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Biomedical subjects

F Ishida

Publications and source records attributed to F Ishida.

At least 55 records · Page 3Linked to original sources
PubMed1996

Serum thrombopoietin (c-Mpl ligand) levels in patients with liver cirrhosis.

To clarify the role of c-Mpl ligand (thrombopoietin: TPO) in liver cirrhosis (LC), we examined serum TPO levels (sTPO) in patients with LC (N = 44), chronic hepatitis (CH; N = 13) and healthy controls (N = 41) by an enzyme-linked immunosorbent assay. Although platelet counts of all LC patients (89 +/- 59 x 10(9)/l; mean +/- SD) were lower than those of controls and CH patients, sTPO levels in LC patients (1.23 +/- 0.51 fmol/ml) were the same as those in controls (1.22 +/- 0.37) and CH patients (1.18 +/- 0.36). Platelet counts were significantly higher in splenectomized patients than in unsplenectomized patients, but the sTPO level did not differ between these two groups. In LC patients, the sTPO level was not correlated with the platelet count, but was correlated with prothrombin time, activated partial thromboplastin time, and total bilirubin, indicating that production of TPO in the liver decreases slightly with the development of liver dysfunction. Our findings suggest that production of TPO is maintained in LC patients and their thrombocytopenia is not due to a defect in platelet production.

Case-Control Studies↗
PubMed1995

The largest variant of platelet glycoprotein Ib alpha has four tandem repeats of 13 amino acids in the macroglycopeptide region and a genetic linkage with methionine145.

Platelet membrane glycoprotein Ib alpha (GPIb alpha) bears the human platelet alloantigen (HPA)-2 and molecular weight (MW) polymorphisms on sodium dodecyl sulfate-polyacrylamide gels. HPA-2 arises from a threonine/methionine dimorphism at residue 145 of the GPIb alpha sequence, whereas different numbers of tandem repeats of a 39-bp sequence encoding 13-amino acids corresponding to a region between serine399 and threonine411 of the GPIb alpha account for the latter. To identify the genetic basis of the MW polymorphism among Japanese, we counted the tandem repeats in 103 individuals. In addition to the reported three variants with one, two, or three tandem repeats, we identified a new variant with four perfect tandem repeats of the 39-bp sequence that corresponded to the largest phenotype. Phenotypic analysis of the MW polymorphism on 12 individuals including all four phenotypes completely accorded in the genotype. We also determined the genotype of HPA-2 and found that methionine145 was in complete linkage disequilibrium, with the larger variants containing three or four tandem repeats. These results imply a model of evolutionary steps in the gene encoding GPIb alpha.

Alleles↗
PubMed1995

Hyperosmolality rapidly reduces atrial-natriuretic-peptide-dependent cyclic guanosine monophosphate production in cultured rat inner medullary collecting duct cells.

The present study was undertaken to explore the acute effect of hyperosmolality on the response of cultured rat inner medullary collecting duct (IMCD) cells to atrial natriuretic peptide (ANP). In contrast to the stimulatory effect of chronic incubation (12 h) in hypertonic medium, it was found that short-term incubation (< 2 h) reversibly suppressed the ANP-dependent cyclic guanosine monophosphate (cGMP) production. Urea, NaCl and mannitol were equi-potent as the osmolyte in suppressing the ANP-dependent cGMP production. Receptor binding assay revealed that hyperosmolality induced a rapid and marked reduction of the maximum binding (Bmax) of ANP without a significant change of the dissociation constant (Kd). Pretreatment with protein kinase C inhibitors (calphostin-C, staurosporin) or with cytoskeleton modulators (cytochalasin-B, colchicine) did not affect the inhibitory effect of hyperosmolality. In conclusion, acute hypertonicity inhibited the ANP-induced cGMP production in contrast to chronic hypertonicity, and reduction of the number of ANP binding sites was considered to be a mechanism responsible for the inhibitory effect of hypertonicity.

Alkaloids↗
PubMed1995

Changes in folate concentration in Yoshida sarcoma after administration of leucovorin or cisplatin.

Both leucovorin (LV) and cisplatin (cis-dichlorodiammine platinum II, CDDP) act as modulators of 5-fluorouracil (5-FUra) by increasing the intracellular concentration of reduced folate. We measured intracellular folate levels following the administration of LV or cisplatin in tumor-bearing rats to determine the optimal schedules for their use as 5-FUra modulators. Donryu rats were inoculated with Yoshida sarcoma cells on the right flank. Seven days after tumor inoculation, the animals were injected with LV or CDDP. The kinetic and dose-related changes in intracellular folate concentration were analyzed by means of a binding assay. Folate levels in the tumor tissues were significantly higher than baseline 1 and 2 h after administration of LV and remained significantly high until 8 h after administration. Folate levels in the tumor tissues were significantly higher than baseline 1 and 2 h after cisplatin administration, then decreased to a rather low level 8 h after, and to a significantly lower level than baseline 24 h after administration. The folate levels in the tumor tissue increased in proportion to the dose of LV, but did not increase when the dose of cisplatin was increased from 1 mg/kg to 8 mg/kg. Repeat high-dose administration of LV and repeat low-dose administration of cisplatin are advocated when they are used as modulators of 5-FUra.

Animals↗
PubMed1995

Repertoire cloning of a human IgG inhibitor of alpha IIB beta 3 function. The OG idiotype.

A patient (OG) with Glanzmann thrombasthenia became refractory to platelet transfusion following the production of IgG antibodies (Ab1) specific for the integrin subunit beta 3. We generated recombinant VH and VL cDNA libraries using IgG-specific mRNA isolated from OG peripheral blood B-lymphocytes that had been selected for binding to antigen (alpha IIb beta 3 adsorbed to plastic dishes). These antigen-specific B-lymphocytes contain rearranged VH DNA segments that belong exclusively to the VH4 gene family. Recombinant Fab were expressed on the surface of filamentous phage coinfected with VH and VL segments cloned into the phagemid pHEN1 or the phage fd-tet-DOG1. To facilitate selection of the desired recombinant Ab1 Fab, we developed a rabbit polyclonal antibody specific for affinity-purified OG anti-beta 3 Fab (Ab2). Ab2 reacts specifically with Ab1, and this interaction is inhibited by purified alpha IIb beta 3. Following three rounds of phage selection on Ab2 adsorbed to plastic dishes and random reassociation of heavy and light chains, we isolated Ab1 Fab and tested their binding to alpha IIb beta 3. Five Id-positive Fab were selected for further characterization. These Fab use one of two VH genes (H21 or H23) complexed with one of three V lambda genes. Subsequent sequence data demonstrated that all three lambda genes are the same clone L22 which uses a germline V lambda gene segment. Fab using H23 bind to alpha IIb beta 3, while those using H21 do not. Based on sequence homology, both H21 and H23 use VH gene segments belonging to the VH4 gene family. Thus, the idiotype OG is restricted to the VH4 gene family and is the first sequenced prototype of human antibodies that bind close to or at a functional epitope(s) of alpha IIb beta 3.

Amino Acid Sequence↗
PubMed1995

The detection of clonal proliferation in granular lymphocyte-proliferative disorders of natural killer cell lineage.

The clonal proliferation of large granular lymphocytes can be detected in patients with T-cell-lineage granular lymphocyte-proliferative disorders (T-GLPD) by Southern blotting T-cell receptor genes. However, this cannot be applied to patients with natural killer-cell-lineage GLPD (NK-GLPD) as it lacks a clonal marker. We therefore investigated the use of two other diagnostic techniques in evaluating clonal proliferation in Japanese patients with NK-GLPD (n = 4) and T-GLPD (n = 3) by chromosomal analysis of peripheral blood mononuclear cells (PBMC) stimulated with either interleukin-2 or phytohaemagglutinin, and Epstein-Barr viral (EBV) genomic DNA analysis. Chromosomal analysis revealed abnormal karyotypes in the PBMC of three of four patients with NK-GLPD, whereas EBV analysis showed a monoclonal terminal configuration in the PBMC in the fourth patient. Southern blots revealed rearrangements of the TCR genes in all three patients with T-GLPD but in none of those with NK-GLPD. It is suggested that these methods may be useful in detecting the abnormal proliferation of large granular lymphocytes in NK-GLPD.

Adult↗
PubMed1995

[A case report of pulmonary sequestration (Pryce I) associated with incomplete lobulation of the left lung].

A 28-year-old man was treated surgically for pulmonary sequestration of Pryce type I associated with incomplete lobulation of the left lung. His chief complaint was hemoptysis. His chest X-ray film showed a mass lesion behind the cardiac shadow. Aortogram revealed a large artery arising from the descending aorta and supplying the left basal segment, and venous blood returning into the left inferior pulmonary vein. The left basal segment had no pulmonary arteries. A bronchogram showed no defects in the bronchial tree. The left basal segment was resected successfully. Histological study showed the trunk of the aberrant artery to be elastic. Differences between histological types of aberrant arteries in pulmonary sequestration of Pryce type I and the pathogenesis of intralobar sequestration were discussed.

Adult↗
PubMed1994

Molecular study of eight Japanese cases of glucose-6-phosphate dehydrogenase deficiency by nonradioisotopic single-strand conformation polymorphism analysis.

Using a newly developed nonradioisotopic method of polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis combined with the direct sequencing using the fluorescence-labeled terminator, we identified seven missense mutations, 527 A-->G, 1003 G-->A, 1159 C-->T, 1160 G-->A, 1229 G-->A, 1246 G-->A, and 1361 G-->A, in eight Japanese patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Except for the 527 A-->G, each mutation has been reported to cause variants G6PD Chatham, G6PD Guadalajara, G6PD Beverly Hills, G6PD "Japan", G6PD Tokyo, and G6PD Andalus, respectively. In addition, a single base deletion in intron 5 was found in the patients with G6PD Guadalajara or G6PD Andalus. The variant with unique 527 A-->G was characterized and designated as G6PD Shinshu. We also characterized G6PD "Japan" and found that the variant had the striking resemblance with G6PD Riverside, bearing a missense mutation in the same codon, but causing a different amino acid substitution. Our modified PCR-SSCP analysis using minigel and ethidium bromide staining could detect six of the eight diverse mutations in the G6PD gene. Because it is easy and requires no special apparatus, this modified method will be useful for screening mutations in the G6PD gene.

Base Sequence↗
PubMed1994

[Pharmacokinetics and changes of reduced folate levels in tumor after administration of cisplatin].

Cisplatin acts as a biochemical modulator of 5-FU to increase the intracellular concentration of reduced folates. To determine the optimum schedule for administering cisplatin as a 5-FU modulator, we analyzed pharmacokinetics of platinum and changes of reduced folate levels in the tumor following administration of cisplatin in Yoshida sarcoma-bearing rats. Clinical kinetics of cisplatin was also investigated. The reduced folate level in the tumor was temporarily increased 2-1.6 fold of the control level 1-2 hours after the rapid injection of cisplatin (4 mg/kg). The folate level 2 hours after the rapid injection of cisplatin increased dose-dependently within the dose of 1mg/kg and reached to the plateau with the doses of 1, 2, 4, 8 mg/kg, although the platinum concentration in plasma and tumor increased linearly correlated with the dose of cisplatin. These findings suggest the modulatory effect through rapid injection of cisplatin is transiently exerted only in the early phase, and not dose-dependently but limitatively with the dose of 1 mg/kg or more. Therefore, repeated administration with low dose or continuous infusion of cisplatin simultaneous with 5-FU derivatives is desirable for combination chemotherapy. Clinically, the minimum effective dose of cisplatin as a modulator was thought to be 10-20 mg/body judging from experimental as well as clinical kinetic study of cisplatin.

Animals↗
PubMed1993

Eosinophilia in myelodysplastic syndrome with a (12;21)(q23;q22) translocation.

Cytogenetic analysis of bone marrow (BM) cells from a patient with myelodysplastic syndrome (MDS) associated with eosinophilia showed a 45,XY,t(12;21)(q23;q22), -17 karyotype. We performed clonal and suspension cultures using the patient's BM mononuclear cells to clarify the mechanism of eosinophilia. Eosinophil colonies formed in the presence of interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF), but not in the presence of IL-3. When BM cells were cultured in suspension in the presence of IL-5, they differentiated to mature eosinophils, and chromosome analysis identified the 45,XY,t(12;21)(q23;q22), -17 karyotype in all metaphases. The patient's serum did not stimulate eosinophil proliferation or differentiation in comparison with normal serum, however, these data suggest that the abnormal clone with 45,XY,t(12;21)(q23;q22), -17 karyotype may have an increased responsiveness to IL-5 and GM-CSF, resulting in eosinophilia.

Aged↗
PubMed1993

An inhibitor of squalene epoxidase, NB-598, suppresses the secretion of cholesterol and triacylglycerol and simultaneously reduces apolipoprotein B in HepG2 cells.

NB-598, a specific inhibitor of squalene epoxidase, suppressed the secretion of cholesterol and triacylglycerol from HepG2 cells into the medium. L-654,969, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, inhibited the secretion of cholesterol as potently as NB-598, but did not suppress the secretion of triacylglycerol. Both compounds decreased the intracellular cholesterol content almost equally, and neither of the compounds reduced the intracellular triacylglycerol content. The suppression of lipid secretion by NB-598 was associated with a significant reduction in apolipoprotein (apo) B secretion into the medium. Therefore, the suppression of lipid secretion by NB-598 may be caused by a reduction in the number of triacylglycerol-rich lipoprotein particles. In contrast, the suppression of cholesterol secretion by L-654,969 may be due to a modulation of lipoprotein lipid composition, since this agent did not reduce the secretion of apo B or triacylglycerol. The secretion of apo A-I was unaffected by either NB-598 or L-654,969. Pulse chase studies using [35S]methionine showed that the suppression of apo B secretion by NB-598 depended on an enhancement of intracellular degradation of apo B. These results indicate that the secretion of apo B from HepG2 cells is not regulated by the lipid synthesis alone, and suggest that the mechanism of the hypolipidemic effect of NB-598 involves the suppression of triacylglycerol-rich lipoprotein secretion from the liver as well as an inhibition of cholesterol synthesis in the liver.

Anticholesteremic Agents↗
PubMed1993

Transfusion-associated graft-versus-host disease in an immunocompetent patient following accidental injury.

We report a case of transfusion-associated graft-vs.-host disease (TA-GVHD) in a previously healthy, 58 year old Japanese man following an accidental injury. Despite intensive treatment, the patient died 22 days after the transfusion. Although many cases of fatal TA-GVHD have been reported in immunocompetent patients, only two are known to have developed this disorder unrelated to a surgical procedure. This is the first such case to be confirmed by HLA typing. Our report suggests that TA-GVHD can occur even in a healthy, immunocompetent recipient. Thus, it seems necessary to establish guidelines for the irradiation of cellular blood products before transfusion.

Accidental Falls↗
PubMed1993

Composite reconstruction of the esophagus.

Composite reconstruction of the esophagus using both the mobilized stomach and free jejunal graft is described. Tension at the anastomotic site can be minimized with interposition of a jejunal autograft between the pharyngeal stump and the mobilized stomach, even when the mobilized stomach is not long enough. Furthermore, problems derived from differing calibers of the pharyngeal stump and the mobilized stomach can be resolved by creating an end-to-side pharyngojejunal anastomosis. Our method is proposed as one procedure for reconstruction of the esophagus when the pull-up organ is too short.

Anastomosis, Surgical↗