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Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 325 records · Page 18Linked to original sources

Human myeloma cell apoptosis induced by interferon-alpha.

Although there have been reports regarding the clinical effectiveness of IFN alpha in the treatment of myeloma patients during this decade, its biological effects on human myeloma cells have still not been clarified. Recently, apoptosis has been considered as one of the most important mechanisms in the programmed cell death of malignant tumour cells induced by chemotherapeutic agents or cytotoxic immunological defence in malignancy-carrying hosts. Among the several pathways which function to induce apoptosis, Fas and the Fas ligand system have been thought to play an important role in inducing tumour-cell apoptosis, particularly in immunological prevention. In this study we investigated myeloma cell apoptosis induced by IFN alpha using five human myeloma cell lines which were established without any additional supplementation of IL-6. In addition, the mRNA expression levels of apoptosis-related genes employing the reverse transcriptase-polymerase chain reaction (RT-PCR) were also analysed with the KMS-12-PE cell line, which was the most sensitive of the five cell lines in terms of apoptosis induced by IFN alpha. Based on the results, it was determined that IFN alpha induced myeloma cell apoptosis in a dose-dependent manner, but the sensitivity to IFN alpha in the cell lines examined varied and one cell line revealed growth stimulation by IFN alpha. In addition, the apoptosis induced by IFN alpha did not seem to be mediated by the Fas/Fas ligand pathway. Finally, the IL-6, IL-6R, IRF1 and IRF2 genes were up-regulated in KMS-12-PE cells cultured with IFN alpha. Therefore these genes may play an important role during apoptosis induced by IFN alpha.

Antineoplastic Agents↗

Evaluation of new improved solution containing trehalose in free skin flap storage.

BACKGROUND DATA: In this study, we evaluated a new intracellular type (IT-K) solution containing trehalose in a rabbit free skin flap storage model. Trehalose is a nonreducing disaccharide that can stabilise cell membranes under various stressful conditions. MATERIAL AND METHOD: Seventy-two free skin flaps of the ear of rabbits were preserved in Euro-Collins (EC) solution or in IT-K solution for 24, 48, and 72 h at 4 degrees C. After completion of preservation, these flaps were replanted to the other ear by microsurgical techniques. Viability study and photo documentation were performed daily for 7 days. Tissue specimens were taken 24 h after vascular anastomosis, fixed in 10% formaldehyde and stained with haematoxylin and eosin (HE). Survival rates were analysed by Fisher's exact test for comparison of the two experimental groups. Values of P < 0.05 were considered to be statistically significant. RESULTS: After 7 days, a survival rate of 100% of flaps were observed in both solutions after 24 h of preservation. After preservation for 48 h in IT-K solution the survival rate was 100%. However, in EC solution survival decreased to 75% (9 of 12 preserved flaps survived). This difference increased to 33.3% (4 of 12 flaps) in EC solution and 91.6% (11 of 12 flaps) (P < 0.01) in IT-K solution when the flaps were stored for 72 h. Light microscopic examination also showed less damage in flaps preserved in IT-K solution than in these preserved in EC solution. CONCLUSION: IT-K solution was superior to EC solution in the preservation of free skin flaps on rabbit ears when stored for 48 and 72 h.

Animals↗

Hemostatic molecular markers before onset of disseminated intravascular coagulation in leukemic patients.

The changes in various hemostatic parameters were examined within a period from 7 days before the onset of disseminated intravascular coagulation (DIC) in 114 patients (i.e. in their pre-DIC state). The changes in prothrombin time (PT) ratio and fibrinogen levels were not significant before the onset of DIC. Plasma fibrinogen and fibrin degradation products (FDP) levels before the onset of DIC were high, but these changes were already significant in 110 non-DIC patients examined. Plasma thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer and soluble fibrin monomer (SFM) levels were high before the onset of DIC. In the 110 leukemic DIC patients, the plasma SFM levels were significantly increased 5 days before, the plasma TAT levels were significantly increased 3 days before, and the D-dimer levels were significantly increased 1 day before the onset of DIC. The plasma tissue factor and plasminogen activator inhibitor-I levels were not significantly changed before the onset of DIC. The PT ratio, fibrinogen, FDP, platelet count, antithrombin, D-dimer, and PPIC levels at 7 days before the onset of DIC were not significantly different from the corresponding values in the non-DIC group, although the hemostatic molecular markers SFM, D-dimer, and TAT are useful for the diagnosis of pre-DIC. Plasma thrombomodulin levels were significantly increased in these patients who died, and plasma antithrombin and protein C activities markedly reduced in the patients who died. The outcome of the diseases underlying DIC is related to vascular endothelial cell injuries.

Biomarkers↗

Fatal hemorrhage in irradiated esophageal cancer patients.

Between 1980 and 1994, 423 patients with esophageal cancer were given curative radiation therapy. Of these patients, 31 died of massive hemorrhage and were used as the subjects of analysis in this study. The incidence of massive hemorrhage in all patients was 7% (31/423). In the 31 patients who died of massive hemorrhage, 27 had local tumors and two had no tumors at hemorrhage (two unknown cases). The mean time interval from the start of radiation to hemorrhage was 9.2 months. In 9 autopsy cases the origin of hemorrhage was a tear of the aorta in 5 cases, necrotic local tumor in 3 cases and esophageal ulcer in 1 case. The positive risk factors for this complication seemed to be excess total dose, infection, metallic stent, and tracheoesophageal fistula. Chest pain or sentinel hemorrhage proceeding to massive hemorrhage was observed in about half of the patients.

Aged↗

Possible involvement of autoreactive CD4 T cells in generation of cytotoxic T lymphocytes on in vitro stimulation with H-2 class I-binding tumor antigen peptide.

We demonstrated that RL male 1-specific cytotoxic T lymphocytes (CTL) were generated in spleen cells from the tumor-rejected CB6F1 mice on in vitro stimulation with Ld-binding pRL1a peptide. We showed that CD4 T cells and antigen-presenting cells were necessary for CTL generation. Furthermore, CTL generation was inhibited by the addition of anti-I-Ad mAb, but not anti-I-Ek/d mAb, to the culture. However, no binding of the pRL1a peptide to the I-Ad molecule could be demonstrated. No inhibition by the pRL1a peptide of I-Ad-restricted IL-2 production by ovalbumin (OVA)-specific CD4 T cell hybridoma DO-11.10 was observed on stimulation with the specific OVA peptide. Moreover, no specific proliferative response or IL-2 production was observed with CD4 T cells in spleen cells from the tumor-rejected mice on stimulation with a range of mitomycin C-treated RL male 1 cells, or with RL male 1 lysate or the pRL1a peptide. Rather, the activation of autoreactive CD4 T cells and the IL-2 production from them were observed. CD4 T cells from CB6F1 mice that had rejected other tumors such as EL4 or MOPC-70A also helped the generation of pRL1a-specific CTL. These findings suggested the involvement of autoreactive CD4 T cells in CTL generation against the pRL1a peptide.

Animals↗

Evolutionary history of free-swimming and sessile lifestyles in urochordates as deduced from 18S rDNA molecular phylogeny.

Whether the ancestral chordates were free-swimming or sessile is a longstanding question that remains to be settled. Vertebrates and amphioxi are free-swimming, but the most basal chordate subphylum (the urochordates) includes both sessile and free-swimming species. Here, 1 report molecular phylogenetic analyses of 18S rDNA of urochordates to deduce which lifestyle is ancestral. This revealed a close relationship between salps and doliolids and paraphyly of the ascidians. An early divergence of larvaceans, which show a tadpole-like body plan throughout life, is also supported by the analyses. Based on this phylogeny, a free-swimming ancestor for chordates is more parsimonious than a sessile ancestor. The evolutionary history of various lifestyles of chordates from this ancestral form is proposed.

Animals↗

Effects of sevoflurane and isoflurane on renal function and on possible markers of nephrotoxicity.

BACKGROUND: Low-flow sevoflurane anesthesia is associated with increasing circuit concentrations of compound A, which is nephrotoxic in rats, but the effect of compound A and low-flow sevoflurane anesthesia on renal function in humans is unclear. The authors compared the effects of high- and low-flow sevoflurane and isoflurane anesthesia on renal function and on several possible markers of nephrotoxicity in humans. METHODS: Forty-two patients without preexisting renal disease underwent either low-flow isoflurane (1 l/min, n = 14), low-flow sevoflurane (1 l/min, n 14), or high-flow sevoflurane (6 l/min, n = 14) anesthesia for body-surface-area surgery scheduled to last at least 4 h. Twenty-four-hour urinary excretion of N-acetyl-beta-glucosaminidase (NAG), beta2-microglobulin, protein, glucose, blood urea nitrogen (BUN), and serum creatinine concentrations were measured before and after anesthesia. RESULTS: There were no differences in blood urea nitrogen, creatinine, and creatinine clearance among the three groups after anesthesia. Increased urinary N-acetyl-beta-glucosaminidase excretions were seen in the low-flow and high-flow sevoflurane groups, but not in the low-flow isoflurane group (P < 0.01). Ten patients in the low-flow sevoflurane group had 24-h urinary excretion of protein that exceeded the normal ranges after anesthesia, but only one patient in the isoflurane and none in the high-flow sevoflurane groups had this. CONCLUSIONS: Low-flow sevoflurane anesthesia was associated with mild and transient proteinuria. However, the observed proteinuria was not associated with any changes in blood urea nitrogen, creatinine, and creatinine clearance in these patients with no preexisting renal disease.

Acetylglucosaminidase↗

Increased thrombopoietin levels in idiopathic thrombocytopenic purpura patients with a poor response to steroid therapy.

The serum thrombopoietin (TPO) levels in 61 idiopathic thrombocytopenic purpura (ITP) patients were found to be slightly increased compared with those of 29 normal subjects. The TPO levels of the 15 ITP patients who had a poor response to steroid therapy (i.e. an unchanged platelet count) were higher than those of the 22 ITP patients who had a good response to steroid therapy (i.e. an increased platelet count) and the normal subjects. The TPO levels in the 15 ITP patients whose platelet count was higher than 10 x 10(4)/microl after the discontinuation of steroid therapy significantly higher than those of the normal subjects. The platelet-associated immunoglobulin G (PAIgG) levels in the ITP patients who had a poor response to steroid therapy were slightly increased compared with the normal subjects and the ITP patients who had a good response to the steroid therapy and the nine ITP patients who did not undergo the steroid therapy. The serum TPO level was negatively correlated only with the megakaryocyte count in the ITP patients, and the megakaryocyte count in the ITP patients who had good responses to the steroid therapy was higher than that in those who had poor responses. These data suggest that serum TPO levels might be important for the prediction of the outcome of ITP patients who receive steroid therapy.

Adolescent↗

Changes in plasma tissue factor pathway inhibitor levels during the clinical course of disseminated intravascular coagulation.

In healthy volunteers, the plasma total tissue factor pathway inhibitor (TFPI) level was 68.7+/-14.1 ng/ml; the plasma free TFPI level, 17.7+/-5.4 ng/ml; the lipoprotein-associated TFPI (LP-TFPI), 51.1+/-12.0 ng/ml; the free TFPI/total TFPI ratio 0.26+/-0.07; and the plasma tissue factor levels were 149+/-46 pg/ml. Plasma tissue factor levels in patients with disseminated intravascular coagulation (DIC) were significantly higher than those in pre-DIC patients or in non-DIC patients. Plasma total-TFPI, free-TFPI and LP-TFPI levels were significantly higher in DIC patients than those in pre-DIC patients or in non-DIC patients. Before the onset of DIC, the plasma levels of tissue factor gradually increased, and 3 days before the onset of DIC they were significantly higher than those in non-DIC patients. The plasma levels of tissue factor reached their highest level 1 day before the onset of DIC and gradually decreased after the onset of DIC. Plasma levels of total-TFPI, free-TFPI, and LP-TFPI gradually increased before the onset of DIC, and the total-TFPI and LP-TFPI reached their highest levels at the onset of DIC. Plasma free-TFPI reached highest level one day after the onset of DIC. During the clinical course of DIC, the plasma level of tissue factor was the first to increase, then that of LP-TFPI and finally the free-TFPI plasma levels. These differences in the peak plasma levels of tissue factor, free-TFPI, and LP-TFPI might be related to the clinical course of DIC.

Disseminated Intravascular Coagulation↗

Clinical applicability of the sweep frequency measuring apparatus for diagnosis of middle ear diseases.

OBJECTIVE: To develop a measuring apparatus that has the ability to sweep both frequency and external auditory meatus static pressure and can display measurement results in a three-dimensional expression. To measure the middle ear dynamic characteristics of normal-hearing subjects and of patients with this apparatus. DESIGN: Investigate 275 ears of 153 normal-hearing subjects and 72 ears with middle ear diseases. RESULTS: The measurement results show fairly distinctive patterns depending on the middle ear conditions, i.e., normal, ossicular chain separation, ossicular chain fixation, secretory otitis media, tympanic membrane perforation, and tympanic membrane atelectasis. The evaluation of patients with ossicular diseases revealed that the rate of correct diagnosis of ossicular chain separation is 84% and that of ossicular chain fixation is 74%. These diagnoses were confirmed by surgery. CONCLUSION: Displaying the measurement results in a three-dimensional expression is helpful to make correct diagnosis in clinical practice. It is especially easy to make a distinction between the ossicular chain separation and ossicular chain fixation. Therefore, it is concluded that this apparatus has a high degree of clinical applicability to the diagnosis of these diseases.

Acoustic Impedance Tests↗

Features of early gastric cancer detected by modern diagnostic technique.

To ascertain how the clinicopathologic features of early gastric cancer detected by current diagnostic tools had changed clinical features, we compared 711 early gastric cancer patients with 933 advanced gastric cancer patients regarding age, sex, and tumor location. We found that the proportion of early gastric cancer cases did not change according to age. However, the proportion of early gastric cancer cases in the proximal part was significantly lower than that observed in the distal part (p < 0.01). We conclude that recent diagnostic improvements have rendered age no longer a major deterrent for early detection of gastric cancer. However, a careful examination of the proximal stomach is called for because it is so hard to detect small lesions in that area.

Adult↗

Biosynthesis of lipoic acid in Arabidopsis: cloning and characterization of the cDNA for lipoic acid synthase.

Lipoic acid is a coenzyme that is essential for the activity of enzyme complexes such as those of pyruvate dehydrogenase and glycine decarboxylase. We report here the isolation and characterization of LIP1 cDNA for lipoic acid synthase of Arabidopsis. The Arabidopsis LIP1 cDNA was isolated using an expressed sequence tag homologous to the lipoic acid synthase of Escherichia coli. This cDNA was shown to code for Arabidopsis lipoic acid synthase by its ability to complement a lipA mutant of E. coli defective in lipoic acid synthase. DNA-sequence analysis of the LIP1 cDNA revealed an open reading frame predicting a protein of 374 amino acids. Comparisons of the deduced amino acid sequence with those of E. coli and yeast lipoic acid synthase homologs showed a high degree of sequence similarity and the presence of a leader sequence presumably required for import into the mitochondria. Southern-hybridization analysis suggested that LIP1 is a single-copy gene in Arabidopsis. Western analysis with an antibody against lipoic acid synthase demonstrated that this enzyme is located in the mitochondrial compartment in Arabidopsis cells as a 43-kD polypeptide.

Amino Acid Sequence↗

Dopamine releases endothelium-derived relaxing factor via alpha 2-adrenoceptors in canine vessels: comparisons between femoral arteries and veins.

1. We investigated the role of vascular smooth muscle alpha-adrenoceptor subtypes in the vasoconstrictor response of femoral arteries and veins to dopamine and whether the vasoconstriction is modified by endothelium-dependent relaxation mediated via the activation of alpha 2-adrenoceptors in ring preparations of femoral arteries and veins from mongrel dogs. 2. Dopamine contracted both arteries and veins in a dose-dependent manner and this contraction was inhibited by pretreatment with phentolamine or prazosin. Pretreatment with yohimbine shifted the dose-response curve for dopamine to the right in femoral veins, but not in arteries. 3. Phenylephrine contracted femoral arteries and veins in a dose-dependent manner and this contraction was inhibited by pretreatment with prazosin. 4. Clonidine produced a bell-shaped dose-response curve in femoral veins and this curve was shifted upwards by pretreatment with NG-nitro-L-arginine (L-NNA). In contrast, femoral arteries were not affected by clonidine. NG-Nitro-L-arginine potentiated contractile responses to dopamine in both veins and arteries. This potentiation was inhibited by yohimbine or by the removal of the endothelium in both arteries and veins. 5. These results suggest that dopamine contracts femoral arteries via stimulation of alpha 1-adrenoceptors and contracts femoral veins via stimulation of both alpha 1- and alpha 2-adrenoceptors and that these contractions are attenuated by the vasodilator action of dopamine via alpha 2-adrenoceptor-mediated release of endothelium-derived relaxing factor.

Adrenergic alpha-Agonists↗

Epstein-Barr virus-associated Hodgkin's disease in HTLV-I seropositive patients: a report of two cases.

Diagnosis of Hodgkin's disease (HD) is quite difficult in the patient with seropositivity for human T cell lymphotropic virus I (HTLV-I). Herein, two cases of Epstein-Barr virus (EBV)-associated HD, which occurred in males with seropositivity for anti-HTLV-I, are reported. One patient is alive and was diagnosed as having interfollicular HD with CD20+CD15-CD30-CD3-CD4-CD8-CD45RO-Read-Sternberg (R-S) cells. Positivity for EBV-encoded RNA 1 (EBER-1) and latent membrane protein 1 (LMP-1) was shown on follicular germinal center cells and R-S cells. In that case, neither T cell receptor (TCR) beta chain rearrangement nor integration of the HTLV-I provirus was demonstrated in the lymph nodes, although atyical lymphocytes (2%) were found in the peripheral blood. The other case pursued an aggressive clinical course and the patient was diagnosed as having an adult T cell leukemia/lymphoma (ATLL) because of the presence of anti-HTLV-I antibody, lymph node swelling, and the appearance of flower-like cells in the peripheral blood. However, an autopsy revealed no obvious ATLL cell infiltration in any of the organs examined. Multiple granulomatous lesions were found in the bone marrow, liver, kidneys, spleen, and lymph nodes. Reassessment of lymph node lesions in biopsies and granulomatous lesions in autopsy samples demonstrated that both lesions contained CD15+CD30+CD3-CD4-CD8-CD20-CD45RO-EBER-1+L MP-1+R-S cells, and they were considered to be a composite lymphoma of HD and ATLL. These two cases therefore suggest that EBV-associated HD can develop in patients with seropositivity for HTLV-I.

Antigens, CD↗

Expression of cytotoxic molecule TIA-1 in malignant lymphomas mimicking fulminant hepatitis.

Involvement of malignant lymphoma in the liver inducing fulminant hepatic failure has rarely been reported. Therefore, a close association between some lymphoma types with severe liver damage and the mechanism underlying the liver damage is intriguing. Three malignant lymphoma cases, which were clinically diagnosed as fulminant hepatitis, were collected from the autopsy records of Kawasaki Medical School (Kurashiki, Japan). All three cases were characterized by the presence of hepatosplenomegaly without superficial lymph node swelling, high elevation of transaminase and lactate dehydrogenase (LDH; especially LDH-2), and a quite aggressive clinical course. Immunohistochemically, the tumor cells in all three cases were positive for T cell intracellular antigen (TIA-1), which is a cytolytic protein in cytotoxic T and natural killer (NK) cells. The lymphomas were CD8+ peripheral T cell lymphoma (case 1), CD56+ T/NK cell lymphoma (case 2), and T cell lymphoma in a patient with mosquito hypersensitivity (case 3). Epstein-Barr virus infection was demonstrated on the tumor cells of cases 2 and 3 using an in situ hybridization method and those cases showed high titers of serum interferon-gamma and Fas. Frequent apoptosis of liver cells, where the lymphoma cells had infiltrated, was revealed by a terminal deoxyribosyl transferase-mediated deoxyuridine nick end-labeling (TUNEL) method. The findings in this study suggest that fulminant hepatic injury is closely associated with cytotoxic molecule TIA-1 expression of the lymphoma cells and that some specific mechanism may be involved in liver damage.

Adult↗

Diffuse brain damage caused by acute twin-twin transfusion during late pregnancy.

BACKGROUND: Monoamniotic twinning is a relatively rare event with increased antenatal and perinatal mortality. We describe a brain damage detected in a surviving monoamniotic twin after intrauterine death of the co-twin at 37 weeks of gestation. RESULTS: Severe entanglement and knotting of the umbilical cords was apparent at the time of delivery and a portion of the cord to the dead twin was narrowed significantly. It was suggested that transfer of blood occurred across placental anastomoses from the survivor to the dead fetus, resulting in transient but severe hypovolemia in the survivor. It is difficult to prevent this type of brain damage because the course of acute twin-twin transfusion is very rapid and the damage has already occurred by the time the death of the twin is diagnosed. CONCLUSIONS: We suggest that elective delivery should be considered in cases of monoamniotic twin pregnancies with additional risk factors.

Adult↗

[Detection of intrathoracic infectious lesions using In-diethylenetriamine pentaacetic bicyclic anhydride-IgG (111In-DTPA-IgG) scintigraphy].

The utility of 111In-DTPA-IgG imaging for the detection of intrathoracic lesions was evaluated in 10 patients with the suspicion of inflammatory or infectious diseases. They were intravenously administered 40 or 80 MBq of 111In-DTPA-IgG, and scanned after 24 or 48 hours. Of these, 8 cases, consisted of 4 cases with pneumonia and 2 cases with lung abscess and one case of pulmonary tuberculosis and one of a tuberculous pleuritis, showed true positive results. Others were one false negative case of pneumonia and one true negative case of lung cancer. Overall sensitivity and specificity were 88.9% and 100%, respectively. There were no cases which showed side effects or abnormal laboratory findings caused by the radiopharmaceuticals administered. Thus, 111In-DTPA-IgG imaging is a useful tool for the detection of intrathoracic infectious lesions.

Adenocarcinoma, Papillary↗

[Analysis of transmission of Burkholderia cepacia isolates in an intrahospital by randomly amplified polymorphic DNA-PCR method].

Strains of Burkholderia cepacia isolated in our hospital from November 1995 to September 1996 were classified with randomly amplified polymorphic DNA-PCR (RAPD-PCR) and conventional biochemical tests (ID test.NF-18, API20NE, and Neg Combo 4J kit), and intrahospital isolates of B. cepacia were analysed. During the period 28 strains from inpatients and 2 from medical apparatus were isolated. Twenty four of 28 (85.7%) were from sputum. In 1996 from January to February, 20 strains were detected from 8 inpatients, and two strains were from the nebulizers at the Trauma and Critical Care Center (TCC). With typing of B. cepacia by conventional methods no epidemiological relations among isolates were found. However, DNA patterns of original isolates from the nebulizers at TCC by RAPD-PCR were identical with those of isolates in sputa from patients in other wards who had stayed at TCC, indicating that TCC was an initial source of transmission and the strain was transmitted with the patients to the wards. These results suggest that RAPD-PCR method might be a useful tool to analyse an epidemiological survey for intrahospital transmission of isolate.

Burkholderia Infections↗