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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 361 records · Page 20Linked to original sources

Possible neoplastic transformation within gastric hyperplastic polyp. Application of endoscopic polypectomy.

A total of 263 gastric hyperplastic polyps, which had been removed endoscopically from 202 patients, were clinicopathologically analyzed. Among these polyps, there were nine polyps with neoplastic components (3.4%), corresponding to adenoma in five lesions and mucosal adenocarcinoma in four lesions. Comparing the neoplastic transformed polyps with the pure hyperplastic polyps, there was no significant difference according to age, gender, location, gross appearance, or size. However, the transformed polyps which were located in the lower third of the stomach were larger in size (mean, 20.8 mm) and were more likely to be found among older patients (mean, 75.8 years) than were the pure hyperplastic polyps (mean size and age: 14.5 mm and 61.8 years). These results may indicate the possibility of a different carcinogenesis belonging to gastric hyperplastic polyps by location, and this finding seems to be significant in the application of endoscopic polypectomy.

Adenocarcinoma, Mucinous↗

Villous adenoma of the duodenum in a patient with familial adenomatosis coli.

A case of familial adenomatosis coli with villous adenoma of the third portion of the duodenum, which falls in the category of a Gardner's syndrome, is described. The patient, who had complained of an abdominal mass which had been diagnosed as a desmoid tumor after surgical resection, had numerous adenomatous polyps throughout the colon confirmed by colonoscopy with biopsy. Endoscopic examination of the upper gastrointestinal tract revealed fundic gland polyposis in the stomach and numerous small adenomas in the duodenum. In addition, there was a pedunculated polyp in the third portion of his duodenum, measuring 30 mm in diameter, the surface of which had a cauliflowerlike appearance. The polyp was removed with the electrocautery snare and was histologically diagnosed as villous adenoma. Our case report supports the concept that villous adenoma, which possesses a high malignant potential, may occur in the upper gastrointestinal tract in patients with familial adenomatosis coli, and careful examination of the upper gastrointestinal tract including the distal duodenum seems to be necessary in the follow-up patients with this disease.

Adenoma, Villous↗

Idiopathic sudden sensorineural hearing loss in patients undergoing long-term haemodialysis.

Idiopathic sudden sensorineural hearing loss (ISHL) has been recently recognized and is increasing in frequency in patients undergoing long-term haemodialysis. Although this is one of the annoying complications impairing quality of life in haemodialysis patients, there has been little clinical evidence about ISHL in haemodialysis patients until now. We have examined retrospectively the clinical features of 6 ISHL patients, 3 males and 3 females, with a mean age of 54 years, who underwent regular haemodialysis with a mean haemodialysis duration of 90 months from 1985 to 1989. Although a specific cause for ISHL could not be identified in this study, more precise clinical features of ISHL in patients undergoing haemodialysis have been elucidated. ISHL seemed to develop more frequently in haemodialysis patients and occurred in patients undergoing haemodialysis for a relatively long time, being independent of the high-frequency-deficit type hearing disturbances usually observed in the early course of haemodialysis therapy. Above all, diabetic haemodialysis patients were more susceptible to ISHL, occurring in 4 cases out of 6. Its prognosis was not necessarily bad, showing a recovery rate of 83%, but more effective therapy should be explored for improving the quality of life in haemodialysis patients.

Adult↗

A new model of diabetic pregnancy with genetic hypertension: pregnancy in spontaneously hypertensive rats with neonatal streptozotocin-induced diabetes.

OBJECTIVE: We designed this study to develop a new animal model of high-risk pregnancy complicated by hypertension and diabetes mellitus. STUDY DESIGN: Female spontaneously hypertensive rats were injected intraperitoneally with 75 mg/kg streptozotocin or vehicle as control at 2 days of age. They were mated with untreated male spontaneously hypertensive rats at 4 to 5 months of age. RESULTS: Hyperglycemia, defined as > 20 mmol/L plasma glucose level, was maintained during pregnancy in streptozotocin-treated spontaneously hypertensive rats, and systolic blood pressure was significantly higher in the streptozotocin-treated group than in controls before delivery (p < 0.01). Furthermore, urinary albumin excretion was significantly increased in the streptozotocin-treated group during and after pregnancy compared with the prepregnant level (p < 0.05), whereas in controls it remained unchanged. The incidence of low birth weight was significantly higher in male neonates from streptozotocin-treated mothers than those from control mothers (p < 0.05). CONCLUSION: Neonatally streptozotocin-treated spontaneously hypertensive rats may be useful for studying the combined effect of hypertension and diabetes mellitus during pregnancy.

Animals↗

The effect of azelastin hydrochloride on pruritus and leukotriene B4 in hemodialysis patients.

Pruritus is a very common complication in chronic hemodialysis (HD) patients, however the exact mechanism for this affliction is still not known. Anti-histaminics usually failed to alleviate uremic pruritus. In others, an anti-allergic drug, which inhibits the release of chemical mediators, such as leukotrienes or histamine from mast cells, was reported to be effective. We evaluated the values of leukotriene B4 and interleukin 6 in HD patients with pruritus and the effect of an anti-allergic drug on these factors. Leukotriene B4, interleukin-6, C3a, C5a, the number of eosinophil and IgE at 0, 15 and 180 minutes after the start of regular HD in 11 HD patients suffering from pruritus and as well as in 11 HD patients without pruritus were examined. These HD patients in both groups showed significantly higher (p < 0.001) values of leukotriene B4 and C3a compared to healthy non-HD subjects. There was no difference in the leukotriene B4, interleukin-6, IgE, C3a and C5a levels between the patients with and without pruritus. Two mg/day of azelastin hydrochloride, an anti-allergic drug was orally given to the pruritus group for 3 weeks. In 5 of 11 patients, the pruritus symptoms disappeared, while in 4 of 11 they improved. Independent of the effect of the drug on pruritus, leukotriene B4 levels significantly decreased compared with those before the administration of this drug in the pruritus group (p < 0.01). Interleukin 6, C3a, C5a and the number of eosinophils demonstrated no significant change. In conclusion, although azelastin hydrochloride was effective in treating pruritus and also suppressed leukotriene B4 levels in hemodialysis patients, the high leukotriene B4 activity itself did not seem to be related to the development of pruritus in these patients.

Histamine Antagonists↗

Renoprotective effect of enalapril in uninephrectomized spontaneously hypertensive rats with neonatal streptozotocin-induced diabetes.

We compared the renoprotective effect between angiotensin-converting enzyme inhibitor, enalapril, and a dihydropyridine-type calcium channel blocker, nicardipine, in a severe form of renal injury in rats. Two-day-old spontaneously hypertensive rats (SHR) were injected with streptozotocin or vehicle as control. UNX was performed at 3 weeks of age, and enalapril or nicardipine was administered in drinking water from 7 weeks of age. Uninephrectomy (UNX) markedly exacerbated hypertension and renal injury in the nondiabetic and diabetic SHR. Enalapril and nicardipine comparably reduced blood pressure in UNX diabetic SHR. However, serum creatinine was significantly elevated in the nicardipine-treated group as compared with the enalapril-treated group at 24 weeks of age (nicardipine-treated group, 67 +/- 4 microM; enalapril-treated group, 49 +/- 3 microM; P < 0.01; untreated group 57 +/- 4 microM). Furthermore, the incidence of glomerular sclerosis was similar between untreated and nicardipine-treated groups, whereas it tended to be reduced in the enalapril-treated group. In a separate experiment of diabetic SHR without UNX, enalapril therapy significantly ameliorated hyperglycemia and albuminuria (P < 0.01). This study showed that a renoprotective effect was seen in enalapril but not in nicardipine in UNX diabetic SHR despite the comparable reduction of blood pressure. This suggests that enalapril may be more effective than nicardipine in delaying the progression of a severe form of diabetic nephropathy.

Analysis of Variance↗

Citalopram, a serotonin reuptake inhibitor, and brain ischemia in SHR.

The effects of citalopram, a serotonin (5-HT) reuptake inhibitor, on cerebral blood flow (CBF) and concentration of 5-HT and its metabolite were investigated in spontaneously hypertensives rats (SHR) subjected to forebrain ischemia. Cerebral ischemia was induced by bilateral carotid artery occlusion. The concentration of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA), increased during cerebral ischemia in most brain regions examined, while that of 5-HT increased only in the frontal cortex and the striatum. Citalopram restored the 5-HIAA concentrations to the preischemic normal levels. Citalopram had no effect on the cortical CBF, before and during ischemia. These results suggest that citalopram attenuates ischemia-induced hypermetabolism of 5-HT in the brain. The effects of citalopram are independent of hemodynamic factors including cerebral blood flow, and are likely to be mediated by a direct inhibition of the neuronal 5-HT reuptake system.

Animals↗

Disparate circadian variations of blood pressure and body temperature in bedridden elderly patients with cerebral atrophy.

Twenty bedridden elderly patients with normal sleep-wake cycles were studied to evaluate the circadian variations of blood pressure, pulse rate, body core temperature, cortisol, and catecholamines with a focus on their relation to cerebral atrophy. Twenty-four-hour blood pressure (BP) and pulse rate monitorings were done with simultaneous measurement of urinary bladder temperature. Urine was also collected every 4 h to measure 17-hydroxycorticosterone and catecholamines. Based on the brain CT, frontal horn index (FHI: maximal distance between bilateral frontal horns/the corresponding width of the skull) was calculated as an index of cerebral atrophy. Analysis by the cosinor method revealed that the significant circadian rhythm with nocturnal decline was observed in only 9 patients (45%) for BP and in 13 patients (65%) for pulse rate. In contrast, 19 of 20 patients (95%) showed significant circadian rhythms of bladder temperature, with the nadirs appearing between 00:06 and 06:54. In the subgroup of mild cerebral atrophy (FHI < 0.30, n = 11), BP and pulse rate fell modestly but significantly during nighttime, whereas they did not fall in the subgroup of moderate to severe cerebral atrophy (FHI > or = 0.30, n = 9). The possibility could not be excluded that the sleep disturbance might result in the relatively high BP during nighttime. Bladder temperature, 17-hydroxycorticosteroids, and catecholamines showed significant nocturnal falls in both groups. In conclusion, nocturnal fall of BP disappeared in the bedridden elderly patients with cerebral atrophy, which cannot be explained by the change in the circadian variation of the sympathetic nervous system, cortisol, or body core temperature.

Aged↗

Small nonpolypoid neoplastic lesions of the colon: endoscopic features with emphasis on their progression.

We investigated the endoscopic and histologic features of 74 nonpolypoid neoplasias of the colorectum measuring 15 mm or less in diameter. Colonoscopically, they were characterized by flat growth, being either slightly elevated with a central depression or else completely flat against the surrounding mucosa. Of the 54 lesions measuring 5 mm or less in diameter, 3 (7%) were diagnosed as cancer, whereas the remaining 51 (93%) were diagnosed as adenomas with moderate epithelial atypia. The lesions measuring more than 5 mm were fewer in number (20), and they were more frequently given the histologic diagnosis of severe epithelial atypia (20%) and cancer (70%). Whereas the endoscopic features of the cases of adenoma with moderate atypia included both complete flatness and flat-topped elevation with a central depression, the lesions diagnosed as adenoma with severe atypia were endoscopically recognized as flat or slightly depressed lesions, and a deep central depression or prominent elevation was noted in the lesions diagnosed as cancer. These findings suggest that some minute nonpolypoid neoplasias may transform to nonpolypoid cancers and invade the submucosa, whereas others do not manifest rapid growth.

Adenoma↗

Small flat cancer of the rectum: clinicopathologic and endoscopic features.

The clinicopathologic and endoscopic features of 15 patients with small flat cancer of the rectum were investigated. Whereas 4 patients had hematochezia, the remaining 11 patients were asymptomatic, and stool positive for occult blood was the only remarkable clinical feature in 8 of them. Endoscopic features were slight elevation with central depression in 8 lesions, flat-topped elevation in 4, and shallow depression with irregular margin in 3. The surface of the tumor was often faint red in color and frequently characterized by mucosal friability. Five flat rectal cancers were missed during initial endoscopy, and they were found by repeated endoscopic examination. Three flat cancers were not identified in the distal rectum until retroflexed colonoscopic observation was performed. Although all tumors were smaller than 2 cm in diameter and 6 of them were under 1 cm, 9 lesions had deeply invaded the submucosal layer and 7 tumors showed lymphovascular permeation. Two lesions of 1 cm or greater had metastasized to perirectal lymph nodes. These results suggest that careful observation during endoscopy is necessary to detect flat rectal cancers, and a U-turn to examine the anorectal junction should be routinely done in the appropriate age group.

Adenocarcinoma↗

Inhibition of acetylcholinesterase modulates the autoregulation of cerebral blood flow and attenuates ischemic brain metabolism in hypertensive rats.

We designed the present study to examine whether or not the inhibition of acetylcholinesterase modulates cerebral microcirculation in hypotension and improves brain metabolism in ischemia induced by bilateral carotid artery occlusion in hypertensive rats. Blood flow to the parietal cortex was determined by the H2 clearance method. Lactate, pyruvate, and ATP were estimated by enzymatic methods. Acetylcholinesterase inhibitor (AChEI, ENA-713), at 0.05, 0.1, or 0.5 mg/kg, was intravenously injected 10 min before either hemorrhagic hypotension or cerebral ischemia. The levels of acetylcholine in the control were 29.3 +/- 8.1 (mean +/- SD) and 39.5 +/- 8.1 pmol/mg in the cortex and hippocampus, respectively, and they were significantly decreased by 15-19% after 60 min of ischemia in the vehicle-treated rats. AChEI preserved the levels to 93-98% of the control (p < 0.05 versus vehicle). The lower limit of autoregulation was 74 +/- 9% of the resting values. The administration of AChEI helped preserve blood flow and lowered the limit to 64 +/- 6% (p < 0.05 versus control). After 60 min of ischemia, lactate increased 6.5-fold and ATP decreased to 64% of the control value. The administration of AChEI dose-dependently reduced the lactate level 1.9- to 3.9-fold and well preserved the ATP level to 94-97% of the control. The inhibition of acetylcholinesterase activity may preserve cerebral autoregulation during hypotension and protect cerebral metabolism against ischemic insult.

Acetylcholine↗

Ischemia-induced release of amino acids in the hippocampus of aged hypertensive rats.

We have recently demonstrated the age-related vulnerability of hippocampal neurons to 20-min forebrain ischemia in spontaneously hypertensive rats (SHR). In the present study, we investigated the effect of aging on the release of amino acids in the hippocampus during transient cerebral ischemia for 20 min. Concentrations of extracellular amino acids and cerebral blood flow in the CA1 subfield were examined by an in vivo brain dialysis technique and a hydrogen clearance method, respectively, in adult (5-7 month) and aged (19-23 month) female SHR. During cerebral ischemia by bilateral carotid artery occlusion, cerebral blood flow to the hippocampus decreased to 20% of the resting values in both groups. After recirculation, both groups showed delayed hypoperfusion which was more prominent in the aged SHR. In the adult rats, concentrations of both aspartate and glutamate increased to approximately 8-fold of the resting values during ischemia. The elevation of these excitatory amino acids in the adult SHR was not significantly different from that in the aged rats. In contrast, the concentration of taurine increased 26-fold in the adult SHR but only 16-fold in the aged rats. Changes in other amino acids were not different between the two groups. These results indicate that an imbalance of excitatory and inhibitory amino acids, e.g., smaller release of taurine, during ischemia may, at least in part, contribute to the age-related vulnerability of hippocampal neurons to transient cerebral ischemia in SHR.

Aging↗

Localization of transforming growth factor-beta and latent transforming growth factor-beta binding protein in rat kidney.

TGF-beta plays an important role in maintaining the renal histological structure, and glomerular and tubular function. TGF-beta is usually secreted in a biologically inactive or latent form with high molecular weight by normal cells. The latent form of TGF-beta is composed of three distinct components: (a) mature TGF-beta (b) TGF-beta latency associated peptide (LAP) (c) latent TGF-beta binding protein (LTBP). LTBP plays a central role in the assembly, secretion and activation of TGF-beta 1. Most cells secrete a large latent TGF-beta with LTBP, while the other cells secrete a small latent TGF-beta without LTBP. However, the precise localization of TGF-beta and LTBP in the kidney is still not known. In the present study, we used the reverse transcription in combination with polymerase chain reaction (RT-PCR) to investigate the precise localization of TGF-beta 1 and LTBP in the microdissected glomeruli, renal tubules and arterioles. Our findings showed that TGF-beta 1 mRNA was detected in all nephron segments, glomeruli, and arterioles. On the other hand, LTBP mRNA was present in the glomeruli and arterioles, while it was absent in every segment of the renal tubules. Moreover, the immunohistochemical study of LTBP showed that the LTBP protein was localized on the glomeruli and arterioles but not on the renal tubules at the same localization as LTBP mRNA. These results indicate that the tubular epithelial cells secrete the small latent TGF-beta 1, while glomerular cells secrete the large latent TGF-beta 1, suggesting that they both have different structures and thus potentially different biological functions.

Animals↗

Effects of maternal diabetes on blood pressure and glucose tolerance in offspring of spontaneously hypertensive rats: relation to birth weight.

1. We studied the effects of maternal diabetes on blood pressure and glucose tolerance in the adult female offspring of spontaneously hypertensive rats. 2. Female spontaneously hypertensive rats were rendered diabetic by neonatal streptozotocin treatment, and then were mated with untreated male spontaneously hypertensive rats. Moderately severe hyperglycaemia was maintained during the gestation. 3. The birth weight was significantly lower in the female offspring of the diabetic dams than in the female offspring of the non-diabetic dams. The systolic blood pressure was significantly higher in the offspring from the diabetic dams than that from the control dams at 6 months of age (192 +/- 4 mmHg versus 213 +/- 4 mmHg, P < 0.01). The heart weight was also significantly increased in the offspring of the diabetic dams. Both the blood pressure and heart weight were inversely related to the birth weight. On the other hand, glucose tolerance was unaffected by maternal diabetes. 4. Maternal diabetes aggravated the severity of hypertension in the adult female offspring of spontaneously hypertensive rats. This suggests the importance of the metabolic environment during fetal growth for the development of hypertension.

Animals↗

Inhibitory action of betaxolol, a beta 1-selective adrenoceptor antagonist, on voltage-dependent calcium channels in guinea-pig artery and vein.

1. The effects of betaxolol, (+/-)-1-[4-[2-(cyclopropylmethoxy) ethyl] phenoxy]-3-(isopropylamino)-2-propanol hydrochloride, a beta 1-selective adrenoceptor antagonist, on voltage-dependent Ca2+ channels were investigated in single smooth muscle cells from guinea-pig mesenteric artery and portal vein using a whole-cell variant of the patch-clamp technique. Ca2+ channel currents were recorded with bath solutions contained 10 mM Ba2+ for arterial cells and 2 mM Ca2+ for venous cells. 2. Betaxolol inhibited Ca2+ channel currents dose-dependently in both mesenteric artery cells and portal vein cells. The two isomers, (+)-betaxolol and (-)-betaxolol (relative beta-antagonistic efficacies of 0.1 and 1, respectively), had similar potencies for inhibiting Ca2+ channel currents in portal vein cells. Propranolol did not inhibit the currents. Thus the inhibitory action of betaxolol on Ca2+ channel currents was independent of the beta-adrenoceptor. 3. The inhibitory action of betaxolol on Ca2+ channel currents was compared with that of diltiazem and of nifedipine in mesenteric artery cells. The current inhibition depended on the stimulation frequency with all drugs (use-dependent block). All drugs also accelerated the current decay and shifted the voltage-dependent inactivation curve in a negative direction. 4. In conclusion, betaxolol inhibited Ca2+ channel currents in vascular smooth muscle cells. The mode of inhibitory action was similar to that of diltiazem and nifedipine. Our results suggest that betaxolol is a unique beta-adrenoceptor antagonist that has a direct inhibitory action on voltage-dependent Ca2+ channels in vascular smooth muscle cells.

Animals↗

Posttraumatic intestinal stenosis: clinical and radiographic features in four patients.

PURPOSE: To characterize posttraumatic intestinal stenosis clinically and radiographically. MATERIALS AND METHODS: The clinical records and radiographic and pathologic findings were reviewed in four patients with posttraumatic stenosis. RESULTS: The patients experienced abdominal symptoms from 1 to 18 weeks after the trauma. While the small intestine was affected in two patients with ileus, the colon was involved in the other two patients with rectal bleeding or diarrhea. Barium studies showed an irregular contour within the severely narrowed intestine in three patients, even 25 weeks after the trauma. In these three patients, pathologic examinations of the resected specimens revealed a circumferential, open ulcer, whereas a scarred ulcer was present in the other patient. CONCLUSION: Posttraumatic intestinal stenosis is clinically characterized by a delayed onset of symptoms that differ according to the site of involvement. This condition should be included in the differential diagnosis of intestinal stenosis.

Abdominal Injuries↗

Cardiovascular and neurohormonal effects of intravenous adrenomedullin in conscious rabbits.

Adrenomedullin is a vasodilative peptide and shows slight homology with calcitonin gene-related peptide. In the present study, we investigated the effects of adrenomedullin on cardiovascular and neurohormonal responses in 13 conscious rabbits. The animals were chronically instrumented with bipolar electrodes on the left renal sympathetic nerve. Intravenous administration of human adrenomedullin (10, 100, 1,000, and 3,000 pmol/kg, n = 6) caused a dose-dependent reduction in mean arterial pressure (0 +/- 2, -1 +/- 2, -19 +/- 2, and -29 +/- 4 mmHg, respectively) concomitant with increases in heart rate, renal sympathetic nerve activity, plasma renin activity, and plasma norepinephrine. The significant reduction in mean arterial pressure induced by 1,000 pmol/kg of adrenomedullin occurred within 1 min after injection and lasted for 15 min (n = 7). In contrast, the significant increases in heart rate and renal sympathetic nerve activity lasted for more than 50 min. When mean arterial pressure was decreased by 15 mmHg by adrenomedullin, the increases in heart rate and renal sympathetic nerve activity were 53 +/- 8 beats/min and 78 +/- 13%, respectively, which were significantly smaller than those induced by intravenous injection of sodium nitroprusside (102 +/- 14 beats/min and 155 +/- 34%, respectively). These results suggest that intravenous adrenomedullin exerts a hypotensive action that is associated with the attenuated reflex-mediated sympathetic activation.

Adrenomedullin↗