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Biomedical subjects

H Hara

Publications and source records attributed to H Hara.

At least 235 records · Page 13Linked to original sources
PubMed1998

[The effects of YM26818: 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea and derivatives on pulmonary surfactant secretion and lung compliance].

To discover a novel compound which has an effect on pulmonary surfactant (PS) secretion, we studied the effects of various compounds on PS secretion by measuring the contents of PS in the bronchoalveolar lavage (BAL) fluid in guinea pigs. In the chemical modification study of ambroxol, which is known as a PS secretagogue, and a compound we discovered from our compounds library, 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea: YM-26818 (the increasing effect on PS in BALF, 34.7% at 50 mg/kg, i.p.). In the surfactant deficient model induced by BAL in guinea pigs, YM-26818 (5 and 10 mg/kg, p.o.) significantly increased the contents of PS in the BAL fluid compared with that of control animals (5 mg/kg: 60.3 +/- 8.0, 10 mg/kg: 59.4 +/- 4.3% increase). Concomitantly by these effects, the recovery of lung compliance was observed in this model (AUC of lung volume, control: 560 +/- 15, YM-26818 5 mg/kg: 898 +/- 51, YM-2681 10 mg/kg: 956 +/- 11 ml.min). These results may indicate that YM-26818 is useful for the therapy of adult respiratory distress syndrome (ARDS) and obstructive pulmonary diseases.

Animals↗
PubMed1998

[Effects of an antidiarrhoeica containing an extract from geranium herb on astringent action and short-circuit current across jejunal mucosa].

A consists of berberine chloride and an extract from geranium herb. To clarify mechanisms of the antidiarrheal effect of Phelloberin-A, we investigated the astringent action by determining its binding activity to rabbit hemoglobin and effects on active transport, which was indicated by short-circuit current (Isc), in rat jejunum by the Ussing chamber technique. The effects of berberine chloride and geranium herb on both the binding activity to hemoglobin and the electrophysiological parameters such as Isc were compared with those of the antidiarrhoeicas, tannic acid, albumin tannate and bismuth subnitrate. Geranium herb, tannic acid and bismuth subnitrate increased significantly the binding activity to hemoglobin at concentrations of > 1 mg/ml, > 0.3 mg/ml and 10 mg/ml, respectively, but berberine or albumin tannate did not. Geranium herb and tannic acid dose-dependently and moderately increased Isc in rat jejunal mucosa and the increase became significant at a concentration of 10 mg/ml. Neither berberine chloride, albumin tannate nor bismuth subnitrate affected Isc. In contrast, cholera toxin, which increases the secretion from intestinal mucosa to the lumen and induces diarrhea, decreased Isc at a concentration of 0.1 mg/ml. The decrease of Isc induced by cholera toxin was antagonized by pretreatment with geranium herb (10 mg/ml), indicating that geranium herb inhibited the toxin-induced increase in secretion. These results suggest that geranium herb possesses an astringent action and moderately increases Isc across the intestinal mucosa. Therefore, the effects may support an antidiarrheal effect of both geranium herb and Phelloberin-A.

Animals↗
PubMed1998

[Anti-migraine effects of lomerizine].

Lomerizine, a novel Ca2+ channel blocker, is under development as an anti-migraine drug. We examined the effects on spreading depression (SD) induced by a brief period of hypoxia (40 to 60 sec) in rat hippocampal slices, the cortical hypoperfusion and cortical c-Fos-like immunoreactivity that follow KCl-induced SD in anesthetized rats as compared with those of flunarizine. Extracellular recording was made from the CA1 subfield. The latency of initiated SD was examined. Lomerizine (1 and 10 nM) and flunarizine (1 microM) significantly prolonged the latency in a concentration-dependent manner. After KCl application to the cortex, cerebral blood flow monitored by the laser Doppler flowmetry was approximately 20 to 30% below baseline for at least 60 min. Lomerizine (0.3 and 1 mg/kg, i.v.) and flunarizine (1 and 3 mg/kg, i.v.) administered 5 min before KCl application inhibited the cortical hypoperfusion that followed KCl application. c-Fos-like immunoreactivity, an indicator of neuronal activation, was detected in the ipsilateral, but not in the contralateral frontoparietal cortex 2 hr after KCl application. Lomerizine (3-30 mg/kg, p.o.) and flunarizine (30 mg/kg, p.o.) significantly attenuated the expression of c-Fos-like immunoreactivity in the ipsilateral frontoparietal cortex. Lomerizine was 3 to 1000 times more potent than flunarizine in the above SD models. These findings suggest that the inhibitory effects of lomerizine and flunarizine on the interval between the initiated and subsequent spontaneous SDs, the cortical hypoperfusion and expression of c-Fos-like immunoreactivity induced by SD are mediated via the effects of Ca2+ entry blockade, which may include an increase in cerebral blood flow and the prevention of excessive Ca2+ influx into brain cells.

Animals↗
PubMed1998

Effects of germinated barley foodstuff in preventing diarrhea and forming normal feces in ceco-colectomized rats.

Germinated barley foodstuff (GBF) derived from the aleurone and scutellum fractions of germinated barley was rich in glutamine and low-lignified hemicellulose. The diarrhea caused by ceco-colectomy could be prevented by feeding GBF to rats. GBF could also increase the protein content and sucrase activity of small intestinal mucosa in this model. This diarrhea-preventive effect of GBF would be based on the water-holding capacity and bulging force under alkaline conditions, e.g. in the small intestine.

Animals↗
PubMed1998

Effects of difructose anhydride III on calcium absorption in small and large intestines of rats.

Difructose anhydride III (DFA III; di-D-fructo-furanose 1,2':2,3' dianhydride) was prepared from inulin with Arthrobacter sp. H65-7 inulin fructotransferase (depolymerizing (inulase II; EC 2.4.1.93). DFA III is not hydrolyzed by enzymes in the small intestine, but is metabolized by microorganisms in the large intestine. We investigated the effects of DFA III on calcium absorption in two experiments. In the in vivo experiment, we examined the effects of DFA III, fructooligosaccharides, and raffinose on calcium absorption in male Sprague-Dawley rats 5 weeks old at start of the experiment and given feed containing 3% of one of these oligosaccharides for two weeks. The apparent calcium absorption was significantly higher in rats fed any of these oligosaccharides than in control rats, and the increase with DFA III was the greatest. Absorption in both the small and large intestines was affected. In rats fed DFA III, the cecal wall thickened and soluble calcium and the amounts of some organic acids were higher than in the control groups. In an in vitro experiment with everted jejunal and ileal sacs of rats, calcium absorption was higher when DFA III was present in the mucosal fluid at all concentrations tested (up to 200 mM). In the jejunal sacs, the increase in calcium absorption depended on the DFA III concentration. In the ileal sacs, the absorption was maximum at 50 mM DFA III and did not increase further at higher concentrations. These results indicate that intact DFA III stimulates calcium absorption in the small intestine, and that cecal fermentation of DFA III may contribute to the increase in calcium absorption by the large intestine.

Administration, Oral↗
PubMed1998

Otoconia biogenesis, phylogeny, composition and functional attributes.

This work consolidates data about these interesting organic crystals of vertebrate inner ears. It addresses 5 aspects of inner ear otoliths not completely understood to date: 1) embryological data that explains the formation of the crystals, 2) the significance of the organic and the inorganic phase of the otolith and the changing patterns of otoconia formation along the evolutionary tree, 3) otoliths contribution for detecting linear acceleration, 4) the effect that altered gravity and aminoglycosides have on the development and adult shape of the crystals, and the evolutionary significance of a changing shape of the crystals from primitive forms (lamprey) to high vertebrate birds and mammals is discussed, 5) functional attributes of the otolithic organs and morphological modifications of the otoliths by physical and chemical insults are presented with an extensive discussion of the most relevant literature published and available to us.

Animals↗
PubMed1998

Correlation between wave components of the second derivative of plethysmogram and arterial distensibility.

The ratio of two wave components (magnitude of b/a constituting the second derivative of the plethysmogram (SDPTG) was correlated with arterial distensibility. Eighty-two subjects (33-93 years old) were classified into three groups according to the thickness of the intima-media complex of the common carotid artery measured by B-mode ultrasonography. One group was non-atherosclerotic (without pathologic thickening) (nAS) and the other two groups atherosclerotic (mild and severe thickening, or plaque formation) (AS-1 and AS-2). Distensibility (D) of the common carotid artery was calculated from arterial dimensions and blood pressure: h/p = D, where h = (Ds-Dd)/Dd; Ds, Dd and p represent the inner diameter of the carotid artery at peak systole, at end diastole and brachial pulse pressure, respectively. The plethysmogram was recorded at the cuticle of the 2nd digit of the left hand, and the SDPTG was determined with a 10 msec time constant. D showed a significant negative correlation with age in all subjects and in the three separate groups. The correlation between age and magnitude of b/a was significantly negative in all subjects. This negative correlation was not observed in the nAS group, while it was significant in both AS-1 and AS-2. The correlation between magnitude of b/a and D was significantly positive in all subjects and in each group. Significant differences were found among the three groups for magnitude of b/a and D. These results suggest that a decrease in magnitude of b/a or in D was proportional to the thickness of the intima-media complex of the carotid artery, that is, the development of atherosclerosis. These results provide direct evidence that magnitude of b/a of the SDPTG is related to the distensibility of the peripheral artery, and suggest that magnitude of b/a is a useful non-invasive index of atherosclerosis and altered arterial distensibility.

Adult↗
PubMed1998

The large intestine compensates for insufficient calcium absorption in the small intestine in rats.

We previously demonstrated that the large intestine compensated for decreased calcium (Ca) absorption caused by renal failure in rats fed a highly fermentable dietary fiber. In this study, we examined whether the large intestine compensated for insufficient Ca absorption in the rat small intestine without ingestion of a fermentable dietary fiber. Rats were fed one of four test diets containing either insoluble (carbonate) or soluble (gluconate, lactate, or citrate) Ca sources. The dietary Ca level was 2.0 g/kg, which is lower than the minimum requirement for rats (3.0 g/kg), to conduct the present study under a condition in which rats can maximally absorb Ca. To prevent Ca absorption in the small intestine, we replaced a primary phosphate (KH2PO4) with secondary phosphates (K2HPO4 and Na2HPO4) in diets. The apparent Ca absorption in the small intestine was estimated by adding chromic oxide (Cr2O3) as an insoluble and an unabsorbed marker to test diets and by measuring the ratio of Ca:Cr in the cecal content. The apparent Ca absorption in the whole intestine was estimated by the intake and fecal excretion of Ca. The apparent Ca absorption in the small intestine was significantly lower from the Ca carbonate diet than from the Ca gluconate, lactate, or citrate diets. The apparent Ca absorption in the whole intestine was not significantly different among the four groups, and the values were similar to the absorption rates in the small intestines of rats fed diets containing soluble Ca sources. These results show the following: (a) In rats fed 0.2% Ca diets containing soluble Ca salts, Ca is mostly absorbed in the small intestine, even in secondary phosphate intakes; (b) In contrast, in rats fed a 0.2% Ca diet containing an insoluble Ca salt (carbonate), Ca is not sufficiently absorbed in the small intestine. However, the large intestine compensates for the small intestinal Ca absorption decreased by dietary secondary phosphates.

Animals↗
PubMed1998

Bile-pancreatic juice-independent increases in pancreatic proteases and intestinal cholecystokinin by dietary protein in rats.

Luminal bile-pancreatic juice (BPJ) is involved in the induction of pancreatic proteases in rats fed a high-protein diet. Recently, we have demonstrated that a BPJ-independent mechanism is responsible for enhancement of pancreatic secretion after feeding of a dietary protein in chronic BPJ-diverted rats. The aim of the present study was to explore the existence of a BPJ-independent mechanism during adaptation of the exocrine pancreas to dietary protein. Rats, whose BPJ was diverted into the ileum through a common bile-pancreatic duct catheter for 5 days (PBD rat), were fed a fat-free diet containing 25% or 60% casein for 3 days. Messenger RNA levels for pancreatic enzymes, cholecystokinin, and secretin in the jejunal mucosa were evaluated by northern blotting method. Pancreatic trypsin and chymotrypsin activities and mRNA levels of their zymogens were higher in PBD rats than in rats whose diverted BPJ was returned into the duodenum (PBD returned rat). In the PBD groups, pancreatic protease activities were further increased by 3-day feeding of a high-protein diet without changes in mRNA levels of these proteases. Cholecystokinin mRNA was increased after feeding of a high-protein diet in the PBD rats. These results indicate that pancreatic proteases are induced by feeding a high-protein diet by a mechanism independent of luminal BPJ, which is associated with an increase in intestinal cholecystokinin mRNA level.

Amylases↗
PubMed1998

Guanidinated casein hydrolysate stimulates pancreatic secretagogue release by direct action to the intestine in rats.

Previously, we observed that pancreatic exocrine secretion was strongly enhanced after duodenal administration of guanidinated casein peptic hydrolysate (HGC) in rats with chronic bile-pancreatic juice (BPJ) diversion. Using a perifusion system of isolated dispersed rat intestinal mucosal cells, we investigated whether this phenomenon depends on a direct effect of protein on the intestine to release pancreatic secretagogues, such as cholecystokinin (CCK). Amylase release from isolated pancreatic acini was used as an assay to measure CCK or other pancreatic secretagogues in the effluents. Mucosal effluent with HGC stimulated amylase release from acini with or without soybean trypsin inhibitor (SBTI). Perifused effluent with low-concentrated SBTI did not stimulate amylase release. These results indicate that HGC stimulates release of pancreatic secretagogue from the intestinal mucosal cells independent of remaining trypsin activity in the isolated mucosa. Effluents with intact casein, its peptic digest, and homoarginine, which is a unique amino acid contained in HGC, were unable to stimulate amylase release from acini. Effluent with a high concentration of SBTI, which is rich in arginine residues, stimulated amylase release, but not with the same tryptic inhibitory effect of lima bean trypsin inhibitor, which is poor in arginine residues. These findings suggest that guanidyl residues in protein structure are responsible for release of pancreatic secretagogues from isolated intestinal mucosal cells. Finally, the increment of amylase release from pancreatic acini in response to the perifused effluent with HGC was eliminated in acini treated with a potent CCK antagonist, FK480. We conclude that in rats with BPJ diversion, HGC stimulates CCK release from the intestine by direct action on intestinal mucosa.

Amino Acids↗
PubMed1998

Prognostic value of tumor cell proliferation and intratumor microvessel density in advanced gastric cancer treated with curative surgery.

To clarify the prognostic value of tumor cell proliferation [proliferating cell nuclear antigen (PCNA)-positive rate assessed by anti-PCNA immunostaining] and intratumor microvessel density (/0.74 mm2, assessed by anti-CD34 immunostaining) in gastric cancer, 192 advanced gastric cancer patients who underwent curative surgery were investigated. Multivariate analysis showed that the following variables were significantly related to prognosis: age (P=0.029), depth of invasion (P=0.005), lymph node metastasis (P=0.006), lymphatic invasion (P=0.038), venous invasion (P=0.0005), PCNA-positive rate (P=0.049) and intratumor microvessel density (P=0. 011). In conclusion, tumor cell proliferation and intratumor microvessel density were independent prognostic factors in patients with advanced gastric cancer undergoing curative surgery.

Adult↗
PubMed1998

[Normal term delivery after adrenalectomy for Cushing syndrome in a pregnant patient--a case report].

This is a case of a 29-year-old female. She visited our hospital with the chief complaint of swelling of the legs and abdominal bloating at the 10th week of pregnancy. Edema and central obesity were observed in the lower extremities. Hematological and biochemical tests revealed hypokalemia. Gynecologically, she was normal. Elevated blood cortisol levels were identified on the hormonal tests, which suggested the existence of Cushing's syndrome. Ultrasound revealed the presence of a tumor in the left adrenal gland, and she was referred to our department for surgery. On September 13, 1994, left adrenalectomy was performed in a right lateral position under inhalation anesthesia and epidural anesthesia. Adjuvand steroid therapy was initiated during surgery and the blood cortisol levels were normalized within 2 months. She delivered a baby girl weighing 2,722 g at the 40th week of pregnancy via a normal transvaginal delivery. Pregnancy rarely occurs in patients with Cushing's syndrome. We think she was the first case in Japan who had normal 40th week transvaginal delivery after adrenalectomy during pregnancy. We present a description of our case here with reference to the relevant literature.

Adrenalectomy↗
PubMed1998

[An adult case of peripheral facial nerve palsy following acute cerebellitis associated with high antibody titers against varicella-zoster virus].

Here we report a case of acute cerebellitis, in which the patient developed right peripheral facial palsy during the recovery phase of cerebellar ataxia. A 67-year-old man developed truncal and limb ataxia following a fever, general fatigue and anorexia. He was diagnosed to have acute cerebellitis. While the ataxia symptoms were improving without any treatment, right peripheral facial nerve palsy developed and an MRI revealed an enhancement of the right facial nerve proximal to the geniculate ganglion. After treatment with acyclovir and corticosteroids, his facial nerve palsy and ataxia both gradually improved. There has been no previous report of an adult case who developed peripheral facial nerve palsy during the recovery phase of acute cerebellitis. This case indicates that a wide spectrum of neurological complications may develop in association with a varicella-zoster virus infection.

Acute Disease↗
PubMed1998

[Immunohistochemical study on the progression of colorectal cancer--with respect to apoptotic index, expression of apoptosis-related gene products, and labeling index of proliferating cell nuclear antigen (PCNA)].

To clarify the biological changes in the development and progression of colorectal cancer, immunohistochemical examination was performed with a particular focus on the activity of apoptosis, the expression of apoptosis-related gene products and cell proliferation activity, assessed by the labeling index of proliferating cell nuclear antigen (PCNA). Seventy-six resected specimens of colorectal cancer were used to investigate the expression of apoptosis-related gene products, Bcl-2 protein and PCNA labeling index, as well as the apoptotic index using the TUNEL method. Seventy-five percent of 60 advanced cancer specimens was negative for Bcl-2 protein, and the proportion was higher than that in early cancer specimens. The apoptotic index (AI) in the advanced cancers was significantly higher than in the early stage of cancers. Meanwhile, the percentage of PCNA-positive cells for the advanced cancers was significantly higher than for early cancer. This study demonstrated a decrease in Bcl-2 protein expression, an increase in tumor cell apoptosis, and opposite an increase of cellular proliferation activity in the progression of colon cancer from early to the advanced stage of the disease.

Apoptosis↗
PubMed1998

[Influences of trabeculectomy combined with the use of mitomycin C on corneal endothelial cells].

We used a specular microscope to evaluate the corneal endothelial cells in 119 eyes before and 2 to 3 weeks after trabeculectomy with topical mitomycin C. The endothelial cell density per square millimeter averaged 2,569 +/- 487 (mean +/- standard deviation) before surgery and 2,444 +/- 536 after surgery, showing a decrease of 4.98%. The hexagonality decreased by 1.7%, the coefficient of variation increased by 1.9, and the average cell area increased by 6.82%. There were no statistical differences as a whole in these values. Decrease in hexagonality was more frequent in eyes with prior intraocular or glaucoma surgery. Eyes treated by laser trabeculoplasty showed a decrease in endothelial cell density, an increase in coefficient of variation and an increase in hexagonality. Eyes with postoperative flat anterior chamber showed significant changes in each parameter. The findings show that trabeculectomy with topical mitomycin C does not significantly affect the corneal endothelial cells at 2 to 3 weeks after surgery.

Administration, Topical↗