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Biomedical subjects

M Nakahara

Publications and source records attributed to M Nakahara.

At least 19 recordsLinked to original sources
PubMed2006

Inhibitor of vascular endothelial growth factor receptor tyrosine kinase attenuates cellular proliferation and differentiation to mature neurons in the hippocampal dentate gyrus after transient forebrain ischemia in the adult rat.

Neurogenesis in the adult hippocampal dentate gyrus is promoted by transient forebrain ischemia. The mechanism responsible for this ischemia-induced neurogenesis, however, remains to be determined. It has been suggested that there may be a close relationship between neurogenesis and the expression of vascular endothelial growth factor, an angiogenic factor. The purpose of the present study was to examine the relationship between vascular endothelial growth factor and cell proliferation in the dentate gyrus after transient forebrain ischemia. The mRNA expression of vascular endothelial growth factor was increased in the dentate gyrus on day 1 after ischemia. Immunohistochemical analysis on day 9 after ischemia, when a significant increase in cell proliferation was seen, showed that the cerebral vessel space in the subgranular zone of the dentate gyrus had not been affected by the ischemia. Neither were the vascular densities on days 1 and 3 after ischemia altered compared with those of non-operated naïve control rats. Furthermore, the distance from the center of the proliferative cells to the nearest cerebral vessel of ischemic rats was comparable to that of the sham-operated rats. We demonstrated that transient forebrain ischemia-induced cell proliferation and differentiation to mature neurons in the hippocampal dentate gyrus was attenuated by the i.c.v. administration of a vascular endothelial growth factor receptor tyrosine kinase inhibitor. These results suggest that vascular endothelial growth factor receptor at the early period of reperfusion may contribute to neurogenesis rather than to angiogenesis in the hippocampal dentate gyrus.

Animals↗
PubMed2006

Laparoscope-assisted anal sphincter-preserving operation preceded by transanal procedure.

BACKGROUND: Transanal intersphincteric resection (ISR) was introduced and has been increasingly performed as an ultimate surgical treatment for extremely low rectal cancer. We considered that high quality and less invasive surgery could be achieved if ISR and laparoscopic surgery were combined. METHODS: Between December 2003 and June 2004, we performed laparoscope-assisted ISR for two patients with very low rectal cancer and total colectomy for two patients with ulcerative colitis complicated by colorectal cancer. In all patients, the transanal procedure was preceded by trans-abdominal laparoscopic rectal excision. RESULTS: Preceding transanal dissection facilitated muscle layer-oriented curative dissection, and more importantly, made subsequent laparoscopic rectal excision effortless as a result of penetrating to the dissected pelvic cavity. All patients showed favorable recovery including postoperative anal function with no complication or recurrent disease. CONCLUSIONS: This procedure is feasible and has favorable short-term results for radical treatment of very low rectal disease, while preserving anal function.

Anal Canal↗
PubMed2006

Importance of lymph vessels in gastric cancer: a prognostic indicator in general and a predictor for lymph node metastasis in early stage cancer.

BACKGROUND: Metastasis to regional lymph nodes (LNs) through lymphatic vessels is common in cancer progression and is an important prognostic factor in many cancers. Recent evidence suggests that tumour lymphangiogenesis promotes lymphatic metastasis. AIMS: To study the role of lymph vessel density (LVD) in gastric cancer and investigate whether LVD is associated with LN metastasis/prognosis. METHODS: Lymphatics of 117 primary human gastric cancer cases were investigated by quantitative immunohistochemical staining for podoplanin. The relation between LVD and LN metastasis and other established clinicopathological parameters was analysed. The relation between LVD and prognosis was also studied. RESULTS: Mean LVD of "hot spots" was 11.6/case. LVD significantly correlated with LN and podoplanin positive lymphatic invasion. High LVD was associated with worse overall survival. In multivariate analysis, positive LVD was a significant independent predictor of overall survival, depth of invasion, and TNM stage. LVD significantly correlated with LN metastasis at surgery and podoplanin positive lymphatic invasion. In multivariate analysis, positive LVD was an independent significant predictor of LN metastasis. CONCLUSIONS: Increased podoplanin expression is significantly associated with LN metastasis, and may play an important role in detecting LN metastasis in gastric cancer. Furthermore, LVD may be a significant prognostic factor in gastric cancer at any stage. In addition, LVD and lymph vessel invasion detected by podoplanin immunohistochemistry are associated with LN metastasis in T1 early gastric cancer. LVD assessment by podoplanin immunohistochemistry may become a useful predictor of LN metastasis in T1 early gastric cancer and may influence the decision making process for additional surgery.

Biomarkers, Tumor↗
PubMed2005

A randomised, placebo controlled clinical trial of the aldose reductase inhibitor CT-112 as management of corneal epithelial disorders in diabetic patients.

AIM: To evaluate the efficacy of topical aldose reductase inhibitor CT-112 (5-[3-ethoxy-4-pentyloxyphenyl]-2,4-thiazolidinedione) on corneal epithelial barrier function in diabetic patients. METHODS: This was a prospective, randomised, double masked placebo controlled study. 34 eyes of 34 diabetic patients were randomly assigned treatment with 0.25% eye drops of CT-112 (n = 22) or a placebo (n = 12) four times a day for 8 weeks. Corneal fluorescein staining and corneal sensation were examined before treatment as well as 4 and 8 weeks after administration. Corneal epithelial permeability to fluorescence was measured with an anterior fluorophotometer. RESULTS: Average scores of superficial punctate keratopathy and corneal sensitivity did not differ significantly between the two groups at any time. Whereas average fluorescein concentrations did not differ significantly for the CT-112 and placebo groups before treatment, they did differ significantly 4 and 8 weeks after treatment (4 weeks, p = 0.0327; 8 weeks, p = 0.0143). CONCLUSION: The topical aldose reductase inhibitor, CT-112 improves the corneal epithelial barrier function in diabetic patients.

Aged↗
PubMed2004

Uptake, retention and organ/tissue distribution of 137Cs by Japanese catfish (Silurus asotus Linnaeus).

The work describes the uptake, retention/biological elimination and organ/tissue distribution of 137Cs by freshwater Japanese catfish (Silurus asotus Linnaeus) under laboratory conditions. The fish were divided into three groups based on their size and age and reared in 137Cs-spiked water. The concentration of 137Cs in the whole body of the live fish was measured at regular intervals up to 60 days. A significant accumulation of 137Cs was found, but a steady state condition was not achieved by the end of the experiment. The bioaccumulation factors at steady state and the required time to reach steady state were estimated to be 1.55 and 255 days, 1.76 and 180 days and 1.99 and 160 days for large, medium and small size fish, respectively. To determine the effective half-life of 137Cs, the fish were transferred and reared in the non-contaminated host water. The concentration of the remaining 137Cs in the whole body of the live fish was measured up to 66 days. The average effective half-life of 137Cs in the fish species was found to be approximately 142 days for fish of all sizes. The distribution of 137Cs in different organs/tissues of the fish was determined. Accumulation of 137Cs in muscle/flesh of the fish was found to be approximately 75% of whole body accumulation. The uptake rate and the retention capability of juvenile fish were found to be higher and therefore, these were more susceptible to 137Cs than adult and old fish, and could be an important source of 137Cs in the human food chain.

Age Factors↗
PubMed2004

Removal of 137Cs in Japanese catfish during preparation for consumption.

Japanese catfish contaminated by (137)Cs have been used to investigate how dressing and cooking methods affect the removal of radioactivity from the fish. During the dressing, 6.0% of the initial (137)Cs activity in live fish was removed by washing them, and a further 30.3% of this activity relative to the washed fish was removed by discarding the nonedible body parts (such as the skeleton, fins, visceral mass, liver, and kidney) and by washing the chopped edible remains. Fish curry was cooked with various spices, vegetable oil, and greens and other vegetables following a method commonly used in Southeast Asian and East Asian countries. The cooking process removed a further 61.6% of the (137)Cs activity relative to the activity in dressed fish. Taken together, this normal domestic fish dressing and culinary process removed 74.7% of the initial (137)Cs activity that had been present in the live fish. During the cooking, the radioactivity removed from the fish pieces was found to be distributed throughout the ingredients of the curry. The cooked pieces retained, on average, 38.5% of the radioactivity present in the raw dressed pieces. Among the ingredients, the gravy was found to contain an average of 34.8% of the activity of the dressed fish. The activity in greens and vegetables was found to vary from 4.0% (in cauliflower) to 7.2% (in potatoes). It may be concluded that normal home preparation and culinary processes removed much of the radioactivity from the fish.

Animals↗
PubMed2002

Relation between ultrasonographic and histologic findings of tracheal invasion by differentiated thyroid cancer.

Between 1988 and 1999 a total of 24 patients with differentiated thyroid cancer invading the airway underwent various types of tracheal resection at the Osaka Police Hospital. Preoperative ultrasonographic (US) findings in these patients were compared with postoperative histologic results of the resected specimens to confirm the relation between the preoperative and postoperative diagnoses and to determine the indications for operative procedures. Preoperative US revealed cancer invasion to the adventitia in 2 cases, to the intercartilage space in 13, and to the tracheal mucosa in 9. Histologically, cancer invasion to the adventitia was confirmed in 4, to the intercartilage space in 10, and to the mucosa in 10. Among 13 cancer invasion instances to the intercartilage revealed by US, overdiagnosis occurred in 3 cases and underdiagnosis in 1. The actual overall diagnostic rate by US was 83.3%, which is a great improvement over other available methods. In conclusion, preoperative US findings of the trachea agreed with the histologic findings of the resected specimens, indicating US to be the first choice when making decisions about resecting the trachea and about the operative procedure.

Carcinoma, Papillary↗
PubMed2002

RGD-CAP (betaig-h3) exerts a negative regulatory function on mineralization in the human periodontal ligament.

In our previous studies, RGD-CAP/betaig-h3 was isolated from a fiber-rich fraction of cartilage and was found to have a negative function on mineralization of hypertrophic chondrocytes. However, the expression and biological function of RGD-CAP in the periodontal ligament (PDL) are not known. We hypothesized that RGD-CAP could be expressed in the PDL and regulate its mineralization. To test this, we investigated the expression of RGD-CAP in human PDL and the effects of RGD-CAP on mineralization of cultured PDL cells. RGD-CAP was detected in the human PDL as multimeric proteins greater than 200 kDa. The RGD-CAP mRNA level decreased in cultured PDL cells exposed to 10(-8) M dexamethasone or 10(-8) M 1alpha,25-dihydroxyvitamin D(3) when these steroids increased alkaline phosphatase (ALP) activity. Furthermore, exogenous RGD-CAP suppressed the ALP activity and bone nodule formation of cultured PDL cells. These findings suggest that RGD-CAP in the PDL modulates the mineralization which affects adjacent alveolar bone metabolism.

Alkaline Phosphatase↗
PubMed2001

Molecular cloning of rabbit hyaluronic acid synthases and their expression patterns in synovial membrane and articular cartilage.

cDNAs for hyaluronic acid synthases (HAS2 and HAS3) were cloned from a cDNA library of cultured rabbit synovial membrane cells. The cDNA encoding the open reading frame of rabbit HAS2 and HAS3 was 1659 nucleotides in length with a predicted molecular mass of about 63 kDa. The amino acid sequence showed that the rabbit HAS2 was 98.7 and 98.4%, and HAS3 was 98.2 and 97.5% identical with human and mouse forms of the proteins, respectively. The predicted sequences for hyaluronic acid (HA) binding motifs and the catalytic domains related to beta 1-4 and beta 1-3 linkages, essential for HA synthesis, were almost conserved in both rabbit HAS2 and HAS3, similarly to human and mouse HASs. RT-PCR analysis and in situ hybridization revealed that the mRNA of HAS2 was highly expressed in the synovial membrane and articular cartilage, whereas the expression of HAS3 mRNA was slightest in these tissues. Thus, it is demonstrated that rabbit HASs are highly conserved in sequence content as compared to the human and mouse homologues described previously, and that HAS2 is predominantly expressed in the synovial membrane and articular cartilage, but HAS3 is not.

Amino Acid Sequence↗
PubMed2001

Failure in the detection of aberrant mRNA from the heterozygotic splice site mutant allele for protein S in a patient with protein S deficiency.

A 29-year-old male patient with acute arterial obstruction and a medical history including thrombosis in the deep veins and pulmonary infarction presented with a reduced level of both protein S (PS) activity and free PS. Sequencing of the genomic PS gene in this patient revealed that the patient was heterozygous for the mutant PS allele, in which a nucleotide substitution occurred at the donor splice site in intron 12 (GT to GA). The patient was heterozygous for PS genes having dimorphic codons for Pro626 (CCA/CCG) and the aberrant allele in this patient was associated with the CCA form. Allelic exclusion of PS expression was demonstrated by use of Pro626 (CCA/CCG) dimorphism and only a normal mRNA sequence derived from the CCG-allele was identified in the patient. These findings suggested that the mutation at the splice site in the PS gene caused either defective production of mRNA or the gene may have produced extremely unstable RNA products, leading to reduced levels of PS activity and free PS in this patient.

Adult↗
PubMed2001

Analysis of mutational effects of a polyhydroxybutyrate (PHB) polymerase on bacterial PHB accumulation using an in vivo assay system.

Polymerase is a central enzyme involved in the biosynthesis of polyhydroxybutyrate (PHB), a well-known bacterial biodegradable polyester. In this study, we have established an in vivo assay system to analyze mutational effects of Ralstonia eutropha polymerase (termed PhbC(Re)) on the level of PHB accumulation in recombinant strains of Escherichia coli. This in vitro evolution system consists of a polymerase chain reaction-mediated random mutagenesis and two assay procedures, a plate assay using a PHB-staining dye and a high-pressure liquid chromatographic assay based on the converting reaction from PHB to crotonic acid. The distribution pattern of the PHB accumulation level of the mutant population using 378 clones arbitrarily selected, suggested that the present level of PhbC(Re) is high and well-optimized. It is noteworthy that many of the amino acid substitutions affecting the PHB accumulation occurred in the conserved positions or regions within an 'alpha/beta hydrolase fold' which is commonly found among hydrolytic enzymes. From a good correlation with the level of PHB accumulation, an activity estimation of the PhbC(Re) would be efficiently achieved by monitoring the level of PHB accumulation using the in vivo assay system established here.

Acyltransferases↗
PubMed2001

A novel splice acceptor site mutation of protein S gene in affected individuals with type I protein S deficiency: allelic exclusion of the mutant gene.

Sequencing studies of the protein S gene (PROS1) in a Japanese patient suffering from recurrent thrombosis revealed the following. The proband and his first daughter, but not the second daughter, were having the type I protein S (PS) deficiency due to a novel point mutation from A to G at the intronic acceptor splice site in intron 13 of the PROS1. In the affected daughter, exclusion of the aberrant allele was assessed by the BstX1 dimorphism of PROS1 at Pro626 (CCG/CCA). The reduced PS activities in the proband and his first daughter were apparently due to defective production of mRNA from the mutant allele.

Alleles↗
PubMed2001

Three-dimensional MR imaging of mammographically detected suspicious microcalcifications.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value and clinical significance of three-dimensional MR imaging of the breast in patients with mammographically detected suspicious microcalcifications. METHODS: Forty patients with suspicious microcalcifications on mammography were evaluated with three-dimensional MR imaging. MR findings were grouped mainly by distribution of abnormal enhancement (linear, focal-clumped, segmental-clumped, segmental-stippled and diffuse-stippled). These findings were compared with the mammography findings according to the criteria of the Breast Imaging Reporting and Data System (BI-RADS) and histopathologic data. RESULTS: Twenty patients had proven malignancies, most frequently ductal carcinoma in situ. For all the cases, linear (100%) and segmental-clumped type (100%) enhancement on MR imaging showed a significantly higher risk for malignancy. Diffuse stippled type (7%) and no enhancement (0%) on MR imaging indicated the lowest possibility of malignancy. 3D-MR imaging showed a sensitivity of 90%, a specificity of 95% and an overall accuracy of 93% in this study. CONCLUSIONS: Three-dimensional MR imaging of the breast can more accurately diagnose ductal carcinoma in situ. Combined with mammography, this procedure is useful for reducing the number of false-positive biopsies and helpful for deciding the better management of patients with mammographically detected suspicious microcalcifications.

Adult↗
PubMed2001

Merits and demerits of operative procedure to the trachea in patients with differentiated thyroid cancer.

Local radical thyroidectomy, including cervical lymph node dissection and combined circumferential resection of the trachea, has been performed over the past 20 years in 31 patients with differentiated cancer invading the trachea. The 5- and 10-year survival rates for these patients were 77.4% and 66.7%, respectively. In 19 of the 31 (61%) cases the recurrent nerve was resected because of direct cancer invasion. Bilateral recurrent nerve palsy occurred in 12 patients, 3 of whom were managed postoperatively using a T-shaped tube for preservation of the larynx. Hoarseness remained in 21 patients. In two patients with recurrent cancer invasion of the larynx, partial laryngectomy and hemilaryngectomy were performed, and reconstruction was done using ear cartilage without postoperative dyspnea or dysphagia. Parathyroid function is an important factor in regard to the quality of life of patients. In 22 patients at least one of the parathyroids was preserved. Postoperative calcium administration was necessary in 14 patients. Our long-term observations indicate that local radical thyroidectomy with combined resection of the trachea can serve as a useful treatment for advanced differentiated cancer invading the airway.

Adult↗
PubMed2001

Hand-assisted thoracoscopic resection for anterior mediastinal masses.

We report three cases of anterior mediastinal disease (pericardial cyst, thymoma, and myasthenia gravis) in which we used a hand-assisted method in combination with thoracoscopic resection via an infrasternal approach in order to improve the maneuverability and safety of the operation. This technique combines the advantages of both thoracoscopic and incisional resection. It shows promise of becoming a less invasive operation that can be used to treat certain mediastinal tumors, both malignant and benign.

Humans↗
PubMed2001

Video-assisted thoracic lobectomy by the substernal hand-assisted method for a metastatic lung tumor.

In lobectomy by video-assisted thoracic surgery (VATS), the surgeon is required to have experience and a high degree of skill in performing the operation. We applied substernal hand-assisted thoracoscopic lobectomy to remove a metastatic lung tumor that originated from colon cancer in one patient and obtained satisfactory results. This method compensates for a current limitation of VATS lobectomy, namely, the fact that the surgeon cannot touch the lesion. The reported method is safe and useful for thoracoscopic surgery. It can be performed easily, even if the surgeon is not experienced in performing VATS lobectomy.

Colonic Neoplasms↗
PubMed2001

Diffusion-weighted MR and apparent diffusion coefficient in the evaluation of severe brain injury.

PURPOSE: To study apparent diffusion coefficient (ADC) maps in severely brain-injured patients. MATERIAL AND METHODS: Four deeply comatose patients with severe brain injury were investigated with single-shot, diffusion-weighted, spin-echo echoplanar imaging. The tetrahedral diffusion gradient configuration and four iterations of a set of b-values (one time of 0 mm2/s, and four times of 1000 mm2/s) were used to create isotropic ADC maps with high signal-to-noise ratio. ADC values of gray and white matter were compared among patients and 4 reference subjects. RESULTS: One patient was diagnosed as clinically brain dead after the MR examination. The patient's ADC values of gray and white matter were significantly lower than those of 3 other brain-injured patients. In addition the ADC value of white matter was significantly lower than that of gray matter. CONCLUSION: The patient with fatal outcome shortly after MR examination differed significantly from other patients with severe brain injury but non-fatal outcome, with regard to ADC values in gray and white matter. This might indicate a prognostic value of ADC maps in the evaluation of traumatic brain injury.

Adolescent↗