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Biomedical subjects

T Koike

Publications and source records attributed to T Koike.

At least 19 recordsLinked to original sources
PubMed2001

Isolation, structure determination, and synthesis of neodysiherbaine A, a new excitatory amino acid from a marine sponge.

[structure: see text] A new excitatory amino acid, neodysiherbaine A (2), was isolated as a minor constituent of the aqueous extract from the marine sponge Dysidea herbacea. The structure was deduced by spectroscopic methods and established unambiguously by the total synthesis. The present synthesis, including as a key step cross-coupling of the 6/5-bicyclic core with an amino acid residue, is useful in constructing its structural analogues.

Alanine↗
PubMed2001

Activation of a novel microglial gene encoding a lysosomal membrane protein in response to neuronal apoptosis.

In an attempt to understand the molecular mechanism of microglial activation in response to neuronal death or degeneration, we have employed cerebellar cell cultures prepared from P7 rats and grown in normal K(+) (5.4 mM) medium. Under this condition, glial cells respond to degeneration and cell death of granule neurons that begins to occur at 4 days in vitro (DIV). Here we describe a novel gene, granule cell death-10 (gcd-10) that is expressed in microglia and up-regulated in an early period of granule cell death. gcd-10 is homologous to the mouse lysosomal-associated multispanning membrane protein (LAPTm5) with hematopoietic origin. Immunocytochemistry and vital staining with acridine orange revealed that GCD-10 was localized at the perinuclear area of cultured microglia and COS 1 cells infected with a GCD-10-expressing adenoviral vector. In cerebellar cell cultures, however, GCD-10 was markedly up-regulated and widely distributed to the cytoplasm, which paralleled the localization of the ED1 antigen, the lysosomal marker. In vivo, gcd-10 is expressed mainly in the brain and the spleen, and was up-regulated upon nerve injury in retina 7 days after optic nerve transection. These findings suggest that gcd-10 is involved in the dynamics of lysosomal membranes associated with microglial activation both in vitro and in vivo.

Animals↗
PubMed2001

Involvement of pRB-related p107 protein in the inhibition of S phase progression in response to genotoxic stress.

pRB family pocket proteins consisting of pRB, p107, and p130 are thought to act as a set of growth regulators that inhibit the cell cycle transition from G1 to S phases by virtue of their interaction with E2F transcription factors. When cells are committed to progressing through the cell cycle at the late G1 restriction point, they are hyperphosphorylated by G1 cyclin-cyclin-dependent kinase and are functionally inactivated. Consistent with such a G1 regulatory role, pRB and p130 are abundantly expressed in quiescent cells. In contrast, p107 is present at low levels in the hypophosphorylated form in quiescent cells. As cells progress toward late G1 to S phases, the levels of p107 increase, and the majority become hyperphosphorylated, suggesting a possible role of p107 in post-G1 cell cycle regulation. In this study, we have demonstrated that a nonphosphorylatable and thus constitutively active p107 has the potential to inhibit S phase progression. The levels of the phosphorylation-resistant p107 required for the S phase inhibition are significantly less than those of endogenous p107. We further show herein that the exposure of cells to the DNA-damaging agent, cisplatin, provokes S phase arrest, which is concomitantly associated with the accumulation of hypophosphorylated p107. Furthermore, the S phase inhibitory response to cisplatin is augmented by the ectopic expression of wild type p107, although it is diminished by the adenovirus E1A oncoprotein, which counteracts the pocket protein functions. Because p107 is a major pRB family protein expressed in S phase cells, our results indicate that p107 participates in an inhibition of cell cycle progression in response to DNA damage in S phase cells.

Amino Acid Substitution↗
PubMed2001

Chiral doublet structures in odd-odd n = 75 isotones: chiral vibrations.

New sideband partners of the yrast bands built on the pi(h11/2)nu(h11/2) configuration were identified in 55Cs, 57La, and 61Pm N = 75 isotones of 134Pr. These bands form with 134Pr unique doublet-band systematics suggesting a common basis. Aplanar solutions of 3D tilted axis cranking calculations for triaxial shapes define left- and right-handed chiral systems out of the three angular momenta provided by the valence particles and the core rotation, which leads to spontaneous chiral symmetry breaking and the doublet bands. Small energy differences between the doublet bands suggest collective chiral vibrations.

Journal Article↗
PubMed2001

Vascular tumor in the mediastinum.

Mediastinal venous hemangioma is a very rare neoplasm. Here, we describe our experience in treating a patient demonstrating such a tumor. The patient, a 23-year-old man, was admitted to our hospital because of a mediastinal cyst. A biopsy of the cystic wall was performed by Video-Assisted-Thoracic-Surgery, in April 1999. Clear serous fluid was found in the cyst, and it was thus incorrectly diagnosed to be a thymic cyst. The cyst continued to increase in size, and the patient began to show an increased temperature after being discharged. A resection of the tumor was performed in June 1999. The cyst was filled with bloody fluid and, according to the pathological analysis, was diagnosed to be a mediastinal venous hemangioma.

Adult↗
PubMed2001

Distribution of bone mineral density in the proximal tibia in mid-teens.

The distribution of bone mineral density (BMD) in the proximal tibia was studied in 94 knees from 47 mid-teens. The subjects were healthy high school freshmen (19 male; 28 female) who engaged in daily physical exercise. We measured BMD at six regions of interest (ROI) at the bilateral proximal tibia (three immediately above and three immediately be-low the physeal line) using dual-energy X-ray absorptiometry (QDR-2000; Hologic, Waltham, MA, USA). Subjects were supine during the measurements, with the knee extended and the foot fixed in a special holding device, ensuring correct rotational alignment of the knee. Measurements were performed using the forearm array scan mode. The precision of this method (coefficient of variation) was 1.1%-4.9% (mean 2.5%) for six ROIs. The BMD of the medial side was higher than that of the lateral side, and the BMD at the center of the metaphysis was higher than that of the epiphysis. The subjects in the present study did not show any misalignment of the knee joints. These findings indicate that the medial side of the proximal tibia already has higher BMD than the lateral side in teenagers with normal alignment of the knee joint, and that the increase in epiphyseal BMD may be slower than that of metaphyseal BMD. It is suggested that this phenomenon should be life-long and may play a role in the progression of osteoarthritis of the knee.

Adolescent↗
PubMed2001

Segmentectomy for roentgenographically occult bronchogenic squamous cell carcinoma.

BACKGROUND: Roentgenographically occult bronchogenic squamous cell carcinomas (ROSCCs) are early squamous cell lung cancers of central type. Some of them cannot be treated with intrabronchial therapy. Although surgical treatment was performed for such tumors, it was unknown whether lobectomy was indispensable or not. METHODS: The clinicopathologic information of the 58 patients who underwent segmentectomy for ROSCCs were collected from 16 hospitals and reviewed retrospectively, compared with 98 patients who underwent lobectomy for ROSCCs. RESULTS: Five-year survival rate of the 58 patients based on lung cancer deaths was 96.8%, and 82.6% including all causes of death. The duration of chest tube drainage in the segmentectomy group was slightly longer than in the lobectomy group. Operative mortality and the frequency of postoperative complications were not statistically different in both groups. Postoperative/preoperative vital capacity and forced expiratory volume in 1 second were higher in the segmentectomy group. CONCLUSIONS: These results suggest that segmentectomy may be an alternative for surgical therapy of carefully selected ROSCCs. More prospective studies are required to fully demonstrate clinical benefit.

Adult↗
PubMed2001

Rho-Rho kinase is involved in smooth muscle cell migration through myosin light chain phosphorylation-dependent and independent pathways.

Although Rho, a small GTPase, has been demonstrated to play an important role in the smooth muscle contraction and relaxation, little is known about the involvement of Rho protein in smooth muscle cell (SMC) migration. In this study the role of Rho-Rho kinase pathway was examined in SMC migration induced by platelet-derived growth factor (PDGF) and lysophosphatidic acid (LPA). C3 transferase, a specific inhibitor of Rho, blocked SMC migration induced by PDGF and LPA. Y-27632, a specific inhibitor of Rho kinase, a direct target molecule of Rho, inhibited PDGF and LPA-induced SMC migration in a concentration dependent manner. Although rapid increase in myosin light chain (MLC) phosphorylation in SMC treated with LPA was observed, no enhanced MLC phosphorylation was detected in response to PDGF. Y-27632 suppressed LPA-induced as well as basal level of MLC phosphorylation. ML-9, a specific inhibitor of myosin light chain kinase (MLCK), inhibited PDGF and LPA-induced SMC migration without the suppression of MLC phosphorylation at 5 min incubation, suggesting that MLCK may contribute to SMC migration via mechanism other than MLC phosphorylation. These results suggest that Rho-Rho kinase pathway is implicated in SMC migration and that different signaling pathways downstream of Rho-Rho kinase may be involved in LPA and PDGF-induced SMC migration. MLC phosphorylation via Rho-Rho kinase pathway appears to be implicated in LPA-dependent SMC migration. Whereas PDGF-mediated SMC migration is independent of increased MLC phosphorylation and other target molecules downstream of Rho-Rho kinase seem to be involved.

Amides↗
PubMed2001

Prognosis of non-small cell lung cancer patients with positive pleural lavage cytology after a thoracotomy: results of the survey conducted by the Japan Clinical Oncology Group.

OBJECTIVE: The purpose of this study was to clarify the prognosis of non-small cell lung cancer patients without pleural effusion whose intrapleural cancer cells were detected by a cytologic examination of pleural lavage fluid obtained immediately after a thoracotomy. METHOD: A questionnaire survey on the survival of the patients with positive pleural lavage cytology from January 1985 to December 1994 was performed by the Japan Clinical Oncology Group. RESULTS: According to the data collected from 15 institutions, 1890 non-small cell lung cancer patients without pleural effusion underwent pleural lavage cytology immediately after thoracotomy and 142 (7.8%) of them were found to have intrapleural cancer cells detected by the cytological analysis. The information of survival on 113 patients was available. This comprised of 64 males and 49 females with a mean age of 64.6 years. The predominant histologic type was adenocarcinoma (74%). Out of these 113 patients, 109 (97%) underwent a surgical resection. The 5-year survival rate was 30% in all patients, 49% in pathological stage I (n=35), 23% in stage II (n=20) and 26% in stage IIIA (n=34). CONCLUSION: Patients with a positive pleural lavage cytology in pathological stage I or II appear to have a poor 5-year survival rate.

Aged↗
PubMed2001

Prognosis of resected non-small cell lung cancer patients with carcinomatous pleuritis of minimal disease.

OBJECTIVE: The purpose of this study was to clarify the prognosis of resected non-small cell lung cancer (NSCLC) patients with carcinomatous pleuritis of minimal disease which might be considered as the next advanced stage of positive pleural lavage cytology. METHOD: The data were collected from a questionnaire survey on the survival of the patients with carcinomatous pleuritis found at thoracotomy from 1985 to December 1994 which was conducted by the Japan Clinical Oncology Group (JCOG). RESULTS: Out of 227 patients with carcinomatous pleuritis found at thoracotomy who had available information on a survival, 100 patients who underwent a resection of the primary tumor had carcinomatous pleuritis of minimal disease defined based on the criteria of the Japan Lung Cancer Society. The mean malignant fluid volume (+/-S.E.) was 37.1 (6.3) ml and the mean number of pleural disseminated nodules was 5.6 (0.9). A lobectomy was performed in 79 patients, a pneumonectomy in 11 and a limited resection in ten. The 3- and 5-year survival rates were 31.8 and 22.8%, respectively. CONCLUSIONS: The prognosis of resected NSCLC patients with carcinomatous pleuritis of minimal disease was unexpectedly good. This indicates that no fine line may exist between positive pleural lavage cytology findings and the aforementioned lesion.

Aged↗
PubMed2001

Overall survival and local recurrence of 406 completely resected stage IIIa-N2 non-small cell lung cancer patients: questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials.

BACKGROUND: the group of completely resected stage IIIA-N2 non-small cell lung cancer patients (NSCLC) is considered to be heterogeneous in various aspects including survival and the recurrent pattern. In the present study, we attempted to clarify the factors which separate these patients into high and low risk groups based on the survival and local recurrence. METHODS: a questionnaire survey on the survival and local recurrence of non-small cell lung cancer patients with pathological stage IIIA-N2 disease who underwent a complete resection from January 1992 to December 1993 was performed by the Japan Clinical Oncology Group as of July 1999. The information on the survival of 406 patients and that of local recurrence in 332 of them was available. RESULTS: the 5-year survival of the 406 patients was 31.0%. In a univariate analysis, the age, clinical and pathological T status, number of N2 stations, pathological N1 disease, operative modality and postoperative radiotherapy were all found to be important prognostic factors. Clinical N2 disease marginally influenced the survival (P=0.07). In a multivariate analysis of these variables including clinical N2 disease, the survival was significantly worse in the case of multiple N2 stations (hazard ratio=1.741), the presence of pathological N1 disease (1.403), pathological T2 or 3 disease (1.399) and an age older than 65 (1.327). The rate of freedom from any local recurrence at the bronchial stump, or in the hilar, mediastinal or supraclavicular lymph nodes at 5 years was 64%. In a univariate analysis of the freedom from local recurrence, the clinical N status, pathological T status, pathological N1 disease and number of N2 stations were all found to be important prognostic factors. A multivariate analysis revealed the freedom from local recurrence to be adversely influenced by multiple N2 stations (hazard ratio=2.05), and the presence of either clinical N1 or 2 (1.733) disease. The 5-year survival and the rate of freedom from local recurrence at 5 years were 43 and 75% in patients with a single N2 station and 17 and 48% in those with multiple N2 stations, respectively. CONCLUSIONS: the number of N2 stations (single vs. multiple N2 stations) was found to be a useful prognostic factor, which can separate completely resected stage IIIA-N2 patients into high and low risk groups regarding both the overall survival and local recurrence.

Adult↗
PubMed2001

Manganese toxicity as indicated by visible foliar symptoms of Japanese white birch (Betula platyphylla var. japonica).

For the purpose of a field diagnosis of Mn toxicity, we showed the possibility of using visible foliar symptoms of Japanese white birch (Betula platyphylla var. japonica Hara) as indicator. To examine the relationship between the expression of visible symptoms and leaf Mn concentrations, white birch seedlings were grown under four different Mn levels: 1 mg Mn l-1 as control, 10, 50 and 100 mg Mn l-1. Foliar symptoms of Mn toxicity for white birch were: (1) chlorosis at entire young leaves in the 50 and 100 mg Mn l-1 treatments; and (2) brown speckles at the leaf marginal and interveinal area for old leaves in the treatments greater than 1 mg Mn l-1. Mn preferably accumulated into the leaf marginal and interveinal area, where the brown speckles were observed. The mechanism determining the expression of symptoms seems to be associated with the physiological state related to leaf age as well as Mn distribution and concentration within a leaf.

Air Pollutants↗
PubMed2001

Stem cell factor prevents Fas-mediated apoptosis of human erythroid precursor cells with Src-family kinase dependency.

The Fas ligand (Fas-L) expressed on mature erythroblasts may induce apoptosis of more immature erythroid cells that express Fas, whereas stem cell factor (SCF) may prevent Fas-mediated cell death in hematopoietic progenitor cells. The manner in which SCF prevents Fas-mediated cell death still is unclear. Given the essential role of SCF and the potentially important involvement of the Fas/Fas-L system in the development of erythrocytes, we studied mechanisms related to SCF prevention of Fas-mediated apoptosis. We used primary cultured human erythroid colony-forming cells (ECFC) derived from CD34+ cells and enriched glycophorin A positive (GPA+) c-kit+ cells in ECFC. Apoptosis of ECFC was induced by an Fas-L mimetic monoclonal antibody CH11. DNA fragmentation and the activation of caspase-3 and caspase-8 were measured using commercially available kits. Characterization of expanded cells was performed using multiparameter flow cytometry. Lyn kinase activity was measured by enolase kinase assays. SCF inhibited the CH11-induced DNA fragmentation of ECFC as well as enriched GPA+ c-kit+ cells in ECFC, but not those of GPA+ c-kit- cells. SCF also inhibited the activation of caspase-3 and caspase-8, without downregulation of the surface expression of Fas, suggesting that SCF prevents apoptosis through uncoupling of Fas ligation from subsequent caspase activation. PP2, a specific inhibitor of Src-family kinases, antagonized the effects of SCF in preventing Fas-mediated apoptosis. We propose that SCF prevents Fas-mediated apoptosis of erythroid progenitor cells in a manner dependent on the activity of Src-family tyrosine kinases. We also identified active Lyn in erythroid cells. These data suggest the presence of a novel Src-family-dependent function of SCF in the development of erythrocytes.

Antibodies, Monoclonal↗
PubMed2001

Serum-free coculture system for ex vivo expansion of human cord blood primitive progenitors and SCID mouse-reconstituting cells using human bone marrow primary stromal cells.

OBJECTIVE: In an attempt to maintain and expand human stem cells, many investigators have used xenogeneic, especially murine, stromal cells and fetal calf serum. Because of the possible transmission of infectious diseases, however, the safety of the delivery of grafts expanded in culture using xenogeneic cells and serum has been debated. Using primary human marrow stromal cells, we established a novel serum-free culture system to expand human primitive progenitors and transplantable stem cells. MATERIALS AND METHODS: Cord blood CD34(+) cells were cultured on a monolayer of human primary marrow stromal cells in the presence of thrombopoietin (TPO), flt3/flk2 ligand (FL), and/or stem cell factor (SCF) under serum-free conditions. After 2 or 4 weeks of culture, cells were examined for clonogenic progenitors and severe combined immunodeficient disorder (SCID) mouse-reconstituting cells (SRC). RESULTS: In the presence of TPO, FL, and SCF, marrow stromal cells supported more than a 100- and 1,000-fold expansion of CD34(+) cells and colony-forming units in culture after 2 and 4 weeks of incubation, respectively. In addition, cobblestone area-forming cells were expanded more than 18- and 60-fold after 2 and 4 weeks of culture, respectively. Furthermore, SRC assay demonstrated augmented engraftment by cultured cells. CONCLUSION: This ex vivo expansion system should prove valuable in clinical settings in which stromal cells are available from recipients or stem cell donors.

Acute Disease↗
PubMed2001

Stem cell factor protects c-kit+ human primary erythroid cells from apoptosis.

OBJECTIVE: It has been reported that stem cell factor (SCF) promotes cell survival in primary cultured human erythroid colony-forming cells (ECFC). Given the heterogeneous nature of ECFC, which may affect interpretation of the data, we purified c-kit+ ECFC and investigated the specificity and mechanisms of the anti-apoptotic effects of SCF on these cells. MATERIALS AND METHODS: Glycophorin A+ (GPA+) c-kit+ cells were purified from primary cultured ECFC derived from purified human CD34+ cells. The GPA+c-kit- and nonerythroid cells were generated from the same CD34+ cells. Apoptosis of ECFC was investigated in the absence or presence of SCF and erythropoietin (EPO) in serum-free medium. DNA fragmentation was measured with enzyme linked immunosorbent assay for oligonucleosome-sized DNA, gel electrophoresis, and annexin V labeling. Characterization of expanded cells and enriched cells was performed using multiparameter flow cytometry. For Akt assay, cells were lysed and the cleared lysates subjected to SDS-PAGE followed by Western blotting. RESULTS: In GPA+c-kit+ cells, deprivation of cytokine caused rapid DNA fragmentation within 4 hours that reached a maximum at 6 hours. This was partially but clearly prevented by SCF or EPO. In contrast, no significant DNA fragmentation was seen in GPA+c-kit- and nonerythroid cells within 24 hours. PP2, a specific Src family kinase inhibitor, but not its inactive analogue PP3, reversed the anti-apoptotic effects of SCF. PP2 also inhibited SCF-induced phosphorylation of Akt. CONCLUSION: These data indicate that SCF protects purified human GPA+c-kit+ cells from apoptosis and suggest that kit-mediated Src kinase activation is involved in Akt activation and cell survival.

Apoptosis↗
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↗