PubMed Health⌕ Search

Biomedical subjects

M Kitano

Publications and source records attributed to M Kitano.

At least 73 records · Page 4Linked to original sources
PubMed1999

Delayed treatment of Na+/H+ exchange inhibitor SM-20220 reduces infarct size in both transient and permanent middle cerebral artery occlusion in rats.

SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate) is a Na+/H+ exchanger (NHE) inhibitor which has been shown to attenuate cerebral edema in the rat transient focal ischemia model. However, to date, the effect of SM-20220 on cerebral infarction has not been examined. The present experiments were designed to investigate these effects, using both transient and permanent middle cerebral artery (MCA) occlusion models in rats. A dose of 1 mg/kg given intravenously 30 min after the onset of transient MCA occlusion reduced the infarcted area. In the permanent MCA occlusion model, SM-20220 reduced the infarcted area when treatment was delayed for 5, 30 or 60 min after the onset of ischemia. The present results show that NHE has a crucial role in the pathogenesis of ischemic brain damage. This NHE inhibitor may be useful for treating stroke because of its effectiveness with both forms of ischemia and because of its postischemic administration.

Amides↗
PubMed1999

Cardioprotection of SM-15681, an Na+/H+ exchange inhibitor in ischemic and hypoxic isolated perfused rat hearts.

We investigated the effects of SM-15681 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide monohydrochloride) on Na+/H+ exchange activity in the myocardium and in ischemic and hypoxic injury in isolated perfused rat hearts. These effects were compared with those of ethylisopropyl amiloride (EIPA). Na+/H+ exchange activity was studied with a NH4Cl prepulse technique under HCO3(-)-free conditions. SM-15681 (10(-8)-10(-7) M) inhibited pH recovery of acidosis in the rat myocardium in a concentration-dependent manner and the IC50 value of SM-15681 (80 nM) was similar to that of EIPA. In perfused rat hearts, SM-15681 (10(-6) M) and EIPA (10(-6) M) significantly improved cardiac functions and prevented enzyme release and abnormal elevation of tissue Ca2+ content during 20 min of reperfusion after 40 min of ischemia and 20 min of reoxygenation after 30 min of hypoxia. We conclude that an Na+/H+ exchange inhibitor, SM-15681, shows cardioprotective effects on ischemia/reperfusion and hypoxia/reoxygenation injury. Our results also support the hypothesis that Na+/H+ exchange contributes to the pathophysiology of cardiac ischemic reperfusion injury.

Amides↗
PubMed1999

Effects of itopride hydrochloride on the delayed rectifier K+ and L-type CA2+ currents in guinea-pig ventricular myocytes.

The effects of itopride hydrochloride, a new drug used to regulate motility in the gastrointestinal tract, on the delayed rectifier K+ current (I(K)) and the L-type Ca2+ current (I(Ca)) were evaluated in guinea-pig ventricular myocytes at concentrations of 1, 10 and 100 microM to determine whether the drug has a proarrhythmic effect through blockade of I(K). Itopride did not affect I(K) at concentrations of 100 microM or less, and no significant effects of 1, 10 or 100 microM itopride were observed on the inward rectifier K+ current (I(K1)) responsible for the resting potential and final repolarization phase of the action potential. We next investigated the effects of itopride on L-type Ca2+ current (I(Ca)). Significant inhibition of I(Ca) was observed at itopride concentrations greater than 10 microM. These results suggested that itopride hydrochloride has an inhibitory effect on I(Ca) at concentrations much higher than those in clinical use.

Action Potentials↗
PubMed1998

Quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in the rat.

The incidence of tongue carcinomas (TCs) induced by oral administration of 4-nitroquinoline 1-oxide in rats is strain dependent. The inbred Dark-Agouti (DA) strain showed a much higher susceptibility to large mass-forming infiltrative TCs than did the Wistar-Furth (WF) strain. Our previous study (M. Kitano et al, Jpn. J. Cancer Res., 87: 1097-1101, 1996) on crosses between these two strains postulated a dominant susceptibility gene in DA and a dominant resistance gene in WF rats. The present study mapped these loci by analyzing the backcrosses to each parent with simple sequence repeat polymorphisms. Five quantitative parameters were analyzed: (a) the number of TCs > 5 mm in diameter; (b) the total number of TCs per rat; (c) the diameter of the largest TCs (DTCmax values); (d) the number of non-TC cancers per rat; and (e) and the number of cancers of any site per rat. All of these parameters were closely correlated (P < 0.0001). DA rats had a semidominant gene (Stc1) favoring the development of 4-nitroquinoline 1-oxide-induced cancers on chromosome 19, closely linked to D19Mit9. Peak linkage was observed 4 cM distal from D19Mit9, with a logarithm of the odds (lod) score of 5.72 for the number of large TCs and 6.08 for the DTCmax. On the other hand, WF rats had a semidominant gene (Rtc1) mapped between D1Mit1 and D1Mit3, approximately 20 cM from D1Mit1, with a peak lod score of 3.30 for both the number of large TCs and the DTCmax. The main effect of Rtc1 seemed to be to reduce the size of the TCs. The action of these genes was dose dependent and cooperative. The final incidence of TC in DA, WF, F1, and backcross rats seemed to be explained by combinations of genotype at these two loci. Possible candidate genes for Stc1 and Rtc1 are discussed.

4-Nitroquinoline-1-oxide↗
PubMed1998

High pressure conditions promote the proliferation of rat cultured mesangial cells in vitro.

Glomerular capillary pressure is involved in the development of chronic renal failure and has at least two effects on mesangial cells: transmembrane hydrostatic pressure and stretch. To clarify whether pure hydrostatic pressure itself affects the proliferation of cultured rat mesangial cells, we compared the cell number under atmospheric pressure condition with high pressure condition. At 24 and 48 h with 0.5% serum, cell number was significantly higher under high pressure condition than under atmospheric pressure condition. At 48 h, cell number under high pressure condition was increased in a pressure-dependent manner. Furthermore, flow cytometric assay indicated that pressure-load could promote DNA synthesis rate at S phase and enhance G1/S progression induced by low concentration of serum (0.5%). These results suggest that pure hydrostatic pressure itself can promote the proliferation of cultured rat mesangial cells by advancing cell cycle progression in vitro.

Air Pressure↗
PubMed1998

Possible rare involvement of O6-methylguanine formation as a significant mutational factor in mouse urinary bladder carcinogenesis models.

O6-methylguanine is known as one of the major premutagenic lesions in the human and rodent carcinogenesis process. O6-methylguanine-DNA methyltransferase (MGMT), which repairs methylated guanine bases, might prevent the G:C to A:T transition, and transgenic mice carrying this MGMT gene have been reported to be less sensitive to the carcinogenicity of certain alkylating agents. Here we utilized MGMT transgenic mice to assess the significance of O6-methylguanine formation during urinary bladder carcinogenesis. In experiment 1, 100 and 60 ppm N-butyl-N(4-hydroxybutyl)nitrosamine was given for 20 weeks to transgenic and non-transgenic mice in their drinking water. The incidences of urinary bladder carcinomas were not different between transgenic mice and non-transgenic mice. The mutational spectrum of the p53 gene was evaluated by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. The pattern of p53 mutations of transgenic and non-transgenic mice did not differ, and the frequencies of mutations were 40% and 42%, respectively. G:C to A:T transition mutations were particularly infrequent (1 of 14 mutations, 7%). In experiment 2, N-methyl-N-nitrosourea, which might induce O6-methylguanine in affected alleles, was given once a week, 3 times (total 5 mg) by direct instillation into the urinary bladder through an abdominal incision. No significant neoplastic lesions were detected, although the experiment was limited by severe toxicity of the treatment. p53 immunostaining was done and there was no difference in transgenic and non-transgenic mice. These results suggest that O6-methylguanine formation might not be a significant mutational factor in these mouse urinary bladder carcinogenesis models.

Adenosine Deaminase↗
PubMed1998

[A case of Pryce type I intrapulmonary sequestration].

A twenty-year-old asymptomatic man hospitalized because of a vascular murmur and abnormal shadow in the left lower lung on X-ray film. An aortogram revealed an abnormal artery arising from the descending thoracic aorta and supplying the left basal segment, which had no other pulmonary arteries. Although lung ventilation scintigraphy demonstrated reduced ventilation to the left lower lobe, bronchogram showed an almost normal bronchial tree except that peripheral branches were slightly thin. A clinical diagnosis of Pryce type I intrapulmonary sequestration was made, and left lower lobectomy was performed successfully. We have analyzed 31 cases of Pryce type I intrapulmonary sequestration in Japan. A vascular murmur is often heard, and a chest X-ray usually shows either a mass shadow or increased vascular markings. In most of those cases, an abnormal artery arises from the descending thoracic aorta and it supplies the left basal segment. Because this type of sequestration causes hemoptysis and infections, surgical intervention is indicated.

Adult↗
PubMed1998

The role of endogenous acid in the development of acute gastric ulcer induced by ischemia-reperfusion in the rat.

We investigated the role of endogenous gastric acid in the development of gastric ulcer from erosion induced by ischemia-reperfusion of the celiac artery in the rat. A half-hour clamping of the celiac artery (ischemia) caused acute gastric erosions 1 hour after reperfusion and such acute injuries progressed to ulcers 48-72 hours after reperfusion without any necrotizing agents. Gastric acid secretion decreased immediately after ischemia and didn't recover until 12 hours after reperfusion. Intraperitoneal administrations of cimetidine (100 mg/kg, every 12 hours) or omeprazole (30 mg/kg, every 24 hours) were started at 1, 6, or 12 hours after reperfusion. When administrations were started 1 hour after reperfusion, both drugs significantly decreased the total damaged area and prevented the progression of gastric erosions to ulcers. However, administrations started 6 or 12 hours after reperfusion failed to inhibit the total damaged area and to prevent ulcer formation. These results suggest that endogenous gastric acid may play an important role in the progression of gastric erosions to ulcers although ischemia itself reduces acid secretion. Furthermore, treatment with anti-acid-secretory drugs in the early stage of mucosal damage may be important for the prevention of ulcer.

Acute Disease↗
PubMed1998

Lack of lateral inhibitory interactions in visual cortex of monocularly deprived cats.

To gain new insight into the effects of monocular deprivation, we studied the visual cortex of adult cats deprived of vision in one eye. Local field potentials were recorded in response to contrast reversal of square-wave gratings modulated in time either by pseudorandom, m-sequences or periodically. We have found that: (1) stimulation of the retinotopic locus of the recording site elicits responses with abnormal waveforms and long latencies from the deprived eye; (2) stimulation of a remote, non-retinotopic locus elicits responses from the non-deprived eye but not from the deprived eye; (3) the monocularly deprived cortex lacks lateral inhibitory interactions which are characteristic of the normal cortex; and (4) steady-state responses showed little difference in spatial-frequency tuning and contrast sensitivity between the deprived and non-deprived eye, mostly conforming to earlier field-potential data in monocular deprivation. Functional lateral interactions appear to be greatly reduced in monocularly deprived cortex.

Animals↗
PubMed1998

Orthokeratinized odontogenic cyst: a clinicopathological and immunocytochemical study of 15 cases.

AIMS: Intraosseous jaw cysts with a solely orthokeratinized lining epithelium have been suggested to differ from the typical odontogenic keratocysts (OKC) by exhibiting a less aggressive behaviour. We report 15 cases of such cyst type under the term of 'orthokeratinized odontogenic cyst (OOC)' and compared their clinical, histological and immunocytochemical features with that of OKC. METHODS AND RESULTS: The cysts of the present series were all solitary lesions, occurred mostly in young male patients, and showed a predilection for the posterior mandible areas. Follow-up of 14 patients, nine of whom were treated by simple enucleation, revealed no recurrence over a period of 3.5-12 years after surgery. None of the patients had any association with the naevoid basal cell carcinoma syndrome. Furthermore, histological and immunocytochemical comparison between OOC and OKC revealed marked differences in their morphology and epithelial expression. The lining epithelium of OOC lacked the typical features of OKC and appeared to show a lower proliferative activity. CONCLUSION: These findings suggest that OOC is clinicopathologically separate from other types of odontogenic cysts and may thus constitute a distinct clinical entity.

Adult↗
PubMed1998

Presence of a threshold for promoting effects of phenobarbital on diethylnitrosamine-induced hepatic foci in the rat.

The dose dependence of the hepatopromoting effects of phenobarbital (PB) was investigated in a rat liver medium-term bioassay (Ito test) to elucidate a practical threshold level. F344 rats were given a single i.p. injection of diethylnitrosamine (200 mg/kg body wt) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, PB at doses of 0, 1, 2, 4, 7.5, 15 or 500 p.p.m. in experiment 1 and 0, 0.01, 0.1 or 0.5 p.p.m. in experiment 2 were fed to the rats for 6 weeks. Experiment 3 was conducted to confirm previous data using the same medium-term bioassay, with PB at doses of 0, 1, 2, 4, 7.5, 15, 30, 60, 125, 250 or 500 p.p.m. fed to the rats. All surviving animals were killed at week 8 in these experiments and their livers were immunohistochemically examined for expression of glutathione S-transferase placental form (GST-P). Quantitative values for GST-P-positive foci in the liver were increased dose dependently in rats given 60-500 p.p.m. PB. However, those for doses in the range 1-7.5 p.p.m. demonstrated a decrease as compared with the control group (0 p.p.m.), with significant differences observed for 1 and 2 p.p.m.. The results for 15-30 and 0.01-0.5 p.p.m. were comparable with the control values. Examination of transforming growth factor-alpha (TGF-alpha)-positive foci also produced similar results to those for GST-P in experiment 1. Immunohistochemical staining of TGF-alpha and GST-P using serial liver sections demonstrated that the TGF-alpha-positive foci comprised a sub-population of the GST-P-positive lesions, being approximately 1/8-1/10th as common in livers of animals treated with PB. TGF-alpha-positive foci were almost always negative on immunostaining for TGF-beta. Western blotting for proteins CYP2B1, 2C6 and 3A2 revealed a good correlation between changes in GST-P-positive foci and CYP3A2 protein expression. The finding of inhibition effects at low doses of PB confirms the presence of a threshold level for promoting effects by PB on liver carcinogenesis in rats.

Animals↗
PubMed1998

Usefulness and limitations of ultrasonography in the initial evaluation of blunt abdominal trauma.

BACKGROUND: In the assessment of blunt abdominal trauma, the reliability of ultrasonography (US) in identifying individual organ injuries remains uncertain, in spite of its usefulness in detecting hemoperitoneum. This study was designed to evaluate the overall diagnostic value of US, including identification of individual organ injuries. METHODS: The accuracy of US in the detection of intra-abdominal injuries and the identification of individual organ injuries was evaluated in 1,239 patients seen during a 15-year period. Accuracy was based on detection of intraperitoneal fluid, free air, or irregular parenchymal lesions. RESULTS: For the detection of injuries, US was 94.6% sensitive, 95.1% specific, and 94.9% accurate. Individual organ injuries were identified with sensitivities of 92.4, 90.0, 92.2, 71.4, and 34.7% for the liver, spleen, kidneys, pancreas, and intestine, respectively. CONCLUSION: US is reliable for the detection of injuries and the identification of solid-organ injuries despite its poor sensitivity for intestinal injuries.

Abdominal Injuries↗
PubMed1998

Experimental odontogenic cysts induced by in vitro 4-nitroquinoline 1-oxide (4NQO) treatment of F344 rat incisor tooth germs.

This study was designed to establish an experimental animal model for elucidating the early stages of odontogenic cysts and tumors. It involves the in vitro treatment of tooth germs with 4-nitroquinoline 1-oxide (4NQO) at the early bell stage and their subsequent transplantation into the kidney subcapsular space. While all tooth germ transplants of the control group not exposed to the carcinogen showed continued tooth development with no pathological lesions, 21 of 23 4NQO-treated tooth germs developed into similar appearing keratinized cysts with or without associated tooth structures. The remaining two transplants failed to develop cysts and formed only a tooth. The present experimental procedure was effective in inducing keratinized cystic lesions that exhibit some similarities to human odontogenic keratocysts or primordial cysts.

4-Nitroquinoline-1-oxide↗
PubMed1998

Sustained cholecystokinin-B/gastrin receptor blockade does not impair basal or histamine-stimulated acid secretion in chronic gastric fistula rats.

Gastrin is a physiologically important secretagogue. It is thought to stimulate parietal cells indirectly by mobilizing histamine from enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin stimulates the secretory activity and growth of the ECL cells via an action on cholecystokinin-B/gastrin receptors. Acute cholecystokinin-B/gastrin receptor blockade is known to inhibit gastrin-stimulated acid secretion but whether sustained cholecystokinin-B/gastrin receptor blockade will impair basal, gastrin- and histamine-stimulated acid secretion remains uncertain. The present study was designed to study the effect of long-term (4 weeks) cholecystokinin-B/gastrin receptor blockade on basal and stimulated acid secretion in conscious rats. The selective cholecystokinin-B/gastrin receptor antagonist YM022 (3 mumol.kg-1.hr-1) was given to gastric fistula rats by continuous subcutaneous infusion via osmotic minipumps for various times from 2 hr to 4 weeks. Basal, gastrin- and histamine-stimulated acid secretion were examined during and after cessation of treatment. Basal and histamine-stimulated acid secretion was not affected by YM022 during the 4 week period of administration, whereas gastrin-induced acid secretion was inhibited. YM022 induced hypergastrinaemia in freely fed rats but did not affect the serum gastrin level in fasted rats. The serum gastrin concentration and gastrin-induced acid secretion returned to control levels 3-7 days after termination of YM022 administration.

Animals↗
PubMed1998

Evaluation of oral mucoadhesive microspheres in man on the basis of the pharmacokinetics of furosemide and riboflavin, compounds with limited gastrointestinal absorption sites.

When sustained-release adhesive and non-adhesive microspheres which release the same drugs at similar rates are administered orally, drug absorption after administration of adhesive microspheres should, if the gastrointestinal residence of adhesive microspheres is prolonged as a result of mucoadhesion, be higher than that after administration of non-adhesive microspheres. The gastrointestinal transit of oral adhesive microspheres in man has been evaluated pharmacokinetically using furosemide and riboflavin, compounds with limited absorption sites in the upper small intestine. In a preliminary experiment with fasted rats it was confirmed that a higher percentage of the drug remained in the stomach and that plasma drug levels were higher when furosemide was administered in the form of adhesive rather than non-adhesive microspheres. Two kinds of sustained-release microsphere, adhesive and non-adhesive, containing furosemide and riboflavin in hard gelatin capsules were prepared and orally administered to 10 healthy fasted volunteers in a cross-over design. Areas under the plasma concentration-time curves (AUC) were 1.8 times larger for furosemide and urinary recovery was 2.4 times higher for riboflavin when adhesive microspheres rather than when non-adhesive microspheres were used. When adhesive microspheres containing riboflavin were administered to fed volunteers, urinary recovery was 2.1 times higher and mean residence time (MRT) was more prolonged than when the microspheres were administered to fasted volunteers. Adhesive microspheres were found to adhere to the gastric or intestinal mucosa with high affinity in man and rats, resulting in prolonged gastrointestinal residence.

Adhesives↗
PubMed1998

Mucoadhesive microspheres containing amoxicillin for clearance of Helicobacter pylori.

In an effort to augment the anti-Helicobacter pylori effect of amoxicillin, mucoadhesive microspheres, which have the ability to reside in the gastrointestinal tract for an extended period, were prepared. The microspheres contained the antimicrobial agent and an adhesive polymer (carboxyvinyl polymer) powder dispersed in waxy hydrogenated castor oil. The percentage of amoxicillin remaining in the stomach both 2 and 4 h after oral administration of the mucoadhesive microspheres to Mongolian gerbils under fed conditions was about three times higher than that after administration in the form of a 0.5% methylcellulose suspension. The in vivo clearance of H. pylori following oral administration of the mucoadhesive microspheres and the 0.5% methylcellulose suspension to infected Mongolian gerbils was examined under fed conditions. The mucoadhesive microspheres and the 0.5% methylcellulose suspension both showed anti-H. pylori effects in this experimental model of infection, but the required dose of amoxicillin was effectively reduced by a factor of 10 when the mucoadhesive microspheres were used. In conclusion, the mucoadhesive microspheres more effectively cleared H. pylori from the gastrointestinal tract than the 0.5% methylcellulose suspension due to the prolonged gastrointestinal residence time resulting from mucoadhesion. A dosage form consisting of mucoadhesive microspheres containing an appropriate antimicrobial agent should be useful for the eradication of H. pylori.

Amoxicillin↗
PubMed1998

Staged reperfusion preserves the coronary flow reserve, especially in the regions not severely damaged by ischemic injury in the canine heart.

The objective of this study was to determine the effects of staged reperfusion on the progressive reduction in coronary blood flow (CBF) and coronary flow reserve during reperfusion and on the infarct size in the canine heart. Fifteen dogs underwent 90 min of left circumflex coronary artery occlusion and 3 hr of reperfusion. In the abrupt reperfusion group, the occluder was released completely at the initiation of reperfusion. In the staged reperfusion group, CBF was maintained at 20% of preocclusion values for 10 min after initiation of reperfusion, then gradually released, and completely released 20 min after initiation of reperfusion. There was no significant difference in CBF between the staged (n = seven) and abrupt (n = eight) groups after 3 hr of reperfusion. The repayment of flow debt in the staged reperfusion group was significantly greater than in the abrupt reperfusion group after 3 hr of reperfusion (260+/-120% vs 100+/-60%, staged vs abrupt at 3 hr, p < 0.03). The ratio of peak reactive hyperemic flow to resting flow in the staged reperfusion group was significantly greater than in the abrupt reperfusion group throughout the reperfusion phase (4.4+/-1.0 vs 2.6+/-0.6 at 3 hr, p < 0.001), and had returned to the preocclusion values after 3 hr of reperfusion. This preservation of the coronary flow reserve in the staged reperfusion group was observed in the epicardium (4.1+/-0.6 vs 2.8+/-0.7, staged vs abrupt at 3 hr, p < 0.01), but not in the endocardium or midmyocardium. Infarct size did not differ significantly between the two groups. Staged reperfusion in this study did not appear to attenuate the reduction of CBF, or to reduce infarct size, however preserved the coronary flow reserve, especially in the regions not severely damaged by ischemic injury.

Animals↗