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Biomedical subjects

M Mihara

Publications and source records attributed to M Mihara.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗

Eradication of Helicobacter pylori increases gastric acidity in patients with atrophic gastritis of the corpus-evaluation of 24-h pH monitoring.

BACKGROUND: Recent studies have shown that the eradication of Helicobacter pylori results in a gastric acid secretion which decreases to normal levels in patients with duodenal ulcer disease. The aim of this study was to evaluate the effect of eradication of H. pylori in a 24-h study of gastric acidity in patients with atrophic gastritis of the corpus. METHODS: Intragastric acidity was measured by continuous 24-h pH monitoring, and the histology of the gastric antrum and corpus were evaluated in 14 H. pylori-positive patients with histologically proven atrophic gastritis of the corpus (10 men, 4 women; mean age, 57 years) before and 1 year after anti-H. pylori therapy. RESULTS: H. pylori was absent in 13 of 14 patients 1 year after treatment. Both gastritis and atrophy scores were significantly lower after eradication therapy (P < 0.01). The 24-h median pH and the percentage of 24-h pH readings above 4.0 units were significantly decreased after eradication therapy (from 5.12 +/- 0.36 to 2.69 +/- 0.21, and from 65.5 +/- 6.6% to 28.2 +/- 6.1%, P < 0.01, respectively.) CONCLUSION: Eradication of H. pylori increases 24-h gastric acidity in patients with atrophic gastritis of the corpus. Improvement of the histology of the gastric antrum and corpus may lead to the normalization of gastric acidity.

Aged↗

The role of endoscopic findings for the diagnosis of Helicobacter pylori infection: evaluation in a country with high prevalence of atrophic gastritis.

BACKGROUND: This study examines endoscopic findings in the diagnosis of Helicobacter pylori (H. pylori) in the Japanese population. MATERIALS AND METHODS: The endoscopic findings (including gastric fold findings and degree of atrophy by the Kimura-Takemoto classification system), histologic severity of inflammation, and glandular atrophy were assessed according to the Sydney system in 642 patients (419 men; 223 women; mean age 43.5 years, range 13-86). H. pylori infection was evaluated by Giemsa staining and serum IgG antibodies. RESULTS: 391 of 642 patients (60.9%) were diagnosed as having endoscopic gastritis. Of the 391 patients with endoscopic gastritis, 318 (82.6%) had histologic gastritis and 310 (79.3%) had H. pylori infection. Of the 251 patients with endoscopically normal stomachs, 43 (17.1%) had histologic gastritis and 32 (12.7%) had H. pylori infection. Atrophic gastritis was the most prevalent finding (56.3%) among those with endoscopic gastritis. The prevalence of H. pylori infection in patients with atrophic gastritis (92.7%) and rugal hyperplastic gastritis (92.3%) was significantly higher than in those with other types of gastritis or with a normal stomach (12. 7%). A markedly high prevalence of H. pylori infection was found in subjects with tortuosity, hyperrugosity, and/or hyporugosity of the gastric folds. CONCLUSIONS: The accurate endoscopic assessment of gastritis according to the Sydney system along with gastric fold findings and the endoscopically identified extent of gastric atrophy are valuable indicators for determining H. pylori infection and histologic gastritis in the Japanese population.

Adolescent↗

Comparison of meal-stimulated serum gastrin response in Helicobacter pylori-positive duodenal ulcer and asymptomatic volunteers with and without H. pylori infection.

BACKGROUND: Duodenal ulcer (DU) patients exhibit raised postprandial gastrin release as compared to that in healthy controls. It is believed that serum pepsinogen I (PG I) concentration reflects the chief cell mass and that hyperpepsinogenemia I plays an important role in the pathogenesis of DU. Currently, strong evidence suggests that Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of DU. MATERIALS AND METHODS: Subjects consisted of 15 patients with H. pylori-positive DU, 10 H. pylori-positive volunteers, and 35 H. pylori-negative volunteers. Blood samples were taken before and at 15, 30, and 60 minutes after eating the test meal, which consisted of 100 gm rice, 130 gm chicken, and 1 egg. The 1-hour integrated gastrin response (IGR) was taken as the area under the serum gastrin time curve, calculated by the trapezoid method. Serum gastrin (SG) and fasting serum PG I concentrations were measured by radioimmunoassay. RESULTS: Meal-stimulated SG response and fasting PG I concentration were significantly higher in DU patients than in H. pylori-positive and -negative volunteers. The DU patients were divided into two groups in accordance with their IGR levels as follows: hyper-IGR and normo-IGR. Serum PG I concentration was significantly higher in the hyper-IGR than in the normo-IGR group. CONCLUSIONS: The DU patients differed in some way (other than H. pylori infection) from the H. pylori-positive healthy volunteers. The fact that hyper-IGR DU patients had higher serum PG I concentrations suggests that patients in this group may be acid hypersecretors.

Adult↗

Effect of smoking and histological gastritis severity on the rate of H. pylori eradication with omeprazole, amoxicillin, and clarithromycin.

BACKGROUND: The combination of omeprazole, amoxicillin, and clarithromycin is a common regimen against Helicobacter pylori. Several recent studies have shown that smoking, high intragastric acidity, and the degree of histological gastritis are associated with H. pylori eradication failure. MATERIALS AND METHODS: One hundred and thirty-seven H. pylori-positive patients were treated with a 1-week regimen composed of omeprazole, 20 mg once daily; amoxicillin, 500 mg; and clarithromycin, 200 mg thrice daily. Success of the treatment was evaluated by histology and the 13C-urea breath test at least 4 weeks after completion of therapy. Data about age, gender, alcohol intake, smoking habits, and previous proton pump inhibitor intake were collected in patient interviews. We evaluated fasting gastric pH and the degree of histological gastritis before eradication of H. pylori. RESULTS: The overall eradication of H. pylori at 4 weeks was successful in 98 of 137 patients (72%). On the multivariate analysis, a low grade of inflammation in the antrum (p </=.01; 95% confidence interval [CI], 2.34-16.75), low grade of activity in the fundus (p </=.05; 95% CI, 1.31-9.65), and smoking (p </=.05; 95% CI, 1.27-6.82) were the significant independent factors predicting treatment failure. CONCLUSIONS: These findings indicate that H. pylori eradication therapy with omeprazole, amoxicillin, and clarithromycin is less effective in patients who smoke and more effective in patients with high scores of antral inflammation and fundal activity at baseline biopsy.

Adult↗

Monoclonality of infiltrating plasma cells in primary pulmonary nodular amyloidosis: detection with polymerase chain reaction.

AIMS: To investigate the relation between localised amyloidosis and immunocytic dyscrasia. METHODS: Open lung biopsy specimens from a 72 year old man with multiple nodules in the right middle and lower lung were stained with haematoxylin-eosin, Congo red, and antibodies against IgG, IgA, IgM, and kappa and lambda light chains. Semi-nested PCR amplification for the immunoglobulin heavy chain (IgH) gene was performed using consensus primers for the VDJ region of the IgH gene, FR3A, LJH, and VLJH. RESULTS: The biopsy specimens contained eosinophilic amorphous material stained with Congro red and anti-kappa light chain, and surrounded by inflammatory cells intermingled with plasma cells. Plasma cells in the adjacent amorphous material showed cytoplasmic staining with anti-kappa. Polymerase chain reaction revealed a discrete amplified band of apparently uniform size with background smear. CONCLUSIONS: Primary AL type localised amyloidosis involves local accumulation of monoclonal plasma cells and their secreted products, as in nodular cutaneous amyloidosis. Localised AL type nodular amyloidosis is a separate entity in amyloidosis.

Aged↗

p73, a gene related to p53, is not mutated in esophageal carcinomas.

A novel gene, termed p73, encodes a protein with a significant homology to p53 and has been mapped at chromosome 1p36.3, which is a locus of multiple suppressor genes for tumors including neuroblastoma and other cancers. Since the 1p36 locus is reported to be deleted and p53 is frequently mutated in esophageal carcinomas, we examined loss of heterozygosity (LOH) and mutation of the p73 gene in 48 untreated esophageal tumors, as well as mRNA expression in 8 tumors. We screened the P1 genomic library to obtain a P1 clone containing the p73 gene and found a polymorphic short tandem CT repeat site at intron 9. Intragenic sequences for 14 PCR primer sets and a primer pair flanking the repeat were also determined for the analysis of PCR single-strand conformation polymorphism (SSCP) and LOH studies, respectively. Expression of p73 mRNA was detectable but at low levels in all 8 tumor tissues by reverse transcriptase PCR. We did not find any type of mutation other than polymorphisms in the 48 esophageal carcinomas, though aberration of the p53 gene on the PCR-SSCP gels was observed in 15 of 38 (39%) tumors of the same set. In addition, LOH for p73 was found in only 2 of 25 (8%) tumors. These results suggest that, at least in esophageal carcinomas, allelic loss or mutation of p73 may not be a main genetic event for the tumorigenesis as it is with p53.

Adenocarcinoma↗