Biomedical subjects

M Fujimoto

Publications and source records attributed to M Fujimoto.

At least 127 records · Page 7Linked to original sources

PubMed1999

An adult case of recurrent arteriovenous malformation after "complete" surgical excision: a case report.

BACKGROUND: Complete surgical excision of arteriovenous malformations (AVM) documented by postoperative angiography is considered a cure. However, recent reports have shown that AVMs in children may recur after negative postoperative angiograms, and some suggest that it may reflect the immaturity of their cerebrovasculature. This case report demonstrates that AVM in adults may also recur, despite postoperative angiograms confirming complete removal. CASE DESCRIPTION: This 28-year-old man presented in 1994 with a focal motor seizure and was found to have an AVM in the right frontal lobe. He underwent surgical excision of the AVM; postoperative angiograms taken immediately after surgery and 15 days later showed no residual AVM. He remained free of symptoms after surgery and it was considered that a complete removal had been achieved. In 1998 he developed a subarachnoid hemorrhage, and subsequent angiograms revealed a small AVM in an adjacent location. CONCLUSION: This is the oldest patient reported in the literature with a recurrence of AVM, despite postoperative angiograms confirming complete removal. Angiographically invisible immature vessels, which might have been left in the surgical field, might have formed a new malformation later. We still believe that such recurrence must be very rare after AVM surgery, but we now recommend follow-up angiography at yearly intervals to our patients.

Adult↗

PubMed1999

Negative regulation of cytokine signaling: STAT-induced STAT inhibitor.

The growth and differentiation of cells that make up multicellular entities such as the blood and immune systems are under the control of glycoprotein mediators known as cytokines. These cytokines bind to membrane receptors on the cell surface and initiate a signaling cascade that ends with the transcription of specific sets of genes within the cell nucleus. Although knowledge is accumulating concerning the intracellular signal pathways that are activated by cytokines, little is known about inhibition of cytokine signals. This review will focus on the negative regulation of the Janus tyrosine kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway by proteins related to STAT-induced STAT inhibitor-1 (SSI-1).

Animals↗

PubMed1999

1,3-Disubstituted benzazepines as neuropeptide Y Y1 receptor antagonists.

A novel class of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Through a blind screening we found the compound 1-N-(3-(N'-(tert-butoxycarbonyl)amino)benzyl)-7-methoxy-(3-(3)-methyl ureido)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (9: IC50 = 1.6 microM). Chemical modifications of 9 gave a potent NPY Y1 antagonist 3-(N-(4-hydroxyphenyl)-N'-methylguanidino)-1-N-(3-(N'-(tert-butoxy carbonyl)amino)benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (14c: IC5(0=43 nM), which had no affinity for NPY Y2 and Y5 receptors.

Benzazepines↗

PubMed1999

Modulation of B lymphocyte antigen receptor signal transduction by a CD19/CD22 regulatory loop.

CD19 and CD22 are B lymphocyte cell-surface molecules that positively and negatively regulate antigen receptor signal transduction, respectively. Biochemical studies with B cells from CD19-deficient and CD22-deficient mice indicated that these two regulatory molecules influenced each other's functions: CD22 expression negatively regulated CD19 tyrosine phosphorylation, while optimal CD22 function was dependent on CD19 expression. Functional CD19 and CD22 interactions were also assessed in vivo by generating CD19/CD22 double-deficient mice. Remarkably, the CD19 mutation was dominant to the CD22 mutation in most instances. B lymphocytes from CD19/CD22-deficient and CD19-deficient mice were functionally equivalent despite the negative influence normally provided by CD22 expression. These data collectively suggest that CD19 activates the CD22/SHP1 inhibitory pathway that then acts primarily on CD19.

Animals↗

PubMed1999

Distribution and antigen specificity of anti-U1RNP antibodies in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a generalized connective tissue disease which is characterized by the presence of several autoantibodies. To determine the prevalence and antigen specificity of anti-U1RNP antibodies (anti-U1RNP) in patients with SSc, serum samples from 223 patients with SSc, 117 patients with systemic lupus erythematosus (SLE), 18 patients with mixed connective tissue disease (MCTD) and 40 healthy control subjects were examined by indirect immunofluorescent analysis (IIF), double immunodiffusion, and immunoblotting using nuclear extract of HeLa cells. Eighteen of the 223 (8%) serum samples from patients with SSc were shown to be positive for anti-U1RNP. The frequency of anti-U1RNP positivity in limited cutaneous SSc (14%) was significantly higher than that in those with diffuse cutaneous SSc (3%). Anti-Sm antibodies were detected in patients with SLE positive for anti-U1RNP, but not in those with SSc positive for anti-U1RNP or those with MCTD. Immunoblotting demonstrated that anti-70-kD antibodies were detected more often in patients with SSc positive for anti-U1RNP and in those with MCTD than in those with SLE. Furthermore, anti-U1RNP was closely correlated with pulmonary fibrosis and joint involvement in patients with SSc. These results suggest that anti-70-kD antibodies are useful in the classification of patients with anti-U1RNP.

Antibodies, Antinuclear↗

PubMed1999

Serum levels of thyroid-stimulating hormone receptor antibodies during IFN-alpha2a treatment of chronic hepatitis C.

Twenty chronic hepatitis C patients with baseline levels of thyroid hormones, antithyroglobulin, and antimicrosomal antibodies within the normal range were monitored by thyroid testing during a 26-week treatment with interferon-alpha2a (IFN-alpha2a). The present study was aimed at retrospectively analyzing thyroid-stimulating hormone (TSH) receptor antibodies, employing stored serum samples obtained from these patients at baseline, at 12 weeks, and at the end of IFN-alpha2a treatment. Ten patients (group A) received IFN-alpha2a at a total dose of 474 million units (MU), and 10 patients (group B) at a total dose of 774 MU. None of the patients produced antithyroglobulin and antimicrosomal antibodies. Two patients in group A exhibited elevated TSH levels without free thyroid hormone alterations while on the treatment. At baseline, 1 patient in group A had a positive TSH binding inhibitory immunoglobulin, and 1 patient in group B was positive for thyroid-stimulating antibody at the end of treatment. Both patients remained euthyroid throughout the treatment. Treatment with IFN-alpha2a may infrequently induce the production of TSH receptor antibodies in chronic hepatitis C patients provided preexisting autoimmune thyroid disease is precluded.

Adult↗

PubMed1999

Pharmacological characterization of PABSA, an orally active and highly potent endothelin-receptor antagonist.

The pharmacological characterization of a nonpeptide endothelin (ET)-receptor antagonist, PABSA [(R)-(--)-2-(benzo[1,3]dioxol-5-yl)-N-(4-isopropyl-phenylsulfon yl)-2-(6-methyl-2-propylpyridin-3-yloxy)-acetamide hydrochloride] was studied. PABSA competitively inhibited the binding of [125I]-ET-1 to A7r5 cells expressing ET(A) receptors and of [125I]-ET-3 to COS cells expressing porcine ET(B) receptors with Ki values of 0.11 and 25 nM, respectively. PABSA inhibited ET(A) receptor-mediated and ET(B) receptor-mediated vasocontraction and ET(B) receptor-mediated vasorelaxation in isolated rabbit vessels with K(b) values of 0.46, 94, and 26 nM, respectively. The antagonist potency of PABSA for ET(A) receptor-mediated vasocontraction was 63- and 87-fold more potent than those of BQ-123 and bosentan, respectively, and was similar to those of TAK-044 and SB209670. Oral administration of PABSA (1-10 mg/kg) caused dose-dependent inhibition of the pressor response to exogenous ET- 1 (0.1 nmol/kg) in conscious normotensive rats. PABSA (10-100 mg/kg, p.o.) reduced blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, spontaneously hypertensive rats (SHRs), and stroke-prone spontaneously hypertensive rats (SHRSPs). The hypotensive effect of PABSA was sustained for > or =24 h in these rats. These results suggest that PABSA is a highly potent ET(A)-receptor antagonist with weak ET(B)-receptor antagonist activity. Because PABSA has a long duration of action in vivo, this antagonist should be useful in the therapy of ET-related disease.

Administration, Oral↗

PubMed1999

Post-stroke treatment with imidapril reduces learning deficits with less formation of brain oedema in a stroke-prone substrain of spontaneously hypertensive rats.

The present study was undertaken to examine the effects of the ACE (angiotensin converting enzyme) inhibitor imidapril, on the brain, when administered after the onset of stroke in a stroke-prone substrain of spontaneously hypertensive rats (SHRSP). Learning deficits and induced lesions in the brain as well as in the kidneys and heart were investigated in detail. SHRSP were divided into two groups with or without salt loading at the age of 4 weeks. The salt loading was performed for 7-9 weeks to increase the incidence of stroke. Within 24 h after the first observation of stroke, animals were subsequently treated with 5 mg/kg imidapril orally once a day or the vehicle for up to the age of 27 weeks. Imidapril attenuated progression of neurological abnormalities such as irritability, hyperkinesia and motor dysfunction, and increased survival rate. In three-panel runway testing, learning deficits did not develop significantly in the imidapril-treated group, and was comparable to that in the non-salt-loaded/non-stroke group. Imidapril reduced oedema formation in the cortex, hippocampus and striatum, and also suppressed lesion formation in the kidneys and heart. Imidapril thus suppressed progression of neurological deficits with loss of learning ability following onset of stroke, and also suppressed formation of oedema in the brain and decreased the number of lesions in other organs. Imidapril-induced reduction of cerebrovascular damage, which presumably occurs in the brain after stroke, may account for the inhibitory effects of imidapril on lesion formation and learning impairment.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Prognostic factors in severe alcoholic liver injury. Nara Liver Study Group.

Severe alcoholic liver injury has been relatively rare, but is gradually increasing in Japan. The clinical features and prognostic factors in severe alcoholic liver injury were retrospectively investigated in 105 patients, consisting of 3 with severe alcoholic hepatitis (SAH), 43 with cirrhosis with superimposed alcoholic hepatitis [liver cirrhosis (LC)+alcoholic hepatitis (AH)], 38 with AH, and 21 with alcoholic cirrhosis. Seven of the 105 patients (6.7%, 2 with SAH and 5 with LC+AH) died of hepatic failure. Patients with SAH showed severe hyperbilirubinemia, reduced hepatic biosynthetic capacity, and marked acute inflammatory reactions, and developed multiple organ failure, such as disseminated intravascular coagulation (DIC), renal failure, acute pancreatitis, or pneumonia. Two SAH patients died within 1 month, whereas five with LC+AH died within 77 days during the second episode of AH. In these nonsurvivors, the serum total bilirubin (T.Bil) level was not normalized, and the hepaplastin test (HPT), serum albumin, cholesterol, and platelet count were not markedly improved after the first episode of AH. In the survivors, elevation of AST lasted longer, and the improvement of T.Bil, hepatic biosynthetic capacity, and the platelet count were much less in patients with LC+AH than in those with AH. Multivariate analysis using the Cox proportional hazards model showed serum C-reactive protein (CRP) and DIC as significant independent prognostic factors among SAH, LC+AH, and AH groups. When factors related to multiple organ failure, such as DIC and renal failure, were excluded, T.Bil and CRP were selected as independent prognostic factors. In patients with LC+AH and AH, CRP, and HPT were shown to be significant independent prognostic factors. These results suggest that SAH with multiple organ failure, and another episode of AH in advanced LC with hyperbilirubinemia and reduced hepatic biosynthetic capacity, are indicative of an extremely poor prognosis in chronic alcoholics.

Adult↗

PubMed1999

beta-Adrenergic receptor subtypes in melanophores of the marine gobies Tridentiger trigonocephalus and Chasmichthys gulosus.

The subtype of beta-adrenergic receptors in melanophores of the marine gobies Tridentiger trigonocephalus and Chasmichthys gulosus was studied. Pigment of denervated melanophores in isolated, split caudal fins was preliminarily aggregated by incubating the specimens in a physiological saline containing 10 microM phentolamine and 30-100 microM verapamil or 2-10 nM melatonin, and the responses of the melanophores to a beta-adrenergic agonist added to the incubating medium were recorded photoelectrically. The beta-adrenergic agonists noradrenaline, adrenaline, isoproterenol, salbutamol and, dobutamine were all effective in evoking a dispersion of melanophore pigment in the presence of phentolamine and verapamil or melatonin. The pigment-dispersing effect of noradrenaline (beta 1-selective agonist) was inhibited by metoprolol (beta 1-selective antagonist), propranolol,- and butoxamine. Whereas, the effect of salbutamol (beta 2-selective agonist) was hardly inhibited by metoprolol, though it was considerably inhibited by propranolol and ICI-118551. It was estimated that beta 1- and beta 2-adrenergic receptors coexist at ratios of 8.6:91.4, in the melanophore of Tridentiger trigonocephalus, and 25:75, in the melanophore of Chasmichthys gulosus, through the analyses of Hofstee plots of the effects of the beta-adrenergic drugs. It was suggested that the relation between the pigment-dispersing effect of a beta-adrenergic agonist on the melanophores and the concentration of the drug follows mass action kinetics, when the effect is mainly caused by the activation of beta 2-adrenergic receptors of the melanophores. However, when it is mainly caused by the activation of beta 1-adrenergic receptors of the melanophores, the relation does not follow mass action kinetics.

Adrenergic alpha-Agonists↗

PubMed1999

[Report of questionnaire survey for methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae in the Kinki District].

In the Kinki District (Hyogo area, Osaka City area, Osaka Outskirts area, Nara area and Wakayama area), a questionnaire survey of 30 institutions was conducted for methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). Median number of their bed was 500 ranging 0 to 1076, 3239 (56%) of the 5815 strains of S. aureus were methicillin-resistant. Although no different prevalence was found among the areas, they were predominantly isolated from sputum of inpatients more than from outpatients, 336 (44%) of the 763 strains of S. pneumoniae were penicillin-resistant. The prevalence rate was the highest in the outpatients in Osaka outskirts. Almost all strains of MRSA were sensitive to vancomycin (VCM) and sulfamethoxazole trimethoprim (ST). Resistant strains were observed in 2% against arbekacin, 6% against amikacin, 44% against minocycline (MINO), and in 54% against gentamicin (GM). Almost all strains of PRSP were sensitive to VCM and ST. Resistant strains were observed in 75% against erythromycin, 50% against MINO, and 75% against GM. This survey identified the trend of hospital infection for MRSA and community infection for PRSP, and sensitive drugs for the treatment.

Cross Infection↗

PubMed1999

Skeletal features and growth patterns in 14 patients with haploinsufficiency of SHOX: implications for the development of Turner syndrome.

We report on clinical features in 14 Japanese patients (4 males and 10 females) with partial monosomy of the short arm pseudoautosomal region involving SHOX (n = 11) or total monosomy of the pseudoautosomal region with no involvement of disease genes on the sex-differential regions (n = 3). Skeletal assessment showed that three patients had no discernible skeletal abnormalities, one patient exhibited short 4th metacarpals and borderline cubitus valgus, and the remaining 10 patients had Madelung deformity and/or mesomelia characteristic of Léri-Weill dyschondrosteosis (LWD), together with short 4th metacarpals and/or cubitus valgus. Skeletal lesions were more severe in females and became obvious with age. Growth evaluation revealed that patients without LWD grew along by the -2 SD growth curve before puberty and showed a normal or exaggerated pubertal growth spurt, whereas those with LWD grew along by the standard growth curves before puberty but exhibited an attenuated pubertal growth spurt and resultant short stature. Maturational assessment indicated a tendency of relatively early maturation in patients with LWD. There was no correlation between the clinical phenotype and the deletion size. These findings suggest that haploinsufficiency of SHOX causes not only short stature but also Turner skeletal anomalies (such as short 4th metacarpals, cubitus valgus, and LWD) and that growth pattern is primarily dependent on the presence or absence of LWD. Because skeletal lesions have occurred in a female-dominant and age-influenced fashion, it is inferred that estrogens exert a maturational effect on skeletal tissues that are susceptible to premature fusion of growth plates because of haploinsufficiency of SHOX, facilitating the development of skeletal lesions.

Adolescent↗

PubMed1999

Synthesis and structure-activity relationship of a new series of potent angiotensin II receptor antagonists: pyrazolo[1,5-a]pyrimidine derivatives.

We have already reported 7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid derivatives, which are potent in vitro angiotensin II (AII) antagonists, but have no oral antihypertensive activity. Removal of the carboxylic acid and replacement of the heteroaromatic system afforded potent in vitro antagonists. Removal of the carbonyl oxygen and changing the position of the biphenyltetrazole substituent were critical to the display of oral activity. To improve the in vitro and oral activities, modifications were made of the substituents at the 3- and 5-positions of the pyrazolo[1,5-a]pyrimidine. Structure-activity studies showed the methyl substituent at the 3-position to be essential for potent in vivo activity. We present the design, syntheses, and biological data of a series of pyrazolo[1,5-a]pyrimidine derivatives, which are orally active AII receptor antagonists.

Angiotensin II↗

PubMed1999

Association between plasma homocysteine concentration and carotid atherosclerosis in hemodialysis patients.

Accelerated atherosclerosis is a major risk for uremic patients undergoing long-term hemodialysis. Because hyperhomocysteinemia may influence this condition, 168 such patients were examined for a possible association between plasma total homocysteine concentration (tHcy) and conventional cardiovascular risk factors. Generalized atherosclerosis was indicated by excessive intimal-medial wall thickness (IMT) of the extracranial carotid artery as measured by B-mode ultrasonography. The results documented tHcy in these patients of 33.0+/-16.9 micromol/L, a significantly higher amount than that of healthy subjects (11.0+/-3.1 micromol/L, p<0.0001). The patients' carotid maximum IMT was 1.79+/-1.16 mm. In multiple regression analyses with forward elimination procedure, carotid maximum IMT was clearly related to age (r = 0.417, p<0.0001), systolic blood pressure (r = 0.262, p = 0.0043), smoking (r = 0.177, p = 0.0076), duration of hemodialysis (r = 0.083, p = 0.0045), and tHcy (r = 0.195, p = 0.0021). These 5 factors accounted for 36.0% of the variation in carotid maximum IMT. Factors determined as unrelated were male gender, diastolic blood pressure, body mass index, total and HDL cholesterol, triglyceride, lipoprotein(a), uric acid, calcium, inorganic phosphate, and parathyroid hormone. Therefore hyperhomocysteinemia, along with advanced age, systolic hypertension and smoking aggravates atherosclerosis in chronic uremic patients.

Age Factors↗

PubMed1999

[Treatment of azoospermic patient with genitourinary tuberculosis: a case report].

A case of azoospermia due to genitourinary tuberculosis is reported with discussion on the treatment of infertility in such a case. A 38-year-old man visited us complaining of 4-year sterility. We suspected obstructive azoospermia due to previous genitourinary tuberculosis because of his treatment history, calcifications in the seminal vesicles and nodules in the right epididymis. After microsurgical epididymal sperm aspiration (MESA) was performed twice without success, we extracted sperm from his testis (testicular sperm extraction, TESE) and fertilized his wife's egg by intracytoplasmic sperm injection.

Adult↗

PubMed1999

[A case of arteriovenous fistula of the lung].

A 29-year-old male was admitted to our hospital for further evaluation of left sided paresis, cyanosis, clubbing finger. The laboratory data revealed polycythemia and hypoxemia. Cerebralarteriogram showed right middle cerebral artery occulusion. Cardiofunctional test showed atrial fibrillation, lower left ventricular function. Cardiac catheterization, pulmonary arteriography and three dimensions CT were performed. Right to left shunt rate was 20.4%. A single large pulmonary arteriovenous fistura with a feeding artery (A10) and a draining vein (V10) was found clearly. In this cases, arteriovenous fistula was large, blood flow was thought to be rapid. We thought transcatheter embolization was not useful. And we performed right lower lobectomy. Postoperative course was not eventful. Cyanosis disappeared, clubbing finger was cured.

Adult↗

PubMed1999

Significance of head-shaking nystagmus in the evaluation of the dizzy patient.

In a series of studies, the phenomenon of head-shaking nystagmus (HSN) was assessed in 50 control subjects and 1364 consecutive dizzy patients who underwent formal electronystagmography (ENG) at the Toronto Hospital Center for Advanced Hearing and Balance Testing. HSN was compared in a series of 30 patients who underwent conventional electro-oculography (EOG) vs magnetic (scleral) coil eye movement recordings. Clinical correlation of HSN to other parameters of the ENG test battery was performed in another sub-series of 300 patients with known diagnoses. HSN was identified in 31.7% of dizzy patients vs 24% of control subjects. No significant difference in its manifestation was noted between active vs passive head-shaking tests or on EOG vs magnetic (scleral) coil eye movement recordings. When compared to other aspects of the ENG test battery, HSN was neither specific nor sensitive for vestibular dysfunction. It nevertheless correlated well with the presence of a caloric reduction and with increasing R/L excitability differences on ENG testing. When present, HSN was characteristically monophasic in 76.8%, biphasic in 22.7% and triphasic in 0.5% of subjects. The initial direction of HSN generally obeyed Ewald's second law, but the reverse was noted in 27% with monophasic and 17.6% of patients with biphasic HSN. In the subseries of 300 patients with known diagnoses, the presence of HSN was statistically significant (p < 0.05) in patients with peripheral vestibular dysfunction vs psychogenic dizziness. Its presence was also significant in well-documented peripheral vestibular disorders such as Meniere's disease (p < 0.01), vestibular neuronitis (p < 0.05) and acoustic neuroma (p < 0.05). Localization of the disease involvement based on the initial direction of HSN was especially unpredictable in patients with Meniere's disease. The significance and usefulness of the head-shake test in the otoneurological evaluation of the dizzy patient is further commented on.

Dizziness↗

PubMed1999

Volume quantification of healthy paranasal cavity by three-dimensional CT imaging.

The volume of the air cavities in the paranasal sinuses is, even at present, not only the simplest but also the most important index employed in the evaluation of the paranasal sinus. We have measured the size of the paranasal cavities in 20 healthy Japanese subjects by reconstructing three-dimensional (3-D) computed tomography (CT) images. To avoid any bias in determining the cavity margin, we first measured bilateral maxillary sinuses of a macaque both by silicone injection and by 3-D reconstruction. Then the CT value for 3-D reconstruction was determined by comparison with the volume measured by direct injection. Each sinus of the healthy volunteers was then measured by 3-D reconstruction imaging. Paranasal sinuses were, individually and on the whole, apparently larger than previously reported: 90.1 ml in males and 72.5 ml in females, on average. Comparing with other body size indices, the increment of the size was quite apparent and the lower prevalence of sinusitis was assumed to play a role in this increased volume of paranasal sinuses in the modern Japanese population.

Adult↗