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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 523 records · Page 29Linked to original sources

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↗

Salmonella colitis: assessment with double-contrast barium enema examination in seven patients.

To completely rule out the possibility of ulcerative colitis, Crohn disease, and other diseases, the authors analyzed the radiographic findings at double-contrast barium enema examination performed in seven patients with colitis caused by Salmonella organisms. In all patients, bacteriologic confirmation of nontyphoid Salmonella infection and radiographs of the upper gastrointestinal tract were obtained. Total colonoscopy was performed in five patients and sigmoidoscopy in one patient. In all patients, the radiographic findings were retrospectively analyzed. The descending colon and sigmoid colon were affected in six patients, whereas the rectum was affected in none. The findings included fine mucosal granularity (seven patients), loss of haustration (six patients), many fine ulcerations (five patients), and multiple ulcers (two patients). The radiographic features simulated those of ulcerative colitis, except for absence of rectal abnormality. It is concluded that double-contrast barium enema examination is useful for detection of fine mucosal changes.

Adolescent↗

CBF and oxygen metabolism in hemodialysis patients: effects of anemia correction with recombinant human EPO.

To investigate the effects of anemia correction with recombinant human erythropoietin (rhEPO) on both cerebral blood flow and oxygen metabolism in hemodialysis (HD) patients, the regional cerebral blood flow (rCBF), oxygen extraction (rOEF), and metabolic rate for oxygen (rCMRO2) were measured by positron emission tomography in five HD patients, and the data were compared with eight nondemented controls who had neither anemia nor uremia. In the HD patients, 1,500 U of rhEPO were administered intravenously three times a week to achieve a 10% increase in hematocrit (Hct) as an absolute value. Before rhEPO administration, the hemispheric rCMRO2 in HD patients was 1.48 +/- 0.09 (SE) ml.min-1.100 ml-1, which was significantly lower than that of 2.18 +/- 0.10 in the controls (P less than 0.01). In contrast, both rCBF and rOEF were significantly greater in the HD patients than the control, being 40 +/- 3 vs. 32 +/- 3 ml.min-1.100 ml-1 for rCBF (P less than 0.02) and 49 +/- 1 vs. 38 +/- 1% for rOEF (P less than 0.001). After treatment with rhEPO, Hct rose significantly from 21 +/- 1 to 31 +/- 1% in HD patients (P less than 0.001). There were significant reductions in both the hemispheric rCBF to 32 +/- 1 ml.min-1.100 ml-1 (P less than 0.01) and rOEF to 42 +/- 1% (P less than 0.01). However, the hemispheric rCMRO2 remained low at 1.58 +/- 0.06 ml.min-1.100 ml-1 even after rhEPO treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Synthesis of fibronectin by isolated glomeruli from nephrectomized hypertensive rats.

The accumulation of extracellular matrix (ECM) is an important feature of most forms of progressive glomerular diseases. In order to examine the relationship between ECM synthesis and glomerulosclerosis, we evaluated fibronectin synthesis by glomeruli with the immunoprecipitation of conditioned media from isolated glomeruli in 5/6 nephrectomized spontaneously hypertensive rats (5/6N-SHR). There was no difference in blood pressure between 5/6N-SHR and control SHR throughout the experiment. Two weeks after the nephrectomy, most of the glomeruli were intact and no difference in the synthesis of fibronectin was observed between either groups. Twenty weeks after the nephrectomy, marked glomerulosclerosis associated with an increase in urinary protein was revealed in 5/6N-SHR but no glomerular lesions in control SHR. The synthesis of fibronectin by isolated glomeruli increased in 5/6N-SHR compared to control SHR. The administration of enalapril or hydralazine + reserpine + hydrochlorothiazide markedly attenuated the glomerular sclerosis and urinary protein excretion to a comparable degree, although the later therapy reduced blood pressure more effectively. These antihypertensive therapies also suppressed fibronectin synthesis in the 5/6N-SHR group at week 20. In conclusion, increased synthesis of glomerular fibronectin appeared to contribute to the glomerulosclerosis caused by subtotal nephrectomy and hypertension.

Animals↗

Age-related changes in P2-purinergic receptors on vascular smooth muscle and endothelium.

The present study examined age-related changes in the vascular relaxation response to adenine nucleotides in hypertensive and normotensive rats. Aortic ring segments from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), age 4-6, 9-10, and 13-14 weeks, were examined for relaxation to adenosine 5'-triphosphate (ATP). The extent of ATP-induced relaxation in aortic ring segments with intact endothelium was unchanged with advancing age. Rubbed (endothelium-denuded) ring preparations at the age of 4-6 weeks showed a dose-dependent relaxation similar to that of the unrubbed rings. With advancing age, the ATP-induced relaxation in the rubbed rings decreased and was abolished. The relaxation response did not differ between the SHR and WKY animals at any age, whether the preparations were rubbed or unrubbed. The stable ATP analogue beta,r-methylene ATP induced a relaxation response similar to ATP in rubbed rings at 4-6 weeks of age. In addition, treatment with 8-phenyltheophylline did not diminish the relaxation induced by ATP. ATP-induced relaxation may be manifested via the direct action on the vascular smooth muscle in young rats and may be altered through the response mediated by endothelium with advancing age. This suggests that the vascular smooth muscle of young rats has a P2-purinergic receptor leading to relaxation and that this receptor activity declines with advancing age. In contrast, a P2-purinergic receptor leading to the generation of endothelium-derived relaxing factor may be activated in endothelial cells with advancing age. The alterations with age of P2-purinergic receptor in the vascular smooth muscle and endothelial cell are not affected by genetic hypertension.

Adenosine Triphosphate↗

Differential modulation by mu- and delta-opioids on baroreceptor reflex in conscious rabbits.

We examined the role of central mu- and delta-opioids on both neurohormonal responses and baroreceptor reflex in conscious rabbits. Both intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, a mu-selective agonist, and [D-Ala2,D-Leu5]-enkephalin, a delta-selective agonist, caused dose-related increases in arterial pressure and renal sympathetic nerve activity, whereas intravenous injection of the same maximum dose of these peptides as that used in the intracerebroventricular experiment did not cause any cardiovascular and neuronal responses. On the other hand, increases in plasma epinephrine, norepinephrine, and glucose levels induced by intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin were significantly greater than those by [D-Ala2,D-Leu5]-enkephalin. Both enkephalins did not cause any responses in plasma renin activity, plasma vasopressin, and serum sodium and potassium concentrations. The sensitivity of the baroreceptor reflex control of renal sympathetic nerve activity using a logistic model was enhanced by a subpressor dose of intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (10 pmol/kg) but not by [D-Ala2,D-Leu5]-enkephalin. Conversely, a mu-selective dose of intravenous naloxone (0.1 mg/kg) attenuated baroreceptor reflex sensitivity. Intravenous naloxone methobromide, which has been shown not to cross the blood-brain barrier, did not change baroreceptor reflex sensitivity, suggesting that naloxone acts at the central nervous system. In conclusion, in conscious rabbits, 1) intracerebroventricular mu- and delta-receptor agonists caused pressor responses and 2) mu-opioid agonist altered baroreceptor reflex control of renal sympathetic nerve activity and produced changes in sympathoadrenal responses.

Animals↗

Decreased endothelium-dependent hyperpolarization to acetylcholine in smooth muscle of the mesenteric artery of spontaneously hypertensive rats.

The endothelium-dependent vascular relaxation to acetylcholine (ACh) in spontaneously hypertensive rats (SHR) may be impaired because of an imbalance of endothelium-derived relaxing factor and contracting factor. However, the role of the endothelium-dependent hyperpolarization remains undetermined. We examined the ACh-induced hyperpolarization and its contribution to relaxation in arteries of SHR. Membrane potentials were recorded from the mesenteric artery trunk of 6-8-month-old male SHR and also Wistar-Kyoto (WKY) rats. Endothelium-dependent hyperpolarization to ACh was unaffected by NG-nitro-L-arginine, indomethacin, or glibenclamide; was reduced by tetraethylammonium or high K+ solution; and was enhanced by low K+ solution or methylene blue, thereby indicating that hyperpolarization is not mediated by nitric oxide (endothelium-derived relaxing factor) but is presumably mediated by a hyperpolarizing factor and is due to an opening of K+ channels that probably differ from the ATP-sensitive ones. Hyperpolarizations to ACh were markedly reduced in SHR compared with findings in WKY rats (maximum, 8 +/- 1 versus 17 +/- 1 mV). In addition, under conditions of depolarization with norepinephrine (10(-5) M), the ACh-induced hyperpolarization was even less and transient in SHR, while it was large and sustained in WKY rats (6 +/- 1 versus 29 +/- 2 mV). Endothelium-dependent relaxations to ACh in arterial rings precontracted with 10(-5) M norepinephrine were far less in SHR than in WKY rats, even in the presence of indomethacin. Furthermore, high K+ solution showed smaller inhibitory effects on the relaxations in SHR than in WKY rats. Endothelium-independent hyperpolarizations and relaxations to cromakalim, a K+ channel opener, were similar between SHR and WKY rats. It would thus appear that the endothelium-dependent hyperpolarization to ACh is reduced in SHR and this would, in part, account for the impaired relaxation to ACh in SHR mesenteric arteries.

Acetylcholine↗

Early computed tomographic findings for thrombolytic therapy in patients with acute brain embolism.

BACKGROUND AND PURPOSE: The benefits and safety of thrombolytic therapy was studied in patients with acute brain embolism. METHODS: We intravenously administered recombinant tissue plasminogen activator (20-30 MU for 1 hour) to 10 patients with acute (less than 6 hours) brain embolism and examined the neurological outcomes in relation to the findings on computed tomography and angiography. RESULTS: The symptoms ameliorated in four patients within 24 hours after onset, and reopening of the occluded arteries occurred in two of the patients immediately after recombinant tissue plasminogen activator infusion. On the initial computed tomographic scan (less than 3 hours), four patients had already demonstrated early indications of brain ischemia, that is, an obscure margin of the lentiform nuclei, reduced tissue attenuation, or effacement of cortical sulci. These patients failed to demonstrate reopening of the occluded arteries, and one developed a massive brain hemorrhage with clinical deterioration. Of the remaining six patients, two obtained clinical improvement with recanalization soon after the therapy and demonstrated little to slight hemorrhagic complications. The outcomes at 1 month were favorable in five patients and poor in three; death occurred in two. CONCLUSIONS: Thrombolytic therapy with recombinant tissue plasminogen activator may be safe and effective when there are no early computed tomographic findings within 3 hours from the onset of embolic stroke.

Adult↗

Leukoaraiosis and dementia in hypertensive patients.

BACKGROUND AND PURPOSE: Although our previous study demonstrated that dementia of the Binswanger type may be a disconnection dementia caused by leukoaraiosis, some hypertensive patients with marked leukoaraiosis do not develop dementia. The goal of the present study is to elucidate the pathophysiology of nondemented hypertensive patients with leukoaraiosis. METHODS: We performed clinical and neuroradiological studies, including positron emission tomography, in eight hypertensive patients with leukoaraiosis. RESULTS: Four patients were demented, and two among the other four who were not demented at the first examination developed dementia during the follow-up period. Digital subtraction angiography of the cervical and intracranial arteries demonstrated stenotic lesions in only one patient. Cerebral blood flow and oxygen metabolism in patients with dementia were markedly reduced in the white matter (59-67% of control values). In contrast, cerebral blood flow in the white matter of patients without dementia was reduced less markedly (74% of control), oxygen extraction fraction in the white matter was significantly increased (130% of control), and oxygen metabolism remained at almost-normal levels not only in the white matter but also in the cortical area. CONCLUSIONS: Hypertension-caused arteriosclerotic changes of the long penetrating medullary arteries may cause misery perfusion and later ischemic damage in the periventricular white matter. Preserved oxygen metabolism in hypertensive patients with leukoaraiosis may represent the early stage of vascular dementia of the Binswanger type.

Adult↗