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Biomedical subjects

A Yamauchi

Publications and source records attributed to A Yamauchi.

At least 73 records · Page 4Linked to original sources
PubMed1999

Secondary myeloid/natural killer cell precursor acute leukemia following essential thrombocythemia.

The de novo leukemic transformation of essential thrombocythemia is a rare event, and usually associated with previous treatments. We describe a patient who received treatments with nitrosourea for long-standing essential thrombocythemia and subsequently developed extramedullary tumors, tentatively diagnosed as lymphoblastic lymphoma. Combination chemotherapy was initially successful, but relapsed with marked bone marrow involvement. Surface marker analysis revealed that the tumor cells had CD5, CD7, CD33, CD34, and CD56 antigens but lacked other T-cell, and B-cell markers. Immunogenotypical studies revealed germline configurations for both T-cell receptors and immunoglobulin genes. These clinical and phenotypical features are consistent with a myeloid/natural killer cell precursor leukemia, a recently proposed distinct clinical entity. To our knowledge, this is the first report of secondary leukemia of myeloid/ natural killer cell precursor origin, and suggest that myeloid/natural killer cell precursor might be a potent target of therapy-related leukemia.

Antigens, CD↗
PubMed1999

Hepatocyte growth inhibitory factor derived from HTLV-I(+) T-cell line is identical to IL-6.

We previously reported that the culture supernatant of the human T-cell leukemia virus (HTLV-I) infected-T-cell line--ATL-2--included factor(s), which had an inhibitory effect on epidermal growth factor (EGF)-stimulated proliferation of primary cultured rat hepatocytes. After crude purification, we arbitrarily named it hepatocyte growth inhibitory factor (HGI). In this study, we further purified HGI and determined its amino acid sequence. For purification, we used 4-steps column chromatography and SDS-PAGE. The purified proteins consisted of two bands of 20 and 27 kDa in SDS-PAGE analysis. Protein extracted from each band had an inhibitory effect on rat hepatocyte growth. Amino acid analysis of the purified 20 kDa band revealed that the 34 amino acids were identical to those of IL-6. The inhibitory effect of the factor was neutralized by an anti IL-6 neutralizing antibody. Using Western blot analysis of HGI, an anti IL-6 antibody recognized both 20 and 27 kDa bands. Consequently HGI was determined to be identical to IL-6, which occurred in higher levels in the sera of adult T-cell leukemia (ATL) patients.

Aged↗
PubMed1999

Differential regulation of adenine nucleotide translocators by hypertonicity in the brain.

To determine the gene(s) induced by hypertonicity in the brain, we performed a differential display analysis using RNA isolated from isotonic and hypertonic rat astrocytes. One cDNA rapidly up-regulated by hypertonicity was isolated, and the DNA sequence revealed that it was identical to adenine nucleotide translocator (ANT)2. ANT2 protein exchanges intramitochondrial ATP for cytoplasmic ADP. Among three ANT isoforms, only ANT2 mRNA was up-regulated markedly from 1 to 4 h after exposure to hypertonicity. Induction of the mRNA did not require de novo protein synthesis. Furthermore, ADP translocase activity in mitochondria of astrocytes was increased significantly by hypertonicity. To see the localization and regulation of ANT2 mRNA in the brain, we performed in situ hybridization of rat brain after intraperitoneal injection of a high concentration of NaCl. Although there were only weak signals in the control, intense hybridization signals were seen in hypertonic rat whole brain. Microscopic examination showed that ANT2 signals were present in the neurons, as well as glial cells. These results suggest that ANT2 may play a role in brain cells to adapt to the hypertonic environment.

Adenosine Diphosphate↗
PubMed1999

Neuroprotective role of Na+/myo-inositol cotransporter against veratridine cytotoxicity.

Na+/myo-inositol cotransporter has been shown to protect cells from the perturbing effects of hypertonic stress by the accumulation of myo-inositol. Here we report a regulatory mechanism for the cotransporter. Induction of myo-inositol cotransporter mRNA was observed after exposure to veratridine, a voltage-gated sodium channel opener. The veratridine-elicited induction was inhibited when Na+ was eliminated from the bath, although calcium chelation failed to modify the gene expression. Veratridine evoked an accumulation of Na+ in the cells, which paralleled the abundance of the mRNA. These results strongly suggested that an increase in Na+ influx due to sodium channel opening affected transcription of the cotransporter gene. Activity of the myo-inositol cotransporter was also up-regulated after veratridine exposure. To clarify the possible roles of myoinositol accumulation under veratridine exposure, we next examined the neurotoxic effects of veratridine when myo-inositol uptake was blocked. Neither 30 microM veratridine nor 500 microM 2-O,C-methylene myo-inositol, a competitive inhibitor of myo-inositol, elicited apparent cytotoxicity. However, a combination of these agents markedly increased cytotoxicity in culture, suggesting that an adequate amount of myo-inositol was necessary when the cells were stimulated with veratridine.

Carrier Proteins↗
PubMed1999

High water intake ameliorates tubulointerstitial injury in rats with subtotal nephrectomy: possible role of TGF-beta.

BACKGROUND: It has been shown that tubulointerstitial injury correlates well with a decline of renal function. In this study, we investigated the effect of high water intake (HWI) on functional and structural parameters in rats with subtotal nephrectomy. METHODS: Two weeks after the ablative procedure, rats were divided into two groups. One group received the treatment with HWI (3% sucrose added to drinking water) for eight weeks. Functional parameters were compared with sham-operated control (CONT) or nephrectomized rats without treatment (NX). Remnant kidneys were then assessed histologically for evidence of interstitial fibrosis and glomerulosclerosis. RESULTS: Creatinine clearance was significantly improved in HWI rats compared with NX rats. Simultaneously, urinary protein was also significantly reduced in HWI rats. HWI predominantly ameliorated interstitial lesions and, to a lesser extent, glomerular lesions. Northern blot analysis demonstrated that transforming growth factor-beta (TGF-beta) mRNA expression was significantly suppressed in HWI rats. In situ hybridization revealed that HWI suppressed TGF-beta mRNA expression mainly in the outer medulla. Fibronectin mRNA was also reduced by the HWI treatment. The changes in TGF-beta and fibronectin mRNA were in parallel with Na+/myo-inositol cotransporter (SMIT) mRNA, which is regulated by extracellular osmolarity. Immunohistochemistry demonstrated that protein expression of TGF-beta and fibronectin coincided with the mRNA expression. CONCLUSION: These results suggest that HWI reduces TGF-beta mRNA expression in medullary interstitium and ameliorates tubulointerstitial injury in rats with reduced renal mass.

Animals↗
PubMed1999

Involvement of histone phosphorylation in thymocyte apoptosis by protein phosphatase inhibitors.

Incubation of rat thymocytes with the inhibitors of protein phosphatase such as calyculin A and okadaic acid resulted in an increase in DNA fragmentation. These effects were dependent on the concentration of the inhibitors and the incubation time. Analyses of the fragmented DNA revealed the production of approximately 50 kbp of DNA and a 180 bp DNA ladder. In addition, a laser scanning-microscopic analysis showed that these compounds caused nuclear condensation. Thus, these results demonstrated that protein phosphatase inhibitors induced thymocyte apoptosis. The inhibitors of protein phosphatase increased the phosphorylation of proteins of approximately 15 kDa. The phosphorylation of proteins preceded the DNA fragmentation induced by these inhibitors. Judging from acetic acid-urea-Triton X-100 gel electrophoresis, the phosphorylated proteins were histone H1 and H2A/H3. Therefore, these results suggest that phosphorylation of histones triggers the DNA fragmentation of thymocytes undergoing apoptosis.

Animals↗
PubMed1999

Liver immunity and glutathione.

Redox processes have been implicated in various biologic processes, including signal transduction, gene expression, and cell proliferation, and several molecules have been identified as redox regulators in cell activation. Glutathione is the oldest and most investigated molecule among them. Although details of the mechanisms by which glutathione regulates various aspects of cell biology remains to be characterized, the relationship between immunodeficiency and cellular glutathione status is well established. Redox dysregulation contributes to the pathogenesis of acquired immunodeficiency syndrome (AIDS). Human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV)-infected rhesus macaques have, on the average, significantly decreased plasma cysteine and intracellular glutathione levels. Liver contains abundant levels of reducing factors. However, glutathione levels in serum and peripheral blood mononuclear cells of cirrhosis patients are lower compared to values detected in healthy individuals. In the present article, the significance of glutathione in regulating the functions of lymphocytes, especially those of liver-associated lymphocytes, has been described. A novel strategy for immune therapy of liver neoplasms with the use of redox-modulating agents has been proposed.

Animals↗
PubMed1999

Response to hypertonicity in mesothelial cells: role of Na+/myo-inositol co-transporter.

BACKGROUND: During peritoneal dialysis, the peritoneal mesothelium is exposed continually to hypertonic dialysates. The purpose of this study is to see if rat mesothelial cells have an osmoregulatory mechanism to adapt to hypertonic environment. METHODS: The intracellular content of organic osmolytes was measured by HPLC methods. Myo-inositol transport activity was measured by Na+-dependent uptake of [3H]myo-inositol. mRNA abundance for the Na+/myo-inositol co-transporter (SMIT) was examined by Northern and slot-blot analyses. RESULTS: In isotonic mesothelial cells, only myo-inositol could be detected. After switching to hypertonic medium made by addition of NaCl, myo-inositol content gradually increased and peaked at 48 h after the switch. The myo-inositol content in hypertonic cells increased > 7-fold over the value in isotonic cells. The contents of betaine and glycerophosphorylcholine (GPC) also increased but were less than that of myo-inositol. Sorbitol was not accumulated in this condition. When glucose was used to increase medium osmolality, all of the four osmolytes were increased by hypertonicity (myo-inositol > sorbitol > GPC > betaine). Thus, myo-inositol is the most abundant osmolyte in the mesothelial cells. Na+-dependent myo-inositol uptake in hypertonic cells was approximately 7-fold the uptake in isotonic cells, reaching a maximum 16 h after switching to a hypertonic medium. The uptake rate increased as medium osmolality increased from 300 to 500 mosm/kg. SMIT mRNA rapidly increased after increasing medium osmolality, reaching a maximum 8 h after the switch. The relative increase in the mRNA abundance was approximately 11 times isotonic levels. CONCLUSIONS: Mesothelial cells respond to extracellular hypertonicity by increasing SMIT mRNA abundance, myo-inositol transport activity and accumulating myo-inositol into the cells.

Animals↗
PubMed1999

Enhanced interstitial expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy.

BACKGROUND: With progressive renal disease, structural derangement increasingly encompasses the tubulointerstitial compartment. Tubulointerstitial injury is a critical determinant of renal functional reserve and prognosis in renal disease. Interstitial cells acquiring characteristic of myofibroblasts are an important contributor to interstitial fibrosis. Caldesmon, a calmodulin or actin binding protein, is a molecular marker of differentiation in smooth muscle cells and has recently been shown by us to be a good marker of mesangial cell activation in IgA nephropathy patients. METHODS. We studied whether the expression of caldesmon in interstitium of the kidney was enhanced in the process of glomerular disease and whether it would be a marker of interstitial activation in specific disease states. We performed immunohistochemical staining with anti-caldesmon antibodies in 38 biopsy specimens from IgA nephropathy patients and analysed them quantitatively with a computer-aided manipulator. Interstitial caldesmon expression were compared with histological changes and clinical parameters. RESULTS: Caldesmon expression was enhanced where interstitial cell infiltration and fibrosis were found. Immunoelectron microscopy revealed that caldesmon staining in the renal interstitium was cytoplasmic, and in the processes of myofibroblast-like cells. Caldesmon expression was more prominent in the intense CD68 infiltrated group than in the low positive cells infiltrated group. Patients showing high intensity of interstitial caldesmon expression had significantly higher urinary protein excretion than those showing low intensity of caldesmon expression. Next, 15 patients were treated with glucocorticoid and heparin for 4-8 weeks and re-biopsies were performed. Caldesmon expression was reduced in concomitant with decreased interstitial cell infiltration. Follow-up of these patients (average 24 months) revealed a significant suppression of urinary protein excretion and significant improvement of creatinine clearance. CONCLUSION: These results suggest that the interstitial caldesmon expression is associated with the progression of IgA nephropathy, and glucocorticoid--heparin therapy may reverse the phenotypic change of interstitial cells during the disease process of glomerulonephritis.

Actins↗
PubMed1999

Causes of stillbirth: an analysis of 77 cases.

OBJECTIVE: To devise preventive measures for stillbirths, which account for more than 70% of perinatal deaths in Japan. METHODS: We retrospectively reviewed the medical records of 77 women with singleton pregnancies who gave birth to stillborn infants at > or = 30 weeks between 1979 and 1996 at our hospital. RESULTS: Major malformations were present in 21 (27%) of 77 infants, including 11 infants with anencephaly. Two infants (2.6%) were severely hydropic. Preeclampsia preceded the stillbirth and might have been an indirect cause of stillbirth in 21 (39%) of 54 women whose infants had normal formations. The cause of stillbirth in 33 non-preeclamptic women was unclear in 15 (28%), abruptio placentae in 9, fetal growth retardation in 3, the HELLP syndrome in 3, chorioamnionitis in 2, and cord accident in 1. Abruptio placentae also occurred in 9 of 21 preeclamptic patients. Thus, abruptio placentae was responsible for 18 (33%) of 54 stillborn infants with a grossly normal appearance. An autopsy was performed on only 13 (24%) of 54 infants with grossly normal appearance and did not provide new information relating to deaths. CONCLUSIONS: The causes of stillbirth were many and varied, with a large proportion having no obvious cause, although autopsies were underused. Increased monitoring for women with preeclampsia and early diagnosis and prompt delivery for women with abruptio placentae might be helpful in reducing the number of stillbirths.

Abruptio Placentae↗
PubMed1999

Localization of rat CLC-K2 chloride channel mRNA in the kidney.

To gain insight into the physiological role of a kidney-specific chloride channel, CLC-K2, the exact intrarenal localization was determined by in situ hybridization. In contrast to the inner medullary localization of CLC-K1, the signal of CLC-K2 in our in situ hybridization study was highly evident in the superficial cortex, moderate in the outer medulla, and absent in the inner medulla. To identify the nephron segments where CLC-K2 mRNA was expressed, we performed in situ hybridization of CLC-K2 and immunohistochemistry of marker proteins (Na+/Ca2+ exchanger, Na+-Cl- cotransporter, aquaporin-2 water channel, and Tamm-Horsfall glycoprotein) in sequential sections of a rat kidney. Among the tubules of the superficial cortex, CLC-K2 mRNA was highly expressed in the distal convoluted tubules, connecting tubules, and cortical collecting ducts. The expression of CLC-K2 in the outer and inner medullary collecting ducts was almost absent. In contrast, a moderate signal of CLC-K2 mRNA was observed in the medullary thick ascending limb of Henle's loop, but the signal in the cortical thick ascending limb of Henle's loop was low. These results clearly demonstrated that CLC-K2 was not colocalized with CLC-K1 and that its localization along the nephron segments was relatively broad compared with that of CLC-K1.

Animals↗
PubMed1999

Autoantibodies to FK506 binding protein 12 (FKBP12) in autoimmune diseases.

Plasma from 126 patients with various autoimmune diseases and 118 healthy subjects were examined to determine the presence of autoantibodies to FKBP12, one of immunophilins. The frequency of IgG and/or IgM anti-FKBP12 autoantibodies detected by ELISA was as follows; SLE (15/39), SSc (11/27), CREST (4/7), RA (2/8), MCTD (0/5), Graves' disease (4/12), IDDM (2/6), PM/DM (0/3), MG (1/4), AIH (2/6), PBC (4/9), and healthy subjects (5/118). The specificity of the autoantibodies was demonstrated by absorption of the plasma samples with r-FKBP12 and other recombinant proteins. In immunoblotting, IgM anti-FKBP12 autoantibodies reacted with two bands of 12 and 24 kD, the latter representing the dimer. Anti-FKBP12 autoantibodies in some patients reacted more strongly with the dimer than the monomer, suggesting that FKBP12 may also exist as the dimer in vivo. The majority of anti-FKBP12 autoantibodies bound to two synthetic peptides corresponding to amino acid residues of FKBP12, Pro16 approximate to Tyr26 and Thr27 approximate to Phe46. These epitopes are phylogenetically well conserved and responsible for the binding to calcineurin and FK506. The autoantibodies inhibited pentamerization of FKBP12 with FK506, calcineurin, calmodulin, and Ca2+ in vitro. These data define the frequent occurrence of a novel set of autoantibodies to a cytosolic protein involved in the regulation of the immune response.

Amino Acid Sequence↗
PubMed1999

Target cell-induced apoptosis in IL-2-activated human natural killer cells.

We demonstrated that tumor cells induce cell death in lymphokine-activated NK (LAK) cells, but not in non-activated NK cells. Cell death in LAK cells involves nuclear condensation and DNA cleavage, all of which are characteristic features of apoptosis. The mechanism involves signaling through integrins and requires src family tyrosine kinases and protease activities. Engagement of an apoptotic signal molecule, Fas, may also trigger LAK cell death by apoptosis. It appears that LAK cells rapidly die by apoptosis after attacking tumor cells. This phenomenon may provide a means for potential tumor target cells to escape from natural immunosurveillance during therapeutic interventions such as those using IL-2 or LAK cells.

Apoptosis↗
PubMed1999

[Clinical study of six thymic carcinomas including long-term survivors].

Six cases of thymic carcinoma (mean age 48.5 years old, one male and 5 females) were treated in our hospital from September 1990 to September 1998. The histological subtypes of thymic carcinoma were squamous cell in 4, undifferentiated in one, and small cell in one. All cases underwent midsternal thoracotomy, 4 had total resection of the tumor and 2 had exploratory thoracotomy due to tumor invasion of the aorta and the main pulmonary artery. Within 2 years after operation, 2 cases without radiation therapy were died of the carcinoma and one case was died of asthma. However, two cases of squamous cell carcinoma have been alive and disease free for 3 and 5 years since the operation followed by mediastinal irradiation. We think that radiation therapy is very effective to control the disease because one of them underwent only exploratory operation prior to irradiation. Another one case who survives 5 years after total resection of the tumor following irradiation revealed swelling of numerous mediastinal lymph nodes, pathologically consisted of non-caseating epithelioid cell granulomas without metastasis of carcinoma, at the time of operation. These lymph nodes were diagnosed as "sarcoid-like reaction" because there was no clinical evidence of generalized sarcoidosis. The "sarcoid-like reaction" may contribute to the 5-year survival of the patient because it is thought to be a local immune response against the cancer cells. A remaining patient, alive 6 months after total resection of the thymic small cell carcinoma following irradiation, received preoperatively three cycles of the intra-arterial administration using CBDCA via bilateral internal mammary arteries. This induction chemotherapy had no response of the tumor size, but it was considered to have a possibility of reducing the size of thymic carcinoma by the use of other agents (CDDP, VDS etc.) because the tumor was fed mainly by the highly developed internal mammary arteries.

Adult↗
PubMed1999

Reduction of BRCA1 protein expression in Japanese sporadic breast carcinomas and its frequent loss in BRCA1-associated cases.

BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian cancer syndrome. To clarify the possible involvement of the BRCA1 protein in mammary carcinogenesis in sporadic and hereditary forms, we have analyzed the BRCA1 protein expression pattern in five breast epithelial cell lines, including a BRCA1-deficient cell line, and 162 breast cancer tissue samples [including 108 sporadic, 35 hereditary (BRCA1 status unknown), and 19 BRCA1-associated cases] from Japanese women. Twelve anti-BRCA1 antibodies were tested by fixation conditions, in which nuclear localization of BRCA1 protein was preserved, and by specificity of the antibodies, which was evaluated in BRCA1-deficient cancer cells. Using monoclonal antibodies applicable to immunohistochemical analysis of paraffin-embedded tissue sections, we found high-level expression of BRCA1 protein in normal mammary epithelium and various degrees of reduced expression in breast cancer cells. Of the 19 BRCA1-associated breast cancer tissues, 15 (79%) showed reduction (8 cases) or complete loss (7 cases) of nuclear expression. Thirty (28%) of 108 sporadic and 6 (17%) of 35 hereditary carcinomas showed reduced BRCA1 protein expression. Reduction of BRCA1 protein expression in sporadic carcinomas was associated with solid-tubular phenotype, with poor tubular differentiation, and with an overexpression of c-erbB-2 protein, which is one of the prognostic factors in breast cancer. Our data suggest that reduced expression of BRCA1 protein may play an important role in mammary carcinogenesis, not only in BRCA1-associated breast carcinomas, but also in sporadic carcinomas, and also suggest that mechanisms other than mutation may be involved in its reduced expression.

Animals↗
PubMed1999

[Complete disruption of thoracic descending aorta without widening of the pseudoaneurysm].

A 41-year-old male was transported to our emergency room 25 minutes after blunt chest trauma. The chest X-ray film and CT scanning demonstrated left pulmonary atelectasis, hemothorax, and widening of mediastinum possibly due to hematoma. Hundred and fifty minutes after arrival to the hospital, we were rush to bring him to the operation theater suspecting serious injury of the thoracic organs in association with bleeding from left thoracic drainage tube without detection of the aortic rupture. The left standard thoracotomy disclosed no injury of the left lung, good continuity and no dilatation of the thoracic descending aorta. But visual blood flow observed through the adventitia of the aortic isthmus led us to the final diagnosis of the aortic rupture. After aortic clamping, the intima of the injured aorta was found to be completely disrupted for a length of 6 cm and was repaired with a vascular prosthesis under the partial cardiopulmonary bypass using a centrifugal pump. His postoperative course was uneventful. We reported a case of complete circumferential aortic rupture without widening of the pseudoaneurysm in the acute stage of the disease.

Adult↗
PubMed1998

Direct transfer of bovine embryos frozen-thawed in the presence of propylene glycol or ethylene glycol under on-farm conditions in an integrated embryo transfer program.

An integrated bovine embryo transfer program was conducted in collaboration with 11 Japanese prefectural livestock experiment stations. The program was conducted to evaluate the practicability of the direct transfer method for bovine embryos frozen-thawed in the presence of propylene glycol (PG) or ethylene glycol (EG) under on-farm conditions. Embryos at the compacted morula to expanded blastocyst stages were collected from superovulated donors on Day 7 or 8 after estrus and equilibrated in 1.6 M PG or 1.8 M EG in Dulbecco's phosphate-buffered saline (DPBS) supplemented with 20% heat-inactivated calf serum. Embryos were then loaded individually into a 0.25-ml straw and placed directly into a cooling chamber of a programmable freezer precooled to -7 degrees C. After 2 min, the straw was seeded, maintained at -7 degrees C for 8 min more, and then cooled to -30 degrees C either at 0.3 degree C/min or 0.5 degree C/min before being plunged into liquid nitrogen. Embryos at the same stages were also frozen in the presence of 1.4 M glycerol (GLY) by a conventional method, which served as a control. The frozen embryos were thawed by allowing the straws to stand in air for 5 to 10 sec and then immersing them in a 30 degrees C water bath. Embryos frozen-thawed in the presence of PG or EG were nonsurgically transferred into the uterine horn without diluting the cryoprotectant. Embryos frozen-thawed in the presence of GLY were nonsurgically transferred after removing GLY either by the stepwise method (GLY-I) or by in situ dilution with 0.3 M sucrose solution (GLY-II). A total of 1,273 (PG: 400, EG: 418, GLY-I: 177, GLY-II; 278) frozen-thawed embryos was transferred into recipients, yielding 545 pregnancies (overall: 42.8%, PG: 36.0%, EG; 44.7%, GLY-I; 48.6%, GLY-II; 46.0%). The pregnancy rate with PG was significantly lower than that with EG or GLY-II (P < 0.05). The pregnancy rate was affected by the type of cryoprotectant, the region where the embryo transfer program was carried out, the developmental stage of the embryos, the parity of the recipients, and corpus luteum (CL) quality of the recipients. There were no differences in rates of abortion and stillbirth among the 3 cryoprotectants. The present study demonstrates that EG can be effectively used as a cryoprotectant for freezing and direct transfer of bovine embryos, and that the direct transfer method is applicable under on-farm conditions.

Animals↗