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Biomedical subjects

Hiroshi Hashimoto

Publications and source records attributed to Hiroshi Hashimoto.

At least 55 records · Page 3Linked to original sources

Effects of antisecretory agents on angiogenesis during healing of gastric ulcers.

BACKGROUND: We studied the effects of a proton pump inhibitor (PPI) and an H2-receptor antagonist (H2-blocker) on angiogenesis during gastric ulcer healing, by examining stromal cell-derived factor (SDF-1) and CXC chemokine receptor 4 (CXCR4) expression in the gastric mucosa. METHODS: Patients with gastric ulcers were allocated to an untreated control group, consisting of patients with active ulcers (GA), healing ulcers (GH), and ulcer scars (GS) or a PPI group (P; given rabeprazole at 20 mg/day), or an H2-blocker group (H; given nizatidine at 800 mg/day). Frozen sections of biopsy specimens were examined by reverse transcription-polymerase chain reaction (RT-PCR) to analyze SDF-1 and CXCR4 mRNA. RESULTS: CXCR4 mRNA levels were elevated in the control (GH and GS patients) group and the H2-blocker group. CXCR4 was significantly elevated in the P-GA subgroup of the PPI group (P<0.01), but its level decreased with time. CONCLUSIONS: In the PPI group, CXCR4 levels were increased in the early phase of ulcer healing and returned to a level similar to that in the control group during the scar phase. These results suggest that PPIs increase the expression of CXCR4 mRNA and thus promote vessel regeneration and maturation, facilitating ulcer healing.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Reactive arthritis after influenza vaccination: report of a case.

We describe a patient with reactive arthritis (ReA) induced by influenza vaccination. A healthy 79-year-old Japanese man began suffering from migrating polyarthritis 2 days after receiving influenza vaccine. He proved negative for rheumatoid factor, showing no evidence for microbial infections such as Streptoccocci, Chlamydia, or Parbovirus B19. Human leukocyte antigen (HLA) typing analysis revealed positive results for HLA-B54 (22), which is one of the cross-reactive antigens to HLA-B27. His arthritis improved with administration of nonsteroidal anti-inflammatory drugs, and recovery was attained within 6 weeks. Reactive arthritis is a rare adverse effect induced by influenza vaccination; however, it is important that it is recognized by all physicians.

Journal Article↗

Inhibitory effect of mizoribine on matrix metalloproteinase-1 production in synovial fibroblasts and THP-1 macrophages.

To investigate the mechanism of antirheumatic action of mizoribine (MZR), we examined the expression of matrix metalloproteinase-1 (MMP-1) and MMP-3 utilizing THP-1 derived macrophage-like cells (THP-1 macrophages) and human synovial fibroblasts (SFs). The cells were respectively stimulated with lipopolysaccharide (LPS) and interleukin-1beta in the presence or absence of MZR in vitro. The concentrations of MMP-1 and MMP-3 in the supernatant were measured by enzyme-linked immunosorbent assay. The secretion of MMP-1 from SFs, as well as THP-1 macrophages, was inhibited by MZR in a dose-dependent manner. Furthermore, a quantitative real-time polymerase chain reaction revealed that MZR decreased the expression of MMP-1 messenger RNA. These findings may be an explanation for the clinical effect of MZR in patients with rheumatoid arthritis.

Journal Article↗

The relationship between initial clinical manifestation and long-term prognosis of patients with systemic lupus erythematosus.

The relationship between clinical manifestations and prognosis was examined and evaluated among systemic lupus erythematosus (SLE) patients. A total of 542 patients with SLE were selected and divided into nine groups according to their main clinical manifestation at the time of initial diagnosis. The relationship between these clinical manifestations and long-term prognosis was evaluated in respect to the survival, remission, relapse rates, the development of a new clinical manifestation, and/or damage index. Patients with neuropsychiatric SLE (NPSLE), accompanied with acute confusional state/seizure disorder, cerebral vascular disease, or pneumonitis had poor survival rates with cause of death related to their major organ involvement. Patients with nephropathy or leukopenia had lower remission rates, and an increase in relapse rates was frequently recognized in patients with pneumonitis. Body damage (damage index) was higher in patients with lupus psychosis, pneumonitis, and/or arthritis. The translation of the main manifestations after diagnosis was confirmed in 64 patients (11.8%), and often observed in patients with autoimmune hemolytic anemia and arthritis. The majority of these manifestations were nephropathy, NPSLE, thrombocytopenia, and pneumonitis, and the prognosis of patients with nephropathy and thrombocytopenia as a new main manifestation had a poor outcome. The results of long-term prognosis in SLE greatly differed with respect to the initial clinical manifestation at the time of diagnosis.

Journal Article↗

Progressive severe anemia due to copper deficiency five years after subarachnoid hemorrhage.

Patients with neurological illnesses often require prolonged enteral or parenteral nutrition. The complications of this type of feeding may be unfamiliar to neurosurgeons and neurologists, however, these complications may be an important source of ongoing morbidity. We present a case of severe anemia due to copper deficiency in a patient requiring enteral nutrition after SAH. The anemia resolved with copper supplements. A high index of suspicion is needed to recognise and treat complications of enteral nutrition.

Anemia↗

Autoimmune hepatitis in primary Sjogren's syndrome: pathological study of the livers and labial salivary glands in 17 patients with primary Sjogren's syndrome.

Although primary Sjogren's syndrome (pSS) is an autoimmune exocrinopathy, the involvement of liver has been reported. Because no study focusing on autoimmune hepatitis (AIH) in pSS has been published, the purpose of the present study was to perform a clinical and histological examination of the liver, focusing on AIH, in 17 pSS patients. The patients had liver enzyme abnormalities without hepatitis virus infection. In all cases, biopsied livers were examined, and in 10 cases biopsied labial salivary glands were also examined histologically. Based on the authors' diagnostic criteria for AIH in pSS, the liver diseases consisted of AIH (eight cases, 47%), primary biliary cirrhosis (PBC; six cases, 35%), non-specified chronic hepatitis (two cases, 12%) and acute hepatitis (one case, 6%). Lymphoplasmacytic infiltrate, with predominancy of CD3(+) T cells, was noted in both the liver and salivary glands in the patients with AIH. The patients with AIH with severe interface hepatitis had a good response to immunosuppressive therapy. The comparison of liver histology between the PBC with pSS group and the PBC without pSS group showed that the incidence of lymphoid non-suppurative cholangitis was higher in PBC with pSS. In conclusion, the present study offers new information on the relatively common occurrence, diagnostic criteria and treatment effects of AIH in pSS.

Adult↗

Extraskeletal myxoid chondrosarcoma: updated clinicopathological and molecular genetic characteristics.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma characterized by distinctive morphological and cytogenetical features. As its name implies, EMC was believed to represent a variant of soft-tissue chondrosarcoma owing to its histological resemblance to chondroblastic tissue in the early stages of cartilage development or chondroid tumors such as skeletal chondrosarcoma. However, the chondroid nature has been a subject of controversy, and its line of differentiation remains to be determined. Consequently, the tumor is provisionally classified into a group of tumors of uncertain differentiation in the revised World Health Organization classification of tumors of soft tissue and bone. Moreover, immunohistochemical and ultrastructural features of neural or neuroendocrine differentiation have been recently reported in a subset of EMC, providing a new insight into their histogenetic nature. Chromosomal rearrangements involving 9q22, such as t(9;22)(q22;q12), and resultant NR4A3 fusion genes are tumor-type specific or pathognomotic for this entity and are assumed to play an important role in the development of EMC. Although the biological mechanisms and functions are largely unknown, the NR4A3-related pathway is considered a potential molecular target for future therapeutic intervention. Because of its protracted but resilient nature, a tenacious and long-term follow up is necessary for any patient.

Chondrosarcoma↗

The efficacy of preanesthetic proton pump inhibitor treatment for patients on long-term H2 antagonist therapy.

UNLABELLED: We previously reported that H2-antagonist medication given for longer than 4 wk may produce complete tolerance to preanesthetic H2 antagonist therapy. In this study, we evaluated the efficacy of preanesthetic proton pump inhibitor (PPI; oral rabeprazol) use in patients receiving regular H2-antagonist (oral famotidine) therapy for more than 4 wk. Forty-eight patients with assumed complete tolerance to H2 antagonists undergoing elective surgery were recruited and randomly assigned to receive either a preanesthetic PPI (rabeprazol 20 mg; n = 24) or H2-antagonist (H2 group; roxatidine 75 mg; n = 24) at 9:00 pm on the day before surgery and 2 h before the induction of anesthesia. Volume of gastric contents and pH values were measured after the induction of anesthesia. Gastric pH value in the PPI group (5.38 +/- 2.42) was significantly higher than in the H2 group (3.27 +/- 1.98; P < 0.01). Gastric volume in the PPI group (8.6 +/- 1.5 mL) was significantly smaller than in the H2 group (15.4 +/- 2.8 mL; P < 0.05; cf. PPI). Fourteen patients in the H2 group were at risk of acid aspiration pneumonia (gastric pH <2.5 or volume >25 mL), whereas only four patients in the PPI group (P < 0.05) were at risk. These data suggest that in patients receiving H2-antagonist therapy for longer than 4 wk, prophylaxis for acid aspiration pneumonia should include preanesthetic PPI medication. IMPLICATIONS: We previously reported that more than 4 wk of administration of H2-antagonists may produce a full tolerance to preanesthetic H2-antagonists. The present study suggests that a proton pump inhibitor may be effective for prophylaxis of acid aspiration pneumonia in patients showing the full tolerance to H2 antagonists.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Analysis of clinical questionnaire of Tokyo Metropolitan Government for Sjogren's syndrome].

Sjögren's syndrome is not one of the forty-five diseases included in the incurable disease treatment research project funded by the government. However, it is approved as a designated incurable disease for government funded treatment in Tokyo. The criteria of approval are based on diagnostic criteria revised in 1999. Complications and other factors are taken into consideration in the recognition standard established independently in Tokyo. In this study we examined the recognition standard of approval and their significance by analyzing the clinical questionnaires of patients with Sjögren's syndrome in Tokyo through 2003. The major objective of the recognition standard (2003) appears to have been the approval of subjects with severe Sjögren's syndrome with such conditions as advanced glandular involvement xerosis affecting their daily lives and visceral complications. However, examinations using biopsy, salivary gland scintigraphy, and contrast sialography can only be performed at an institution with appropriate facilities. For an approval process that is impartial and accomplished with ease, we believe that combinations of simple multiple tests should be considered as auxiliary items which could be substituted for the aforementioned examinations. In addition, future investigation is necessary to examine the high cost incurred in requiring findings within six months for an approval application, performing of annual invasive tests, and the validity of the process for determining the approved or unapproved status using the present clinical questionnaire profiles.

Humans↗

Infantile fibrosarcoma of thigh--a case report.

Infantile fibrosarcoma is a rare soft tissue malignant tumor, when it occurs, it is usually seen in the first year of life. The clinical course of infantile fibrosarcoma is more favorable and metastasis is rare compared with that in adulthood. While adult fibrosarcoma are common in the thigh, infantile fibrosarcoma affect chiefly the distal portions of the extremities. Standard treatment is primarily wide surgical excision. In this case report, we present our experience of an infantile fibrosarcoma of thigh with good clinical course 36 months after tumor resection and the usefulness of detecting the ETV6-NTRK3 gene fusion in differential diagnosis.

DNA-Binding Proteins↗

Vertebral fracture and bone mineral density in women receiving high dose glucocorticoids for treatment of autoimmune diseases.

OBJECTIVE: To evaluate the factors influencing the occurrence of vertebral fracture in patients receiving high dose glucocorticoids (GC). METHODS: A cross-sectional study was performed on women who had received at least 0.5 mg/kg of oral glucocorticoid for the treatment of autoimmune diseases for more than 1 month between 1998 and 2003. Logistic regression analysis and chi-square test were used to examine the effects of glucocorticoid dose and other factors on vertebral fractures. Receiver-operating characteristics curve (ROC) analysis was used to determine the bone mineral density (BMD) cutoff value for the risk of vertebral fracture. RESULTS: The study population comprised 160 women, including 35 with vertebral fractures. In ROC analysis, the BMD threshold of the risk of fracture for postmenopausal women (0.787 g/cm2 , T score -2.1) was lower than that for premenopausal women (0.843 g/cm2 , T score -1.7). Among patients with fractures, 7 of 16 premenopausal patients had normal BMD values (T score > -1), whereas only one of 19 postmenopausal patients showed a comparable level of BMD. Additionally, vertebral fracture was more frequent for patients with high total cholesterol values (> 280 mg/dl) than for those with normal total cholesterol values (< 220 mg/dl). Moreover, patients with high total cholesterol values had lower BMD values than those with normal total cholesterol values. CONCLUSION: The fact that vertebral fracture frequently occurred in premenopausal patients with normal BMD and evidence that hyperlipidemia correlated with fracture suggest the pathology of vertebral fracture secondary to high dose glucocorticoid therapy is multifactorial and possibly involves lipid metabolism.

Adolescent↗

[A case of a ureteral inflammatory pseudotumor].

The patient was a 28-year-old woman. In February 2002, she visited another physician due to acute pyelonephritis. Based on CT findings, a lower ureteral stricture caused by a benign extraureteral tumor was diagnosed. The patient was being monitored by periodic exchange of ureteral stents. In February 2003, the patient visited our department seeking a second opinion. Retrograde pyelography showed an elliptical filling defect in the lower urinary tract. Ureteroscopy showed that the surface of the tumor was mostly smooth, regular and partially papillary. Biopsy was performed, and histological analysis revealed only nonspecific inflammation. In December 2003, based on a diagnosis of benign ureteral tumor, we performed partial resection of the right urinary tract and ureterocystoneostomy. As rapid intraoperative pathological analysis confirmed an inflammatory pseudotumor, total nephroureterectomy was avoided.

Adult↗

[Solitary genital leiomyoma of the tunica dartos: a case report and review of the literature in Japan].

We report a case of solitary genital leiomyoma arising from the tunica dartos of the scrotum. A 43-year-old man complained of a slightly tender left scrotal mass that had enlarged over approximately 17 years. On physical examination, the tumor was pedunculate and attached to the lower pole of the left scrotum. The tumor was clearly separate from scrotal contents such as the testis, epididymis, and spermatic cord. Ultrasonography showed the tumor to be 20.0 X 23.5 mm in diameter. Other laboratory examination findings were normal. Under local anesthesia, the tumor was resected at its base with overlying skin. On histopathological examination, the tumor consisted of interlacing bundles of smooth muscle cells, which were positive for vimentin, desmin, and a-actin. The tumor was diagnosed as leiomyoma arising from the scrotal tunica dartos. As solitary genital leiomyoma of the tunica dartos is rare, we have presented this case history and reviewed 23 cases that occurred in Japan.

Adult↗

Crystal structures of type II restriction endonuclease EcoO109I and its complex with cognate DNA.

EcoO109I is a type II restriction endonuclease that recognizes the DNA sequence of RGGNCCY. Here we describe the crystal structures of EcoO109I and its complex with DNA. A comparison of the two structures shows that the catalytic domain moves drastically to capture the DNA. One metal ion and two water molecules are observed near the active site of the DNA complex. The metal ion is a Lewis acid that stabilizes the pentavalent phosphorus atom in the transition state. One water molecule, activated by Lys-126, attacks the phosphorus atom in an S(N)2 mechanism, whereas the other water interacts with the 3'-leaving oxygen to donate a proton to the oxygen. EcoO109I is similar to EcoRI family enzymes in terms of its DNA cleavage pattern and folding topology of the common motif in the catalytic domain, but it differs in the manner of DNA recognition. Our findings propose a novel classification of the type II restriction endonucleases and lead to the suggestion that EcoO109I represents a new subclass of the EcoRI family.

Amino Acid Sequence↗

CD72 polymorphisms associated with alternative splicing modify susceptibility to human systemic lupus erythematosus through epistatic interaction with FCGR2B.

We previously reported association of FCGR2B-Ile232Thr with systemic lupus erythematosus (SLE) in three Asian populations. Because polymorphism of CD72, another inhibitory receptor of B cells, was associated with murine SLE, we identified human CD72 polymorphisms, tested their association with SLE and examined genetic interaction with FCGR2B in the Japanese (160 SLE, 277 controls), Thais (87 SLE, 187 controls) and Caucasians (94 families containing SLE members). Four polymorphisms and six rare variations were detected. The former constituted two major haplotypes that contained one or two repeats of 13 nucleotides in intron 8 (designated as *1 and *2, respectively). Although association with susceptibility to SLE was not detected, the *1 allele was significantly associated with nephritis among the Japanese patients (P=0.024). RT-PCR identified a novel alternatively spliced (AS) transcript that was expressed at the protein level in COS-7 transfectants. The ratio of AS/common isoforms was strikingly increased in individuals with *2/*2 genotype when compared with *1/*1 (P=0.000038) or *1/*2 (P=0.0085) genotypes. Using the two Asian cohorts, significant association of FCGR2B-232Thr/Thr with SLE was observed only in the presence of CD72-*1/*1 genotype (OR 4.63, 95% CI 1.47-14.6, P=0.009 versus FCGR2B-232Ile/Ile plus CD72-*2/*2). Minigene assays demonstrated that the 13-nucleotide repeat and 4 bp deletion within the same haplotype of intron 8 could regulate alternative splicing. The AS isoform lacks exon 8, and is deduced to contain 49 amino acid changes in the membrane-distal portion of the extracellular domain, where considerable amino acid changes are known in CD72(c) allele associated with murine SLE. These results indicated that the presence of CD72-*2 allele decreases risk for human SLE conferred by FCGR2B-232Thr, possibly by increasing the AS isoform of CD72.

Adult↗