those results suggest that IMP-SPECT and MRI of the brain is useful tool for neurological assessment in handicapped patients with athetotic cerebral palsy.

Adolescent↗
PubMed1995

[The role of thoracotomy for malignant mediastinal tumors (MMT)-- survey of consecutive 223 patients].

To elucidate the role of surgery for MMT, 214 patients during past 34 years were historically divided into the early (1960-1971, n = 80), intermediate (1972-1981, n = 79) and late series (1982-1993, n = 64). The thoracotomy rate for MMT, the rate of thoracotomy after preoperative diagnosis was done, and the number of postoperative survivors were significantly higher in the late series, compared with the early series. The intermediate series located between the early and late series. Nine patients in the late series undergoing chemo-radiation therapies obtained a good result after complete resection of the residual tissue. We conclude that surgical treatment of MMT should be based on accurate preoperative diagnosis and a distinct role for multidisciplinary treatment, especially regarding malignant thymoma, malignant lymphoma and malignant germ cell tumor.

Adolescent↗
PubMed1995

Posterior sub-Tenon injections of repository corticosteroids in uveitis patients with cystoid macular edema.

Repository corticosteroid was injected into the posterior sub-Tenon space in 29 cases (39 eyes) of cystoid macular edema (CME) secondary to uveitis. There were 12 cases of Behçet's disease, 7 cases of sarcoidosis, one case of tuberculous uveitis, and 9 cases of etiology unknown uveitis. In some of the patients injections were repeated 2 to 7 times at intervals of more than 2 weeks. Twenty-two of the 39 treated eyes (56.4%) showed visual improvement in at least two lines of visual acuity. Fifteen of the 22 eyes had maintained improved visual acuity over 6 months. Eleven eyes showed no improvement in vision. Most of them already had poor visual acuity (0.2 or less) before the injections. Complications of the treatment included cataract in 6 eyes, glaucoma in one, and blepharoptosis in one. Injection of repository corticosteroids into the posterior sub-Tenon space is of value in the treatment of CME secondary to uveitis. However, we have to beware of the complications of treatment.

Adolescent↗
PubMed1995

[Comparison of granisetron alone and granisetron plus dexamethasone or hydroxyzine hydrochloride for the prevention of nausea and vomiting during chemotherapy including cisplatin].

The comparative study among granisetron alone and granisetron combined with hydroxyzine hydrochloride or dexamethasone was undertaken for the prevention of nausea and vomiting during chemotherapy including cisplatin in patients with advanced head and neck carcinomas. The results indicated that the combination antiemetic therapies were more effective than granisetron alone for acute nausea and vomiting, whereas a significant difference was not observed among these three groups in the acute adverse effects. Otherwhile, there were statistically significant improvements in the prevention of delayed nausea and vomiting for patients receiving granisetron combined with the other antiemetic drugs, especially the combination antiemetic therapy with dexamethasone. These results confirm the antiemetic activity of granisetron in acute nausea and vomiting induced by cisplatin and show that it has an additive effect in combination with dexamethasone.

Adult↗
PubMed1995

[Slowly progressive memory impairment without generalized dementia--a clinical and radiological study].

We report a patient with a ten-year history of slowly progressive recent memory decline without additional cognitive impairment in presenility. A right-handed Japanese barber first experienced forgetfulness at the age of 59. Neurological examination at age 64 revealed no abnormality except for severe impairment in memorizing. Brain CT-scans were normal. In spite of gradually deteriorating memory, he was capable of organizing his work until the age of 67 years. At age 69, he showed intense recent memory defect and disorientation in time, but immediate memory span and remote memory beyond the retrograde gap were better preserved. Intelligence quotient (IQ) on the Wechsler adult intelligence scale-R remained 85 (verbal IQ, 88: performance IQ, 83). Neurological examination was negative. He showed no signs of aphasia, agnosia, or apraxia. Minimal organic personality changes were noticed. Brain CT-scans and MRI revealed mild atrophy of the temporal lobes and hippocampal formation on both sides. I123-IMP single photon emission computed tomography (SPECT) disclosed a decrease of cerebral blood flow in both the inferior temporal and superior frontal regions. SPECT after acetazolamide administration showed augmented accumulation in areas with decreased accumulation at baseline. Despite progressive memory impairment, the absence of aphasia, agnosia, or apraxia differentiates our case from more common Alzheimer's disease. A degenerative disorder of focal cerebral atrophy or "simple senile dementia" of presenile onset was suspected of causing the underlying pathophysiological changes.

Aged↗
PubMed1995

Mechanisms of eosinophilia in mice infested with larval Haemaphysalis longicornis ticks.

Infestation of larval Haemaphysalis longicornis ticks induced a threefold increase of eosinophils in the peripheral blood of normal WBB6F1- +/+ mice 2 days after tick infestation. In genetically mast cell-deficient WBB6F1- W/Wv mice, a threefold increase of blood eosinophils was observed 6 days after the tick infestation. However, marked infiltration of eosinophils was detected in the tick infestation sites of the WBB6F1- +/+ mice but not the WBB6F1- W/Wv mice. When the mast cell deficiency of WBB6F1- W/Wv mice had been rescued locally by intradermal injections of WBB6F1- +/+ mouse-derived cultured mast cells, a rapid increase of blood eosinophils and tissue infiltration of eosinophils were revealed following tick infestation. The intravenous (i.v.) injection of immune spleen or lymph node cells obtained from WBB6F1- +/+ mice 10 days after tick infestation led to significant eosinophilia in naive recipient mice. Treatment with anti-Thy-1.2 or anti-CD4 monoclonal antibody (mAb) and complement (C) completely abolished the eosinophilia; the early response (2 days after tick challenge) is dependent on mast cells at the feeding site, and the late response (6 days after tick challenge) is dependent on T lymphocytes. Since amplified interleukin-5 (IL-5) cDNA was detectable in the spleen cells 4 days after tick infestation, the late response might be mediated by IL-5. The infiltration of eosinophils at the feeding site of skin appeared to be dependent on mast cells.

Animals↗
PubMed1995

[MHC and non-MHC gene effects on the development of experimental autoimmune uveoretinitis].

Experimental autoimmune uveoretinitis (EAU) can be induced in rats by interphotoreceptor retinoid-binding protein (IRBP), and served as a model for human uveitis. Using IRBP-derived peptide R16, we investigated the MHC and non-MHC genes' effect on the regulation and susceptibility to EAU. EAU-high susceptible LEW (RT1l), EAU-low susceptible WKAH (RT1k), and WKAH.1L rats which carry RT1l and WKAH background were immunized with 2 nmol of R16. One hundred percent of LEW rats developed EAU and 92.9% of WKAH. 1L rats. Only, 18.8% of WKAH rats developed EAU. Among these strains tested, the severity of EAU was 2.06 in LEW, 1.23 in WKAH.1L, and 0.38 in WKAH. R16 evoked substantial proliferative responses in all these strains. The present data suggest that both MHC and non-MHC genes play distinct roles in development of EAU.

Animals↗
PubMed1995

Pharmacodynamics of 15(S)-hydroperoxyeicosatetraenoic (15-HPETE) and 15(S)-hydroxyeicosatetraenoic acid (15-HETE) in isolated arteries from guinea pig, rabbit, rat and human.

The vasoactive properties of 15(S)-hydroperoxyeicosatetraenoic acid (15-HPETE) and 15(S)-hydroxyeicosatetraenoic acid (15-HETE) were characterized in aortic rings of guinea pig (GPA), rat (RA) and rabbit (RbA), as well as pulmonary arteries from guinea pigs (GPPA) and humans (HPA). Four distinct patterns of activity were identified: 1) Cyclooxygenase-dependent relaxation (in GPA, GPPA and HPA). This could be speculated to be due to release of prostaglandin I2 or to conversion of 15-H(P)ETE to another vasorelaxant eicosanoid(s). The endothelium was the main source of this activity in GPA but not in HPA. 2) Cyclooxygenase-independent relaxation mediated by both endothelium and the smooth muscle proper (only in RA). 3) Endothelium-dependent contraction associated with the release of unknown factor(s) (in GPA, GPPA and HPA). 4) Endothelium-independent contraction (in RbA). Nitric oxide was not involved in the relaxation of GPA and RA, nor was endothelin in the contraction of GPA. 15-HPETE and 15-HETE always elicited analogous responses in the same preparations, probably because of rapid metabolism of 15-HPETE into 15-HETE or, even more likely, because both eicosanoids have identical modes of action. We concluded that depending on factors such as the species, the dose of the compounds and the presence of other vasoregulators, the overall response to 15-HPETE or 15-HETE may be vasodilation or vasoconstriction. In addition, the type of responses elicited with 15-HPETE and 15-HETE in RbA and RA differed conspicuously from those expressed in GPA, GPPA and HPA.

Animals↗
PubMed1995

C-fos gene expression in rat retinal cells after focal retinal injury.

PURPOSE: To examine the expression of c-fos proto-oncogene in the rat retina after focal retinal injury. METHODS: A penetrating wound was made by pushing a 22-gauge hypodermic needle through the retina into the vitreous. The retinas were analyzed by in situ hybridization using single-stranded RNA probes for c-fos transcripts and by immunocytochemistry using anti-S100 protein antibody. RESULTS: Thirty minutes after the penetrating wound, c-fos mRNA was expressed in the inner nuclear layer (INL) and the ganglion cell layer (GCL) of the retina. Immunocytochemistry before in situ hybridization demonstrated c-fos mRNA surrounding the S-100 protein immunoreactive cytoplasm in the middle layer of the INL. CONCLUSIONS: Focal retinal injury of the rat retina induced the expression of c-fos mRNA in retinal cells. In the INL, it is suggested that the major cells that express c-fos mRNA after focal retinal injury were the Müller cells. These results suggest that c-fos may be involved in the transcription in the Müller cells after injury to the retina.

Animals↗
PubMed1995

Brain SPECT imaging for laminar heterotopia.

Brain perfusion SPECT was performed in an epileptic patient with a rare form of diffuse subcortical laminar heterotopia using 99mTc-HMPAO. MRI demonstrated generalized laminar heterotopia underlying the cortical mantle. Interictal SPECT imaging revealed identical or increased perfusion of the laminar heterotopia as compared with that of the overlying cortical mantle. Moreover, SPECT revealed low perfusion in the left temporal lobe that agreed with the seizure type of complex partial seizures and the EEG finding of frequent generalized spike-wave complexes with a slight left-sided dominance. Brain SPECT imaging may be useful for appropriate diagnosis of gray matter heterotopia and for detection of functionally focal abnormality associated with epilepsy.

Adult↗
PubMed1995

[A case of acute idiopathic pandysautonomia with SIADH].

We reported a 6-year-old girl with acute idiopathic pandysautonomia (AIPD) associated with syndrome of inappropriate secretion of anti-diuretic hormone (SIADH). She showed various symptoms indicating the impairment of widespread sympathetic and parasympathetic nervous functions and SIADH, which followed common cold. Sural nerve biopsy showed severe reduction of both myelinated and unmyelinated fibers. The main site of the lesion of AIPD has been assumed to be the peripheral autonomic nervous system. However, there are a few reports indicating the involvement of the central nervous system in AIPD. The present case also indicates the involvement of hypothalamus in addition to the peripheral autonomic nervous system.

Acute Disease↗