Biomedical subjects

Kenji Nakamura

Publications and source records attributed to Kenji Nakamura.

At least 37 records · Page 2Linked to original sources

PubMed2005

Deficiency of protein kinase Calpha in mice results in impairment of epidermal hyperplasia and enhancement of tumor formation in two-stage skin carcinogenesis.

We generated a mouse strain lacking protein kinase Calpha (PKCalpha) and evaluated the significance of the enzyme in epithelial hyperplasia and tumor formation. PKCalpha-deficient mice exhibited increased susceptibility to tumor formation in two-stage skin carcinogenesis by single application of 7,12-dimethylbenz(a)anthracene (DMBA) for tumor initiation and repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) for tumor promotion. Tumor formation was not enhanced by DMBA or TPA treatment alone, suggesting that PKCalpha suppresses tumor promotion. However, the severity of epidermal hyperplasia induced by topical TPA treatment was markedly reduced. In mutant mice, the number of 5-bromo-2'-deoxyuridine-labeled epidermal basal keratinocytes increased 16 to 24 hours after topical TPA treatment as in the case of wild-type mice, but significantly decreased at 36 and 48 hours. Furthermore, the regenerating epithelium induced by skin wound significantly decreased in thickness but was not structurally impaired. The enhanced tumor formation may not be associated with epidermal hyperplasia. The induction levels of epidermal growth factor (EGF) receptor ligands, tumor growth factor alpha (TGF-alpha), and heparin-binding EGF-like growth factor, in the skin of mutant mice by TPA treatment were significantly lower than those in the skin of wild-type mice. PKCalpha may regulate the supply of these EGF receptor ligands in basal keratinocytes, resulting in a reduced epidermal hyperplasia severity in the mutant mice. We propose that PKCalpha positively regulates epidermal hyperplasia but negatively regulates tumor formation in two-stage skin carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2005

Highly extended conformation of polyelectrolytes incorporated into hybrid threadlike micelles studied by small angle neutron scattering.

SANS measurements revealed that polyelectrolytes, sodium salt of partially sulfonated polystyrenes, incorporated into enormously long hybrid threadlike micelles formed in aqueous solution with a cationic surfactant, cetyltrimethylammonium bromide, have a highly extended conformation with high confinement along the micelles with a radius of 2.3 nm.

Journal Article↗

PubMed2005

A serious clinical course of a very elderly patient with takotsubo cardiomyopathy.

An 86-year-old woman was admitted to our hospital because of vomiting and anorexia. Although serum cardiac markers, an electrocardiogram, and echocardiography suggested acute myocardial infarction, emergency cardiac catheterization revealed akinesis of the left ventricular apex without significant coronary artery stenosis. She was diagnosed as having takotsubo cardiomyopathy. The left ventricular dysfunction was considered transient and reversible but did not improve at all, contrary to our expectations. She died of worsening heart failure on day 14. We discuss this serious clinical course of a very elderly patient with takotsubo cardiomyopathy.

Aged, 80 and over↗

PubMed2005

Impact of large tumor size on survival after resection of pathologically node negative (pN0) non-small cell lung cancer.

BACKGROUND: The current TNM staging system first adopted the tumor size of 3 cm for subdivision of stage I and II disease. The aim of the present study was to evaluate the impact of tumor size on survival in patients with pathologically node negative (pN0) non-small cell lung cancer after complete resection. METHODS: We retrospectively reviewed the records of 603 patients with pN0 non-small cell lung cancer patients (403 men and 200 women) who underwent a complete resection in five national chest hospitals between 1992 and 1996, with follow-up duration of more than 5 years, and analyzed tumor size and survival. Survival rate was estimated by the Kaplan-Meier method, and differences were compared by log-rank test. For the multivariate analysis, the Cox proportional hazard model was used to identify variables that significantly affected survival. RESULTS: There were 355 adenocarcinomas, 208 squamous cell carcinomas, and 40 large cell carcinomas completely resected. No significant prognostic differences were seen among three groups with smaller-sized tumors (< or =2 cm [n = 171], 2.1 to 3 cm [n = 202], and 3.1 to 5 cm [n = 170]); however, patients with a tumor size greater than 5 cm (n = 60) showed a significantly worse prognosis. The 5-year survival rates were 79.6%, 72.7%, 68.1%, and 46.6%, respectively, in these four groups. Multivariate analysis showed the tumor size to be an independent prognostic predictor in patients with pN0 tumors. CONCLUSIONS: We found that a tumor size of greater than 5 cm was an independent prognostic predictor in pN0 disease; therefore, upgrading the T factor of tumor diameter to greater than 5 cm may be necessary in the next reversion of the TNM staging system.

Adult↗

PubMed2005

A gene-targeted mouse model for chorea-acanthocytosis.

Chorea-acanthocytosis (CHAC) is a hereditary neurodegenerative disorder with autosomal recessive transmission, in which selective degeneration of striatum has been reported in brain pathology. Clinically, CHAC shows Huntington's disease-like neuropsychiatric symptoms and red blood cell acanthocytosis. Recently, we identified the gene, CHAC, encoding a novel protein, chorein, in which a deletion mutation was found in Japanese families with CHAC. In the present study, we have identified the mouse CHAC cDNA sequence and the exon-intron structures of the gene and produced a CHAC model mouse introducing no. 60-61 exon deletion corresponding to a human disease mutation by a gene-targeting technique. The mice began to show acanthocytosis and motor disturbance in old age. In behavioral observations, locomotor activity was significantly decreased and the contact time at social interaction test was decreased significantly in the model mice. In the brain pathology, many apoptotic cells were observed in the striatum of the mutant mice. In neurochemical determinations, the dopamine metabolite, homovanillic acid, concentration decreased significantly in the portion including the midbrain of the mutant mice. These findings are consistent with the human results reported elsewhere and indicate that the CHAC model mice showed a mild phenotype with late adult onset. The CHAC model mouse therefore provides a good model system to study the human disease.

Acanthocytes↗

PubMed2005

Membrane fixation of vascular endothelial growth factor receptor 1 ligand-binding domain is important for vasculogenesis and angiogenesis in mice.

Vascular endothelial growth factor (VEGF) regulates vasculogenesis and angiogenesis by using two tyrosine kinase receptors, VEGFR1 and VEGFR2. VEGFR1 null mutant mice die on embryonic day 8.5 (E8.5) to E9.0 due to an overgrowth of endothelial cells and vascular disorganization, suggesting that VEGFR1 plays a negative role in angiogenesis. We previously showed that the tyrosine kinase (TK) domain of VEGFR1 is dispensable for embryogenesis, since VEGFR1 TK-deficient mice survived and were basically healthy. However, the molecular basis for this is not yet clearly understood. To test the hypothesis that the specific role of VEGFR1 during early embryogenesis is to recruit its ligand to the cell membrane, we deleted the transmembrane (TM) domain in TK-deficient VEGFR1 mice. Surprisingly, about half of the VEGFR1(TM-TK)-deficient mice succumbed to embryonic lethality due to a poor development of blood vessels, whereas other mice were healthy. In VEGFR1(TM-TK)(-/-) mice with growth arrest, membrane-targeted VEGF was reduced, resulting in the suppression of VEGFR2 phosphorylation. Furthermore, the embryonic lethality in VEGFR1(TM-TK)(-/-) mice was significantly increased to 80 to 90% when the genotype of VEGFR2 was changed from homozygous (+/+) to heterozygous (+/-) in 129/C57BL6 mice. These results strongly suggest that the membrane-fixed ligand-binding region of VEGFR1 traps VEGF for the appropriate regulation of VEGF signaling in vascular endothelial cells during early embryogenesis.

Animals↗

PubMed2005

Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos.

The hemangioblast in the mesoderm gives rise to both angioblasts and hematopoietic stem cells. The movement of hemangioblast precursor cells in the fetal trunk is a critical event in early embryogenesis. Vascular endothelial growth factor (VEGF) signaling is likely involved in this migration given the partial disturbance of VEGF receptor (VEGFR)-positive cell accumulation and migration in VEGFR2 null mice or mice with a truncated VEGFR1. However, it is not clear how the VEGF system regulates this migration or its direction. We show here that the expression of VEGF-A is dominant in the anterior portion of the embryo, whereas VEGFR1 and VEGFR2 are expressed in the posterior portion of the embryo. An inhibitor of VEGFR kinase blocked the migration of VEGFR-positive cells in a whole-embryo culture system. In addition, VEGFR-positive cells migrated toward a VEGFR1- or VEGFR2-specific ligand in vitro. Furthermore, VEGFR-positive cells derived from wild-type or VEGFR2(+/-) mice moved rapidly anteriorly, whereas cells derived from VEGFR2(+/-) mice carrying a truncated VEGFR1 [VEGFR1(TM-TK)(-/-)] migrated little when injected into wild-type mice. These results suggest that the VEGF-A protein concentrated in the anterior region plays an important role in the guidance of VEGFR-positive cells from the posterior portion to the head region by interacting with VEGFR in the mouse embryo.

Animals↗

PubMed2005

Ventricular septal perforation in a patient with takotsubo cardiomyopathy.

An 84-year-old woman was admitted with anorexia and because the serum cardiac markers, electrocardiogram and echocardiography suggested acute myocardial infarction she underwent emergency cardiac catheterization. Coronary angiography revealed no significant coronary artery stenosis, but left ventriculography revealed akinesis of the left ventricular apex with shunt flow to the right ventricle. The diagnosis was a rare case of takotsubo cardiomyopathy complicated by ventricular septal perforation. The patient died of cardiogenic shock on the day of admission day.

Aged↗

PubMed2005

[Sleep survey of medical residents at a National University Hospital].

In order to ascertain the workload and lifestyle of medical residents prior to the introduction of a new medical resident training system, 102 residents at a national university hospital were monitored for four consecutive weeks to ascertain their life habits. Valid responses were obtained from 76% of the respondents for a total of 2,722 person days. It was found that the average length of sleep was 5.7 h on weekdays and 6.8 h on weekends. Of the 102 residents, 40% slept less than six hours a night and 17% slept less than five hours a night. The time spent sleeping was particularly short among surgical residents. Given that lack of sleep not only affects the health of the residents negatively, but also compromises the safety of medical care that they provide, the new medical residency training system will need to monitor and analyze the wellbeing, including sleep patterns, of medical residents.

Adult↗

PubMed2005

Radiofrequency ablation in a porcine lung model: correlation between CT and histopathologic findings.

OBJECTIVE: The objective of our study was to investigate the time course changes of the ablated lesion after radiofrequency ablation in the porcine lung and the correlation between CT and histopathologic findings. CONCLUSION: Ground-glass attenuation on CT led to overestimation of the size of necrotic lesions. The layered structural findings on CT were consistent with the histopathologic findings. Although CT findings reflect the histopathologic findings, attention should be paid to the dissociation of ablated lesions and high-density areas in clinical interpretation of CT images.

Animals↗

PubMed2005

Balloon-occluded retrograde transvenous obliteration of gastric varices with gastrorenal shunt: long-term follow-up in 78 patients.

OBJECTIVE: Our aim was to evaluate the long-term clinical results after balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices with spontaneous gastrorenal shunt. MATERIALS AND METHODS: A total of 78 patients with cirrhosis and with gastric varices, successfully treated by B-RTO, were enrolled in this study. Recurrence and bleeding of gastric varices and worsening of esophageal varices were endoscopically evaluated. Univariate and multivariate analyses were used to assess the prognostic factors for worsening of esophageal varices and survival. RESULTS: Recurrence of gastric varices was found in two patients; the 5-year recurrence rate was 2.7%. Bleeding of gastric varices occurred in only one patient after B-RTO; the 5-year bleeding rate was 1.5%. Worsening of esophageal varices was observed in 29 patients, and the worsening rates at 1, 3, and 5 years were 27%, 58%, and 66%, respectively. These esophageal varices were endoscopically treated to prevent rupture. Multivariate analysis showed the presence of esophageal varices before B-RTO was a prognostic factor for worsening (relative risk, 4.956). At a median follow-up of 700 days (range, 137-2,339 days), the survival rates at 1, 3, and 5 years were 93%, 76%, and 54%, respectively. The prognostic factors associated with survival were presence of hepatocellular carcinoma (relative risk, 24.342) and the Child-Pugh classification (relative risk, 5.780). CONCLUSION: B-RTO is an effective method for gastric varices with gastrorenal shunt and provides lower recurrence and bleeding rates. We believe that B-RTO can become a standard treatment for gastric varices with gastrorenal shunt, although treatment of worsened esophageal varices may be necessary after B-RTO.

Adult↗

PubMed2005

[Evaluation of pre-operative administration of TS-1 in patients with advanced gastric or colorectal cancer--estimation of pathological effectiveness for postoperative adjuvant chemotherapy with TS-1].

We performed surgical resections in 6 cases of advanced gastric cancer and 4 cases of colorectal cancer after preoperatively treating them with TS-1 at a daily dose of 80-100 mg/body for 2 weeks, and evaluated whether one can estimate their sensitivity to TS-1 by a pathological examination. Case 1 of type 3 advanced gastric cancer underwent surgery after one week interval following oral administration of TS-1 at a daily dose of 80 mg/body for 2 weeks. Surprisingly, the pathological examination revealed complete disappearance of cancer cells in the resected stomach and no cancer cells in the regional lymphnodes, judged grade 3 in pathological effectiveness. Case 2 of type 2 advanced gastric cancer was treated with TS-1 at a daily dose of 100 mg/body for 2 weeks and underwent surgery after a three-week interval due to the complication of pneumonia. The pathological effectiveness was judged grade 2 in the resected stomach, and no cancer cells were detected in the regional lymphnodes. In both cases, the postoperative course was uneventful, and no adverse effects were detected. In these cases, their high sensitivity to TS-1 was clearly confirmed, and now they have been treated with TS-1 for the postoperative adjuvant chemotherapy, and have undergone regular check-ups at our outpatient clinic in good condition. Recently, we performed the same protocol in 6 cases of advanced gastric cancer including these 2 cases and also in 4 cases of advanced colorectal cancer. This protocol was found useful for evaluating the pathological effect by TS-1. We consider the protocol quite useful and helpful in determining a suitable regimen for postoperative adjuvant chemotherapy.

Adenocarcinoma↗

PubMed2004

Correlation between dynamic computed tomographic and histopathological findings in the diagnosis of small hepatocellular carcinoma.

BACKGROUND/AIMS: To determine the characteristic image findings on dynamic computed tomography (CT) for small hepatocellular carcinoma (HCC), we evaluated the correlation of histopathological and radiological findings with respect to the angioarchitecture in small HCCs. METHODS: CT and early- and late-phase dynamic CT findings of 80 small HCCs (< or =3 cm) were divided into iso-, high, low, and mixed density. We studied the correlation between the imaging findings and the histopathological findings as follows: differentiation grade; presence of fibrous capsule; presence of Glisson's sheath, and growth pattern. RESULTS: High-density early-phase CT and low-density late-phase CT correlated significantly with moderately/poorly differentiated HCCs, which have a fibrous capsule, no Glisson's sheath, and an expansive growth pattern. In contrast, well-differentiated HCCs with a Glisson's sheath and a replacing pattern (early HCC) appeared as iso-dense lesions in the early and late phases. Well-differentiated HCCs (non-early wHCC) demonstrated various density images in the early phase and low-density images in the late phase. CONCLUSIONS: Dynamic CT is an economic and simple diagnostic tool for planning treatment of small HCC lesions because of the multistep nature of HCC carcinogenesis and the hemodynamic changes of tumor blood flow.

Adult↗

PubMed2004

Focus on the conditions of resection and reconstruction in gastric cancer. What extent of resection and what kind of reconstruction provide the best outcomes for gastric cancer patients?

To assess the roles of the extent of gastric resection and duodenal food passage reconstruction in gastric cancer, we examined a consecutive series of 1,061 patients who underwent total or partial (proximal and distal) gastrectomies with or without duodenal food passage reconstruction between August of 1974 and January of 2002, and received gastrectomies with D2-3 lymph node dissection. Patients who underwent distal or proximal gastrectomy were found to have significantly better survival rates than those who underwent total gastrectomy in stages 1A (10-year survival: 86.6 and 78.9 vs. 61.6%), 2 (56.5 and 65.6 vs. 34.4%), 3A (45.9 and 33.3 vs. 15.2%), and 4 (5-year survival rates: 23.7 and 50.0 vs. 7.1%). Additionally, patients with duodenal food passage reconstruction or double tract reconstruction also showed significantly better survival rates than those without duodenal food reconstruction in stages 1A (10-year survival: 86.4 and 82.5 vs. 61.7%), 1B (69.9 and 90.6 vs. 54.1%), 2 (60.5 and 63.3 vs. 16.5%), and 3A (39.9 and 47.4 vs. 23.1%). In multivariate analysis, the independent prognostic factors were age at operation, depth of tumor, duodenal food passage reconstruction, and lymph node metastasis. Our results indicate that both the extent of gastric resection and duodenal food passage reconstruction were important factors in the outcome of gastric cancer patients, and that surgeons should perform minimal gastric resection with preservation of the duodenal food passage when the gastric stump is tumor-free.

Adenocarcinoma↗

PubMed2004

Induction concurrent chemoradiation therapy for invading apical non-small cell lung cancer.

OBJECTIVE: Although non-small cell lung cancer (NSCLC) involving the superior sulcus has been generally treated with radiation therapy (RT) followed by surgery, local recurrence is still a big problem to be solved. We investigated a role of induction therapy, especially induction concurrent chemoradiation therapy (CRT), on the surgical results of this type of NSCLC. METHOD: We retrospectively reviewed 30 patients with NSCLC invading the apex of the chest wall who underwent surgery from 1987 to 1996. Ten patients (57 +/- 8 years) received surgery alone, 9 (55 +/- 13 years) received RT (42 +/- 7 Gy) followed by surgery and 11 (51 +/- 9 years) received cisplatin based chemotherapy and RT (47 +/- 5 Gy) as an induction therapy. RESULTS: Two and 4-year survival rates were 30% and 20% in patients with surgery alone, 22% and 11% in patients with induction RT, and 73% and 53% in patients with induction CRT, respectively. The survival was significantly better in patients with induction CRT than those with induction RT or surgery alone. Univariate analysis demonstrated that curability (yes versus no: p = 0.027) and induction therapy (surgery alone and RT versus CRT: p = 0.0173) were significant prognostic factors. Multivariate analysis revealed that only induction therapy (p = 0.0238) was a significant prognostic factor. CONCLUSIONS: Induction CRT seems to improve the survival in patients with NSCLC invading the apex of the chest wall compared with induction RT or surgery alone.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Altered agonist sensitivity and desensitization of neuronal mGluR1 responses in knock-in mice by a single amino acid substitution at the PKC phosphorylation site.

mGluR1 and mGluR5 of the metabotropic glutamate receptor family are coupled to inositol trisphosphate-Ca2+ signal cascades and evoke distinct Ca2+ responses in neural cells and heterologously expressing cells. In heterologous cells, stimulation of recombinant mGluR1 evokes a single-peaked Ca2+ response whereas mGluR5 elicits an oscillatory Ca2+ response. The distinct Ca2+ responses are interchangeable by single amino substitution of aspartate for threonine at the corresponding position of the carboxy-terminal cytoplasmic regions of mGluR1 and mGluR5, respectively. In this investigation, we generated knock-in mice, termed mGluR1 D854T mice, in which aspartate of mGluR1 was replaced with threonine. We examined the effect of this D854T substitution on Ca2+ and current responses mediated by mGluR1 in cultured cerebellar Purkinje cells. Stimulation of mGluR1 D854T by a group 1 mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG) evoked, as in wild-type mGluR1, only single-peaked Ca2+ responses as measured by Ca2+ fluorometric analysis. We then examined mGluR1-induced inward currents carried by nonselective cation channels during whole-cell recordings from cultured Purkinje cells. The mGluR1 D854T mutation abolished the responsiveness of mGluR1 to low concentrations of DHPG (0.5-500 nM) and reduced its desensitization during prolonged agonist application. mGluR1 D854T homozygous mutants showed no apparent behavioural abnormality as analysed by motor movement tests. These results indicate that, although additional modulatory mechanisms seem to be required to produce oscillatory Ca2+ responses of mGluR1, the single amino acid substitution at position 854 of mGluR1 is capable of influencing the kinetics of neuronal mGluR1 responses, most probably through PKC-mediated phosphorylation.

Amino Acid Sequence↗

PubMed2004

Catheter interventional therapy in an elderly patient with deep vein thrombosis and a brain tumor.

A 92-year-old woman with a brain tumor developed swelling of the left lower extremity. Venography showed considerable thrombi from the left common iliac vein to the femoral vein. Following implantation of a temporary inferior vena cava filter, catheter aspiration therapy and catheter-directed thrombolysis were performed. Venography after 3 days showed disappearance of the thrombi and an improvement in vein flow. A permanent inferior vena cava filter was implanted. Local intensive thrombectomy and thrombolysis by catheter together with a temporary inferior vena cava filter were effective treatments in this elderly patient with deep vein thrombosis.

Aged↗

PubMed2004

TIPS versus transcatheter sclerotherapy for gastric varices.

OBJECTIVE: The purpose of our study was to compare the efficacy and long-term results of transjugular intrahepatic portosystemic shunt (TIPS) with those of transcatheter sclerotherapy for the treatment of gastric varices. MATERIALS AND METHODS: A total of 139 cirrhotic patients with gastric varices underwent endovascular treatment. Of the 139 patients, 104 without hepatocellular carcinoma were enrolled; 27 patients were treated with TIPS, and 77 patients with transcatheter sclerotherapy. Bleeding of gastric varices and survival rates were compared between the TIPS and transcatheter sclerotherapy groups. Multivariate analysis was used to identify the prognostic factors for gastric variceal bleeding and survival. Changes in liver function were evaluated in each group. RESULTS: The cumulative gastric variceal bleeding rate at 1 year was 20% in the TIPS group and 2% in the transcatheter sclerotherapy group (p < 0.01). The prognostic factor associated with gastric variceal bleeding was the treatment method. The cumulative survival rates at 1, 3, and 5 years were, respectively, 81%, 64%, and 40% in the TIPS group and 96%, 83%, and 76% in the transcatheter sclerotherapy group (p < 0.01). The prognostic factors for survival were the treatment method and the Child-Pugh classification of liver disease. For patients categorized in Child-Pugh class A, the survival rate was higher in the transcatheter sclerotherapy group than in the TIPS group (p < 0.01). For patients in Child-Pugh classes B and C, no significant difference was seen between the two groups. Liver function tended to improve in the transcatheter sclerotherapy group. CONCLUSION: Transcatheter sclerotherapy may provide better control of gastric variceal bleeding than TIPS. Transcatheter sclerotherapy may contribute to a higher survival rate than TIPS in patients with Child-Pugh class A disease.

Analysis of Variance↗