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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 19 recordsLinked to original sources

Attenuation of ischemic and postischemic damage to brain metabolism and circulation by a novel Ca2+ channel antagonist, NC-1100, in spontaneously hypertensive rats.

We investigated the effect of a newly synthesized Ca2+ channel antagonist, NC-1100, on cerebral blood flow (CBF) and metabolism in spontaneously hypertensive rats. The rats received a bolus injection of 0.2 or 1.0 mg/kg NC-1100 i.v. and 1-h cerebral ischemia was then induced by bilateral carotid artery occlusion (group 1). The rats in group 2 were continuously infused with NC-1100 0.03 or 0.1 mg/kg per min, starting immediately after bilateral carotid artery occlusion, for the 1 h of ischemia and following 3-h recirculation. Group 1: during ischemia, CBF in all rats decreased to 6-8% of the resting values. At 1 h cerebral ischemia, brain tissue lactate increased 11.5-, 10.1- and 9.8-fold of the normal control given vehicle or NC-1100, 0.2 and 1.0 mg/kg, respectively. The ATP levels were better preserved by NC-1100 administration; 0.61 +/- 0.04 (mean +/- S.E.M.), 0.80 +/- 0.09 and 0.97 +/- 0.14 mmol/kg (P < 0.05 vs. vehicle), respectively. Group 2: during recirculation, CBF in NC-1100-treated rats returned to 83-90% of the resting values, but to only 65% in the vehicle group. Postischemic brain lactate at 3 h was less well preserved and ATP was dose dependently better preserved in NC-1100- than vehicle-treated rats. It is considered that pre- as well as postischemic administration of a Ca2+ channel antagonist, NC-1100, is beneficial to attenuate and also ameliorate the metabolic and circulatory derangement in the ischemic brain.

Adenosine Triphosphate

Developmental expression of macronuclear specific antigen in Paramecium caudatum.

We obtained a monoclonal antibody (MA-1) specific for macronuclei of the ciliate Paramecium caudatum and P. dubosqui. Immunoblotting showed that the antigen was a polypeptide of 50 kilodalton (kDa). During the process of nuclear differentiation in P. caudatum, the MA-1 antigens appeared in the macronuclear anlagen immediately after four out of eight post zygotic nuclei differentiated morphologically into the macronuclear anlagen. Afterwards, the antigens could be detected in the macronucleus through the cell cycle, and disappeared when the macronucleus began to degenerate in exconjugant cells. These results suggest that the antigens may play a role in the differentiation and function of the macronucleus.

Animals

Comparison of effects of enalapril and captopril on serum potassium concentration in the treatment of malignant hypertension.

To compare the effects of enalapril and captopril on blood pressure, serum creatinine (S-Cr), and potassium (S-K) levels, patients with malignant hypertension treated with either 5-10 mg of enalapril (eight cases) or 75-400 mg of captopril (eight cases) were investigated retrospectively. After 2 weeks of treatment, the average blood pressure fell from 214/138 to 132/89 mmHg on enalapril and from 240/145 to 147/95 mmHg on captopril. The percent change in mean blood pressure during the 2 weeks of treatment with enalapril (-35.6 +/- 4.0 SE%) was similar to that with captopril (-35.8 +/- 2.8%). S-Cr did not change in both groups, while S-K increased significantly from 3.9 +/- 0.2 to 5.2 +/- 0.2 mEq/l on enalapril and from 3.6 +/- 0.2 to 4.2 +/- 0.1 mEq/l on captopril. S-K at the second week was significantly higher in the enalapril than in the captopril group. The maximum S-Cr concentration during the treatment was correlated with the corresponding S-K concentration similarly in both groups. These results indicate that both enalapril and captopril increase S-K without deterioration of renal function in patients with malignant hypertension and that the way these drugs are used in clinical practice may be more likely to result in elevated S-K with enalapril.

Adult

Elevated plasma nilvadipine concentration after single and chronic oral administration to patients with chronic liver disease.

Fourteen normotensive patients with liver disease (6 with cirrhosis and 8 with chronic hepatitis) and 7 healthy volunteers were given a single oral dose of nilvadipine 2 mg. In addition, nilvadipine 4 mg was administered orally twice daily for several months to 6 hypertensive patients with mild liver dysfunction and 18 hypertensives with normal liver function. A significant increase in plasma nilvadipine was found in the patients with cirrhosis as compared both to the normal and chronic hepatitis subjects; the time to peak concentration was similar among the three groups. The peak plasma nilvadipine concentration was closely correlated both with the serum albumin level and the retention of indocyanine green. Changes in blood pressure, pulse rate and various vasoactive hormones following a single oral dose of nilvadipine did not differ between the groups. Thus, an increase in plasma nilvadipine relative to the level in normal subjects was demonstrated in patients with cirrhosis following a single oral dose, as well as in patients with slight liver dysfunction following long-term oral administration.

Administration, Oral

Familial primary biliary cirrhosis associated with impaired concanavalin A-induced lymphocyte transformation in relatives. Two family studies.

The familial occurrences of biochemical and immunological abnormalities and histocompatibility antigens were studied in 18 healthy first-degree relatives of patients with primary biliary cirrhosis (PBC) in two families. In each of these two families, there were two members who suffered from PBC. All relatives had normal serum aspartate aminotransferase, alkaline phosphatase, bilirubin, total cholesterol, and immunoglobulins except the two, who had a mild elevation of alkaline phosphatase without cholestasis. Autoantibodies were present in some relatives; five (28%) for antithyroglobulin antibody and antithyroid microsomal antibody, one (6%) for antimitochondrial and antinuclear antibody, and one (6%) for rheumatoid factor. Abnormalities of T or B lymphocytes in peripheral blood were detected in two (11%) relatives. Impairment of concanavalin A-induced lymphocyte transformation determined by ethidium bromide fluoroassay was found in seven (39%) relatives, although an abnormal response for phytohemagglutinin was detected in none of the relatives. The HLA haplotypes were not necessarily associated with positive autoantibodies or impaired concanavalin A-induced lymphocyte transformation in these families. These findings suggest that impairment of concanavalin A-inducible lymphocytes (mainly suppressor T cells) is one of the contributing factors in the development of PBC.

Adolescent

Radiographic features in ischemic jejunoileitis: serial changes and comparison with pathologic findings.

Serial radiographic examinations of the small intestine, including double-contrast studies, were performed in 13 patients with ischemic jejunoileitis, nine with the stricturing form and four with the transient form. Thumbprinting was observed in five (38%) patients and thickening of the folds in four (31%) at the acute stage of the disease. Tubular narrowing with irregular contours and dilated proximal bowel was observed in six (46%) patients and appeared on day 27 or later. Pathologic findings of the resected specimen in eight patients with the stricturing form revealed annular stricture with relatively shallow ulcers; the irregular contours of the tubular narrowing on radiographs were consistent with a granular or nodular appearance and/or multiple fissures on pathologic study. Eccentric deformity and sacculation were demonstrated in only one patient with the stricturing form. In addition, double-contrast study revealed small ulcers in three (23%) patients. Our results indicate that radiographic findings accurately reflect the clinical course and pathologic findings in this disease.

Adult

Comparison of withdrawing antihypertensive therapy between diuretics and angiotensin converting enzyme inhibitors in essential hypertensives.

One hundred thirteen patients with essential hypertension receiving single or multiple antihypertensive agents were enrolled in the study. All had had mild to severe hypertension before treatment, but their diastolic blood pressure (DBP) at study entry was lower than 90 mm Hg for all measurements. In half of the subjects, non-thiazide diuretics (n = 35) or angiotensin-converting enzyme inhibitors (ACEI, n = 37) were discontinued, and their remaining drugs were maintained throughout the study. The other patients (n = 41) continued all their medications. Forty-one percent of subjects remained normotensive for 12 months after withdrawal of diuretics, and 37% of patients with ACEI discontinuation remained normotensive, although the recurrence of hypertension after withdrawal of ACEI tended to be earlier than its recurrence after withdrawal of diuretics. Serum uric acid and creatinine concentration decreased after diuretic withdrawal, but not after ACEI withdrawal. Diuretic withdrawal resulted in an increase in serum potassium, but ACEI withdrawal induced a decrease in serum potassium. Withdrawal of diuretics or ACEI both significantly reduced plasma renin activity. The present study may be indicative of the ability to withdraw some medications in many patients being treated with multiple antihypertensive agents.

Adult

Prostaglandins A and J arrest the cell cycle of cultured vascular smooth muscle cells without suppression of c-myc expression.

The effects of prostaglandins (PGs) A and J, which are anti-tumor eicosanoids, on the proliferation of cultured vascular smooth muscle cells were investigated. Serum-stimulated DNA synthesis was potently inhibited by PGA1, PGA2, PGJ2, and delta 12-PGJ2 in similar dose-dependent fashions. The effects of PGA1 and PGA2 were reversible when they were removed from the culture media, whereas recoveries were only partial in the cells treated with PGJ2 and delta 12-PGJ2. PGs were effective even if they were added immediately before entry into S phase. Inhibition of DNA synthesis was sustained when hydroxyurea, which blocks cell cycle at the G1/S border, was added after the removal of PGA2, and vice versa; PGs blocked DNA synthesis when they were added after the removal of hydroxyurea. Levels of c-myc mRNA formed two peaks during the G1 phase, at 1-2 h and at 8-12 h. The PGs did not affect the first elevation, but enhanced the second and sustained it up to 18-24 h, whereas in controls, c-myc mRNA decreased quickly after entry into S phase. The rate of degradation of c-myc mRNA was much smaller in PG-treated cells than in nontreated cells. We conclude, therefore, that PGA and PGJ inhibit a crucial event(s) in the cell cycle occurring at the G1/S border, but that this inhibition is not accompanied by the reduction in c-myc gene expression in contrast with some types of tumor cells treated with PGs.

Animals

Effects of salt loading on glucose tolerance, blood pressure, and albuminuria in rats with non-insulin-dependent diabetes mellitus.

We studied the effects of salt loading on glucose tolerance, blood pressure, and albuminuria in rats with mild non-insulin-dependent diabetes mellitus (NIDDM). Two-day-old male Wistar Kyoto (WKY) rats were injected intraperitoneally (IP) with either 75.0 mg/kg streptozotocin (STZ) or vehicle as control. Salt loading was performed as 1% NaCl of drinking solution from 4 weeks until 12 weeks of age (estimated sodium intake: control, 3.14 +/- 0.28 mEq/d in tap-water group, 11.9 +/- 0.95 mEq/d in salt-loaded group; NIDDM, 2.93 +/- 0.16 mEq/d in tap-water group, 12.0 +/- 2.59 mEq/d in salt-loaded group). Oral glucose tolerance, glycosylated hemoglobin (GHb), and pancreatic insulin content at 12 weeks did not differ between the salt-loaded group and tap-water group in both NIDDM and control rats. Urinary sodium excretion was increased in salt-loaded groups of control and NIDDM rats, but systolic blood pressure did not differ among the groups (control, 151 +/- 6 mm Hg in tap-water group, 150 +/- 3 mm Hg in salt-loaded group; NIDDM, 152 +/- 3 mm Hg in tap-water group, 157 +/- 2 mm Hg in salt-loaded group). Urinary albumin excretion was significantly increased in salt-loaded groups (1,790 +/- 272 micrograms/d in control, 1,617 +/- 174 micrograms/d in NIDDM rats) compared with tap-water groups (691 +/- 75 micrograms/d in control, P less than .05; 616 +/- 69 micrograms/d in NIDDM rats, P less than .001), irrespective of STZ injection, but endogenous creatinine clearance was not different among the groups. Furthermore, renal growth was more greatly increased in salt-loaded groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Elevation of serum erythropoietin after subtotal parathyroidectomy in chronic haemodialysis patients.

After successful subtotal parathyroidectomy (PTX) in 10 chronic haemodialysis patients, significant elevation of Epo was observed, from 48.4 +/- 17.8 mU/ml(M +/- SEM) at preoperative state to 103.3 +/- 34.7 mU/ml at 6 h and 163.4 +/- 50.2 mU/ml at 12 h after PTX. Significant reductions in both PTH-m and ionized calcium (iCa) were confirmed. Since Epo did not increase in the cases with an inadequate PTX and ovariectomy, an abrupt reduction in PTH with a decrease in iCa may play some role in the elevation of Epo.

Adult

Esophageal ulcer complicated by Reiter's syndrome. A case report.

A 40-year-old woman with Reiter's syndrome had low-grade fever, a psoriasislike eruption on feet and hands, and multiple esophageal ulcers. She had keratoderma blennorrhagica, aseptic vaginitis, and ileosacral arthritis, but no ocular lesions. The patient was HLA-B27 negative. Radiographic and endoscopic examinations of the upper gastrointestinal (GI) tract showed multiple round or irregularly shaped small ulcers in the middle and distal portion of the esophagus. One month later, all esophageal ulcers disappeared spontaneously. A case like this of Reiter's syndrome with esophageal involvement has not been reported before.

Adult

Preserved thyroidal secretion of thyroxine in acromegalic patients with suppressed hypophyseal secretion of thyrotrophin.

OBJECTIVE: We have assessed the mechanisms which maintain euthyroidism in acromegalic patients despite the suppression of thyrotrophin (TSH) secretion. MATERIALS: Fourteen untreated patients with acromegaly were analysed. Ten patients were also studied after pituitary surgery. METHODS: Thyroid hormones, growth hormone (GH), insulin-like growth factor-I (IGF-I) and thyroidal uptake of radioactive iodine, thyrotrophin releasing hormone (TRH) test and basal metabolic rate (BMR) were measured before and after pituitary surgery. RESULTS: Nine patients had palpable goitres. The TSH response to TRH stimulation was suppressed in eight patients, who maintained normal serum levels of total T3, T4 and free T4. The patients with normal TSH response had lower levels of free and total T4 than controls. The response of TSH to TRH correlated inversely with the serum level of total and free T4, and also with the plasma level of IGF-I (r = -0.74, P less than 0.05, n = 9). After pituitary surgery, the serum levels of total and free T4 were elevated for at least up to 6 months, with a decrease in the T3/T4 ratio and the BMR. CONCLUSION: GH may have a direct stimulatory action on the thyroid secretion of T4 possibly via increased IGF-I, despite suppressed TSH secretion. The post-operative elevation of serum T4 suggests the persistent secretion of T4 from the thyroid gland, in spite of instantaneous normalization of the accelerated conversion of T4 to T3, even after reduction of excess GH secretion.

Acromegaly

Effects of acute superior cervical ganglionectomy on cerebral blood flow and metabolism in stroke-prone spontaneously hypertensive rats subjected to cerebral ischaemia.

1. The effects of acute bilateral superior cervical ganglionectomy on cerebral blood flow and metabolism were investigated in stroke-prone spontaneously hypertensive rats (SHRsp), before and during cerebral ischaemia. 2. The resting cerebral blood flow was comparable between the control and denervated animals. 3. There was no significant difference in cerebral blood flow or concentration of tissue energy metabolites (adenosine triphosphate [ATP], lactate and pyruvate) between the sham-operated control and denervated animals during ischaemia. 4. The results suggest that sympathetic innervation of cerebral vessels originating from superior cervical ganglia may not play a major role in the progression of cerebral ischaemia in SHRsp.

Animals

Inhibition of ischemia-induced dopamine release by omega-conotoxin, a calcium channel blocker, in the striatum of spontaneously hypertensive rats: in vivo brain dialysis study.

The effect of omega-conotoxin GVIA (CgTX), an N-and L-type voltage-sensitive calcium channel (VSCC) blocker, on the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum before and during transient cerebral ischemia in spontaneously hypertensive rats was studied using an in vivo brain dialysis technique. Continuous perfusion of CgTX in the striatum was started 20 min before ischemia and concentrations of dopamine and DOPAC in the dialysate were measured using HPLC with an electro-chemical detector. Before ischemia, both 10 and 100 microM CgTX significantly lowered the concentration of dopamine, to 49% of the basal values. DOPAC concentrations also decreased significantly, by 28 and 17%, respectively. Forebrain ischemia, produced by bilateral carotid artery occlusion, reduced striatal blood flow to less than 6% of the resting value in each group. During 20 min of ischemia, the vehicle group showed a marked increase in dopamine (175 times the basal concentration). In the 10 or 100 microM CgTX perfusion group, in contrast, dopamine release was significantly attenuated, to 38 or 29% of the vehicle group, respectively. DOPAC concentrations decreased during ischemia to 58% of the basal value in the vehicle group and 49% in both CgTX groups. These results indicate that the massive release of striatal dopamine during ischemia depends largely on the influx of extracellular calcium via CgTX-sensitive VSCCs.

3,4-Dihydroxyphenylacetic Acid

Anisakiasis of the colon: radiologic and endoscopic features in six patients.

The radiologic and endoscopic findings in six patients with anisakiasis of the colon were analyzed. The diagnosis was based on the demonstration of Anisakis larvae at radiography or on elevated serum levels of antibodies to this parasite. All patients reported abdominal symptoms 12-23 hours after the ingestion of raw fish. Double-contrast barium enema examination, performed 2-4 days after the onset of syptoms in all the patients, revealed that the right side of the colon was frequently affected by edema, which was radiographically demonstrated as luminal narrowing and thumbprinting. In addition, the worm was shown at radiography in four patients. Colonoscopy, performed 1-7 days after the onset of symptoms, revealed edematous mucosa, characterized by narrowing and multiple smooth and round protrusions, in all four of the patients studied, but it failed to demonstrate the worm in any patient. The authors believe that the demonstration of these features, together with a history of raw fish ingestion, is essential for the diagnosis of this disorder.

Adult