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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 307 records · Page 17Linked to original sources
PubMed1996

Role of endothelin as a mitogen in experimental glomerulonephritis in rats.

Recent studies have revealed that endothelin-1 (ET-1) is a potent mitogen for mesangial cells in vitro. To determine whether ET-1 exerts the mitogenic action on mesangial cells in vivo, we examined the glomerular expression of ET-1 and its receptors in a rat model of mesangial proliferative glomerulonephritis and assessed the effect of a specific endothelin A (ET(A)) receptor antagonist, FR139317, on mesangial cell proliferation in this model. The levels of preproET-1 mRNA expression and ET-1 protein production in glomeruli increased markedly on days 4 and 7 after disease induction, and the levels changed in concordance with the glomerular cell proliferation. In contrast, the level of ET(A) receptor mRNA initially decreased on day 1, and thereafter increased on days 4 and 7. Administration of FR139317 to rats with experimental glomerulonephritis induced a significant reduction in mesangial cell proliferation. In addition, in situ hybridization of preproET-1 mRNA and double-immunolabeling of ED-1 and OX-7 in a mirror image section revealed that the principal cell expressing ET-1 in glomeruli were infiltrating macrophages on day 1, and they were replaced by mesangial cells on day 4. These findings indicate that ET-1 functions as a potent mitogen for mesangial cells in vivo in an autocrine or paracrine fashion.

Animals↗
PubMed1996

Immunological and chemical types of reversible hypothyroidism; clinical characteristics and long-term prognosis.

OBJECTIVE: Spontaneous improvement occurs in about one-half of patients with primary hypothyroidism who reside in an iodine-sufficient area of Japan, but the pathogenetic factors related to reversible hypothyroidism are still not fully understood. We therefore investigated the clinical features and prognosis of patients with reversible hypothyroidism with or without iodine excess and antithyroid antibodies. DESIGN: Amelioration of hypothyroidism was diagnosed when the elevated serum TSH concentrations (serum TSH concentration > or = 40 mU/l) decreased by 50% or more during an iodine restriction period of 2-15 weeks without replacement therapy. Reversible hypothyroidism occurred in a post-partum group (n = 20) and a non-post-partum group (n = 91). The latter was then further classified into chemical (n = 28), immunological (n = 20), and mixed (n = 43) groups, according to the presence of iodine excess (serum non-hormonal iodine level > 50 micrograms/l or a history of excess iodine ingestion), antithyroid autoantibody, or both, respectively. MEASUREMENTS: Clinical characteristics and long-term prognosis were compared among the four groups. The rate at which hypothyroidism recovered was expressed as the number of days required for a 50% decrease in the serum TSH concentration. The level of thyroid echogenicity was measured by 10-MHz ultrasonography. RESULTS: In the chemical group, the mean age, male:female ratio, and serum non-hormonal iodine concentrations were all higher than those in the immunological group. The estimated rate at which hypothyroidism recovered was rapid (6.1 +/- 3.1 (mean +/- SD) days), the levels of thyroid echogenicity were near normal, and a histological examination (n = 7) revealed either colloid goitre or a normal thyroid in the chemical group. In the immunological and post-partum groups, the recovery rate was slow (16.8 +/- 9.6 days and 16.2 +/- 5.8 days, respectively). The levels of thyroid echogenicity were markedly reduced but increased after the spontaneous recovery of the thyroid function in both groups. Aspiration cytology suggested lymphocytic infiltration in all patients examined in the immunological (n = 6) and post-partum groups (n = 4). Relapse to overt hypothyroidism was observed more frequently in the immunological (38%) and mixed groups (35%) than in the chemical group (5%). CONCLUSION: Thyroid damage was more severe, recovery slower and the rate of relapse higher in the immunological than in the chemical type of reversible hypothyroidism.

Adult↗
PubMed1996

Reversible primary hypothyroidism with blocking or stimulating type TSH binding inhibitor immunoglobulin following recombinant interferon-alpha therapy in patients with pre-existing thyroid disorders.

OBJECTIVE: Treatment with recombinant interferon-alpha (rIFN-alpha) may induce autoimmunity. We have evaluated the effect of rIFN-alpha on pre-existing thyroid disease with special reference to changes in TSH receptor antibody. DESIGN AND PATIENTS: Five patients, who had a history of autoimmune thyroid disease diagnosed between 2 and 16 years earlier (three patients had Graves' disease while two had Hashimoto's thyroiditis), were treated with rIFN-alpha for chronic hepatitis C. Before, during and after rIFN-alpha therapy, we determined thyroid function, antithyroid antibody, thyroid echogenicity and the surface phenotype of the peripheral and intrathyroidal lymphocytes. RESULTS: Four of the patients developed overt hypothyroidism after 4-7 months of rIFN-alpha therapy, and two of them had a preceding history of low-uptake thyrotoxicosis. Recovery of thyroid function was observed in all four patients. Strongly positive blocking type TSH receptor antibody was detected and an increase in the percentage of CD19 positive cells in the intrathyroidal lymphocytes was also observed in three of the patients even though the goitre size increased in two of them. One of the patients became thyrotoxic later when stimulating type TSH receptor antibody became positive. Another patient suffered from reversible hypothyroidism although stimulating type TSH receptor antibody remained strongly positive throughout the clinical course. CONCLUSIONS: Our data thus indicated a high incidence of an unusual type of reversible hypothyroidism with TSH receptor antibodies in patients with chronic hepatitis C and pre-existing autoimmune thyroid disease after recombinant interferon-alpha therapy through a mechanism involving both the humoral and cellular immune systems.

Adult↗
PubMed1996

Difficulty in differentiating thyrotropin secreting pituitary microadenoma from pituitary-selective thyroid hormone resistance accompanied by pituitary incidentaloma.

A 33-year-old woman with inappropriate secretion of TSH and a 2-mm pituitary microadenoma is described. She had a high serum free T4 concentration (31 pmol/L) with an inappropriately nonsuppressible serum TSH concentration (0.93 mU/L). The alpha/TSH molar ratio was 2.3 and magnetic resonance imaging with gadolinium enhancement identified an area of low signal intensity in the left lateral pituitary gland. However, TSH secretion was not completely autonomous. There was a significant response to exogenous TRH stimulation and suppression by T3 administration. Therefore, it was difficult to rule out a nonfunctioning pituitary adenoma with concomitant pituitary selective thyroid hormone resistance syndrome. A 2-mm microadenoma was excised via transsphenoidal surgery. The tumor cells were immunoreactive to antisera to alpha-subunit and minimally immunoreactive to antisera to TSHbeta. The patient's thyroid function normalized after surgery without medication. Because the adenoma could become large and intractable if the patient was treated inadequately, early diagnosis and treatment are important in patients with TSH secreting adenomas.

Adenoma↗
PubMed1996

Secondary amyloidosis in patients with rheumatoid arthritis: diagnostic and prognostic value of gastroduodenal biopsy.

Upper gastrointestinal endoscopy was performed in patients with rheumatoid arthritis (RA) during the period 1989-1991, and biopsy specimens were obtained from the stomach and from the duodenum for examining amyloid deposits. Among 407 patients, gastrointestinal amyloidosis was confirmed in 54 (13.3%). Twenty-two patients were regarded as having slight amyloid deposits, while 32 patients were categorized as having marked amyloid deposits. The incidence of clinical manifestations suggestive of systemic amyloidosis was more frequent in the marked deposits group than in the slight deposits group (47% vs 14%, P<0.05). Among the patients who died of manifestations associated with amyloidosis, the survival period following endoscopy was shorter in the marked deposits group than in the slight deposits group. These findings suggest that gastroduodenal biopsies may be useful for diagnosing secondary amyloidosis and that the degree of amyloid deposits seems to be correlated with the clinical manifestations of RA.

Amyloid↗
PubMed1996

Jejunal angiodysplasia confirmed by intravascular injection technique in vitro. Report of a case and review of the literature.

Angiodysplasia of the small intestine is a rare but important cause of gastrointestinal bleeding. We present a 64-year-old man with repeated melena in whom the diagnosis of multiple angiodysplasia of the jejunum was suggested by angiography. The affected segment of the small intestine, in which reddish patches were detected by intraoperative endoscopy, was removed. The combined technique of injecting a dye and a water-soluble contrast medium into the resected specimen revealed areas of dilated vessels, which were diagnosed histologically as angiodysplasia. This case suggests that angiodysplasia of the small intestine can be recognized clinically before the operation and that the intravascular injection technique is useful in confirming the diagnosis in the resected specimen in vitro. We describe this case in detail and review other cases of small intestinal angiodysplasia reported in the English literature.

Angiodysplasia↗
PubMed1996

The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation.

Endothelium-dependent relaxations are achieved by a combination of endothelium-derived prostacyclin (PGI2), nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). However, it remains to be fully clarified whether the relative contribution of these three mechanisms to endothelium-dependent relaxations varies as a function of the vessel size. This study was designed to clarify this point. Acetylcholine (ACh)-induced endothelium-dependent relaxations were examined in isolated blood vessels taken from the aorta and the proximal and distal mesenteric arteries of the rat. The contributions of PGI2, NO, and EDHF were evaluated by the inhibitory effects of indomethacin, N omega-nitro-L-arginine methyl ester (L-NAME) in the presence of indomethacin, and KCl in the presence of indomethacin and L-NAME, respectively. The membrane potentials were recorded with microelectrodes. The expression of endothelial No synthase (eNOS) was examined by both immunostaining and immunoblotting. The contribution of PGI2 was negligible in three different-sized blood vessels. The contribution of NO was most prominent in the aorta, whereas that of EDHF was most prominent in the distal mesenteric arteries. The resting membrane potential was significantly deeper and the ACh-induced hyperpolarization was greater in the distal mesenteric arteries than those in the aorta. The expression of eNOS was the highest in the aorta and the lowest in the distal mesenteric arteries. These results indicate that the importance of EDHF increases as the vessel size decreases in endothelium-dependent relaxations in the rat mesenteric circulation.

Acetylcholine↗
PubMed1996

Association between thyroid cancer of cribriform variant and familial adenomatous polyposis.

A case of a 20 year old Japanese woman who developed thyroid cancer exhibiting unusual cribriform structures while being followed up for familial adenomatous polyposis/Gardner's syndrome is reported. The patient presented with osteomas, pigmented retinal lesions, and adenomas of the duodenum and the papilla of Vater, in addition to numerous adenomatous polyps in the colorectum. On ultrasonography, the thyroid cancer was localised to the right lobe and was identified as an irregular, internal echo tumour with a peripheral hypoechoic zone, measuring 1.8 cm in diameter. Histological examination of the resected tumour showed a concomitance of papillary proliferation and cribriform structures with follicles of varying sizes. These features can be distinguished from sporadic thyroid cancer.

Adenocarcinoma↗
PubMed1996

Dysplasia in ulcerative colitis: is radiography adequate for diagnosis?

PURPOSE: To determine to usefulness of barium enema examination in detecting dysplasia in patients with ulcerative colitis. MATERIALS AND METHODS: Radiographic findings of 22 areas of dysplasia in 10 patients (seven men, three women; aged 34-81 years at diagnosis) were reviewed. Serial changes in radiographic features of four areas of dysplasia in three patients were retrospectively investigated. RESULTS: Fourteen of 22 areas of dysplasia were shown on radiographs. Dysplasia in the rectum or sigmoid colon was depicted less frequently than that in other segments of the colon. Radiographic features were classified as obvious nodular protrusions (seven lesions), irregular mucosa (five lesions), or nodular protrusions with irregular mucosa (two lesions). Six of the seven areas of dysplasia shown as irregular mucosa were accompanied by minute spiculations in the margin of the colonic lumen. There was no correlation between radiologic features and histologic grade of dysplasia. CONCLUSION: Barium enema examination may be used as a complementary method of cancer surveillance with endoscopy. These methods show about two-thirds of lesions associated with dysplasia.

Adult↗
PubMed1996

Changes in arterioles, arteries, and local perfusion of the brain stem during hemorrhagic hypertension.

Cerebral arterioles have been regarded as the primary sites of autoregulatory responses, whereas the role of large arteries in the cerebral autoregulation is poorly understood. The goal of this study was to determine in vivo whether the basilar artery and its primary branches act as resistance vessels under hypotensive conditions by simultaneously measuring their diameters and local brain stem blood flow with laser-Doppler flowmetry. In 10 anesthetized rats, blood flow to the brain stem was well maintained during stepwise hemorrhagic hypotension when mean arterial blood pressure fell from 116 +/- 3 to 50 mmHg and decreased gradually between 50 and 30 mmHg. Diameter of the basilar artery (n = 10) and its large branches (n = 22), measured through an open cranial window, increased by 10% from the baseline value at 50 mmHg and reached their maximum at 30 mmHg (314 +/- 9 from 244 +/- 6 mum, and 149 +/- 4 from 117 +/- 3 mum, respectively). Small branches (n = 15) dilated to a larger extent compared with the larger arteries throughout hypotension and reached the maximum at 30 mmHg (69 +/- 3 from 48 +/- 2 mum). Below 30 mmHg, there was a steep fall in blood flow and reduction in diameter of all-sized arteries. Thus small vessels contribute to reductions in cerebrovascular resistance throughout the entire autoregulatory-range in the brain stem circulation. Large arteries, such as the basilar artery and its branches, also contribute to reductions in cerebrovascular resistance around the lower limits of cerebral blood flow autoregulation and may thus play a significant role in maintaining blood flow to the brain stem during severe systemic hypotension.

Animals↗
PubMed1996

Circadian blood pressure in patients in a persistent vegetative state.

We examined circadian variations in blood pressure, pulse rate, and other physiological variables, including hormone levels, in 16 patients in a persistent vegetative state (mean age -/+ SE; 66.1 -+/ 3.9 yr). Cerebrovascular accident was responsible for brain damage in 12 (75%) of the 16 patients. Blood pressure was measured for 24 h with an ambulatory blood pressure monitoring device. We monitored the temperature of the urinary bladder and measured urinary excretion of epinephrine, norepinephrine, 17-hydroxycorticosteroids, water, and sodium. When data were analyzed by analysis of variance, significant circadian changes were observed in body temperature and urinary excretion of hormones and sodium, but not in blood pressure or pulse rate. Individual analysis of rhythmicity using the cosinor method detected small but significant circadian variations in blood pressure and pulse rate in five of six patients who showed a simple organized response to noxious external stimuli. The disappearance of variation in blood pressure in patients in a vegetative state appeared to be related, in part, to the lack of response to external stimuli. Our findings suggest that the circadian variation in blood pressure may largely depend on external environmental factors.

Adult↗
PubMed1996

Effect of endothelin 1 on fibrinolysis and plasminogen activator inhibitor 1 synthesis in rat mesangial cells.

Endothelins (ETs) have been known to have a variety of biological functions such as mitogenic stimulation, natriuresis and the stimulation of the proteolytic activity in addition to vasoconstrictive action, which may participate in the process of glomerular diseases pathophysiologically. In this study, the effects of ET-1 on fibrinolysis, plasminogen activator inhibitor 1 (PAI-1) synthesis and PAI-1 mRNA expression were examined in cultured rat mesangial cells (MCs). The addition of ET-1 (10(-11) to 10(-7) M) into MC cultures reduced fibrinolytic activities assayed by fibrin autography in a dose-dependent manner. For the assay of PAI-1 synthesis, MC culture media metabolically labeled with 35S-methionine were analyzed by SDS-PAGE with fluorography and immuno-precipitation using rabbit antirat PAI-1 antibody. Exposure to ET-1 for 24 h produced a clear dose-dependent effect on the PAI-1 release from the MCs. PAI-1 mRNA expression was also enhanced in parallel with the concentration of ET-1 in the conditioned media. These findings indicate that ET-1 participates in fibrinolysis and the PAI-1 synthesis by MCs, which may thus regulate the degradation of the extracellular matrix in the glomerular microenvironment.

Animals↗
PubMed1996

Hyperinsulinemia and left ventricular geometry in a work-site population in Japan.

The present study was designed to test whether hyperglycemia or hyperinsulinemia influences left ventricular mass and geometry. An echocardiogram and 75-g oral glucose tolerance test were performed in 210 normotensive and 180 mildly to moderately hypertensive male workers in a bus company who were free from cardiac diseases and were not taking medication for hypertension and diabetes mellitus. When we divided subjects into four groups according to the left ventricular geometric pattern using left ventricular mass index of 110 g/m2 and relative wall thickness (ratio of 2 x posterior wall thickness to end-diastolic left ventricular diameter) of 0.44, body mass index and systolic blood pressure were higher in those with concentric hypertrophy and eccentric hypertrophy. In addition, hemoglobin A(Ic) level and the sum of fasting and 2-hour postload serum glucose levels were higher in subjects with concentric hypertrophy. In subjects without diabetes mellitus (n=336), 2-hour postload serum insulin level and the sum of fasting and 2-hour postload serum insulin levels tended to be higher in those with concentric hypertrophy and concentric remodeling. In multiple regression analysis, the sum of glucose levels (or hemoglobin A(Ic) level) in all subjects and the sum of insulin (or 2-hour postload insulin) levels in subjects without diabetes mellitus significantly correlated with relative wall thickness, independent of age, systolic blood pressure, and body mass index. Neither glucose nor insulin levels correlated with left ventricular mass index. Our results suggest that hyperglycemia and hyperinsulinemia may promote concentric changes in the left ventricle in normotensive and mildly to moderately hypertensive men.

Adult↗