Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 397 records · Page 22Linked to original sources

PubMed1997

Increased serum levels of thrombopoietin in patients with thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, or disseminated intravascular coagulation.

The serum levels of thrombopoietin (TPO) were measured in 16 patients with thrombotic thrombocytopenic purpura (TTP), 12 with hemolytic uremic syndrome (HUS), 10 with aplastic anemia (AA), 10 with disseminated intravascular coagulation (DIC), and 71 with idiopathic thrombocytopenic purpura (ITP). The serum TPO levels were measured with a sensitive sandwich enzyme-linked immunosorbent assay. The serum TPO level in the ITP group (1.68 +/- 0.85 fmol/ml) were not significantly increased compared with those of the normal subjects. The TPO levels in the TTP (2.77 +/- 1.38 fmol/ml) and HUS groups (5.77 +/- 4.41 fmol/ml) were higher than those of the normal subjects. The patients with AA (12.7 +/- 8.0 fmol/ml) and those with DIC (13.3 +/- 5.7 mol/ml) had significantly higher serum TPO levels than did the normal subjects and ITP patients. The TPO levels were well correlated with the platelet counts in the TTP patients, and were negatively correlated with the platelet counts in the ITP patients. These results suggest that the serum TPO levels in some thrombocytopenic diseases are regulated not only by the platelet count and the megakaryocyte mass, but also by other factors.

Adult↗

PubMed1997

Pregnancy and delivery in patients with von Willebrand's disease.

OBJECTIVE: To explore the obstetrical problems that are encountered in women with von Willebrand's disease (vWD). METHODS: Case histories of 6 women whose pregnancies were complicated by vWD were reviewed retrospectively over an 11-year period. The disease had been diagnosed before pregnancy in only 2 cases. The 6 women had a total of 10 deliveries, 3 induced abortions, and 1 spontaneous abortion. RESULTS: Although all 6 women had Type-I vWD, their laboratory data and bleeding symptoms varied. The 10 full-term deliveries were all vaginal. Heat-treated concentrated Factor-VIII preparations were administered in 2 cases, in both of which abortions were induced during the 2nd trimester. Genital bleeding persisted in the second case, so that the administration of Factor VIII was repeated, and the patient underwent uterine curettage on the 12th day after abortion. Desmopressin was administered before the early induction of abortion in 1 case. The patient with persistent genital bleeding after spontaneous abortion received Factor VIII for 5 consecutive days. CONCLUSION: Bleeding problems occurred about 1 week after delivery or at the time of induced abortion in the 6 women with vWD. Thus, such patients require special care during pregnancy.

Abortion, Induced↗

PubMed1997

Oral sustained-release cisplatin preparation for rats and mice.

A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II): cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin-ethylcellulose-stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg-1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg-1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 +/- 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 +/- 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL-1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10-16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL-1 in mice serum in which the total cisplatin concentration was 0.30 mg mL-1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.

Administration, Oral↗

PubMed1997

[Sporadic diarrhea caused by Vibrio cholerae non-O1 and characteristics of the isolates].

In 1996, we examined five domestic and eight imported cases of sporadic diarrhea caused by Vibrio cholerae non-O1 in Tokyo. The domestic cases occurred during the summer, from June to September, while the imported cases were seen throughout the year. The major clinical symptoms of the patients were watery diarrhea (100%) with an average frequency of 5.5 times/day, abdominal pain (77%), vomiting (31%) and fever (15%). A total of 13 strains isolated from these 13 cases had the typical biochemical characteristics of Vibrio cholerae, and were classified into 11 kinds of serovars (O2, O5, O8, O9, O12, O14, O27, O51, O88, O97, and O161). All strains produced hemolysin, and two strains produced NAG-ST, while no strain produced cholera toxin.

Adult↗

PubMed1997

Circadian rhythm of the cyanobacterium Synechocystis sp. strain PCC 6803 in the dark.

The cyanobacterium Synechocystis sp. strain PCC 6803 exhibited circadian rhythms in complete darkness. To monitor a circadian rhythm of the Synechocystis cells in darkness, we introduced a PdnaK1::luxAB gene fusion (S. Aoki, T. Kondo, and M. Ishiura, J. Bacteriol. 177:5606-5611, 1995), which was composed of a promoter region of the Synechocystis dnaK1 gene and a promoterless bacterial luciferase luxAB gene set, as a reporter into the chromosome of a dark-adapted Synechocystis strain. The resulting dnaK1-reporting strain showed bioluminescence rhythms with a period of 25 h (on agar medium supplemented with 5 mM glucose) for at least 7 days in darkness. The rhythms were reset by 12-h-light-12-h-dark cycles, and the period of the rhythms was temperature compensated for between 24 and 31 degrees C. These results indicate that light is not necessary for the oscillation of the circadian clock in Synechocystis.

Circadian Rhythm↗

PubMed1997

Decreased expression of full-length mRNA for cBCD541 does not correlate with spinal muscular atrophy phenotype severity.

Spinal muscular atrophy (SMA) is characterized by degeneration of spinal cord anterior horn cells and muscular atrophy and has three phenotypes based on clinical severity and age of onset. One of the responsible genes for SMA is the survival motor neuron (SMN) gene, which is homozygously absent or interrupted in more than 90% of SMA patients. The cBCD541 (BCD) gene is a highly homologous copy of the SMN gene, which has a single synonymous transition in the coding region and may compensate for the loss of the SMN gene. To evaluate the effects of the BCD gene expression on the phenotypes of SMA, we examined lymphocyte mRNA from 9 SMA patients lacking the SMN gene, 10 asymptomatic parents, and 15 control subjects. We amplified mRNA fragments containing exon 7 of the SMN or BCD genes using reverse transcription-polymerase chain reaction since the transcript lacking exon 7 encodes a putative protein with a different C-terminal end. We used glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcript as an internal control, and the relative expression level of the SMN or BCD gene was shown as the ratio of SMN or BCD transcript to GAPDH transcript (S/G ratio). The mean S/G ratios of the patients were significantly lower than that of the parents and controls. However, among the patients examined in this study, there was no relationship between the S/G ratios and phenotypes of SMA. The results showed that the BCD gene expression was not related to the phenotypes of SMA. Furthermore, there was an overlap between the S/G ratios in patients and controls. As our discrimination study showed that the S/G ratio reflected the expression of the BCD transcripts in patients and the SMN transcripts in controls, this finding suggested that the BCD gene expression per se does not compensate for the loss of the SMN gene.

Adolescent↗

PubMed1997

Expression of neural cell adhesion molecule L1 in human lung cancer cell lines.

To investigate neuron-specific antigens, hybridoma cells were produced between mouse spleen cells immunized with human neuroblastoma cells (IMR-32) and mouse myeloma cells. 247 hybridoma clones were harvested and one of them was further cultured for recloning. Eventually, one hybridoma clone was obtained and its antibody was designated N-A8. The characteristics of this antibody were determined by immunostaining and flow cytometry. First, the antibody recognized the surface antigens of IMR-32 cells. Second, unexpectedly, N-A8 was reactive not only with human neuroblastoma cell lines but also with human lung cancer cell lines. As analyzed by immunoprecipitation method and SDS-PAGE, the molecular size of the antigen recognized by N-A8 was 210 kDa. The antigen was then purified by affinity chromatography and identified as neural adhesion molecule L1 by amino acid sequence analysis. By the present investigation, it was clearly demonstrated that L1 is expressed in human lung cancer cells.

Animals↗

PubMed1997

Identification of rat serum alkaline phosphatase isoenzyme by means of wheat germ agglutinin.

Wheat germ agglutinin (WGA) precipitates bone type serum alkaline phosphatase (sALP) isoenzyme specifically. The precipitates are composed of the macromolecules of WGA and "bone type sALP" (WGA-ALP complex). In order to use bone type sALP as a marker in polyacrylamide gel electrophoresis (PAGE), a method to separate "bone type sALP" from the "WGA-ALP complex" was established by using N-acetyl-D-glucosamine (GlcNAc)-Sepharose 6E column chromatography. It was concluded that this method is useful for clinical examination in the rat.

Alkaline Phosphatase↗

PubMed1997

Prolongation of ischaemic tolerance of rat skeletal muscle by trehalose.

Trehalose is a disaccharide that can stabilise cell membranes under various stressful conditions. We have studied the effect of trehalose on the ischaemic tolerance of fat skeletal muscle flaps. A rat gracilis model was used to evaluate the prolongation of ischaemic preservation of the modified solution in which trehalose was substituted for glucose in Euro-Collins solution. Four groups of animals were studied. In two groups, flaps were preserved in Euro-Collins solution or trehalose Euro-Collins solution for various ischaemic intervals (6, 12, 24, 48, 72, and 96 hours). In two additional groups, after storage for various periods in the two solutions, muscle flaps were replanted into the original animals with microvascular anastomoses, and were investigated by light and electron microscopy on the seventh postoperative day. Trehalose Euro-Collins solution significantly prolonged ischaemic tolerance compared with Euro-Collins solution alone at 24 and 48 hours.

Animals↗

PubMed1997

[Dynamic behavior of guinea pig middle ear].

The dynamic behavior of the middle ear was studied in living guinea pigs by using a laser Doppler vibrometer coupled to a compound microscope. Placing glass microbeads 20 microns in diameter on four points of the tympanic membrane and six points of the ossicles, their velocity amplitudes were measured under a constant stimulus of 65 dB SPL. Velocity responses of the four points on the tympanic membrane differed over the frequency range from 0.1 kHz to 3 kHz. At low frequencies, the malleus and incus rotated around an axis running from the malleus head to the incus short process. At middle frequencies, the whole ossicle had a piston-like motion. At high frequencies, the malleus and incus rotated around a vertical axis running through the ossicles, while the stapes had a hinge-like movement.

Animals↗

PubMed1997

[Study of hemostatic molecular marker].

We examined hemostatic molecular markers in various thrombotic disorders. The efficacy of treatment in relation to the disseminated intravascular coagulation (DIC) score when the treatment was begun showed that greater efficacy was achieved in Pre-DIC than in DIC patients. The outcome was poorer with increasing DIC score, suggesting that early treatment is important. The sensitivity in some of molecular markers was high for both DIC and Pre-DIC. Receiver operating characteristic analysis suggest that soluble fibrin monomer level could be the most useful marker for the diagnosis of DIC. In examination of these markers in deep vein thrombosis, pulmonary embolism, acute myocardial infarction, and cerebral infarction, plasminogen activator inhibitor-1 and activated protein C-protein C inhibitor complex were useful marker for the diagnosis. Increased plasma GMP-140 was suggested to be the activation of platelets. The patients with high levels of plasma thrombomodulin (TM) considered to be a marker of vascular endothelial injuries became poor outcome. We will term these patients with high TM as systemic vascular endothelium injuries syndrome, and treat those by protecting the vascular endothelium.

Biomarkers↗

PubMed1997

Thymic interdigitating cells express thioredoxin (TRX/ADF): an immunohistochemical study of 82 thymus and thymoma samples.

Thymic ID cells are involved in the differentiation of mature T cells which are resistant against apoptosis. TRX/ADF is a potent thiol-related reducing agent, acts as a redox regulator, and it can attenuate the induction of apoptosis of T lineage lymphocytes. In the present study, 42 thymoma-free thymus and 40 thymoma samples were examined to identify the expression of TRX/ADF in human thymic tissue. TRX/ADF high-producer (TRXh) cells with cytoplasmic protrusions were found distributed in the thymic medulla. These TRXh cells were negative for CD3, a lymphocyte marker, keratin, an epithelial cell marker, and CD68 or lysozyme, macrophage/monocyte markers, but were positive for S100 protein and HLA-DR complex. Our results revealed that the TRXh cells in the thymic medulla were ID cells. As TRX/ADF has an important and fundamental role in cellular responses acting against oxidative stress, TRX/ADF may provide an explanation of cellular interaction between the medullary ID cells and the mature T cells.

Adolescent↗

PubMed1997

Effects of Albunex infusion on left ventricular inflow velocity in dogs.

This study examined the effects of Albunex (sonicated 5% human serum albumin) infusion on left ventricular inflow velocity by Doppler echocardiography. Left ventricular pressure and left ventricular inflow velocity were recorded simultaneously under eight different conditions in dogs: 1) baseline 1 (control), 2) Albunex 0.2 ml/kg, 3) baseline 2, 4) Albunex 0.5 ml/kg, infusion of dextran 100 ml, 5) baseline 3, 6) Albunex 0.2 ml/kg, 7) baseline 4, and 8) Albunex 0.5 ml/kg. In the normal state (no dextran), Albunex (0.2 ml/kg) caused no hemodynamic changes or inflow velocity changes. In contrast, infusion of Albunex (0.5 ml/kg) caused time velocity integrals of early filling to increase from the baseline (5.51 +/- 1.13 vs 7.19 +/- 1.14 cm, p < 0.05). After dextran infusion (100 ml), Albunex (0.2 ml/kg) caused peak early filling velocity to increase (62.4 +/- 6.9 vs 67.3 +/- 9.4 cm/sec, p < 0.05), and infusion of Albunex (0.5 ml/kg) also caused peak early filling velocity to increase from baseline (64.6 +/- 8.5 vs 73.7 +/- 14.5 cm/sec, p < 0.05). Infusion of Albunex (0.5 ml/kg) after dextran infusion caused increases in left ventricular pressure at the mitral valve opening (12.7 +/- 3.1 vs 15.2 +/- 3.3 mmHg, p < 0.05) and in left atrial driving force (13.5 +/- 3.6 vs 16.7 +/- 5.9 mmHg, p < 0.05). Clinicians should be cautious about using Albunex at doses of greater than 0.2 ml/kg when evaluating the pressure gradient of the left ventricle in patients with elevated left ventricular diastolic pressure. In patients with normal hemodynamics, Albunex infusion at doses of less than 0.2 ml/kg apparently did not affect the velocity measurement.

Albumins↗

PubMed1997

[Adjuvant chemotherapy for non-small cell lung cancer].

Surgery is the first choice for patients in the early stage of non-small cell lung cancer (NSC-LC). But, even for pathologic stage I patients, the post-operative survival remains unsatisfactory; the five-year survival rate is around 70 percent, in spite of potential curative resections. Therefore, post-operative adjuvant chemotherapy is considered to be necessary to improve the survival. Although many prospective randomized studies of post-operative adjuvant chemotherapy have been conducted, the efficacy of post-operative chemotherapy for NSCLC has not been proved (a consensus report of post-operative adjuvant treatment for NSCLC, 3rd IASLC Workshop, Bruges, August 1993). It has been recently reported by the West Japan Study Group for Lung Cancer Surgery (WJSG) that oral administration of UFT (a mixture of tegafur and uracil) as a post-operative adjuvant chemotherapy is effective for patients with complete resected NSCLC (stage I to III) and that UFT administration is tolerable with mild adverse effects in most patients. In order to improve postoperative survival of patients with more advanced stage NSCLC (e.g., bulky N2, III b), we has introduced biochemical modulation therapy using 5-FU, UFT combined with CDDP.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

[Transfer of genes to human airway epithelial cells in vitro via DNA virus vectors].

Transfer of genes via DNA virus vectors to human airway epithelial cells is not fully understood. We tested the effects of multiplicities of infection (moi) and incubation time on the efficiency of gene transfer by adenovirus vectors and AAV vectors in cultures of human airway epithelial cells. The cells were exposed to Ad-CMV-lacZ or AAV-CMV-LacZ for 1 to 48 hours at different moi from 0.1 to 100. Efficiency of transduction was assessed as the percentage of cells that expressed LacZ, and was measured by using X-gal staining. A dose-dependent relationship was found between vector moi and the percentage of cells that expressed LacZ. For both vectors, gene expression was greater when incubation time was longer (up to 12 hours), which suggests that the uptake of vectors into the cells is not selective. Efficiency of transduction did not differ between adenovirus and AAV vectors at the same moi. These results suggest that (1) gene transfer via DNA virus vectors increases in a moi-dependent fashion, and that (2) gene expression of the DNA virus vector may be increased by prolonged exposure of the vector to human airway epithelial cells.

Adenoviridae↗

PubMed1997

Postoperative adjuvant chemotherapy for non-small-cell lung cancer. West Japan Study Group for Lung Cancer Surgery. The Japan Lung Cancer Research Group on Postsurgical Adjuvant Chemotherapy.

Given that no therapeutic methods of postoperative adjuvant chemotherapy for non-small-cell lung cancer have been established, we selected UFT (tegafur and uracil) for investigation because UFT is less injurious to the host than intensive chemotherapies. The second study of the West Japan Study Group for Lung Cancer Surgery showed that the 5-year survival rates were 64.1% in the UFT group (UFT 400 mg/day for 1 year after surgery) and 49.1% in the control group (surgery alone). Thus, the survival rate for all patients was improved significantly in the UFT group as compared with the control group (log rank test, P = .033; generalized Wilcoxon test, P = .019). To establish the usefulness of long-term oral administration of UFT as an adjuvant therapy for completely resected non-small-cell lung cancer, the nationwide Japan Lung Cancer Research Group on Postsurgical Adjuvant Chemotherapy is now conducting a comparative study of surgery alone versus surgery and UFT in patients with pathologic stage I adenocarcinoma.

Antineoplastic Agents↗

PubMed1997

[Current status of low-dose CDDP. 5-FU therapy for solid malignant tumors--nationwide questionnaire survey].

A nation-wide questionnaire survey was undertaken concerning low-dose anticancer therapy of CDDP plus 5-FU, which involves (5-10 mg CDDP/body/day + 300-500 mg/body/day) for 4-6 weeks. Out of 1,525 cases from 130 institutions, 847 cases with evaluable lesions were collected from 79 institutions. The response rate was 56.4% in esophageal cancer, 34.3% in gastric cancer, 35.3% in colorectal cancer, 47.2% in liver cancer and 35.9% in lung cancer, respectively. Adverse effects were found to be fewer and compliance was much better than the conventional therapy. Such figures suggest that the present regimen may be more effective than any so far. Problems for medical administration such as unlicensed CDDP for colorectal cancer were pointed out, which hinder the forthcoming third phase study.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Effects of Euro-Collins, University of Wisconsin, and new extracellular-type trehalase-containing Kyoto solutions in an ex vivo rat lung preservation model.

BACKGROUND: We have previously reported the effects of trehalose-based extracellular-type Kyoto (ET-K) solution in lung preservation. Now, we have developed a new ET-K solution by adding three substances--N-acetyl cysteine, dibutyryl cyclic AMP, and nitroglycerin, to ET-K solution. We studied the effects of new ET-K solution in lung preservation, and compare it with Euro-Collins (EC) and University of Wisconsin (UW) solutions using an ex vivo rat reperfusion model. METHODS: The perfusion circuit was initiated by 30 ml of fresh mixed venous blood obtained from three haparinized rats. By means of a double-head roller pump, the blood passed from the venous blood reservoir through the pulmonary artery to be perfused in the examined lung. The lung effluent was returned at the same flow rate to the deoxygenator fresh lung. Four experimental groups were allocated. In group 1 (fresh group, n=6), lung was flushed with saline and reperfused immediately. In the other groups (group 2: new ET-K group, n=6; group 3: UW group, n=6; and group 4: EC group, n=6), lung was flushed with the new ET-K and prostanglandin E1 (PGE1), UW and PGE1, and EC and PGE1, respectively. After 17-hr preservation, the preserved lung was reperfused. RESULTS: In all six animals of the EC group, ventilation of the experimental lung was discontinued at 20 min after reperfusion because of the exudate in the endotracheal tube that resulted from pulmonary edema. The shunt fraction, pulmonary arterial pressure, and peak inspiratory pressure in the new ET-K and UW groups were significantly better than those in the EC group, but were almost equal to those in the fresh group. CONCLUSION: The postpreservation pulmonary functions with the new ET-K solution were better than those with the EC solution, and were equal to those with the UW solution. This new solution is expected to contribute to the increase in donor lungs for clinical lung transplantation. In addition, this ex vivo rat reperfusion model is simple and highly reliable, and can be widely used in the studies of pulmonary preservation.

Adenosine↗