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Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 73 records · Page 4Linked to original sources
PubMed2001

Expression of neural cell adhesion molecules (polysialylated form of neural cell adhesion molecule and L1-cell adhesion molecule) on resected small cell lung cancer specimens: in relation to proliferation state.

BACKGROUND AND OBJECTIVES: Alteration of homotypic cell-cell adhesion has been suggested to play an important role in tumor progression. The present study examined the relationship between neural cell adhesion molecules and state of proliferation of small cell lung cancer (SCLC) cells. METHODS: Seventeen surgically resected specimens of SCLC were immunohistochemically examined, by using monoclonal antibodies against neural cell adhesion molecule (NCAM) and its polysialic acid side chains, and L1 cell adhesion molecule (L1-CAM). Ki-67 labeling indices were also determined immunohistochemically. RESULTS: All patients were positive for L1-CAM. Fifteen patients (88.2%) were positive for NCAM. Among the fifteen patients, nine (60.0%) were positive for NCAM PSA side chain. The probability of survival of the NCAM without PSA side chain group was significantly higher than that of the NCAM with PSA side chain group (log-rank test; P = 0.500). CONCLUSIONS: The expression of NCAM with PSA side chains might be a prognostic factor and NCAM a marker for SCLC. L1-CAM may be synthesized independent of state of proliferation of individual tumor cell and may affect clinical feature of SCLC.

Adolescent↗
PubMed2001

Mitochondrial respiration as an early marker of viability in cardiac-arrested rat lungs.

BACKGROUND: To evaluate the possibility of using pulmonary mitochondrial respiratory functions as early markers of ischemic lung viability in non-heart-beating donors, we investigated the roles of the mitochondria in ischemia-reperfusion injury of cardiac-arrested rat lungs. MATERIALS AND METHODS: Male Lewis rats were exposed to various periods of postmortem warm ischemia (0, 1, and 2 h at 21 degrees C). After a pulmonary artery flush and cold preservation (1 h at 4 degrees C), the rat lungs were reperfused using an isolated rat lung model. Each experimental group consisted of three subgroups (n = 7 in each subgroup) to examine pulmonary functions and biochemical measurements. RESULTS: The pulmonary functions after reperfusion were exacerbated after a 1-h postmortem warm ischemia and worsened after a 2-h warm ischemia following cardiac arrest. The mitochondrial respiratory control ratios already significantly decreased after a 1-h warm ischemia compared with nonischemic rat lungs, at which time the value was almost equivalent to that after a 2-h ischemia. There were no significant changes in the state 3 and 4 respiration of the mitochondria, the pulmonary lactate levels, or the lipid peroxide levels in the lung tissues and mitochondria during the first 1-h period of warm ischemia. The adenine nucleotide levels significantly decreased with the prolongation of the period of warm ischemia, but did not seem to be practical, because their determination required a much longer time than that of the mitochondrial respiratory control ratio. CONCLUSION: These results suggested that the mitochondrial respiratory control ratio may be a useful early marker for lung viability after cardiac arrest.

Adenine Nucleotides↗
PubMed2001

A novel selectin blocker alleviates oxidative stress of lung reperfusion injury.

BACKGROUND: The importance of reactive oxygen species released through interaction of leukocyte/endothelial cell in ischemia-reperfusion injury of the lung is not yet fully understood. A novel selectin blocker, OJ-R9188, which inhibits the interaction, may alleviate oxidative stress and pulmonary dysfunction after warm ischemia-reperfusion. MATERIALS AND METHODS: Rat lungs were reperfused at 37 degrees C for 60 min with an ex vivo model and were divided into three groups (n = 10). In the fresh group, lungs were reperfused immediately after harvest. In the OJ-R (-) and OJ-R (+) groups, lungs were reperfused after warm ischemia at 37 degrees C for 90 min. In the OJ-R (+) group, rats received 100 microg per body of OJ-R9188 intravenously 10 min before the harvest. The electron spin resonance method was used to assess the direct scavenging activity of OJ-R9188. RESULTS: Both shunt fractions and wet/dry weight ratios of the lung tissue after reperfusion in the OJ-R (+) group were significantly lower than those in the OJ-R (-) group. Oxidative DNA damage in the alveolar wall of the OJ-R (+) group, assessed by immunohistochemical quantitation of 8-hydroxy-2'-deoxyguanosine, was significantly lower than that of the OJ-R (-) group. Immunostaining of 3-nitro-l-tyrosine, which represents nitric oxide-mediated oxidative damage, was also more intense in the OJ-R (-) group than in the OJ-R (+) group. Direct scavenging activity of OJ-R9188 was not observed, and the number of leukocytes infiltrated to the lung tissue as seen by myeloperoxidase activity was not different between the OJ-R (-) and OJ-R (+) groups. CONCLUSIONS: A novel selectin blocker, OJ-R9188, improves pulmonary function after warm ischemia-reperfusion and alleviates reperfusion-induced oxidative alveolar damage.

Animals↗
PubMed2001

The prognostic significance of malignant pleural effusion at the time of thoracotomy in patients with non-small cell lung cancer.

Surgery is usually not indicated for malignant pleural effusion (PE) due to its poor prognosis. However, PE is first detected at thoracotomy, and it is difficult to judge an appropriate mode of resection. Forty-nine patients with lung cancer were first diagnosed as PE and/or pleural dissemination (PD) at thoracotomy. The histological types were 36 adenocarcinoma, ten squamous cell carcinoma and three large cell carcinoma. Sixteen patients had only PE, 17 had only PD, and 16 had both PE and PD. Ten patients underwent only exploratory thoracotomy, seven partial resection, 27 lobectomy and five panpleuropneumonectomy. The overall survival rate was 26.7% at 3 years. The patients with PE and/or PD seemed to have a poorer survival compared to our previous study. The patients with only PE showed a significantly better prognosis than the patients with only PD (P=0.0001) or with PD+PE (P=0.019). The patients who underwent exploratory thoracotomy showed poor survival. There were significant differences in the survival in relation to the extent of the primary tumor. In conclusion, the patients with T1-2 of primary tumor and only a small amount of PE without PD can be expected to show long-term survival after tumor resection.

Aged↗
PubMed2001

Measurement of stapes mobility in guinea pigs and rabbits.

In tympanoplasty, it is essential to know the condition of the stapes. However, it has been difficult to evaluate stapes mobility in routine measurement. With the eye on improving future clinical practice, in this study we developed a new, easy system of measuring stapes mobility quantitatively and, as a first step, applied it to measurement of the relationship between the load and displacement of the stapes in guinea pigs and rabbits. The stapes displacement increased linearly with an increase in load in the small displacement region, and increased nonlinearly in the large displacement region. The slope of the regression line of this stiffness curve in the small displacement region was used as an index of the stapes mobility. The values in the guinea pigs and rabbits were 16+/-7 N/m and 115+/-25 N/m, respectively. A significant difference between the two species was observed.

Animals↗
PubMed2001

Analysis of elastic properties of outer hair cell wall using shell theory(1).

In this study, the mechanical properties of the lateral wall of the outer hair cell (OHC) are determined theoretically. First, the cell is modeled as a cylindrical two-layer shell consisting of the plasma membrane and the cortical lattice. When the stiffness of the plasma membrane is set to be 1.0 mN/m based on the estimated value of Tolomeo et al. [Biophys. J. 71 (1996) 421-429], and Poisson's ratio of the plasma membrane is assumed to be 0.90, the relationships between the stiffness, Poisson's ratio and the orthotropism of the cortical lattice are obtained by comparing the measurement results of cell inflation by Iwasa and Chadwick [J. Acoust. Soc. Am. 92 (1992) 3169-3173] with the numerical ones obtained with our model. Next, the obtained relationships between these mechanical properties of the cell are applied to the model, and the result of the cell length change due to the axial compression measured by Hallworth [J. Neurophysiol. 74 (1995) 2319-2329] is compared with that obtained from our numerical analysis. As a result, the axial and circumferential stiffnesses of the cortical lattice are evaluated to be 4.6 mN/m and 13 mN/m, respectively. Then, the contribution of the cortical lattice to the stiffness of the OHC lateral wall is examined. When the stiffness of the plasma membrane is less than 1.0 mN/m, the mechanical properties of the cortical lattice obtained from the two-layer shell model are nearly the same as those of the cell lateral wall obtained from the one-layer orthotropic shell model. Therefore, it is concluded that the stiffness of the cortical lattice is responsible for that of the whole lateral wall of the OHC. Moreover, the mechanical properties of the OHC obtained in this study are compared with those reported previously, and it is suggested that the one-layer orthotropic shell model is sufficient for further analyses of the motility and force production of the OHC.

Biomechanical Phenomena↗
PubMed2001

Distribution of protein motors along the lateral wall of the outer hair cell.

The outer hair cell (OHC) plays an important role in the normal functioning of the cochlea, and cochlear amplification is believed to be based on OHC electromotility. This electromotility putatively arises from a conformational change of molecules, i.e., 'protein motors', which would be distributed along the plasma membrane. Although it has been assumed that protein motors are distributed in a restricted area of the plasma membrane, details of such distribution remain unclarified. In this study, first, in order to understand the difference in the stiffness along the cell axis, the local deformation of the OHC in response to hypotonic stimulation is analyzed by measuring the displacement of microspheres attached randomly to the lateral wall of the cell. As a result, the stiffness is expected to be constant throughout the region except in the apical part of the cell, and the stiffness of the apical part is expected to be higher than that of the other regions. Then, the local elongation and contraction of the OHC in response to sinusoidal voltage stimulation are analyzed by measuring the displacement of the microspheres in the same way as in the case of the hypotonic stimulation. From the two measurements mentioned above, it is concluded that there are no motors in the apical and basal parts of the cell, and that the motors are equally distributed along the cell lateral wall in the middle part of the cell.

Animals↗
PubMed2001

Patterning the protochordate neural tube.

The complex vertebrate nervous system has evolved from a simpler nervous system such as that seen in present-day protochordates. Through a recent accumulation of gene-expression data, together with fine anatomical studies, we are now able to identify both how the neural tube was patterned when it first evolved and what is truly novel in the vertebrate neural tube. We are entering a new era in the understanding of how the evolution of novel vertebrate structures is linked to genetic evolution.

Animals↗
PubMed2001

The significance of dihydropyrimidine dehydrogenase (DPD) activity in bladder cancer.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the pathway of uracil and thymine catabolism. DPD is also the principal enzyme involved in the degradation of 5-fluorouracil (5-FU), which is one of the anticancer chemotherapeutic agents currently used in the treatment of bladder cancer. Little is known about the significance of DPD activity in human cancers. We investigated the activity of DPD in 74 bladder cancers and the relationship between the DPD activity and the sensitivity to 5-FU. The levels of DPD activity in bladder cancer and normal bladder tissues were determined by the 5-FU degradation assay. The sensitivity to 5-FU was assessed by the microculture tetrazolium dye (dimethylthiazolyl-2-5-diphenyltetrazolium bromide; MTT) assay. The activity of DPD was approximately 2-fold higher in bladder cancer tissues compared with normal bladder tissues. DPD activity in invasive bladder cancers was approximately 2-fold higher than that in superficial cancers. In addition, the levels of DPD activity in grade 2 and grade 3 bladder cancers were approximately 3-fold and 4-fold higher than that in grade 1 cancers, respectively. Patients with superficial bladder cancer with a low DPD activity had a slightly longer postoperative tumour-free period than those with a high DPD activity over a 2-year follow-up period, but this was not significant. There was an inverse correlation between DPD activity in bladder cancer cells and their sensitivity to 5-FU. Furthermore, 5-chloro-2,4-dihydroxypyridine (CDHP), a potent DPD inhibitor, enhanced the sensitivity to 5-FU. The present study has demonstrated that the level of DPD activity correlated with the progression of the stage and an increase in the grade of the bladder cancer. These results suggest that an elevated DPD activity might be associated with the malignant potential of the bladder cancer. In addition, it might be possible to overcome 5-FU insensitivity by using DPD inhibitors in the treatment protocols of 5-FU-based chemotherapy for bladder cancers.

Adult↗
PubMed2001

Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC).

OBJECTIVES: To clarify prognostic factors in resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC). METHODS: A total of 95 consecutive patients who underwent complete tumor resection and mediastinal dissection for pT1-2N1M0 NSCLC between 1976 and 1997 were retrospectively reviewed. p53 status and proliferative activity were evaluated immunohistochemically. RESULTS: The extent of N1 stations and p53 status proved to be significant prognostic factors. The 5-year survival rate for tumor without hilar node (#10) involvement was 66%, significantly higher than that for tumor with #10 involvement (39%, P<0.01). The 5-year survival rate for tumor with aberrant p53 expression was 37%, significantly lower than that for tumor without aberrant p53 expression (74%, P<0.01). There proved to be no significant difference in the prognosis between pT1 disease and pT2 disease; the 5-year survival rates for pT1 and pT2 diseases were 62 and 56%, respectively. Age, gender, performance status, grade of tumor differentiation, histological type, or proliferative activity were not significant factors. Multivariate analysis of prognostic factors using Cox's proportional hazard model confirmed these results. CONCLUSIONS: Involvement of the hilar node and aberrant p53 expression were significant factors to predict a worse prognosis in resected T1-2N1M0 NSCLC.

Biomarkers, Tumor↗
PubMed2001

Expression of Set-alpha during morphogenesis of mouse lower first molar.

The detailed in situ expression pattern of the Set-alpha gene has been studied. Previously we showed that Set-alpha is a differentially expressed gene in the embryonic mouse mandible at day 10.5 (E10.5) gestational age. Cells expressing Set-alpha were widely distributed in both the epithelial and underlying ectomesenchymal cells at E10.5. At E12, they were slightly aggregated in an area where tooth germ of the lower first molar is estimated to be formed. At E13.5, Set-alpha was strongly expressed in the tooth germ. At the cap stage, Set-alpha was expressed in the enamel organ and dental papilla. At the bell stage, Set-alpha was distinctly expressed in the inner enamel epithelial and dental papilla cells facing the inner enamel epithelial layer, which were intended to differentiate into ameloblasts and odontoblasts, respectively. Interestingly, Set-alpha was also expressed in several embryonic craniofacial tissues derived from the ectoderm. This study is the first report that Set-alpha is distinctly expressed in the developing tooth germ, and suggests that Set-alpha plays an important role in both the initiation and the growth of the tooth germ, as well as in the differentiation of ameloblasts and odontoblasts.

Animals↗
PubMed2001

Localization of activated caspase-3-positive and apoptotic cells in the developing tooth germ of the mouse lower first molar.

This study examined the immunohistochemical detection of activated caspase-3, and its association with apoptosis, during tooth morphogenesis of the mouse lower first molar. The distribution of cells positive for caspase-3 closely corresponded with the localization of the terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate-biotin nick end labelling (TUNEL)-positive apoptotic cells through the developmental course of tooth germs from embryo day 12 (E12) to E19, thus showing that the apoptosis occurring in the developing odontogenic tissue was induced by the activation of the caspase family. The specific distribution pattern of apoptotic cells in the developing odontogenic epithelial tissue from the initiation (E12) of tooth germ to the completion of tooth crown morphology (E19) also suggests that apoptotic events are related not only to a deletion of functionally suspended cells, but also participate in initiation and the completion of tooth morphogenesis. Electron microscopic examination revealed that apoptotic cells were present in the primary enamel knot, and these apoptotic cells were phagocytized by neighbouring odontogenic epithelial cells, thus indicating the prompt disposal of any dead cells by epithelial cells.

Animals↗
PubMed2001

Comparison of plasma alpha glutathione S-transferase concentrations during and after low-flow sevoflurane or isoflurane anaesthesia.

BACKGROUND: We evaluated the effect of low-flow sevoflurane anaesthesia, in which compound A is generated, and isoflurane anaesthesia, in which compound A is not generated (n=13 in each group), on hepatocellular integrity using alpha glutathione S-transferase (GST). Alpha GST is a more sensitive and specific marker of hepatocellular damage than is aminotransferase activity and correlates better with hepatic histology. METHODS: Sevoflurane or isoflurane were delivered without nitrous oxide with a fresh gas flow of 1 l/min. Concentrations of compound A in the circuit were measured hourly, and plasma alpha GST concentrations were measured perioperatively. RESULTS: Mean duration of anaesthesia was 338+/-92 min in the sevoflurane group and 320+/-63 min in the isoflurane group. Mean compound A concentration in the sevoflurane group was 28.6+/-9.0 ppm. There was no significant difference in alpha GST concentrations between the sevoflurane and isoflurane groups during or after anaesthesia. CONCLUSION: These results indicate that low-flow sevoflurane and isoflurane anaesthesia have the same effect on hepatic function, as assessed by plasma alpha GST concentrations.

Adult↗
PubMed2001

Urinary trypsin inhibitor concentration can predict the immunological insult of chemotherapy and complications after bone marrow transplantation.

Urinary trypsin inhibitor has attracted attention as an index of the systemic inflammatory response syndrome. In this study, the urine concentration of trypsin inhibitor was measured to compare the immunological insult of conventional chemotherapy and conditioning chemotherapy for bone marrow transplantation. We also investigated whether urinary trypsin inhibitor was a useful index of the complications and outcome of bone marrow transplantation. Urinary trypsin inhibitor concentration was determined before chemotherapy, on the day after finishing chemotherapy (day 0 of transplantation), and during recovery of the white cell count, in 17 patients (seven receiving conventional chemotherapy and 10 receiving conditioning for bone marrow transplantation). Urinary trypsin inhibitor concentrations were significantly higher after conditioning for bone marrow transplantation than after conventional chemotherapy (P < 0.001), indicating that conditioning was more invasive. After bone marrow transplantation, the incidence of severe complications and the mortality rate were higher in patients whose urinary trypsin inhibitor concentrations rose during recovery of the white cell count. Comparison of urinary trypsin inhibitor concentrations suggested that conditioning for bone marrow transplantation was more invasive than conventional chemotherapy. This study also suggested that the urine concentration of trypsin inhibitor could be useful for predicting the risk of complications and outcome of bone marrow transplantation.

Adolescent↗
PubMed2001

Increased hepatocyte growth factor in serum in acute graft-versus-host disease.

Hepatocyte growth factor (HGF) was reported to be effective in preventing acute graft-versus-host disease (GVHD) in a murine model. We examined serum HGF concentrations in 38 patients receiving allogeneic bone marrow transplants, and investigated the relationship of serum HGF concentrations to severity of acute GVHD. More HGF was present in sera from patients with than without acute GVHD. Serum HGF correlated significantly with grade of acute GVHD. Furthermore, serum HGF correlated with serum concentrations of C-reactive protein, gamma-glutamyltranspeptidase (GTP), and aspartate aminotransferase (AST). Serum concentrations of HGF in transplanted patients without GVHD were consistently low, while those in patients with acute GVHD increased with exacerbation. We conclude that HGF was produced during induction of the GVH reaction, and probably increased as a physiological response.

Acute Disease↗
PubMed2001

Origin and evolution of the neural crest: a hypothetical reconstruction of its evolutionary history.

The neural crest has long been regarded as one of the key novelties in vertebrate evolutionary history. Indeed, the vertebrate characteristic of a finely patterned craniofacial structure is intimately related to the neural crest. It has been thought that protochordates lacked neural crest counterparts. However, recent identification and characterization of protochordate genes such as Pax3/7, Dlx and BMP family members challenge this idea, because their expression patterns suggest remarkable similarity between the vertebrate neural crest and the ascidian dorsal midline epidermis, which gives rise to both epidermal cells and sensory neurons. The present paper proposes that the neural crest is not a novel vertebrate cell population, but may have originated from the protochordate dorsal midline epidermis. Therefore, the evolution of the vertebrate neural crest should be reconsidered in terms of new cell properties such as pluripotency, delamination-migration and the carriage of an anteroposterior positional value, key innovations leading to development of the complex craniofacial structure in vertebrates. Molecular evolutionary events involved in the acquisitions of these new cell properties are also discussed. Genome duplications during early vertebrate evolution may have played an important role in allowing delamination of the neural crest cells. The new regulatory mechanism of Hox genes in the neural crest is postulated to have developed through the acquisition of new roles by coactivators involved in retinoic acid signaling.

Animals↗