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Biomedical subjects

Hiroshi Hashimoto

Publications and source records attributed to Hiroshi Hashimoto.

At least 145 records · Page 8Linked to original sources
PubMed2002

Decreased IL-4 producing CD4+ T cells in patients with active systemic lupus erythematosus-relation to IL-12R expression.

The balance of interferon-gamma (IFN-gamma) and/or interleukin-4 (IL-4) producing T cells and interleukin-12 receptor (IL-12R) expression on T cells were evaluated in patients with active systemic lupus erythematosus (SLE). Assessment of intracellular IFN-gamma and/or IL-4 were conducted with cytoplasmic staining. IL-12R presenting T cells were also assessed by flowcytometry without in vitro stimulation. In SLE, the number of IFN-gamma producing CD4+ T cells was increased, and the absolute number of IL-4 producing CD4+ T cells was significantly decreased. Although the ratio of IL-12R presenting CD4+ T cells was significantly greater, the absolute number did not increase. The ratio of IFN-gamma/IL-4-producing CD4+ T cells correlated with the SLE disease activity index (SLEDAI) and was significantly higher among patients with lupus nephritis. Therefore, the imbalance of IFN-gamma/IL-4 producing CD4+ T cells was due to the decrease in IL-4 producing CD4+ T cells and may play an important pathogenic role in active SLE.

Arthritis, Rheumatoid↗
PubMed2002

Quantification and comparison of pulmonary emboli formation after pneumatic tourniquet release in patients undergoing reconstruction of anterior cruciate ligament and total knee arthroplasty.

UNLABELLED: The amount of emboli formed (percentage of total emboli area to the right atrial area [%Ae]) after tourniquet release in invasive procedures of the medullary cavity is empirically much larger than that in noninvasive procedures, even if the tourniquet duration is similar. Thus, we compared %Ae between arthroscopic reconstruction of the anterior cruciate ligament (ACL, n = 20) and total knee arthroplasty (TKA, n = 20). The right atrium was continuously monitored by transesophageal echocardiography to assess %Ae. Peak %Ae +/- SD (ACL, 4.1% +/- 3.4%; TKA, 20.7% +/- 16.7%) appeared 30-40 s after tourniquet release in both groups. However, %Ae in the TKA group was always larger than the peak %Ae in the ACL group. In addition, although the ET(CO(2)) significantly increased after tourniquet release in both groups, increase of ET(CO(2)) (1.1% +/- 0.3%) in the ACL group was significantly larger than that in the TKA group (0.5% +/- 0.2%). An increase in ET(CO(2)) was inversely proportional to peak %Ae (P < 0.01; r = 0.703). Therefore, the present data suggest that the risk of acute pulmonary embolism after tourniquet release may be more frequent during TKA than ACL. IMPLICATIONS: We compared emboli formation after tourniquet release in patients undergoing arthroscopic reconstruction of the anterior cruciate ligament (ACL, n = 20) and total knee arthroplasty (TKA, n = 20) using transesophageal echocardiography. The present data suggest that the risk of acute pulmonary embolism after tourniquet release could be more frequent during TKA than ACL.

Acute Disease↗
PubMed2002

Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma.

h-warts/LATS1 is a human homolog of the Drosophila warts tumor suppressor gene, which functions as a component of the mitotic apparatus. LATS1-deficient (Lats1(-/-)) mice have been reported to develop ovarian stromal tumors and soft tissue sarcomas. We investigated the status of the h-warts/LATS1 in 50 human soft tissue sarcomas to address its potential function as a tumor suppressor in human sarcoma development. In our RT-PCR assay, 7 (14%) (3 of 4 myxoid liposarcomas, 3 of 7 leiomyosarcomas, 1 of 9 malignant fibrous histiocytomas) of 50 sarcomas examined had no or a reduced expression of the h-warts/LATS1, indicating down-regulated gene expression. We further analyzed alterations of the h-warts/LATS1 in these seven sarcomas. Using microsatellite markers for chromosome 6q23-25.1, to which the h-warts/LATS1 is localized, an allelic loss of this locus was detected in one leiomyosarcoma, in which a missense point mutation of the h-warts/LATS1 was detected by PCR single-strand conformation polymorphism. Clusters of CpG dinucleotides in a 5' putative promoter region were hypermethylated in the other six sarcomas. Our data suggest that the molecular alterations of the h-warts/LATS1 could be of pathologic importance in human sarcomagenesis.

Base Sequence↗
PubMed2002

Lack of interaction between amiodarone and mexiletine in cardiac arrhythmia patients.

Amiodarone has pharmacokinetic interactions with various therapeutic agents, including phenytoin, flecainide, and cyclosporine. Mexiletine is metabolized by CYP2D6 and CYP1A2. The objective of this study is to evaluate the effect of amiodarone on the pharmacokinetics of mexiletine through its inhibition of various cytochrome P450 (CYP) subtypes. In a series of 181 inpatients with supraventricular tachyarrhythmias, 26 inpatients received mexiletine and amiodarone therapy (MEX + AMD group), and the others received mexiletine therapy (MEX group). In 10 inpatients of the MEX + AMD group, the mexiletine clearance (CL(MEX)/F) before and after coadministration of amiodarone was compared. CL(MEX)/F was also compared in the MEX and MEX + AMD groups after the start of amiodarone therapy. Serum mexiletine, amiodarone, and desethylamiodarone concentrations were measured by an HPLC method. The CL(MEX)/F was estimated by the Bayesian method using population pharmacokinetic analysis. There was no significant difference in CL(MEX)/F before and after 1-month coadministration of amiodarone in 10 inpatients of the MEX + AMD group. Although serum amiodarone and desethylamiodarone concentrations gradually increased with time after the start of amiodarone therapy in these patients, CL(MEX)/F showed no change at 3 and 5 months after the start of amiodarone therapy. There was no significant difference in CL(MEX)/F of the MEX group and the MEX + AMD group. The results suggest that the pharmacokinetics of mexiletine is not affected by amiodarone in patients with cardiac arrhythmias.

Aged↗
PubMed2002

Impairment of mycophenolate mofetil absorption by calcium polycarbophil.

The effect of calcium polycarbophil on the absorption of mycophenolate mofetil, an immunosuppressive agent, was evaluated in healthy subjects. In vitro studies were performed to further evaluate the mechanism of the potential interaction. In the in vitro study, the release of mycophenolate mofetil from a cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, a randomized crossover design with two phases was used. In one phase, 6 male healthy volunteers received 1000 mg of mycophenolate mofetil alone (treatment 1); in the other phase, they received 1000 mg of mycophenolate mofetil and 2400 mg of calcium polycarbophil fine granules concomitantly (treatment 2). They received 30 mg of lansoprazole for 5 days and, on the 6th day, received mycophenolate mofetil and 2400 mg of calcium polycarbophil fine granules concomitantly (treatment 3). The serum concentration of mycophenolic acid was measured by high-performance liquid chromatography. In the in vitro study, the release from a cellulose membrane in the presence of calcium or iron ions was slower than that in the absence of these metal ions. In the in vivo study, the AUC0-12 and C(max) in treatment 2 were less than those in treatment 1. About 50% and 25% decreases in AUC0-12 in treatment 2 and treatment 3 were observed compared with those in treatment 1, respectively. These findings suggest that when mycophenolate mofetil and calcium polycarbophil were coadministered concomitantly, a decrease in mycophenolate mofetil absorption was observed. Therefore, it appears clear that the concomitant administration of mycophenolate mofetil and calcium polycarbophil should be avoided.

Absorption↗
PubMed2002

Sequence analysis of 193.4 and 83.9 kbp of mouse and chicken genomic DNAs containing the entire Prkdc (DNA-PKcs) gene.

The catalytic subunit of DNA-dependent protein kinase plays critical roles in nonhomologous end joining in repair of DNA double-strand breaks and V(D)J recombination. In addition to the SCID phenotype, it has been suggested that the molecule contributes to the polymorphic variations in radiosensitivity and susceptibility to cancer in mouse strains. Here we show the nucleotide sequence of approximately 193-kbp and 84-kbp genomic regions encoding the entire Prkdc gene (also known as DNA-PKcs) in the mouse and chicken, respectively. A large retroposon was found in intron 51 in the mouse but not in the human or chicken. Comparative analyses of the genome strongly suggested that the region contains only two genes for Prkdc and Mcm4; however, several conserved sequences and cis elements were also predicted.

Animals↗
PubMed2002

[Nephrogenic adenoma of the bladder in children].

We report an unusual case of a 3-year-old girl with multiple nephrogenic adenomas in the urinary bladder following previous surgical intervention. When she was 6-month-old, right vesicoureter-alreflux (VUR) and left marked hydronephrosis with ectopic urethral opening were found. The left renal pelvis and ureter were incompletely duplicated with a short common segment. Bilateral ureterocystoneostomy and closure of ectopic opening of the left ureter were performed. Left ureteral orifice resulted in double barreled pattern. Postoperative voiding-cystourethrography revealed VUR in the ureter belonging to the lower part of the left kidney. At the age of 3 year, cystoscopic examination revealed multiple papillary lesions in the urinary bladder. These lesions were resected transurethrally and the pathologic diagnosis was nephrogenic adenoma. The patient is the 27th case of nephrogenic adenoma of bladder reported in the Japanese literature.

Adenoma↗
PubMed2002

Anti-TS1-RNA: characterization of novel antibodies against sequence-specific RNA by random RNA selection in patients with Sjögren's syndrome.

OBJECTIVE: To define a novel RNA epitope recognized by serum from a patient with Sjögren's syndrome (SS) from a randomized RNA epitope library and investigate the epitope reactivity of the anti-RNA antibodies in patients with various connective tissue diseases. METHODS: Serum from a patient with SS was used to select ligands from a library of RNA oligomers with a central region of 25 degenerate nucleotides. Bound RNA was recovered by reverse transcription, PCR amplification, and subcloning. The relationship between the antibodies to the selected RNA and disease specificity was studied using immunoprecipitation. RESULTS: From the random RNA library, several unique RNA sequences were obtained. Sera from 32 of 61 patients with SS (52.5%) precipitated with one of the selected RNA (TS1-RNA), whereas sera from 8 of 41 patients with systemic lupus erythematosus (19.5%) and 3 of 25 patients with rheumatoid arthritis (12.0%) precipitated. Although the frequency of reactivity to the TS1-RNA was higher in anti-SSA/Ro positive sera, the presence of either native or recombinant SSA/Ro antigen showed no detectable competition, and no apparent sequence homology was found between the TS1-RNA and hY RNA. CONCLUSION: These data suggest that anti-TS1-RNA is a novel antibody against sequence-specific RNA in many patients with SS.

Antibodies, Antinuclear↗
PubMed2002

Detection of SYT-SSX fusion transcripts in paraffin-embedded tissues of synovial sarcoma by reverse transcription-polymerase chain reaction.

OBJECTIVE: To assess the feasibility of detecting SYT-SSX fusion transcripts in paraffin-embedded tissues of synovial sarcoma by reverse transcription-polymerase chain reaction (RT-PCR). METHODS: RT-PCR was used to amplify the SYT-SSX fusion transcripts using archival formalin-fixed paraffin-embedded tumor specimens from a series of 37 synovial sarcoma cases. To investigate the specificity of the SYT-SSX fusion transcripts, a variety of non-synovial sarcoma tumors were included in the study as negative controls. The detected messages derived from fusion genes were confirmed by subsequent sequence analysis. RESULTS: SYT-SSX fusion transcripts were detected in 33 of 37 (89.2%) synovial sarcomas. None of the 34 cases of non-synovial sarcoma tumors showed amplified products of SYT-SSX fusion transcripts, although PBGD mRNA was detected in all specimens. Among 33 SYT-SSX-positive synovial sarcomas, 22 tumors had an SYT-SSX 1 fusion transcript, whereas 6 tumors had an SYT-SSX2 fusion transcript. Fusion types can not be distinguished in the remaining 5 cases. There was a significant relationship between SYT-SSX fusion type and histologic subtype. All 10 biphasic synovial sarcomas had the SYT-SSX1 fusion, whereas all tumors with SYT-SSX2 were of monophasic morphology (P < 0.05). CONCLUSIONS: RT-PCR can be applied to archival formalin-fixed paraffin-embedded tumor tissues as a sensitive and reliable technique for the diagnosis and differential diagnosis of synovial sarcoma. There is an association between SYT-SSX fusion type and histological subtype. SYT-SSX2 fusion transcripts can only be found in monophasic synovial sarcoma.

Adolescent↗
PubMed2002

Role of DNA methylation in transcription of human endogenous retrovirus in the pathogenesis of systemic lupus erythematosus.

OBJECTIVE: We recently reported that transcription of human endogenous retrovirus (HERV) clone 4-1-like sequences is increased in patients with systemic lupus erythematosus (SLE). We therefore investigated the role of DNA methylation in the transcription of this HERV. METHODS: The effect of a demethylating agent, 5-aza-deoxycytidine (5-aza C), on the transcription of HERV clone 4-1 in healthy individuals and patients with SLE was examined using reverse transcriptase-PCR and real-time quantitative PCR. RESULTS: 5-aza C increased clone 4-1-like messenger RNA in healthy controls, but not in patients with SLE. CONCLUSION: Defects of methylation may contribute to the transcription of HERV in patients with SLE and this may be related to the pathogenesis of SLE.

Adult↗
PubMed2002

[A case of renal infarction treated by thrombolytic therapy with systemic intravenous injection of tPA (tissue plasminogen activator)].

A 55-year-old woman affected by mitralism presented with severe right flank pain of sudden onset. Biochemical examinations showed elevated serum lactate dehydrogenase, and abdominal enhanced computed tomography (CT) demonstrated hypoperfusion of the right kidney. Infarction of the right kidney was highly suspected, and she was immediately treated by systemic intravenous injection of 12,000,000 units of tissue plasminogen activator (tPA) per day for 3 days and 120,000 units of urokinase per day for 8 days. After the thrombolytic therapy, abdominal enhanced CT revealed marked improvement of enhancement of right renal parenchyma and decrease of serum LDH. Although thrombolytic therapy with selective intraarterial infusion is considered to be a useful treatment modality for renal infarction, systemic administration of tPA may also be effective judging from the clinical course of the present case.

Female↗
PubMed2002

[A case of erythropoietin-producing renal cell carcinoma with polycythemia].

The patient was a 46-year-old man with gross hematuria and left lumbar pain. Computed tomography revealed a large left renal tumor with hemorrhage. Serological examination revealed polycythemia and a high erythropoietin level. After left radical nephrectomy, polycythemia and serologically high level of erythropoietin disappeared. Histopathological findings showed renal cell carcinoma composed of spindle cells. Based on the above mentioned clinical course, we diagnosed this case as erythropoietin-producing renal cell carcinoma with polycythemia. It is suggested that erythropoietin not only causes polycythemia but also stimulates proliferation of the tumor, because the majority of erythropoietin-producing renal cell carcinomas have been reported to be highly advanced. This patient had no evidence of disease one year after the operation.

Carcinoma, Renal Cell↗
PubMed2002

[A case of spermatic granuloma difficult to differentiate from malignant tumor].

A 33-year-old man visited our hospital with complaint of painless left intrascrotal mass. A hard and rough induration in contact with the left testis was palpable. The laboratory data including beta-human churionic gonadotropin, alpha fetoprotein and lactate dehydrogenase were normal. Ultrasound sonography showed a large hypoechoic lesion at the left epididymis. Surgical exploration of this lesion indicated a malignant tumor of the epididymis or spermatic cord, and left high orchiectomy was performed. A milk-white nodule 6 cm in diameter was found in the resected specimen. Pathological diagnosis was spermatic granuloma. Fourteen cases of spermatic granuloma have been reported in the last twenty years in Japan. All of them were relatively small nodules and epididymectomy was performed for most of them. We selected radical orchiectomy because of a large nodule with suspicion of malignant lesion.

Adult↗