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Biomedical subjects

M Mihara

Publications and source records attributed to M Mihara.

At least 37 records · Page 2Linked to original sources
PubMed2000

Polyglutamation of antifolates is not required for induction of extracellular release of adenosine or expression of their anti-inflammatory effects.

Methotrexate (MTX) exerts an anti-inflammatory effect, reportedly by enhancing the release of adenosine, through an accumulation of 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR). To examine the role of polyglutamation in promoting anti-inflammatory effects by antifolates, we tested whether a new antifolate designed to be resistant to intracellular polyglutamation (MX-68) exhibited anti-inflammatory effects and stimulated adenosine release. Both MX-68 and MTX (at concentrations greater than 0.1 microM) increased the release of adenosine from Daudi cells in vitro. Inhibition of AICAR synthesis suppressed adenosine release by MX-68 and MTX. The anti-inflammatory effects of antifolates were estimated using the murine air pouch model, in which a BALB/c mouse was intraperitoneally injected with MX-68 or MTX once a week for 3 weeks. MX-68 (0.5 mg kg(-1) week(-1)), as well as MTX, inhibited infiltration of leukocytes into the air pouch. This inhibitory effect was suppressed in the presence of an adenosine A(2) receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX). These results suggest that MX-68, like MTX, exerts anti-inflammatory effects through the accumulation of AICAR and release of adenosine. These results suggest that polyglutamation of antifolate is not required for expression of anti-inflammatory effects.

2-Aminoadipic Acid↗
PubMed2000

Apoptosis and p53 are associated with effect of preoperative radiation in oral squamous cell carcinomas.

This study was carried out to elucidate whether apoptosis and p53 can be used to stratify oral cancer patients into groups with a favorable or unfavorable response to preoperative radiation therapy. Thirty-two patients were evaluated. The apoptosis index was 1.7+/-0. 9% in the ineffective cases, and it was significantly lower than effective cases (3.2+/-1.2%). While 14 of 16 effective cases (86.7%) did not express p53, 13 of 16 ineffective cases (81.3%) overexpressed p53. These results suggest that mutated p53 in tumors is associated with a poor response to radiation which may be related to evasion of apoptosis in oral cancer.

Aged↗
PubMed2000

Identification of the homozygously deleted region at chromosome 1p36.2 in human neuroblastoma.

BACKGROUND: We have identified for the first time a homozygously deleted region within the smallest region of overlap at 1p36.2-3 in two neuroblastoma cell lines. PROCEDURE: The 800-kb PAC contig covering the entire homozygously deleted region was made and sequenced. To date, approximately 70% of sequencing has been accomplished, and the estimated length of the deleted region was 500 kb. RESULTS: Currently, we have found six genes within the region, which include three known genes as well as three other genes that have been reported during processing of our present project for the last 3(1/2) years. We report here the results of expression and mutation analyses of those genes. CONCLUSIONS: Full sequencing for the region of homozygous deletion as well as further analyses of the genes mapped within the region may reveal whether or not there is a neuroblastoma suppressor gene as proposed by the Knudson's two-hit hypothesis.

Child, Preschool↗
PubMed2000

Survival and recurrence after hepatic resection of 386 consecutive patients with hepatocellular carcinoma.

BACKGROUND: Although hepatic resection is one of the most effective treatments for hepatocellular carcinoma (HCC), the longterm results of hepatic resection of this malignancy are far from satisfactory. The potential benefits of hepatectomy for patients with HCC have not been fully delineated. This study aimed to identify surgical outcomes of 386 consecutive patients with HCC undergoing hepatic resection. STUDY DESIGN: The retrospective study looked at records of 293 men and 93 women. The mean age was 63.2 years. Preoperative transarterial chemoembolizaton and portal vein embolization were performed in 138 patients (35.8%) and 8 patients (2.1%), respectively. Sixty-two patients (16.1 %) had major hepatectomy and the other 324 (83.9%) had minor hepatectomy. Thirty-seven of 386 patients (9.6%) had a noncurative operation. RESULTS: The 30-day (operative) mortality rate was 4.1%, and there were 11 additional late deaths (2.9%). Two hundred fourteen of 327 patients (65.4%) had recurrence after curative resection. Unfavorable factors for survival and recurrence were resection between 1983 and 1990, Child class B or C, cirrhosis, a high value of indocyanine green retention-15, a large amount of intraoperative blood loss, stage IV disease, positive surgical margin, vascular invasion, and postoperative complications. Preoperative transarterial chemoembolization increased the recurrence rate and showed no contribution to prognosis. Currently, 106 patients (27.5%) are alive: 7 (1.8%) after more than 10 years and 43 (11.1%) after more than 5 years. Mean and median overall survivals after operation were 38 months and 29 months, respectively. The 5-year and 10-year overall or disease-free survival rates after hepatic resection were 34.4% and 10.5% or 23.3% and 7.8%, respectively. CONCLUSIONS: The longterm survival rate after operation remains unsatisfactory mainly because of the high recurrence rate. Preoperative transarterial chemoembolization should be avoided because of a high risk of postoperative recurrence. Treatment strategies for recurrent HCC may play an important role in achieving better prognosis after operation, especially in patients with more than Child class B, cirrhosis, high values of indocyanine green retention-15, massive intraoperative blood loss, stage IV disease, positive surgical margin, vascular invasion, and postoperative complications.

Adult↗
PubMed2000

High incidence of reflux oesophagitis after eradication therapy for Helicobacter pylori: impacts of hiatal hernia and corpus gastritis.

BACKGROUND: Although several recent studies have shown that the eradication of Helicobacter pylori provokes reflux oesophagitis, the results are conflicting. AIM: To investigate the prevalence of reflux oesophagitis in patients after eradication of H. pylori and consider its association with hiatal hernia and corpus gastritis. METHODS: A total of 286 patients who underwent H. pylori eradication therapy and 286 age- and disease-matched H. pylori-positive controls who did not undergo eradication therapy were followed prospectively. All patients and controls underwent endoscopy at 1-year intervals or when upper gastrointestinal symptoms recurred. The presence of hiatal hernia and histology of the gastric corpus were evaluated at the time of initial endoscopy. RESULTS: The estimated prevalence of reflux oesophagitis within 3 years was 18% after eradication therapy and 0.3% without therapy. Patients who developed reflux oesophagitis after therapy had a greater prevalence of hiatal hernia (P=0.0008) and more severe corpus gastritis (P=0.0005) before therapy. Cumulative prevalence of reflux oesophagitis was 26% in patients with hiatal hernia, 7.7% in those without hiatal hernia, 33% in those with corpus atrophic gastritis and 13% in those without corpus atrophic gastritis. When patients had both hiatal hernia and corpus gastritis, the prevalence of reflux oesophagitis was 37%. The newly developed reflux oesophagitis was classified as mild in 35 out of 36 (97%) patients who developed reflux oesophagitis after eradication therapy. CONCLUSIONS: Eradication of H. pylori increased the prevalence of reflux oesophagitis in our patient group. The presence of hiatal hernia and corpus gastritis are closely related to the development of reflux oesophagitis after H. pylori eradication therapy.

Adolescent↗
PubMed2000

Cetraxate, a mucosal protective agent, combined with omeprazole, amoxycillin, and clarithromycin increases the eradication rate of helicobacter pylori in smokers.

BACKGROUND: Our previous study demonstrated that Helicobacter pylori eradication was less effective in smokers than in non-smokers. Cetraxate is an anti-ulcer drug that increases gastric mucosal blood flow. AIM: To evaluate the effect of cetraxate combined with new triple therapy for the eradication of H. pylori in smokers. METHODS: This study had a single-centre, double-blind, randomized non-placebo design. A total of 106 consecutive H. pylori-positive smoking patients were randomly allocated to one of two regimens: one group received omeprazole (20 mg), amoxycillin (1500 mg), and clarithromycin (600 mg) for 7 days (OAC, n=55). The other group recieved OAC plus cetraxate (600 mg) for 7 days (OAC + CET, n=51). The success of H. pylori eradication was evaluated by histology and the 13C-urea breath test at 4 weeks after completion of treatment. RESULTS: By intention-to-treat analysis, the H. pylori eradication rate was 55% in the OAC group and 92% in the OAC + CET group (P<0.01). By per protocol analysis, the H. pylori eradication rate was 58% in the OAC group and 94% in the OAC + CET group (P<0.01). CONCLUSION: Cetraxate combined with new triple therapy increases the eradication of H. pylori in smokers.

Adult↗
PubMed2000

Negative association between Helicobacter pylori infection and reflux esophagitis in older patients: case-control study in Japan.

BACKGROUND: Recent studies have clarified a close association between H. pylori infection and gastritis, peptic ulcer disease, and gastric cancer, but there is little information concerning the relationship between H. pylori infection and reflux esophagitis (RE). We investigated the relationship between H. pylori, RE, and corpus gastritis. SUBJECTS AND METHODS: Ninety-five patients with RE and 190 sex- and age-matched asymptomatic healthy controls demonstrating no localized lesions in the upper GI tract were studied and evaluated for H. pylori infection, histologic gastritis, serum gastrin, and pepsinogens (PGs). RESULTS: H. pylori infection was significantly lower in RE patients than in asymptomatic controls (41% vs. 76%, p <.01). Histologic gastritis of both the antrum and corpus was significantly less frequent (antrum; p <.01, corpus; p <. 01), and serum levels of PGI and the PG I/II ratio were significantly higher in RE patients than in controls (PGI; p <.05, PG I/II ratio; p <.01). When the subjects were divided into two age groups (59 years of age and younger and 60 years of age and older), a significant difference was found only among patients over 60 years of age (29% vs. 85%, p <.01). Among subjects in this age group, gastritis in both the antrum and corpus were significantly milder in RE patients than in controls. Although the prevalence of H. pylori infection was similar between the two groups of patients under 59 years of age, corpus gastritis was significantly milder in patients than in controls (p <.05). CONCLUSIONS: A significantly low prevalence of H. pylori infection was found in RE patients over 60 years of age but not in those under 59 in comparison with sex- and age-matched controls. The relative lack of corpus gastritis might play a role in the pathogenesis of RE in our population through preservation of the acid secretion area.

Age Factors↗
PubMed2000

Factors that affect results of the 13C urea breath test in Japanese patients.

BACKGROUND: The 13C urea breath test (UBT) is considered to be the most accurate way of diagnosing Helicobacter pylori infection. Our objective was to investigate the accuracy of the UBT in Japanese patients and the association of UBT values with histological findings. MATERIALS AND METHODS: A total of 169 consecutive patients were studied by endoscopy with histology, by serology with IgG antibody and test serum pepsinogen (PG), and by UBT. The association between UBT values and histological findings and the PG I / II ratio were analyzed in H. pylori-positive patients. RESULTS: Of 169 Japanese patients, 135 were H. pylori-positive on both histology and serology analysis, 27 were H. pylori-negative on both histology and serology analysis, and 7 patients showed differing results. Using a cutoff value of 2.5 per thousand, test sensitivity was 100%, while specificity was 96%. Among the 135 H. pylori-positive patients, a significant relation was observed between UBT value and H. pylori colonization density of the corpus and antrum, neutrophil activity of the antrum, atrophy, and intestinal metaplasia of the corpus in the H. pylori-positive patients. Also, UBT values correlated with the PG I /II ratio. In multivariate analysis, the PG I /II ratio was the most important factor related to UBT values (odds ration [OR], 4. 99; 95% confidence interval, 1.60-15.55). CONCLUSIONS: The UBT is an accurate method for detecting H. pylori infection in the Japanese population, which shows a high prevalence of atrophic gastritis. Values are affected by H. pylori infection and by the severity of atrophic gastritis.

Adolescent↗
PubMed2000

Enhancement of adenovirus-mediated gene transfer into dermal fibroblasts in vitro and in vivo by polyethylene glycol 6000.

Gene therapy directed to the skin requires efficient transfer of the desired gene into cutaneous cells. In this study, we examined several chemical substances present in various ointments by enhancement of virus infectivity. The recombinant adenovirus vector, AxCALacZ, was used to infect dermal fibroblasts with some chemicals both in vitro and in vivo, and the expression of the LacZ gene was determined by X-Gal reaction. As the result, it was shown that PEG 6000 had the highest ability to enhance the exogenous gene expression in cultured fibroblasts with little toxicity. In vivo, it was also demonstrated that fibroblasts in mouse skin were efficiently gene transfer by adenovirus vector and 20% PEG 6000-treatment. These results suggest that this chemical treatment appears to be a simple, safe, convenient, and effective method for facilitating virus-mediated gene therapy in the skin.

Adenoviruses, Human↗
PubMed2000

Evaluation on the occurrence of Tsutsugamushi disease in Tottori Prefecture.

In Tottori Prefecture, we gathered the data of all patients known to have been infected with tsutsugamushi disease (TD) over a span of 49 years, from 1950 to 1998. The total number of patients reported so far has been 19, 16 of which occurred after 1988. Recently, it has been observed that the incidence tended to increase. Of the 13 laboratory confirmed patients, 7 came from Saji Village and Chizu Town, in the Yazu district, a place whereby, a body of water known as the Sendai River partly passes through, and is located in the eastern region of Tottori Prefecture. The remaining 6 came from Nichinan Town in the Hino district, a locality whereby the Hino River partly passes through; in the western part of the same prefecture. Both are mountainous areas, where corniferous trees such as Japanese cedars and pines grow. These results indicate that the occurrence or prevalence of TD in Tottori Prefecture was restricted only to particular places. Seasonal occurrence was during April and May in Nichinan, while October and November in Yazu, particularly in Saji, with one exceptional case in Chizu in which TD occurred during spring. It is likely that the causative chigger mite is the Leptotrombidium pallidum (L. pallidum). The causative agent in Yazu was the Gilliam strain only of Orientia tsutsugamushi (O. tsutsugamushi), while in the latter, it was the Karp, Kato or some unknown strains with antigen(s) common to the Gilliam, Karp and Kato strains. The seasonal difference in the occurrence among the three places may be caused by the difference in temperature because the average autumn/spring temperature difference in the 2 districts was 2-3 degrees C lower in Nichinan than in the Saji-Chizu areas. As a result, the activity of larval chigger mites may be temporarily halted or stopped by the relatively lower temperature in Nichinan during autumn.

Aged↗
PubMed2000

Association of preoperative radiation effect with tumor angiogenesis and vascular endothelial growth factor in oral squamous cell carcinoma.

This study examined the relationship between tumor angiogenesis and the radiation-induced response, evaluated based on pathological changes, in oral squamous cell carcinoma patients treated with preoperative radiation therapy. Forty-one cases of squamous cell carcinoma treated with preoperative radiation therapy were investigated. Tumor angiogenesis was assessed by scoring the intratumor microvessel density (IMVD). Expression of vascular endothelial growth factor (VEGF) was also evaluated before and after preoperative radiotherapy. There was no correlation between IMVD in the specimens before therapy and the pathological response to radiation therapy. However, radiation therapy decreased IMVD in the specimens after therapy. A significant association was observed between VEGF expression and resistance to radiation therapy: only 4 of the 21 patients whose tumors exhibited a high level (2 + or 3 + ) of VEGF staining experienced a major (3 + or 4 + ) pathological response to radiation therapy. Furthermore, an increasing level of VEGF expression after radiation therapy was observed in non-effective (0 to 2 + ) response cases. These results suggest that VEGF expression and the induction of this protein are related to radiosensitivity and could be used to predict the effects of preoperative radiation therapy on oral squamous cell carcinoma.

Adult↗
PubMed2000

Allelic loss of the region of chromosome 1p35-pter is associated with progression of human gastric carcinoma.

In order to identify the region on distal chromosome 1p that is thought to include one or more tumor suppressor genes for gastric carcinoma, 39 gastric carcinomas were examined for allelic loss using 11 polymorphic microsatellite markers and 1 marker of single strand conformation polymorphism. Loss of heterozygosity (LOH) was found in 18 (46%) of 39 informative patients. The regions with high frequency of loss of heterozygosity were the loci at D1S548 (6 / 17; 35.3%) and D1S2843 (7 / 20; 35%), and we found three commonly deleted regions on chromosome 1p35-pter. The frequency of allelic loss in the region of chromosome 1p35-pter was significantly associated with advanced-stage gastric carcinoma, but not with early-stage tumor or with the histology. These results suggest that allelic loss at chromosome 1p35-pter may play a role in the progression of gastric carcinoma.

Adenocarcinoma↗
PubMed2000

CTLA4Ig inhibits T cell-dependent B-cell maturation in murine systemic lupus erythematosus.

Long-term administration of CTLA4Ig prevents the onset of disease in systemic lupus erythematosus-prone (SLE-prone) NZB/NZW F1 mice. To determine the mechanism of this effect, we engineered an adenovirus that expresses murine CTLA4Ig. Administration of a single high dose of this virus results in long-term expression of CTLA4Ig in the serum and absence of an immune response to the adenoviral vector. We administered Ad-CTLA4Ig to 19- to 22-week-old NZB/NZW F1 mice and evaluated the effect on anti-DNA antibody-producing B cells. We show that CTLA4Ig has a beneficial effect on murine SLE for as long as it is present in the serum. This effect is associated with decreased expansion of both the IgM and IgG autoreactive B-cell population, inhibition of immunoglobulin class switching, decreased frequency and altered pattern of somatic mutation, and a marked decrease in the numbers of activated CD4-positive T cells. In contrast, intrinsic B-cell hyperreactivity and the survival of plasma cells in the bone marrow, both of which are less dependent on T-cell help, appear to be unaffected by CTLA4Ig. High-dose CTLA4Ig did not induce permanent tolerance in this autoimmune disease model. Furthermore, although the mice survived in a conventional housing facility, treatment with Ad-CTLA4Ig was immunosuppressive.

Abatacept↗
PubMed2000

[A case of aseptic osteomyelitis with heel ulcer improved by steroid application].

A 43-year-old male patient was admitted to our hospital because of left heel pain and fever. He had had swelling of the left ankle joint and pain 4 years prior to this, and 4 years later, he was admitted to another hospital when left heel ulcer and fever developed. The ulcer was diagnosed and treated as a diabetic ulcer because of hyperglycemia. In spite of good control of blood sugar, the ulcer became enlarged and the pain deteriorated, so he was transferred to orthopedics. Antibiotics produced no response, and culture from a specimen of the ulcer was negative. However, severe inflammatory response was seen in blood examination. MRI and scintigram of his left foot showed disseminated low intensity areas and accumulation in the tarsal bone area, so osteomyelitis was suspected. A biopsy of the ulcer showed infiltration of inflammatory cells into the dermis. We considered amputation of the left lower leg at first. However the biopsy result suggested an autoimmune mechanism, so prednisolone was administered. As a result, the ulcer and pain both diminished. This case was similar to pyoderma gangenosum, however this diagnosis cannot explain osteomyelitis or all its symptoms. We expect that there must be other case report with the same symptoms.

Adult↗
PubMed2000

Identification of the full-length KIAA0591 gene encoding a novel kinesin-related protein which is mapped to the neuroblastoma suppressor gene locus at 1p36.2.

The distal region of a short arm of chromosome 1p is frequently deleted in many human cancers including neuroblastoma (NBL), in which it has been narrowed down to the smallest region of overlap between D1S244 and D1S214 (approximately 7 cM). During the search for the candidate tumor suppressor genes mapped within the region, we found the KIAA0591 gene which encoded a new human kinesin-related protein with a homology to human axonal transporter of synaptic vesicles (ATSV). The kinesin is an intracellular motor protein and often associated with neuronal differentiation and survival. Here we identified a complete open reading frame of the KIAA0591 gene by screening a cDNA library derived from human substantia nigra. The KIAA0591 protein contains a possible pleckstrin homology (PH) domain at its carboxy-terminus. However, it did not possess a force-generating motor domain which is well conserved among kinesin superfamily members (KIFs). Northern blot analysis demonstrated that KIAA0591 mRNA was preferentially expressed in both adult and fetal brains, kidney, skeletal muscle and pancreas. KIAA0591 was expressed in favorable NBLs at higher levels than in unfavorable NBLs, although RT-PCR SSCP analysis showed no mutation within the coding region of the KIAA0591 gene, when 8 neuroblastoma tissues and 15 neuroblastoma-derived cell lines were examined. Thus, the full-length KIAA0591 gene may be a novel member of human KIF superfamily which lacks motor domain and might function as a tumor suppressor in an epigenetic but not a classic Knudson's manner.

Amino Acid Sequence↗
PubMed1999

Absence of mutation of the p73 gene localized at chromosome 1p36.3 in hepatocellular carcinoma.

Accumulating evidence has demonstrated that aberration of the p53 tumour-suppressor gene is one of the pivotal genetic events in hepatocellular carcinogenesis. Recent reports suggest that the product of hepatitis B virus (HBV) interacts with p53 and that the hepatitis C virus (HCV) core protein reduces p53 expression. A novel p73 gene, which is related to p53, has recently been identified and mapped to chromosome 1p36.3, which is a locus of multiple tumour-suppressor genes for many cancers, including hepatocellular carcinoma (HCC) and neuroblastoma. Here, we investigated mRNA expression, allelotype and mutation of p73 in 48 HCCs obtained from untreated patients. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed that p73 mRNA was expressed ubiquitously at low levels in all the tumour tissues, as well as in the adjacent normal liver tissues. The frequency of p73 loss of heterozygosity was observed in 20% of HCCs, but PCR-single strand conformation polymorphism (SSCP) analysis showed no mutations in the 48 tumours except for three types of polymorphisms. These results suggest that p73 may play a role in hepatocellular carcinogenesis in a different manner from a Knudson two-hit model. The regulatory mechanism of interaction between p73 and hepatitis viruses remains to be determined.

Base Sequence↗