Biomedical subjects

I Murakami

Publications and source records attributed to I Murakami.

At least 55 records · Page 3Linked to original sources

PubMed1997

Prevention of gastric ulcer relapse induced by indomethacin in rats by a mutein of basic fibroblast growth factor.

We found indomethacin aggravates healed gastric ulcers (ulcer relapse) in rats. In the present study, we examined the effects of human basic fibroblast growth factor (bFGF) mutein CS23 (TGP-580) and histamine H2-receptor antagonists (H2-RAs) on ulcer relapse in this model. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Indomethacin (1 mg/kg/day) given s.c. for 2 weeks starting 4 weeks after the operation aggravated the healed ulcer; the areas with and without indomethacin were 4.8 +/- 1.4 and 0.4 +/- 0.3 mm2, respectively. Drugs were given orally once daily for 4 weeks starting 2 days after the operation or for the 2-week indomethacin administration period. Treatment with ranitidine (100 mg/kg), cimetidine (100 mg/kg) and TGP-580 (0.1 mg/kg) for 4 weeks accelerated the healing. The aggravation by indomethacin was significantly inhibited by pretreatment with TGP-580 and mildly inhibited by cimetidine but not ranitidine. When the drugs were co-administered with indomethacin for 2 weeks, the aggravation was significantly prevented by ranitidine and mildly inhibited by cimetidine and TGP-580. Both TGP-580 and H2-RAs can prevent the ulcer relapse induced by indomethacin but via different modes of action: TGP-580 inhibits relapse mainly by acting on the process of healing, while H2-RAs act mainly on the process of aggravation.

Acetic Acid↗

PubMed1997

Role of endogenous basic fibroblast growth factor in the healing of gastric ulcers in rats.

Recently, it has been pointed out that growth factors play an important role in the healing of gastrointestinal ulcers. In the present study, we examined the role of endogenous basic fibroblast growth factor (bFGF) in the healing of gastric ulcers in the rat. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Time-dependent changes in the area and bFGF content in the ulcerated area and distribution of bFGF in the ulcerated mucosa were examined. Effects of bFGF mutein CS23 (TGP-580) and a monoclonal antibody for bFGF (MAb 3H3) on the healing of the gastric ulcers and angiogenesis in the ulcer bed were also examined. The content of bFGF in the ulcerated area increased with time as the ulcer healed and reached a maximum 7 days after ulcer formation. In the gastric ulcer bed, many cells such as fibroblasts and macrophages were positively stained immunohistochemically by anti-bFGF antiserum. MAb 3H3 (0.1 mg/rat/day, i.v.) inhibited angiogenesis in the ulcer bed and significantly delayed ulcer healing, while TGP-580 (0.001-0.1 mg/kg x 2/day, p.o.) increased the number of microvessels in the ulcer bed and accelerated the healing. These results suggest that endogenous bFGF may play an important role in the healing of gastric ulcers in the rat and that the angiogenic properties of bFGF (TGP-580) may be involved in its effect on ulcer healing.

Animals↗

PubMed1997

A retrospective evaluation of maternal serum screening for the detection of fetal aneuploidy.

A retrospective evaluation of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) levels in maternal blood in the second trimester was conducted for cases of aneuploid pregnancies identified from a series of women who underwent amniocentesis. Blood samples were collected from 1078 women just before genetic amniocentesis was performed, mainly for individuals of advanced maternal age (greater than 35 years). Twenty-five maternal serum samples from pregnant women with an aneuploid fetus, including 14 with Down's syndrome, were available for analysis of all three parameters. An algorithm to detect Down's syndrome was used for this analysis with a risk of > or = 1:299 classified as screen-positive, this being found for 20.4 per cent of the cases (220/1078). The actual Down's syndrome detection rate was 85.7 per cent (12/14), whereas the detection rate for all aneuploidies was 72.0 per cent (18/25). Those that were not detected were two cases of trisomy 21, one trisomy 18, two trisomy 13, three sex chromosome abnormalities, and one case of an additional marker chromosome. The data indicate that this tri-analyte test should be provided after thorough genetic counselling and informed decision-making regarding maternal serum screening for women who wish for a prenatal diagnosis.

Adult↗

PubMed1996

Comparison of lens biochemistry and structure between BSO-treated and glucocorticoid-treated developing chick embryos.

In this paper various changes in glutathione level, which were influenced by balance of its synthesis, degradation, transport and utilization, were analysed in chick embryos administered with glucocorticoid (GC) or buthionine sulfoximine (BSO; an inhibitor of glutathione synthesis). When BSO (30 mumol egg-1) was administered twice to chick embryos on day 14 and 15, the GSH in both the lens and the liver decreased to 15-20% and 30-40% of the age-matched control level, respectively, between 24 and 48 hr after the second treatment, then began to recover. Although this decline in the GSH level in these tissues was greater and more prolonged in embryos treated with BSO than with GC, the former embryos maintained lens transparency even up to 144 hr by a visual examination. However, histological changes in the lens occurred after 96 hr and more significantly 144 hr after second administration of BSO. The changes mainly consisted of pale epithelial cells on the anterior peripheral surface of the lens, irregular height of the epithelial cells at the equator, clefts between the epithelium and the cortex and swelling of almost all the cortical fibers. These observations may suggest that BSO treatment could produce the beginning of a cataract. Embryos with GC-cataract revealed the following changes at 48 hr: loss of transparency, elevation of LPO (TBA-reacting substance) in the lens, the blood and the liver. These were not observed in BSO-treated embryos during the experimental period. The GC-cataract may well depend on the generation of LPO. BSO cataract, having a distinct mechanism compared to that caused by GC, develops more slowly in GSH-depleted lenses. The BSO-treated chick embryos will be a useful model to screen the risk factors which accelerate cataract formation.

Animals↗

PubMed1996

Assimilation-type and contrast-type bias of motion induced by the surround in a random-dot display: evidence for center-surround antagonism.

As a mechanism to detect differential motion, we have proposed a model of "a motion contrast detector" that has a center-surround antagonistic receptive field with respect to the direction of motion. Supporting evidence has been obtained in the studies of induced motion, motion capture, and motion aftereffect. In order to obtain further evidence in a more strictly controlled situation, we examined the perceptual bias of motion in a center stimulus induced by another, surrounding motion. By using a stochastic random-dot display configured in a center-surround concentric fashion, we measured the % signal in the center stimulus that made the stimulus perceptually stationary in the presence of a moving surround. Measurements were done for various stimulus sizes and eccentricities. The amount of bias changed as a function of stimulus size and eccentricity. At several eccentricities, smaller stimulus sizes tended to yield assimilation-type biases, whereas larger sizes tended to yield contrast-type biases. However, a spatial scaling procedure revealed that the amount of bias was a simpler function of "scaled" stimulus size that was obtained by dividing the physical size by a scaling factor at each eccentricity. In the scaled profile, assimilation-type bias changed to contrast-type bias with increasing size, reached the peak of contrast-type bias at a certain size, and decreased slightly with further increasing size. Furthermore, a model of a difference of Gaussians, DOG, function well approximated the behavior of the profile. From these results, we concluded that the process specific to perceiving relative motion is mediated by a motion contrast detector, which is possibly located in area MT.

Humans↗

PubMed1996

Surface representation in the visual system.

Perception of surface accompanies the impression that a certain area of the visual field is occupied by some quality, such as color, brightness and transparency. This does not mean, however, that information about surface quality must be obtained throughout the area. It has been shown in many situations that our visual system has ability to interpolate information obtained at the border of the surface and to perceive homogeneous surfaces. The most dramatic demonstration of this is the perceptual filling-in at the blind spot. In order to understand the neural representation of surface in the visual system, we conducted a series of experiments using macaque monkeys. First, we examined if neurons in the primary visual cortex (V1) respond when a homogeneous surface is presented on the receptive field. Neurons representing the parafoveal visual field were tested and it was found that about one third of neurons showed significant responses when the cell's receptive field was contained in a homogeneous surface. Then we examined neuron activities in the retinotopic representation of the blind spot in V1. Although there is no retinal input in the blind spot, a homogeneous surface is perceived within the blind spot as a result of filling-in. We tested whether neurons in this region were activated when a homogeneous surface was perceived in the blind spot as a result of filling-in. We found some neurons in V1 were activated by stimuli which lead to the filling-in. These results indicate that when a surface area is perceived, neurons are activated throughout the region in V1 topographically corresponding to the perceived surface and not restricted to the region representing the border of the surface.

Animals↗

PubMed1996

Laparoscopic-assisted creation of a vagina.

The applicability of laparoscopy for colpopiesis using pelvic peritoneum was examined in two women with the Mayer-Rokitansky-Kuster-Hauser syndrome. Using a modification of laparoscopic guidance proved advantageous for safe dissection of the vesicorectal space and accurate suturing of the pelvic peritoneum without laparotomy. A sufficient vaginal cavity was achieved in both patients. This modification of the original procedure, featuring introduction of a laparoscope, thus provides effective and safe conditions for creation of a new vagina.

Adult↗

PubMed1996

Nicergorine-induced lichen planus-like eruption.

A case of a lichen planus-like eruption due to nicergorine on the lower legs of an 84-year-old woman is reported. She presented with slightly pruritic, erythematous plaques of six months' duration. She had taken eight kinds of drugs, including nicregorine for cerebral arteriosclerosis, for two years. After nicergorine was discontinued, the eruption gradually disappeared. Readministration of nicergorine induced a similar eruption within two months. Histologic findings were identical in the two biopsy specimens obtained at the first visit and from the recurrent lesion. To our knowledge, this is the first report on nicergorine-induced lichen planus-like eruptions.

Aged↗

PubMed1996

Detection of p53 gene mutations in cytopathology and biopsy specimens from patients with lung cancer.

In order to ascertain the feasibility of detecting p53 gene mutations in patients with lung cancer in a nonsurgical diagnostic setting before starting treatment, we screened for p53 gene mutations in tumor specimens obtained using diagnostic methods such as fiberoptic bronchoscopy, thoracentesis, and percutaneous needle aspiration. We examined 206 specimens from 66 patients diagnosed with primary lung cancer at Hiroshima University Hospital between October 1991 and July 1993 using the polymerase chain reaction/denaturing gradient gel electrophoresis technique. p53 gene mutations were found in 64 of 159 (40%) cytologically positive specimens, but in none of 47 cytologically negative specimens. The PCR-based assay did not increase the sensitivity of the cytopathologic examination in detecting malignant cells. The type and location of the p53 gene mutation was the same in cytologically positive specimens obtained by different methods, but from the same patient. Of the 66 patients, p53 gene mutations were found in 27 (41%) at the time of the first nonsurgical diagnostic examination: 7 of 12 (58%) with small cell carcinoma, 9 of 20 (45%) with squamous cell carcinoma, and 11 of 34 (32%) with adenocarcinoma of the lung. The incidence of p53 gene mutation for each histologic subtype was comparable to previously published data examining surgically and/or autopsy-obtained specimens. These results indicate that detection of p53 gene mutations in a nonsurgical, diagnostic setting is feasible. This technique will make it possible to assess the significance of p53 gene mutations in relation to survival and response to therapy before starting treatment, in future prospective studies.

Adenocarcinoma↗

PubMed1996

A new type of familial central diabetes insipidus caused by a single base substitution in the neurophysin II coding region of the vasopressin gene.

We studied the genetic basis of familial neurohypophyseal diabetes insipidus in a Japanese family. The members had polyuria and a deficiency of plasma vasopressin (AVP). Polymerase chain reaction (PCR) amplified exons of the AVP-neurophysin-II gene were subcloned and sequenced. Exons 1 and 3 were normal, but nucleotide 1884 Guanine (G) in exon 2 was substituted with Thymine (T), which induced a substitution of glycine (Gly) for valine (Val). To examine the presence of this mutation in the affected subjects, we designed two mutated primers. One of them induced a new endonuclease restriction site in the PCR fragments from normal, and the other induced a new endonuclease restriction site from patients with the mutation. DNA fragments from two affected members of this family were amplified with this primer, and the PCR products were digested by endonuclease and resolved by electrophoresis. The results indicated that these subjects had both normal and mutant alleles, indicating that the mutation was heterozygous. We concluded that this mutation caused neurohypophyseal diabetes insipidus in this family.

Arginine Vasopressin↗

PubMed1996

[Effects of lansoprazole on indomethacin-induced gastric bleeding and mucosal lesions in rats].

The effects of lansoprazole given intravenously on indomethacin-induced gastric bleeding and mucosal lesions were investigated in rats in comparison with those of omeprazole, famotidine and ranitidine. Lansoprazole inhibited gastric bleeding induced by indomethacin with an ID50 value of 0.29 mg/kg. Omeprazole and famotidine significantly inhibited gastric bleeding, but ranitidine provided negligible inhibition. A correlation was found between the inhibitory action of lansoprazole on gastric bleeding, and acid secretion, and its inhibitory action on gastric bleeding was almost completely abolished by adding 50 mM-HCl to the gastric perfusate, suggesting that lansoprazole's inhibitory action on gastric bleeding was mainly due to its antisecretory action. Lansoprazole inhibited the development of gastric lesions induced by indomethacin with an ID50 value of 0.10 mg/kg, whereas histamine H2-receptor antagonists did not display a potent inhibitory effect. ID50 values for omeprazole, famotidine and ranitidine were 0.69, 2.58 and 24.6 mg/kg, respectively. These results indicate that lansoprazole has a potent inhibitory action on indomethacin-induced gastric bleeding and mucosal lesions and that it is useful in the treatment of acute gastric mucosal lesions.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

[Effects of intravenous lansoprazole on acute gastric mucosal lesions and acid secretion].

The effects of lansoprazole given intravenously on gastric mucosal lesions, gastric bleeding and acid secretion were investigated in rats in comparison with those of omeprazole, famotidine and ranitidine. Lansoprazole inhibited the formation of gastric mucosal lesions in rats induced by water-immersion stress or aspirin with ID50 values of 0.26 and 0.99 mg/kg, respectively, and also inhibited gastric bleeding induced by hemorrhagic shock or water-immersion stress with ID50 values of 0.46 and 1.22 mg/kg, respectively. Lansoprazole was more potent than omeprazole, famotidine and ranitidine in inhibiting gastric mucosal lesions and hemorrhagic shock- or stress-induced bleeding. Famotidine and ranitidine showed negligible inhibition of water-immersion stress-induced gastric bleeding. Lansoprazole strongly inhibited water-immersion stress-stimulated acid secretion in rats, whereas famotidine and ranitidine did not show a potent inhibitory effect. These results indicate that lansoprazole exerts prominent inhibitory actions against the formation of gastric mucosal lesions and gastric bleeding by inhibiting acid secretion, and they show that it is superior to histamine H2-receptor antagonists in inhibiting stress-induced gastric bleeding.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

Role of capsaicin-sensitive sensory neurons and nitric oxide in the protective effect of lansoprazole, a proton pump inhibitor, on the gastric mucosa in rats.

The mucosal protective effect of lansoprazole, a proton pump inhibitor, was examined in ethanol- and acidified taurocholate-induced rat gastric lesion models. The formation of gastric lesions was markedly inhibited by prostaglandin E2 but hardly inhibited by cimetidine, ranitidine and famotidine. Lansoprazole (3-30 mg/kg, p.o.) inhibited the formation of gastric lesions in a dose-dependent manner, with ID50 values of 8.5 (ethanol) and 4.1 mg/kg, p.o. (acidified taurocholate). The protective effect of lansoprazole was significantly decreased by functional ablation of capsaicin-sensitive sensory neurons or prior administration of indomethacin or N(omega)-nitro-L-arginine methyl ester (L-NAME), a selective inhibitor of nitric oxide (NO) synthesis. The inhibitory effect of L-NAME was antagonized by prior administration of L-arginine, a substrate of endogenous NO, but not D-arginine. The antisecretory effect of lansoprazole on the basal acid secretion in pylorus-ligated rats was not affected by any of these treatments. Lansoprazole (5 and 15 mg/ml) administered directly into the gastric chamber obviously increased both the production of NO in the mucosa and mucosal blood flow, which was prevented by pretreatment with L-NAME. These results suggest that capsaicin-sensitive sensory neurons, NO and prostaglandins are involved in the mucosal protection afforded by lansoprazole possibly via an increase in mucosal blood flow, but are not involved in the antisecretory action of lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

[Anesthetic management of ten Jehovah's Witness patients].

We experienced the anesthetic management of 10 Jehovah's Witness patients. Some patients accepted either blood products, autologous blood transfusion with closed circuit, or Cell Saver. The patients' families expressed their wish that blood transfusion could be done in life threatening situations against the patient's wish in some cases. It would be desirable to clear up an acceptable standard and write out it in each medical institution to avoid conflicts with the patient and families. Prior agreement is required among medical staffs on refusal of blood transfusion.

Adult↗

PubMed1996

Neuroendocrine pharmacology of three serotonin releasers: 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAi) and p-methylthioamphetamine (MTA).

Serotonin (5-hydroxytryptamine, 5-HT)-releasing drugs are important experimental tools to examine the role of serotonergic nerve terminals in the secretion of hormones. The drugs 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAI) and p-methylthioamphetamine (MTA) have been suggested to be 5-HT releasers. The present study characterized MBDB, MMAI and MTA by using their effects on the secretion of the hormones adrenal corticotrophin (ACTH), corticosterone, prolactin, oxytocin and renin. The time course of the effect of MBDB, MMAI and MTA (5 mg/kg, i.p.) showed that the peak effect on plasma ACTH occurred 10 min after the injection, whereas the prolactin response did not reach a maximum until 30 min after injection. MBDB increased plasma renin concentration within 10 min, whereas the effect of MTA was significant only at 30 min after injection. All three 5-HT releasers decreased HR (within 5 min) and blood pressure (at 15 min after injection). MBDB, MMAI and MTA increased plasma ACTH, corticosterone, prolactin and renin levels in a dose-dependent manner, whereas no changes were observed in plasma vasopressin concentrations. MTA and MMAI, but not MBDB, significantly increased plasma oxytocin concentrations in a dose-dependent manner. Pretreatment of rats with fluoxetine blocked the ACTH response to MBDB and MMAI, but not to MTA. The prolactin response to all three 5-HT releasers was blocked by fluoxetine. The oxytocin response to MTA and MMAI was inhibited by fluoxetine. The renin responses to all three 5-HT releasers were not significantly inhibited by fluoxetine. The results suggest that MBDB, MMAI and MTA can increase the secretion of several hormones, at least in part, through stimulation of serotonergic neurotransmission. However, these three 5-HT releasers seem to have effects on other (and as yet uncharacterized) mechanisms that can stimulate the secretion of some hormones.

3,4-Methylenedioxyamphetamine↗

PubMed1995

Alterations in telomeric repeat length in lung cancer are associated with loss of heterozygosity in p53 and Rb.

In the two-stage model of controlling cellular senescence in cultured human fibroblasts, retinoblastoma (Rb) and p53 proteins may be key factors regulating the mortality stage 1 mechanism. In addition, the critical loss of telomeric DNA due to the end-replication problem may result in the mortality stage 2 mechanism. Cells which acquire telomerase activity can overcome the M2 mechanism by stabilizing telomere length and thus become immortal (telomere hypothesis). At present it is known whether cellular immortality is a prerequisite for all human cancers. To investigate this question and the applicability of the two-stage model to human cancers, we analysed the relationship between alterations of telomere length and other genetic changes in lung cancer. Among 60 primary lung cancer tissues, telomere length alterations were observed in 16 tumors (26.7%) including 14 with short and two with elongated telomeres. Ten of them revealed allelic loss of both p53 and Rb genes, and remaining six showed no abnormalities in both genes. We propose that inactivation of both p53 and Rb genes may promote cell divisions causing telomere shortening in lung cancer as in the two-stage model, while there may be another pathway to overcome both M1 and M2 mechanisms, especially for adenocarcinoma.

Base Sequence↗

PubMed1995

Motion aftereffect after monocular adaptation to filled-in motion at the blind spot.

Although the blind spot encodes no visual information, one never perceives an odd blob or blank there, but sees a complete scene of the world even when viewing monocularly. This phenomenon called "filling-in" might be related to mechanisms essential to surface perception, but the neural representation has still been unclear. To determine at what stage the computation for filling-in is established in the visual system, whether prolonged observation of a filled-in motion including the blind spot of one eye could cause motion aftereffect at the corresponding visual field of the other eye was examined. The result was positive--interocular transfer of motion aftereffect was obtained at the tested eye. This finding suggests the possibility that real motion and filled-in motion share a common motion pathway in an early stage in the human visual system.

Adaptation, Ocular↗

PubMed1995

Modulation of motion aftereffect by surround motion and its dependence on stimulus size and eccentricity.

As a mechanism to detect differential motion, we have proposed a model of 'a motion contrast detector' and have shown that it can explain the perceptual change from motion capture to induced motion with increasing stimulus size and decreasing eccentricity. To further test the feasibility of the model, we examined the effect of surround motion on the motion aftereffect (MAE) elicited in the center. Using a drifting grating surrounded by another drifting grating, the duration of MAE in the center after adaptation was measured for various surround velocities (Expt 1). MAE was stronger when the surround moved oppositely to, than together with, the center. This finding was consistent with some previous reports. Using similar stimuli, MAE was measured at various stimulus sizes and eccentricities by the cancellation technique (Expt 2). The effect of surround modulation turned out to vary with both size and eccentricity. We examined if the apparent dependence on eccentricity could reflect a simpler effect of cortical size when the data were rescaled according to a linear scaling factor. We interpret our results in terms of motion contrast detectors, possibly located in the area MT.

Adaptation, Ocular↗