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S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 577 records · Page 32Linked to original sources

Alternative splicing of CD79a (Ig-alpha/mb-1) and CD79b (Ig-beta/B29) RNA transcripts in human B cells.

The CD79a (Ig-alpha/mb-1) and CD79b (Ig-beta/B29) molecules form a membrane heterodimer that is non-covalently associated with surface membrane immunoglobulin and is the major signaling component of the B cell antigen receptor complex. We have defined variant RNA transcripts for both CD79a (Ig-alpha/mb-1) and CD79b (Ig-beta/B29) which appear to arise by alternative splicing. These splice variants are predicted to encode truncated forms of these molecules that result in the deletion of the entire extracellular Ig-like domain of CD79b and of a major portion of the extracellular domain of CD79a. The presence of these short transcripts in a variety of human B cells and B cell lines was established by an RNAse protection assay. The definition of these variant transcripts provides a basis for a continuing effort to define variant protein products of CD79a and CD79b and examine their role in B cell physiology.

Alternative Splicing↗

TNF-alpha regulates IL-4-induced Fc epsilon RII/CD23 gene expression and soluble Fc epsilon RII release by human monocytes.

We examined the regulatory effects of TNF-alpha on IL-4-induced gene expression of the low-affinity receptor for IgE (Fc epsilon RII/CD23) in human monocytes and IL-4-induced soluble Fc epsilon RII (sFc epsilon RII) release from monocytes. IL-4-induced Fc epsilon RII expression on the surface of monocytes was reduced by TNF-alpha as early as 1 day after culture and the effect of TNF-alpha increased with prolonged culture. The present analysis was designed to examine whether or not TNF-alpha could suppress IL-4-induced Fc epsilon RII mRNA expression and enhanced IL-4-induced sFc epsilon RII release. The addition of TNF-alpha to monocyte cultures with IL-4 significantly reduced Fc epsilon RII expression on the surface of monocytes and significantly increased sFc epsilon RII release from monocytes. Over time, there was an inverse relationship between the disappearance of cell surface Fc epsilon RII and the appearance of sFc epsilon RII in culture supernatants. Fc epsilon RII mRNA expression in monocytes cultured with IL-4 was not affected by TNF-alpha when examined at 6 h after cultivation. When the cells were cultured with TNF-alpha for more than 24 h, however, TNF-alpha down-regulated IL-4-induced Fc epsilon RII mRNA levels. This correlated with the kinetics of down-regulation of IL-4-induced Fc epsilon RII expression on the surface of monocytes by TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Case report: the first report of idiopathic hypereosinophilic syndrome involved with lung and middle ear.

It has been reported that various organs are involved in idiopathic hypereosinophilic syndrome. Frequently, the heart, lung, skin, and nervous system are involved. Involvement of the middle ear, however, has not yet been reported. In this article, the authors describe the first case of hypereosinophilic syndrome involving the lung and middle ear. A 39-year-old woman had a 4-month history of low grade fever, non-productive cough, and a feeling of fullness and hearing loss in both ears. Peripheral blood cell count showed eosinophilia. Bilateral tympanic cavities were obstructed with granulation tissue, and she was diagnosed as obliterative otitis media. The granulation tissue consisted of foamy histiocytes and eosinophils. Chest X-ray film and computed tomography showed patchy infiltrative shadow in the lung. Histologic examination of the open lung biopsied specimen showed alveolar spaces infiltrated by eosinophils. After treatment with 30 mg oral prednisolone daily, there was a rapid improvement in her clinical condition. Based on the clinical course and the histologic findings of this case, obliterative otitis media may be caused by eosinophilic infiltration and eosinophilic pneumonia.

Adult↗

Elevation of serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in bronchial asthma.

We have previously shown the elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) in patients with bronchial asthma during asthma attacks. In the present study, we extended our earlier study by measuring serum sVCAM-1 levels by ELISA in 45 patients with bronchial asthma (23 atopic and 22 non-atopic) during asthma attacks and in stable conditions in order to assess further the state of adhesion molecules in allergic inflammation of bronchial asthma. The levels of sVCAM-1 in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sVCAM-1 levels, serum tumor necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. The nature of change in serum TNF-alpha levels correlated with the nature of change in serum sVCAM-1 levels, but serum TNF-alpha levels did not correlate with serum sVCAM-1 levels. These results suggest that higher levels of sVCAM-1 during asthma attacks may reflect the up-regulation of VCAM-1 expression in allergic inflammation, and that a soluble form of VCAM-1 molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of VCAM-1 in vitro, however; the regulatory mechanism in the elevation of serum sVCAM-1 levels remains to be clarified.

Adult↗

Epidural anaesthesia blocks changes in peripheral lymphocytes subpopulation during gastrectomy for stomach cancer.

To examine the effects of surgery and anaesthesia on cell-mediated and humoral immunity, we investigated changes in subpopulations of peripheral T cells and B cells during gastrectomy. Twenty-one patients with gastric cancers who underwent total or subtotal gastrectomy were randomly assigned to receive thiopental/N2O general anaesthesia supplemented with either epidural (epidural group, n = 12) or enflurane(enflurane group, n = 9). The changes in peripheral lymphocyte subpopulations were detected and quantified using single and double label analysis of monoclonal antibodies against lymphocyte membrane surface markers (Leu series). Subpopulations were measured before induction, and 1 and 2 hours after skin incision. In the enflurane group, B cells (Leu12+), total T cells (Leu4+), inducer T cells (CD4+, Leu8+) and the CD4/CD8 ratio decreased and suppressor T cells (CD8+, Leu15+) increased significantly after skin incision. Whereas, the epidural group showed no change in the number of B cells and each T cell subpopulation during the study. These data suggest that epidural anaesthesia blocks the effect of stress induced by major surgery on fluctuation of peripheral lymphocyte subpopulations which may be associated with suppression of immunity.

Aged↗

Analysis of the role of TFIIE in basal transcription and TFIIH-mediated carboxy-terminal domain phosphorylation through structure-function studies of TFIIE-alpha.

The general transcription factor TFIIE recruits TFIIH at a late stage of transcription initiation complex formation and markedly stimulates TFIIH-dependent phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II. To study this function of TFIIE in more detail, systematic deletion mutations were introduced into the large subunit of TFIIE (TFIIE-alpha) and were analyzed with regard to their effects on TFIIH-dependent CTD phosphorylation, TFIIE-dependent basal and enhancer-dependent transcription, and interactions of TFIIE-alpha with both TFIIE-beta and TFIIH. The amino (N)-terminal half of TFIIE-alpha, which possesses several putative structural motifs, was sufficient for the phosphorylation and transcription activities and for TFIIE-beta interactions, whereas a site effecting both strong interactions with TFIIH and large stimulatory effects on transcription and CTD phosphorylation was localized to an acidic region near the carboxy (C) terminus. The fact that these activities appear to be tightly linked supports the idea that TFIIE interacts physically and functionally with TFIIH and that CTD phosphorylation is essential for transcription under normal conditions. The present results suggest that TFIIE, via its effect on TFIIH, may act as a checkpoint for formation of a preinitiation complex.

Base Sequence↗

A type I cell-specific protein is a biochemical marker of epithelial injury in a rat model of pneumonia.

In this study we determined whether the alveolar fluid content of a specific epithelial type I cell protein, rTI40, can be used as a biochemical marker for lung injury. A model of alveolar epithelial injury was developed by instilling Pseudomonas aeruginosa bacteria (PA103) into the airspaces of anesthetized, ventilated rats. After 6 h, the alveolar fluid content of rTI40 from PA103-treated rats was increased over 80-fold in comparison to alveolar fluid from control rats (P < 0.05). This increase in rTI40 correlated with both morphological evidence of injury to alveolar epithelial type I cells and increased permeability of the alveolar epithelium to protein tracers. In contrast, the lactate dehydrogenase activity of alveolar fluid from PA103-treated rats was elevated only threefold over control values at 6 h (P < 0.05). In a second study using a less injurious strain of P. aeruginosa (PA103 exsA::omega), the alveolar fluid content of rTI40 was the same as control values. These findings indicate that the alveolar fluid content of a type I cell-specific protein can be used as a sensitive and specific biochemical marker of type I cell injury.

Animals↗

Relationship between age and nephrotoxicity following single low-dose cisplatin (CDDP) injection in rats.

We studied nephrotoxicity following a single injection of cisplatin (CDDP) at low dose (1 mg/kg) in two groups of rats aged 52 weeks (adult, A group) and 9 weeks (young, Y group). Renal platinum (Pt) was detectable in both groups 3 h after the CDDP injection, and, from 6 h to 3 d after injection, its level in the A group was higher than that in the Y group. Compared with the levels in age-matched normal rats (non-treated rats examined at time zero), the plasma urea nitrogen and creatinine levels in the A group were significantly increased, beginning 3 d after CDDP injection, while those in the Y group showed little change for 10 d after injection. Beginning 3 d after CDDP injection, the level of renal metallothionein in the Y group increased, while that in the A group decreased remarkably. The renal tissue levels of the heavy metals Zn, Cu, Mn showed similar patterns. There were no significant changes in the renal lipid peroxide (LPO) level in either the A and Y group at any time measured after CDDP injection compared with the value in the respective age-matched untreated group. Morphological evaluation demonstrated degeneration of the proximal tubules in the A group 3 d after CDDP injection. These results suggested that the renal disorders observed following CDDP injection in the A group were caused by mechanisms other than LPO such as decreased tissue metabolic function associated with aging.

Aging↗

Inhibitory activity of 8-azadecalin derivatives towards 2,3-oxidosqualene:lanosterol cyclases from baker's yeast and pig's liver.

The inhibitors of 2,3-oxidosqualene:lanosterol cyclase were investigated by comparative studies between pig's liver and Baker's yeast. The fundamental skeleton of the inhibitors was 8-azadecalin. To the nitrogen atom, an isoprenoid-like chain [nerylacetone (Z-form), geranylacetone (E-form) or its hydrogenated form] was attached by the reaction of reductive amination with NaCNBH3. Among the three forms, the Z-isomer was the most potent inhibitors toward both the pig's liver and yeast cyclases. To examine the effect of carbon chain length (lipophilicity), various fatty acids (C6-C18) were appended to the 8-azadecalin derivatives. Strong inhibitory activity was observed for those compounds having carbon chains around C12. Interestingly, the amide compounds (not the carbocationic intermediate) exhibited remarkably strong inhibition toward the liver cyclase, whereas they had an insignificant effect on the yeast cyclase (about 10(2)-fold less active). The yeast cyclase needed the amine functionality (carbocationic intermediate), which was prepared by using LiAlH4 from the corresponding amides, to exhibit potent inhibition. We found that N-dodecyl-8-aza-4,4,10 beta-trimethyl-trans-decal-3 beta-ol (7i) was the most potent inhibitor (IC50 = 1 microM) toward the yeast cyclase amongst any known material. Kinetic studies showed that the inhibition pattern was dependent only on whether the side chains on the 8-azadecalin were linear or branched; the compounds having isoprenoid-like chains were non-competitive inhibitors, while those having linear hydrocarbon chains (amides or amines) were competitive inhibitors.

Animals↗

Differential staining of DNA strand breaks in dying cells by non-radioactive in situ nick translation.

Various lines of evidence indicate the involvement of DNA strand breaks (DSB) in the regulation of physiological states of cells, especially in cell death. Currently, cell death is divided into two categories, apoptosis and necrosis. As lysosomal integrity is maintained in apoptosis, while disrupted in necrosis, it is possible to assume that necrotic chromatin is exposed to digestion by various lysosomal enzymes. We have therefore investigated whether apoptotic DSB and necrotic DSB can be discriminated by in situ nick translation (INT) under various conditions of protease pretreatment. Used models of apoptosis and necrosis were the rat thymus with an intraperitoneal injection of hydrocortisone (10 mg/100 g body weight (b.w.)) and rat liver with an intraperitoneal injection of CCl4 (100 microliters/g b.w.), respectively. As results, we found that necrotic DSB was readily detected by INT without protein digestion, whereas apoptotic ones were not. These results indicate that the environment around DSB and/or the nature of DSB in apoptosis differs from that of necrosis, and that INT is a convenient molecular histochemical tool to discriminate both types of cell death in frozen sections.

Acid Phosphatase↗

Gap junctions between fibroblasts in rat myotendon.

We applied conventional and freeze-fracture electron microscopy to study intercellular contacts between the processes of fibroblasts in the myotendon of the rat exterior digitorium longus. The results showed well defined gap junctions between the cell processes, while other cell junctional structures such as tight junctions and desmosomes were not recognizable. The present study suggests that the gap junctions represent a structure to coordinate the activities of fibroblasts distributed in the myotendon of the muscle.

Animals↗

Pneumatosis cystoides intestinalis after chemotherapy for hematological malignancies: report of 4 cases.

Pneumatosis cystoides intestinalis (PCI) is known to be a relatively rare condition which is characterized by gas cysts in the gastrointestinal mucosa. We treated four cases of PCI accompanied by hematological malignancies during chemotherapy treatment. All cases suffered from abdominal discomfort. Abdominal X-ray films revealed gas cysts in the intestine. PCI was observed during leukocytopenic states, and three cases had septicemia. Etoposide was administered to three cases, and prednisolone to all cases. It is considered that PCI sometimes occurs in patients with hematological malignancies during a period of leukocytopenia, and may be caused by intestinal mucosal damage due to myelosuppressive agents and immunosuppression from prednisolone.

Adult↗

Chronic bronchobronchiolitis obliterans associated with Stevens-Johnson syndrome.

We report a case of bronchobronchiolitis obliterans associated with Stevens-Johnson syndrome diagnosed using bronchography and bronchoscopy in a 25-year-old man with dyspnea. Eighteen months prior to admission, the diagnosis of Stevens-Johnson syndrome due to anticonvulsant therapy was made at another hospital. On admission, the patient was wheezing and had overinflation of the lungs, with marked obstructive pulmonary dysfunction. Ventilation and perfusion scintigrams revealed multiple ventilation and perfusion defects but not mismatch. Bronchography revealed central bronchiectasis and obstruction of the peripheral bronchi. Occlusion of the fifth right basal bronchus was observed with fiberoptic bronchoscopy. Bronchography and bronchoscopy provide useful information for the diagnosis of this disease.

Adult↗

[A case of Sjögren's syndrome complicated with cryoglobulinemia, nephrogenic diabetes insipidus, and renal tubular acidosis].

A 68-year-old woman had been complained of xerostomia since she was 30 years old. Further symptoms of polyuria, polyposia and insomnia had been developed since she was 35 years old. The biopsy material from a minor salivary gland demonstrated the infiltration of lymphocytes into mesenchyme which was compatible with Sjögren's syndrome. She admitted to our hospital because of myalgia in bilateral gastrocnemius and petechiae in both lower extremities in addition to the complaints described above. Complete blood cell counts on admission revealed hemoglobin 9.7 g/dl, platelet count 12.5 x 10(4)/microliters, and white blood cell count 3,300/microliters. Marked polyuria, polyposia (more than 5,000 ml/day, respectively) and low urine gravity (1.005) were observed, although the serum creatinine level showed normal value. Serologic examination showed that the elevation of total serum protein concentration (9.5 g/dl) with marked elevation of serum IgG level (6,190 mg/dl). Her immunoglobulins contained cryoglobulin (cryocrit 20%), and immunoelectrophoresis demonstrated the existence of IgG-kappa monoclonal protein. A positive anti-nuclear antibody at 1:320 dilution, a positive rheumatoid factor and a positive antibody to SS-A (Ro) were also observed. The serial studies of blood gas analysis could not demonstrated the presence of metabolic acidosis. Together with the result of elevated plasma antidiuretic hormone level and results of vasopressin test, Fishberg's concentrating test and the tests of the overload of NH4Cl or bicarbonate, she was diagnosed Sjögren's syndrome with both diabetes insipidus and subclinical renal tubular acidosis. She was initially medicated with prednisolone (40 mg/day, orally), then she was given six courses of intravenous cyclophosphamide (750 mg/body/month).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Renal Tubular↗

IgH and L chain variable region gene sequence analyses of twelve synovial tissue-derived B cell lines producing IgA, IgG, and IgM rheumatoid factors structure/function comparisons of antigenic specificity, V gene sequence, and Ig isotype.

In the present study, the complete sequences of the Ig H and L chain variable region genes of twelve RF+ B cell lines from two patients with RA were analyzed. Seven of the RF-producing B cells used VH3 family genes, four used VH4 genes, and one a VH1 gene. All but two of the cell lines expressing VH3 genes utilized different family members; among the VH4-expressing cells, a more restricted pattern was noted. V kappa gene use was restricted to the V kappa I and III families; V lambda gene use was more diverse, involving five different families. Computer comparisons of the expressed VH genes with their presumed germline progenitors indicated significant differences in every instance; eight of the corresponding VL genes also were significantly different. In many cases, assignment of the germline D segment(s) incorporated into the rearranged VH genes was impossible. These differences from the germline gene segments indicated the extensive changes induced by rearrangement, enzymatic activities, and somatic mutation. In hopes of defining a structural reason for the disparate antigen specificities of these cells, the CDR3 amino acid sequences of the multi- vs. the mono-reactive RF-producers were compared. Although CDR3 length was not appreciably different between these two sets of mAb, a greater than two-fold increase in charged amino acids was found in the H chain CDR3 of the multireactive RF. This relationship did not exist for the L chain CDR3. Thus, these sequence data indicate the use of a broad base of Ig V gene segments that have undergone extensive diversification. Based on the localization of R substitutions in the CDR of most of the V genes studied, the diversification appears to be antigen driven and selected. The significance of these findings for the evolution of these B cell clones into isotype-switched producers that are heterogeneous for antigen specificity (mono- vs. multi-reactivity) is discussed.

Aged↗

[Primary adenocarcinoma of the tunica vaginalis testis expressing CA19-9 antigen].

A 47-year-old man presented with a 10-year history of left scrotal swelling. No solid mass detected on sonogram, dark-red colored fluid aspirated, equivocal cytology, and elevated serum CA19-9 level prompted surgical exploration. Frozen section reported no malignancy of thickening of the tunica vaginalis. The final pathology adenocarcinoma, however, necessitated left radical orchiectomy and hemiscrotal resection, demonstrating no malignancy at the left testis nor epididymis. CA19-9 level was high (104,200 U/ml) in the fluid obtained at the first surgery and the tumor cells were positively stained for CA19-9. Imaging study including abdominal CT scan and upper G-I series and normalization of CA19-9 level denied other tumor existing. In conclusion, this is to our knowledge the first case report of adenocarcinoma of the tunica vaginalis expressing CA19-9 antigen.

Adenocarcinoma↗