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Biomedical subjects

K Murakami

Publications and source records attributed to K Murakami.

At least 73 records · Page 4Linked to original sources
PubMed2001

Environmental survey of salmonella and comparison of genotypic character with human isolates in Western Japan.

To estimate the prevalence and distribution of salmonellae, especially Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis), in Western Japan, an investigation was conducted of the chicken industry and environmental sources between 1995 and 1998. Salmonellae were isolated from 34 of 90 samples (37.8%) of raw chicken parts, 34 of 98 faecal samples (34.7%) at 35 broiler farms, 11 of 59 samples (18.6%) of liquid eggs, and from 71 of 272 samples (26.1%) of swab specimens from equipment and cracked or faecally soiled shell eggs at the processing facilities. Salmonellae, including S. Enteritidis, were also isolated from swab samples of henhouses associated with one of the shell-egg processing facilities (11 samples out of 55, 20%). In the broiler meat production environment, S. Infantis was dominant. Twenty-two of 36 sewage samples (61.1%) and 16 of 72 samples (22.2%) taken from 5 rivers contained salmonellae including S. Enteritidis. S. Enteritidis isolates were analysed with pulsed-field gel electrophoresis using enzyme Bln I. Thirty-four isolates from shell-egg processing facilities and henhouses, obtained over several years, had the same pulsed-field profile as isolates obtained from four individual outbreaks that occurred in this location in 1997. One of the clonal lines of S. Enteritidis, among multiple serovars of salmonellae in the environment, was thought to have distributed in reservoirs, laying hens, for several years, and continued to cause outbreaks in this area.

Animals↗
PubMed2001

Aluminum-induced apoptosis in PC12D cells.

The addition of aluminum-maltol complex to PC12D cells induced a time-dependent and concentration-dependent growth inhibition as well as cell death, whereas aluminum chloride or maltol alone did not affect the viability of PC12D cells. Apoptosis of differentiated PC12D cells was assessed by using terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine-5'-triphosphate nick end labeling (TUNEL) technique to detect DNA strand breaks in situ. The number of TUNEL-positive cells treated with aluminum-maltol increased with time in the treatment cultures. The ability of aluminum ion to elevate intracellular reactive oxygen species was determined by fluorescence in PC12D cells loaded with the oxidant-sensitive dye 2',7'-dichlorofluorescin diacetate. Aluminum ion incorporated to PC 12D cells causes apoptotic cell death by enhancing the generation of reactive oxygen species.

Aluminum↗
PubMed2001

The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.

Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.

Adiponectin↗
PubMed2001

Hyperplastic vascular smooth muscle cells of the intrarenal arteries in angiotensin II type 1a receptor null mutant mice.

BACKGROUND: Angiotensin II (Ang II), which contracts vascular smooth muscle cells (VSMCs), has been reported to regulate VSMC growth. Recently formed transgenic mice without angiotensinogen or Ang II receptors showed vascular alterations. However, it is still unclear how their VSMCs alter. We explored the role of Ang II via the Ang II type 1a receptor (AT1a) in VSMCs in vivo using AT1a null mutant mice. METHODS: We analyzed the ultrastructure of the intrarenal arteries in AT1a null mutant mice that were homozygous for a targeted disruption of AT1a receptor gene using light and electron microscopy. RESULTS: The structural changes of the intrarenal arteries in AT1a null mutant mice showed the wall thickening, which in the interlobar, arcuate, and proximal interlobular arteries consisted of two additional populations of VSMCs, on the luminal and abluminal sides of the media. The luminal overpopulation of smooth muscle cells (SMCs) was arranged in a longitudinal direction separated by increased interposed elastic laminae. The abluminal overpopulation of SMCs ran in circumferential directions separated from the main population. The cytological structure of VSMCs in AT1a null mutant mice was smaller in size, contained more organelles for protein synthesis and secretion than in control mice, and had poorly developed contractile apparatus. CONCLUSIONS: The lack of AT1a signaling causes structural abnormalities in the renal vascular system and transforms the phenotype of VSMCs into cell proliferation, induces the escape of VSMCs from the circular mechanical integrity, and results in increased synthesis of extracellular matrices.

Animals↗
PubMed2001

Guidelines in the management of Helicobacter pylori infection in Japan.

BACKGROUND: In preparation of the approval of Helicobacter pylori therapy by the Japanese national health system, the board of directors of the Japanese Society for Helicobacter Research decided to prepare guidelines on the diagnosis and treatment of H. pylori infection for physicians in routine medical practice. METHODS: A guidelines preparation committee was formed and six meetings were held. Then, in December 1999, a consensus meeting was held in Kobe to obtain the opinions of general practitioners as well as experts from Europe, North America, and Asia. RESULTS: Helicobacter pylori eradication therapy is recommended in gastric or duodenal ulcer patients. Helicobacter pylori eradication therapy is recommended or gastric mucosa associated lymphoid tissue (MALT) lymphoma but it should be done at specialist institutions. The significance of H. pylori eradication therapy is still under evaluation in patients with hyperplastic polyps, chronic atrophic gastritis, non-ulcer dyspepsia and in patients after endoscopic mucosal resection of gastric cancer and after gastrectomy for gastric cancer. When diagnosing H. pylori infection, at least one of the tests requiring endoscopic biopsy (e.g. rapid urease test, histology, or culture) and tests not requiring biopsy (e.g. measurement of H. pylori antibody or urea breath test) should be used. Multiple tests are recommended to increase the accuracy. The drugs of first choice currently covered by the national health insurance system in Japan are: lansoprazole (30 mg) 1 capsule twice daily, amoxicillin (250 mg) 3 capsules twice daily, and clarithromycin (200 mg) 1-2 tablets twice daily. These three drugs should be administered after breakfast and dinner for 1 week. CONCLUSION: These guidelines are intended for utilization in routine medical practice after the Japanese national health system begins to cover the management of H. pylori infection.

Amoxicillin↗
PubMed2001

A comparative evaluation of osteosynthesis with lag screws, miniplates, or Kirschner wires for mandibular condylar process fractures.

PURPOSE: This study compared the clinical and radiologic outcomes of open treatment of mandibular condylar process fractures using lag screws, miniplates, or Kirschner wires. PATIENTS AND METHODS: Open reduction and internal fixation was performed for severely displaced or dislocated mandibular condylar process fractures in 23 patients (26 fractures) using Eckelt lag screws, in 10 patients (10 fractures) using Kirschner wires, and in 21 patients (22 fractures) using miniplates. Clinical and radiologic evaluations were made 6 months postoperatively and at final follow-up (mean, 18.4 months; range, 7 to 106 months). Radiologic evaluation included accuracy of reduction of the fractured condylar processes and changes in ramus height. RESULTS: Most fractured condylar processes (approximately 90%) were repositioned precisely in all groups. A shortening of the ramus of more than 5 mm was observed significantly more frequently (P <.05) in the miniplate group than in the lag screw group at 6 months. The condyles were severely resorbed in 2 or 3 patients in each group. All of these patients were associated with malunion, and partial bone resorption of the condyles was seen during the first 6 months. The relation between reduction or screw position and bone healing in patients treated with lag screws indicated that correct reduction and screw insertion allowed normal bone healing. The patients in all groups showed satisfactory clinical results. No significant intergroup differences were noted in maximum mouth opening and laterotrusion. However, deviation during mouth opening was significantly greater (P <.05) in cases treated with miniplates than with lag screws. CONCLUSION: Lag screw osteosynthesis may be more advantageous for restoration of ramus height than miniplates or Kirschner wires.

Adult↗
PubMed2001

Detergent-resistant membrane domains are required for mast cell activation but dispensable for tyrosine phosphorylation upon aggregation of the high affinity receptor for IgE.

Aggregation of the high affinity receptor for IgE (FceRI) on mast cells results in the rapid phosphorylation of tyrosines on the beta and gamma chains of the receptor by the Src family kinase Lyn, which initiates the signaling cascades leading to secretion of inflammatory mediators. The detergent-resistant membranes (DRMs) have been implicated in FcepsilonRI signaling because aggregated receptors emigrate to DRMs that are enriched in certain signaling components. We evaluated the role of DRMs in FcepsilonRI signaling by disruption of DRMs using a cholesterol-binding agent, methyl-beta-cyclodextrin (MBCD). While treatment of rat basophilic leukemia cells with MBCD inhibits degranulation and Ca(2+) mobilization upon aggregation of FcepsilonRI, MBCD hardly affects the aggregation-induced tyrosine phosphorylation of FcepsilonRI as well as other signaling molecules such as phospholipase C-gamma1 (PLC-gamma1). MBCD delocalizes phosphatidylinositol 4,5-bisphosphate from DRMs, which may prevent MBCD-treated cells from producing inositol 1,4,5-trisphosphate by means of activated PLC-gamma1. These data suggest an indispensable role for DRMs in the Ca(2+) response rather than tyrosine phosphorylation, and support a model of receptor phosphorylation in which aggregated FcepsilonRI is tyrosine phosphorylated outside DRMs by constitutively associated Src family kinase Lyn via a transphosphorylation mechanism.

Animals↗
PubMed2001

Simultaneous squamous cell carcinomas of the uterine cervix and upper genital tract: loss of heterozygosity analysis demonstrates clonal neoplasms of cervical origin.

Five cases of cervical squamous cell carcinoma with synchronous superficial squamous cell carcinoma in the upper genital tract were genetically analyzed to demonstrate the possibility of a clonal neoplastic process. In these cases, the cervical lesions were squamous cell carcinoma in situ (cases 1, 2, and 3) and invasive squamous cell carcinoma (cases 4 and 5). Loss of heterozygosity (LOH) analyses with a panel of microsatellite markers revealed a monoclonal process in four of the five cases. Homogeneous LOH throughout the microdissected lesions was most frequently detected on 6p and 6q (3 cases), followed by 11p and 11q (2 cases), loci known to be commonly lost in typical cervical squamous cell carcinoma. In two cases, genetic progression in terms of additional LOH was found in the upper genital tract but not in the cervix. Most of these squamous cell carcinomas were monoclonal neoplasms originating from the cervical mucosa with subsequent superficial migration of the tumor clone to the upper genital mucosa, and in some cases, genetic progression.

Aged↗
PubMed2001

Pioglitazone improves left ventricular diastolic function and decreases collagen accumulation in prediabetic stage of a type II diabetic rat.

This study investigated the effect of pioglitazone, an insulin sensitizer, on metabolic abnormalities and oxidative stress as a cause of myocardial collagen accumulation in prediabetic rat hearts. Twenty male diabetic rats and 9 male nondiabetic age-matched rats were used. The diabetic rats were divided into two groups: diabetic treated and untreated. Pioglitazone was mixed in rat chow fed to the diabetic treated group (0.01%). Treatment duration was 5 weeks. At baseline (15 weeks) and 20 weeks of age, blood glucose, lipid, insulin, and plasma malondialdehyde-thiobarbituric acid (MDA) levels were measured and Doppler echocardiography was tracked. At 20 weeks of age, left ventricular collagen content was studied. Blood glucose, plasma insulin, and triglyceride levels in the diabetic treated group were significantly lower than those in the untreated diabetic group. Deceleration time (ms) of early diastolic inflow in the treated diabetic group decreased significantly compared with the untreated diabetic group (65 +/- 8 vs. 77 +/- 8, p < 0.01). Ratio of left ventricular weight to body weight (mg/g) and ratio of left ventricular collagen content to dry weight (mg/100 mg) were decreased in the treated diabetic group (1.5 +/- 0.1, 1.3 +/- 0.3) compared with the untreated diabetic group (1.7 +/- 0.2, p < 0.01; 1.7 +/- 0.3, p < 0.05). Plasma MDA concentration (nmol/ml) significantly decreased (2.9 +/- 0.3 at baseline to 2.3 +/- 0.3 at 20 weeks, p = 0.001) in the treated diabetic group, and was lower than that in the untreated diabetic group (3.2 +/- 0.7 at 20 weeks, p < 0.05). Pioglitazone improved glucose and lipid metabolism and reduced oxidative stress in the left ventricle, which decreased left ventricular collagen accumulation and improved left ventricular diastolic function of prediabetic rat hearts.

Animals↗
PubMed2001

Cross reaction of recombinant equine infectious anemia virus antigen to heterologous strains and application for serological survey among horses in the field.

Cross reactivity of equine infectious anemia virus (EIAV) antigen prepared using a recombinant baculovirus containing the p26 gene of strain P337-V70 was examined by the agar gel immunodiffusion (AGID) test and enzyme-linked immunosorbent assay (ELISA). Serum samples serially collected from 13 horses experimentally infected with six different EIAV strains (two or three horses per strain) were subjected to the test. Positive reactions were observed in the AGID test and ELISA before or soon after the first feverish period and continued persistently in most of the horses. The results with recombinant antigens were essentially the same as those with the virion antigen prepared from horse cell cultures both in the AGID test and ELISA. The reactivities of the antigens were further compared using serum samples collected from horses in 1999 in certain districts of Mongolia where equine infectious anemia has been prevalent, and from horses in Japan in 1973 when EIA had not been eliminated completely from Japanese horses. These results were completely concurrent. Generally, recombinant antigens have high specificity but low cross reactivity to heterologous strains. However, the present study showed that the recombinant EIAV p26 antigen has cross reactivity to the heterologous strain and is useful for diagnosis of EIA in the field.

Animals↗
PubMed2001

A potential use of a synthetic retinoid TAC-101 as an orally active agent that blocks angiogenesis in liver metastases of human stomach cancer cells.

TAC-101 (4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid) is a novel, synthetic retinoid that is effective against liver metastases of human gastrointestinal cancer cells such as the human stomach carcinoma line AZ-521 in animal models, and is currently in use in phase I cancer trials. However, the mechanism of its antimetastatic action is still poorly understood. Tumor metastasis depends on angiogenesis, and various retinoids have been found to exhibit antiangiogenic activity. Based on these findings we here examined the antiangiogenic effects of TAC-101. Oral administration of TAC-101 (2-8 mg/kg/day) resulted in a drastic suppression of the AZ-521 cell-induced angiogenesis in a mouse dorsal air sac assay system, compared to the vehicle alone. Immunohistochemical analysis with antibody against the endothelial marker CD31 revealed a significant reduction in microvessel density in liver metastases from animals treated with TAC-101 (8 mg/kg p.o.), compared to liver metastases from the untreated control animals. The ability of TAC-101 (8 mg/kg p.o.) to prevent experimental liver metastasis of AZ-521 cells in athymic nude mice was comparable with that of the known angiogenesis inhibitor TNP-470 (30 mg/kg s.c.). TAC-101 also affected angiogenesis in chorioallantoic membranes and some functions of endothelial cells associated with angiogenesis, whereas the retinoid failed to suppress AZ-521 cell proliferation directly. These data suggest that the TAC-101 is an orally active antiangiogenic agent and that this antiangiogenic property may contribute to its efficacy against liver metastasis of human stomach cancer cells.

Administration, Oral↗
PubMed2001

[Bartonella henselae infection in domestic cat and dog fleas].

We studied on the infection of domestic cat and dog fleas with Bartonella henselae by polymerase chain reaction (PCR). A total of 62 fleas (36 Ctenocephalidis felis from cats, 24 C. felis from dogs and 2 Ctenocephalidis canis from dogs), stored in 70% ethanol, were analyzed by PCR for B. henselae specific DNA. Of the 62 fleas, C. felis from cats and dogs were positive for B. henselae specific DNA in 12 of the 36 (33.3%) and in 5 of the 24 (20.8%), respectively, and C. canis from dogs was positive in 2 of the 2 (100%). Our results demonstrated that pet fleas were infected with B. henselae, and suggest that flea transmission of B. henselae between cats or dogs may occur, and direct transmission of B. henselae from pet fleas to human may cause cat scratch disease.

Animals↗
PubMed2001

[Serological cross-reaction among Bartonella henselae, Chlamydia pneumoniae and Coxiella burnetii by indirect fluorescence antibody method].

We studied the serological cross-reactions among Bartonella henselae, Chlamydia pneumoniae and Coxiella burnetii by indirect fluorescence antibody (IFA) method, using sera from 8 patients with cat scratch disease (CSD), 13 patients with C. pneumoniae infection and 12 patients with acute Q fever. B. henselae IgG antibody was negative in 13 patients with C. pneumoniae infection, and was positive in 3 (titers being 1:64) of 12 patients with Q fever, whereas B. henselae IgM antibody was negative in all the patients with C. pneumoniae infection or Q fever. C. burnetii IgG antibody was removed by absorption of these 3 sera with C. burnetii antigens, whereas B. henselae IgG antibody did not change. C. pneumoniae IgG antibody was positive in 3 (titers being 1:125 in two, 1:32 in one) of 8 patients with CSD. Both C. pneumoniae and B. henselae IgG antibody titers were significantly reduced by absorption of these 3 sera with B. henselae antigens. C. burnetii IgG or IgM antibodies were negative in all patients with CSD. In conclusion, no serological cross-reaction between B. henselae and C. burnetii was observed. On the other hand. B. henselae IgG antibody cross-reacted to C. pneumoniae antigens, whereas C. pneumoniae IgG antibody did not cross-react to B. henselae antigens. Our findings suggest that determination of B. henselae IgG or IgM antibodies were not influenced by C. pneumoniae and C. burnetii antigens.

Bartonella henselae↗
PubMed2001

Detection of serum thermolabile beta-2 macroglycoprotein (Hakata antigen) by enzyme-linked immunosorbent assay using polysaccharide produced by Aerococcus viridans.

Although a serum thermolabile beta-2 macroglycoprotein (TMG) may play a role in host defense as a lectin, little is known of its related physiological functions, mainly due to a lack of appropriate methods for tracing the functions of TMG. We identified a polysaccharide from Aerococcus viridans, PSA, which reacts with TMG, and based on this finding, we developed an enzyme-linked immunosorbent assay to trace the functions of TMG. Using ethanol precipitation and DEAE-Sepharose and Sephacryl S-400 column chromatographies, we isolated PSA from cultured medium of A. viridans, and it exhibited specific binding against TMG in blood samples. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the isolated PSA showed ladder bands that implied the existence of repeating units composed of D-glucose, N-acetyl-D-glucosamine, D-mannose, and D-xylose, as confirmed by gas chromatography-mass spectrometry. SDS-PAGE and immunochemical analysis, using rabbit anti-TMG antibody, showed that PSA specifically binds solely to intact serum TMG but not to TMG heated at 56 degrees C for 30 min, a condition under which antigenicity is lost. TMG in serum samples bound to PSA in a dose-dependent manner, and this binding was clearly suppressed by addition of PSA. These observations indicate that PSA is a useful adsorbent to TMG and can be used to develop appropriate methods for tracing the functions of TMG.

Antibodies, Bacterial↗
PubMed2001

Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes.

PPARgamma is a ligand-activated transcription factor and functions as a heterodimer with a retinoid X receptor (RXR). Supraphysiological activation of PPARgamma by thiazolidinediones can reduce insulin resistance and hyperglycemia in type 2 diabetes, but these drugs can also cause weight gain. Quite unexpectedly, a moderate reduction of PPARgamma activity observed in heterozygous PPARgamma-deficient mice or the Pro12Ala polymorphism in human PPARgamma, has been shown to prevent insulin resistance and obesity induced by a high-fat diet. In this study, we investigated whether functional antagonism toward PPARgamma/RXR could be used to treat obesity and type 2 diabetes. We show herein that an RXR antagonist and a PPARgamma antagonist decrease triglyceride (TG) content in white adipose tissue, skeletal muscle, and liver. These inhibitors potentiated leptin's effects and increased fatty acid combustion and energy dissipation, thereby ameliorating HF diet-induced obesity and insulin resistance. Paradoxically, treatment of heterozygous PPARgamma-deficient mice with an RXR antagonist or a PPARgamma antagonist depletes white adipose tissue and markedly decreases leptin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re-emergence of insulin resistance. Our data suggested that appropriate functional antagonism of PPARgamma/RXR may be a logical approach to protection against obesity and related diseases such as type 2 diabetes.

3T3 Cells↗
PubMed2001

Improvement of left ventricular diastolic dynamics in prediabetic stage of a type II diabetic rat model after troglitazone treatment.

Troglitazone, an oral antidiabetic agent, has hypoglycemic effects in insulin-resistant animal models and humans. This study was conducted to evaluate its effect on left ventricular diastolic dynamics of a spontaneous diabetic (DM) rat model. Twenty DM rats and 20 age-matched nonDM rats were used, and 10 of each group were treated with troglitazone as a 0.2% food admixture for 10 weeks. At 5 and 15 weeks of age, Doppler echocardiography and M-mode echocardiography were performed. Troglitazone treatment significantly improved the left ventricular diastolic dynamics of DM rats: deceleration time (msec) of early diastolic inflow decreased significantly (treated 52 +/- 3 vs untreated 64 +/- 5, p = 0.0002), and peak velocity of early transmitral inflow (cm/sec) increased significantly (treated 96 +/- 7 vs untreated 86 +/- 8, p = 0.0216). The data suggest that troglitazone improves left ventricular diastolic dynamics of a DM rat model at prediabetic stage.

Animals↗
PubMed2001

Inhibition of in situ expression of aromatase P450 in leiomyoma of the uterus by leuprorelin acetate.

We have shown that in situ estrogen synthesized in leiomyoma of the uterus plays a possible role in the promotion of leiomyoma cell growth via an autocrine/paracrine mechanism. In the present study, we demonstrated that leuprorelin acetate, a GnRH agonist widely used for treatment of uterine leiomyoma by down-regulation of pituitary-ovarian function, suppressed the expression of aromatase P450 (an estrogen synthetase) in leiomyoma cells. Given the role of in situ estrogen in leiomyoma cell growth, the inhibition of in situ estrogen synthesis may play a role in GnRH agonist-induced rapid regression of leiomyomas. Quantitative RT-PCR revealed that in women receiving no medication uterine leiomyomas express aromatase P450 mRNA at levels 20 times higher than that in the surrounding myometrium. Leuprorelin acetate treatment (1.88 mg every 4 wk, sc injection) for 12-24 wk reduced the expression of aromatase P450 mRNA in leiomyoma tissue as well as in the myometrium, to approximately one tenth of that in the myometrium of untreated women. Suppression of aromatase P450 expression was also demonstrated by Western blot analysis and aromatase activity assay of microsomal fractions prepared from leiomyomas. On the other hand, no differences in the levels of activity and mRNA of aromatase P450 were observed between leiomyoma cells obtained from women treated with and without leuprorelin acetate injections when cells were cultured ex vivo and stimulated by various combinations of stimulants such as dexamethasone + IL-1beta. The addition of various concentrations of E2 did not affect the aromatase activity of leiomyoma cells, suggesting that deprivation of circulating (ovarian) estrogen is not a cause of decreased expression of aromatase during leuprorelin acetate therapy. On the other hand, 8-d treatment with leuprorelin acetate (100 nmol/liter) reduced dexamethasone + IL-1beta-induced activity and a mRNA level of aromatase by 28% and 42%, respectively. These results indicated that leuprorelin acetate inhibits the expression of aromatase P450 in leiomyoma cells, which contributes to the rapid regression of leiomyoma during leuprorelin acetate therapy.

Antineoplastic Agents, Hormonal↗