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Biomedical subjects

N Shimizu

Publications and source records attributed to N Shimizu.

At least 235 records · Page 13Linked to original sources

Prognostic value of vascular endothelial growth factor expression in primary lung carcinoma.

To investigate whether an association exists between vascular endothelial growth factor (VEGF) expression and tumor prognosis in primary lung carcinoma, we used immunohistochemical techniques to analyze microvessel density and VEGF expression in lung carcinoma tissue from 98 patients. Tissue had been fresh-frozen at the time of operation and preserved for more than 5 years. The results indicated that VEGF expression was positive for 50 of the 98 patients (51.0%), with 27 (27.6%) being weakly positive and 23 (23.5%) being strongly positive. The microvessel density in tissue showing weakly positive and strongly positive VEGF expression was significantly higher than that in VEGF-negative tumor tissue (P < 0.05: negative vs. weakly positive, P < 0.01: negative vs. strongly positive), we showed demonstrating that VEGF expression was significantly associated with intratumoral microvessel density. The 5-year survival rates were 8.7% for strongly VEGF-positive patients, 43.9% for weakly VEGF-positive patients and 79.2% for VEGF-negative patients, respectively (P < 0.01: negative vs. weakly positive or strongly positive). Furthermore, multivariate analysis employing multiple regression analysis indicated that VEGF expression correlates highly with the overall survival rates of patients with primary lung carcinoma. Two variables, N status and VEGF expression, were found to be significant prognostic factors (P < 0.01). The results of this study suggest that VEGF expression is associated with intratumoral microvessel density. VEGF expression may constitute important independent prognostic evidence that can help us in predicting the outcomes of patients with primary lung carcinomas.

Adult↗

Different expression of positive and negative regulators of hepatocyte growth in growing and shrinking hepatic lobes after portal vein branch ligation in rats.

Portal vein branch embolization is often performed before hepatectomy to prevent postoperative liver failure. It is, however, still not clear how the embolized lobe shrinks and the non-embolized lobe proliferates in counterbalance. We investigated the expression of positive and negative regulators of hepatocyte growth to clarify the mechanisms of liver growth and atrophy in a rat portal vein ligation (PVL) model compared with partial hepatectomy (PH). A significant increase in DNA synthesis within the non-ligated lobe reached a peak at 36 h, a delay of 12 h as compared with PH, while no increase occurred in the ligated lobe. Expression of hepatocyte growth factor mRNA remarkably increased in the non-ligated growing lobe between 6 and 24 h, but was only slightly elevated in the ligated shrinking lobe. Contrarily, negative regulators of hepatocyte proliferation, such as TGF-beta1 and IL-1beta, were strongly expressed in the ligated shrinking lobe. Thus, the changes of portal venous flow and/or pressure caused by PVL may contribute to induction of different kinds of growth factors between the ischemic and non-ischemic lobes; these factors possibly regulate liver regeneration and atrophy after PVL.

Animals↗

[Second reconstructions after failure of free-tissue transfer in the head and neck region].

A retrospective study was performed on 74 patients seen in our hospital between 1990 and 1999 who underwent head and neck reconstructive surgery involving a free flap. Reconstructive surgery was unsuccessful in 5 cases (6.8%). A pedicled myocutaneus flap was used in two cases for the second reconstruction attempt, while a second free flap (jejunum) was used in two other patients. In these cases, a bilateral neck dissection was performed prior to the second free flap reconstruction and neck infection was found. The head and neck artery and vein were unsuitable as recipient vessels in the second operation. Instead, the cephalic vein was used as a source of vein grafts and as a recipient vein.

Adult↗

The myocilin (MYOC) gene expression in the human trabecular meshwork.

PURPOSE: We previously reported a novel cytoskeletal protein with a myosin-like domain which is localized in the ciliary rootlet and basal body of connecting cilium of photoreceptor and hence we named it 'myocilin'. It was soon realized that myocilin is identical to a protein called TIGR (trabecular meshwork inducible glucocorticoid response protein) which was found to be responsible for the pathogenesis of juvenile open angle glaucoma. In this study, we employed in situ RNA hybridization to examine the myocilin (MYOC)/ TIGR gene expression in the trabecular meshworks of glaucomatous and nonglaucomatous eyes. METHODS: The glaucomatous specimens were obtained by trabeculectomy from the patients with primary open angle glaucoma (POAG), chronic angle closure glaucoma (CACG) and steroid glaucoma, respectively, and the nonglaucomatous specimens were obtained from a victim of traffic accident at autopsy and from a patient with maxillary sinus carcinoma at enucleation for the operation. The in situ RNA hybridization was carried out with digoxigenin-labeled sense and antisense RNA probes. RESULTS: In all cases, hybridization signals were detected primarily in the trabecular meshwork cells and secondarily in the fibroblast-like cells of corneoscleral wall. CONCLUSIONS: Myocilin gene is expressed clearly in the trabecular meshwork cells of both glaucomatous and nonglaucomatous eyes.

Aged↗

[Proper usage of thiazolidinediones].

For the proper usage of thiazolidinedione, 5 preparations including troglitazone, pioglitazone and rosiglitazone in Japan and USA, the package insert of preparation were carefully reviewed from the point of view on indication of pathophysiology of Type 2 Diabetes Mellitus, mono or combined therapy and safety including hepatotoxicity, fluid accumulation. Careful reading of the package insert and patient leaflet, if any, is essential for the proper and safe usage of this important and prospective medicine. True usefulness waits for many long-term multi-center mega-size clinical trials.

Chromans↗

[A case of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II)].

We reported a male infant with multiple acyl CoA dehydrogenase deficiency, probably due to electron transfer flavoprotein dehydrogenase deficiency. He was noted to have severe muscle weakness, a high serum creatine kinase (CK) level up to 6920 IU/L, lipid storage myopathy and fatty liver at 6 months of age. A GC/MS analysis of urinary organic acids showed excess excretion of dicarboxylic acids, including glutaric, 2-hydroxyglutaric, adipic, suberic, sebacic, malonic, ethylmalonic and methylsuccinic acids. On a urinary acylglycine analysis, hexanoylglycine and suberylglycine were increased, but not isovalerylglycine, in amount. No ketosis was noted. The muscle pathology showed increased oil-red O positive lipid droplets of various sizes indicative of lipid storage myopathy. There was diffuse decrease in the activity of cytochrome c oxidase. No ragged-red fibers were noted. His clinical symptoms improved remarkably after the administration of riboflavin (100 mg/day) and L-carnitine (1000 mg/day). He was then diagnosed as having probable riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. The glutaryl CoA dehydrogenase activity in lymphocytes was normal, as were the alpha- and beta-subunits of electron transfer flavoprotein. These findings led us to suspect electron transfer flavoprotein dehydrogenation deficiency. Although he had several episodes of short-term deterioration in clinical and laboratory findings, he developed normally with normal intelligent till 10 years of age.

Acyl-CoA Dehydrogenases↗

[Two cases of thymic carcinoma effectively treated by preoperative chemotherapy].

A 67-year-old man was admitted with left pleural effusion on chest X-ray film. Chest CT scans showed an anterior mediastinal tumor, left pleural dissemination and pleural effusion. Percutaneous needle biopsy yielded a diagnosis of epitherial carcinoma. The patient underwent 3 courses of systemic chemotherapy (CDDP + ADM + VCR + CPA). At achievement of partial response, the tumor was completely resected. Examination of the resected tumor revealed partial response to chemotherapy. A 49-year-old woman was admitted our hospital with supraclavicular lymph nodes swelling. Chest CT scans showed an large mediastinal tumor. Percutaneous needle biopsy yielded a diagnosis of squamous cell carcinoma of thymus. The patient underwent 3 courses of systemic chemotherapy. At achievement of partial response, the tumor was completely resected. Examination of the resected tumor revealed partial response to chemotherapy. These cases indicate the usefulness of preoperative chemotherapy for advanced thymic carcinoma to reduce tumor size and to control local invasion, distant metastasis before operation.

Aged↗

[Computer databases on cancer-related genes].

A database of mutations in various cancer-related genes has been constructed and named as KMcancerDB (Keio Mutation DataBase for cancer-related genes). This KMcancerDB utilizes a database software called MutationView which we designed to compile various mutation data and to provide graphical presentation of data analysis through the network using ordinary internet browser softwares such as Netscape. Currently, the KMcancerDB accommodates 1261 mutation data of different genes for cancers in 9 different organs/tissues (breast, stomach, uterus, liver, prostate, colon, ovary, thymus and retinoblastoma). KMcancerDB is accessible through http:¿mutview.dmb.med.keio.ac.jp. OMIM is an important document database for human Mendelian traits and hereditary diseases. The information from OMIM is also used in MutationView/KMcancerDB. Some display windows of OMIM and KMcancerDB are presented.

Computer Communication Networks↗

Streptozotocin-induced diabetic hyperglycaemia produces more EEG activity than normoglycaemia and hypoglycaemia during and after anoxia loading in rats.

The brain requires oxygen and glucose for energy metabolism. Electroencephalogram (EEG) was recorded to determine the effect of glucose concentration on the cerebral function in hypoxic episode. Rats were divided into 3 groups: a streptozotocin-induced diabetic hyperglycaemic group, a normoglycaemic group, and an insulin-induced hypoglycaemic group. Hypoxia was induced by ventilating with 100% N2 for 3 min. EEG amplitude both 5 and 10 min after anoxia loading was higher in the diabetic hyperglycaemic than in the normoglycaemic group, though not significantly. Time for decreasing the EEG amplitude during anoxia loading was significantly longer in the hyperglycaemic than in the normoglycaemic group. Time for recovering the EEG amplitude after anoxia loading was significantly shorter in the hyperglycaemic group and was longer, though not significantly, in the hypoglycaemic group than in the normoglycaemic one. These results suggest the brain is more tolerant to hypoxia during diabetic hyperglycaemia than during normoglycaemia.

Animals↗

[A new sedation technique with propofol during spinal anesthesia].

We compared our new sedation technique with propofol during spinal anesthesia (Group B, n = 50) with a previously described method by Mackenzie et al. (Group A, n = 20). In Group A, propofol was started at a rate of 6 mg.kg-1.h-1 for 10 minutes, followed by continuous infusion at a rate of 4 mg.kg-1.h-1 till the end of surgery. In Group B, propofol 0.4 mg.kg-1 was administered by a bolus injection at the beginning. One-hundred and fifty minutes after the first injection, propofol 0.2 mg.kg-1 was added. The third dose of 0.1 mg.kg-1 of propofol was given 150 seconds after the second dose, followed by continuous infusion at a rate of 4 mg.kg-1.h-1 till the end of surgery. When adequate sedation was not obtained in Group B, propofol 0.1 mg.kg-1 was added by bolus fashion occasionally. In Group A, it took 9 min. 29 sec. to complete adequate sedation assessed by Mackenzie and Grant's sedation score. On the other hand, in Group B, it was 7 min. 27 sec. (P < 0.05 compared with Group A). There was neither excitation nor movement during sedation in Group B, while 5 patients experienced such events in Group A. The blood concentrations of propofol in Group B was 0.946 +/- 0.076 microgram.ml-1 and 0.693 +/- 0.136 microgram.ml-1 at 5 minutes and 10 minutes after the beginning of propofol, respectively. These values were significantly lower than those reported by Kugimiya. Our newly developed method for sedation with propofol during spinal anesthesia would be safer and more effective than that previously described by Mackenzie et al.

Adolescent↗

[Labial adhesion in a reproductive woman with difficulties of sexual intercourse and urination: a case report].

A 27-year-old female patient consulted us with chief complaints of difficulties of sexual intercourse and urination. On examination, the labia was found to be extensively fused at the midline, with a pinhole opening. We diagnosed it as labial adhesion. We operated on it under lumbar anesthesia. Four months after the operation, there were no symptoms of recurrence. Labial adhesion is thought to be caused by inflammation, lack of sexual activity and estrogen deficiency. It is not uncommon in children and post-menopausal women, but is extremely rare in reproductive women.

Adult↗

[Three cases of pulmonary mucoepidermoid carcinoma].

Three cases of pulmonary mucoepidermoid carcinoma, which were surgically treated in our hospital, were reported. The first case was 28-year-old male, who had hemoptysis, underwent right upper lobectomy and mediastinal lymph node dissection on October 31, 1973. The tumor located and obstructed the ostium of right B2. The diameter was 2.3 x 1.8 cm. The second case was 63-year-old male, who had obstructive pneumonia, underwent left upper lobectomy and mediastinal lymph node dissection on November 18, 1998. The tumor located and obstructed the ostium of lingular bronchus, and the diameter was 1.8 x 1.2 cm. The third case was 25-year-old male, who had obstructive pneumonia, underwent left sleeve lower lobectomy and mediastinal lymph node dissection on May 26, 1999. The tumor located in ostium of left B6, and it obstructed lower bronchus and expanded into the lung. The diameter was 4 x 2 cm. All cases were diagnosed as low grade malignancy with no lymph node metastasis. The first case survived without recurrence at least 5 years as far as we followed, and the others are surviving until now without any signs of recurrence. These three cases were 0.19% of total resected lung cancers in our hospital from 1969 to 1999.

Adult↗

Telomerase activity and Bcl-2 expression in non-small cell lung cancer.

Bcl-2 and p53 are the most relevant proteins in apoptosis and tumor development. Telomerase functions in the maintenance of telomeres and is indispensable for immortalization. Bcl-2 was reported as a direct modulator of telomerase activity, and a correlation between p53 and telomerase activity was reported. The aim of this study was to determine the relationships between Bcl-2, p53, and telomerase activity in non-small cell lung cancer. Immunostaining for Bcl-2, p53, and Ki-67 was performed in 64 surgically resected non-small cell lung cancers, and a fluorescence-based telomeric repeat amplification protocol assay for semiquantitative analysis of telomerase activity was done. Twenty-eight (44%) and 33 (52%) cases showed positive staining for Bcl-2 and p53, respectively. Bcl-2 expression was associated with negative lymph node involvement (P = 0.0248). p53 expression was associated with tumor size (P = 0.0244), p stage (P = 0.0391), and proliferative activity (P = 0.0004). Telomerase activity was detected in 89.1% and was closely associated with aggressive clinicopathological features. Telomerase activity was higher in p53-positive tumors (P < 0.0001), but represented no correlation with Bcl-2 expression (P = 0.3239). Interestingly, when the cases were stratified by histological grade and the level of Ki-67 labeling index, Bcl-2 expression was more clearly associated with favorable clinicopathological features and lower telomerase activity only in low-grade tumors. In conclusion, p53 is closely associated with telomerase activity. In low-grade tumors, Bcl-2 is inversely correlated to telomerase activity. Our results suggest that the biological role of the Bcl-2 protein alters according to tumor aggressiveness, thereby cofunctioning with telomerase against genetic instability.

Adenocarcinoma↗

[Eradication model employing Mongolian gerbils treated with chemical carcinogen and infected with Helicobacter pylori--implications for human cancer prevention].

To explore the 'causal link' between Helicobacter pylori(Hp) infection and stomach carcinogenesis, we have established experimental models of stomach carcinogenesis in Mongolian Gerbils(MGs) using the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and N-methyl-N-nitrosourea(MNU). The incidence of adenocarcinoma was significantly higher in animals treated with Hp than in the controls. Eradication of Hp was effective in reducing the incidence of adenocarcinoma. No gastric carcinoma was found without any chemical carcinogen. Hp infection enhances glandular stomach carcinogenesis not only of well-differentiated type but also poorly differentiated type and signet ring cell type. Eradication of Hp, apparently a gastric promoter rather than gastric carcinogen, may be useful as a measure for prevention of stomach cancer.

Adenocarcinoma↗

[Morphology and immunophenotyping in hematological malignancies].

We evaluated 443 outpatients and inpatients in Keio University Hospital between 1994 and 1999. Morphologic features from peripheral blood and bone marrow aspiration were evaluated in our hematology laboratory, using Wright-Giemsa, peroxidase staining films and other cytochemistry. Immunophenotype was determined by cell surface antigen analysis by laser flow cytometry, FACscan, using various monoclonal antibodies. Information on cytogenetic and molecular genetic characteristics can be also integrated for diagnosis. One hundred fifty patients were diagnosed with acute leukemia, in which 59 cases were ALL and 91 cases were AML. Seventy-four cases were MDS, 76 cases were myeloproliferative disorders, 21 cases were CLL related disorders, 104 patients were malignant lymphoma, and 18 cases were multiple myeloma. The ratio of male to female was 1.7. The probability of diagnostic rate by Immunophenotyping was estimated by Discriminant analysis in 189 patients, using multivariate analysis of immunophenotype compared to morphology. The average probability by immunophenotypic analysis for diagnostic rate was 91.7%, in which the probability for NHL was very high of 97.1%. Thus, morphologic and immunophenotypic analysis is most essential and basic approach in laboratory hematology, from the perspective of rapid and precise diagnostic methods. Recent advance appreciates the rapid contribution for diagnosis by immunophenotypic analysis. Furthermore, Tele-hematology would contribute the standardization for morphologic method in the near future.

Bone Marrow Cells↗

[Preliminary report: use of clinical criteria for the determination of pediatric brain death and confirmation by radionuclide cerebral blood flow].

The medical records of all brain dead patients (n = 228) at the Hospital for Sick Children, Toronto from January 1990 to December 1999 were reviewed. A radionuclide cerebral blood flow study (RCBFS) as a supportive and confirmatory test was performed on 27 patients and the clinical diagnosis of brain death was confirmed on all of them. A RCBFS was performed on 10 out of 27 patients because full clinical evaluation could not be performed due to severe facial injuries or cervical injuries. A RCBFS was performed on 17 patients who underwent a full clinical evaluation, of which 15 cases were due to uncertainty in the clinical etiology of the deep coma and 2 cases were due purely to the need to persuade the family. In recent years, RCBFS was not used as extensively on patients who underwent a full clinical evaluation, reflecting social acceptance and a higher level of clinical certainty in diagnosing brain death in children. This study supports the opinion that brain death can be accurately diagnosed in pediatric patients with clinical criteria alone and confirmatory tests are not necessary in most cases.

Adolescent↗