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Biomedical subjects

N Tanaka

Publications and source records attributed to N Tanaka.

At least 469 records · Page 26Linked to original sources

Analysis of strain distribution in the medial collateral ligament using a photoelastic coating method.

The strain distribution over the entire medial collateral ligament (MCL) was measured using a photoelastic coating method. This new approach utilized a polyurethane monomer as a photoelastic coating film. The initial experiments investigating MCL strain measurement showed that this film had a high sensitivity for strain and good adhesion to the ligament. It was confirmed that strain distribution could be obtained qualitatively over the entire ligament using this method. The mechanism of MCL injury was studied by applying this polyurethane coating film to the entire MCL in a femur-MCL-tibia complex. When simple tension was applied to the complex, strain concentrations were centred at the tibial insertion site, and all the specimens ruptured at the MCL tibial insertion site. With application of a valgus bending moment, increased strain was seen in the MCL from the medial femoral condyle to the medial epicondyle. Histological analysis demonstrated midsubstance ligament ruptures in this same region. For both tests, rupture sites and increased strain concentration sites correlated. In addition, an impingement phenomenon of the MCL on the medial femoral condyle can be seen during application of valgus force, and this phenomenon may explain the higher incidence of MCL injuries on the femoral side seen in the clinical setting. This polyurethane coating method allows for direct and visual measurements, and can qualitatively measure the strain behaviour over the entire MCL surface. This new technique represents a significant improvement over previous point-by-point strain measurement methods.

Animals↗

Immunohistochemical investigation of new suppressor oncogene p130 in oral squamous cell carcinoma.

New onco-suppressor gene p130 is one of the Rb family forms and is reported to undergo allelic loss in hepatocellular, prostate, and breast carcinomas; however, no report of p130 has been made in oral tumors. The present study dealt with the expression of p130 and Rb proteins by immunohistochemical staining in oral squamous cell carcinomas (n = 110) and oral mucosa. The site of the carcinomas included tongue (n = 48), gingiva (n = 32), oral floor of the mouth (n = 15), oropharynx (n = 6), buccal mucosa (n = 5), and others (n = 4). Histologically there were 65 well-differentiated carcinomas, 33 moderately differentiated carcinomas, and 12 poorly differentiated ones. Positive staining for p130 and Rb was localized to suprabasal cell layers of the normal oral epithelium. In the oral squamous cell carcinoma, positive staining for p130 and Rb was observed in well-differentiated carcinomas (p130, 66.2%; Rb, 78.5%), more than in poorly differentiated ones (p130, 16.7%; Rb, 50.0%). In immunoelectron microscopic features, p130 protein was localized in the nucleus and mitochondria. The expression of p130 was related to the degree of tumor differentiation as that of Rb. It is suggested that p130 gene may be associated with the development of a wide variety of human malignancies rather than the progression.

Adult↗

Postoperative chemo-endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor-positive stage II breast cancer. Nishinihon Cooperative Study Group of Adjuvant Therapy for Breast Cancer.

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991. we studied the effects of postoperative adjuvant therapy for Japanese women with stage 11 breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER- tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER- patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease-free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments <0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P<0.01). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.

Adult↗

Overexpression of the p21 sdi1 gene induces senescence-like state in human cancer cells: implication for senescence-directed molecular therapy for cancer.

Normal cells in a culture enter a nondividing state after a finite number of population doubling, which is termed replicative senescence, whereas cancer cells have unlimited proliferative potential and are thought to exhibit an immmortal phenotype by escaping from senescence. The p21 gene (also known as sdi1), which encodes the cyclin-dependent kinase inhibitor, is expressed at high levels in senescent cells and contributes to the growth arrest. To examine if the p21sdi1 gene transfer could induce senescence in human cancer cells, we utilized an adenoviral vector-based expression system and four human cancer cell lines differing in their p53 status. Transient overexpression of p21sdi1 on cancer cells induced quiescence by arresting the cell cycle at the G1 phase and exhibited morphological changes, such as enlarged nuclei as well as a flattened cellular shape, specific to the senescence phenotype. We also showed that p21sdi1-transduced cancer cells expressed beta-galactosidase activity at pH 6.0, which is known to be a marker of senescence. Moreover, the polymerase chain reaction-based assay demonstrated that levels of telomerase activity were significantly lower in p21sdi1-expressing cells compared to parental cancer cells. These observations provide the evidence that p21sdi1 overexpression could induce a senescence-like state and reduce telomerase activity in human cancer cells, suggesting that these novel p21sdi1 functions may have important implications for anticancer therapy.

Adenoviridae↗

Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxycillin and clarithromycin increases the cure rate of Helicobacter pylori infection.

AIM: To evaluate the efficacy of polaprezinc, a mucosal protective agent, in combination with a 7-day triple therapy containing lansoprazole, amoxycillin and clarithromycin, as a treatment for Helicobacter pylori. METHODS: Sixty-six consecutive patients suffering from dyspeptic symptoms with H. pylori infection were randomly allocated to one of two regimens: one group (LAC; n = 31) received lansoprazole 30 mg b.d., amoxycillin 500 mg b.d. and clarithromycin 400 mg b.d. for 7 days. The other group (LACP; n = 35) received the LAC regimen plus polaprezinc 150 mg b.d. for 7 days. H. pylori status was evaluated by rapid urease test, histology and culture at entry and 4 weeks after treatment. RESULTS: Five patients did not complete the treatment: no follow-up endoscopy was performed on two patients in the LAC group; one patient in the LAC group and two in the LACP group had their treatment stopped due to severe diarrhoea. By per protocol analysis, H. pylori eradication was achieved in 24 of the 28 evaluable patients (86%; 95% CI: 72-100%) after LAC therapy, and in 33 of the 33 evaluable patients (100%) after LACP therapy (P < 0.05). On intention-to-treat analysis, the rates of eradication were 24 of 31 patients (77%; 95% CI: 62-93%) in the LAC group, and 33 of 35 patients (94%; 95% CI: 86-100%) in the LACP group (P < 0.05). CONCLUSION: A 7-day triple therapy with lansoprazole, amoxycillin and clarithromycin is effective in H. pylori eradication, but this regimen is significantly improved by the addition of polaprezinc.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Hyperpigmentation caused by hyperthyroidism: differences from the pigmentation of Addison's disease.

Two cases of hyperthyroidism with hyperpigmentation are presented. In both cases, hyperpigmentation was seen on the lower extremities, most strikingly on the shins, backs of the feet and the nail bed. Histology of the pigmented skin showed basal melanosis and heavy deposition of haemosiderin around dermal capillaries and sweat glands. Treatment with mercazol in both cases resulted in no significant waning of pigmentation. Distribution of hyperpigmentation, haemosiderin deposition and poor response to the treatment may be characteristic features of the pigmentation caused by hyperthyroidism, and may represent differences from the pigmentation seen in Addison's disease.

Addison Disease↗

Functional expression of Fas and Fas ligand on human intestinal intraepithelial lymphocytes.

Intestinal intraepithelial lymphocytes (IEL) constitute the first lymphoid compartment to encounter dietary antigens and intestinal pathogens. IEL are proposed to be involved in the defence against bacterial and viral invasion and to play an important role in mucosal immunity. Fas (CD95/APO-1) is a surface receptor that induces apoptotic cell death upon ligation with Fas ligand (FasL). The aim of this study was to examine the expression and function of Fas and FasL on freshly isolated normal human colonic IEL. The expression and function of Fas and FasL on IEL isolated from 40 normal colonic specimens were examined by flow cytometry, reverse transcriptase-polymerase chain reaction, immunohistochemistry, and DNA-release cytotoxicity assay. Virtually all CD3+ IEL (95.2 +/- 4.3%) expressed Fas and were sensitive to agonistic anti-Fas antibody, whereas only 56.6 +/- 8.4% of peripheral T lymphocytes expressed Fas and were resistant to the antibody. We also detected FasL mRNA and protein (40.1 +/- 4.2%) on IEL, and found that IEL exerted FasL-mediated cytotoxicity against Fas-expressing target cells. These findings suggest that human IEL are activated in situ but are tightly regulated by the constitutive expression of functional Fas and FasL to maintain homeostasis of the mucosal immune system.

Adult↗

Laryngeal mask airway insertion using propofol without muscle relaxants: a comparative study of pretreatment with midazolam or fentanyl.

We determined the effects of pretreatment with midazolam or fentanyl on the ease of laryngeal mask airway insertion using propofol without a muscle relaxant. One hundred and eighty ASA class I or II patients were randomly allocated to one of three groups, 60 patients per group, to receive either placebo (Group C), midazolam 0.05 mg kg-1 (Group M) or fentanyl 2 micrograms kg-1 (Group F), respectively. Following intravenous administration of these drugs, Group C received propofol 2.5 (Group C-2.5) or 3.0 mg kg-1 (Group C-3.0). Group M and Group F received propofol 2.0 or 2.5 mg kg-1 (Group M-2.0, M-2.5, F-2.0 and F-2.5, respectively). There was a smaller incidence of severe head and limb movements on LMA insertion in Group M-2.5, Group F-2.0 and Group F-2.5 than in Group C-2.5. Airway obstruction and inadequate jaw relaxation, which were occasionally recognized in Group C and Group F patients, were not observed in Group M-2.5. Overall the ease of LMA insertion was significantly better in Group M-2.0, Group M-2.5 and Group F-2.5 than in Group C-2.5, however, the blood pressure in Group F after LMA insertion was significantly lower than in Group M. We conclude that pretreatment with midazolam 0.05 mg combined with propofol 2.5 mg kg-1 provides safe and satisfactory conditions for LMA insertion.

Adult↗

Further improvement of the thermal stability of a partially stabilized Bacillus subtilis 3-isopropylmalate dehydrogenase variant by random and site-directed mutagenesis.

A thermostabilized mutant of Bacillus subtilis 3-isopropylmalate dehydrogenase (IPMDH) obtained in a previous study contained a set of triple amino acid substitutions. To further improve the stability of the mutant, we used a random mutagenesis technique and identified two additional thermostabilizing substitutions, Thr22-->Lys and Met256-->Val, that separately endowed the protein with further stability. We introduced the two mutations into a single enzyme molecule, thus constructing a mutant with overall quintuple mutations. Other studies have suggested that an improved hydrophobic subunit interaction and a rigid type II beta-turn play important roles in enhancing the protein stability. Based on those observations, we successively introduced amino acid substitutions into the mutant with the quintuple mutations by site-directed mutagenesis: Glu253 at the subunit interface was replaced by Leu to increase the hydrophobic interaction between the subunits; Glu112, Ser113 and Ser115 that were involved in the formation of the turn were replaced by Pro, Gly and Glu, respectively, to make the turn more rigid. The thermal stability of the mutants was determined based on remaining activity after heat treatment and first-order rate constant of thermal unfolding, which showed gradual increases in thermal stability as more mutations were included.

3-Isopropylmalate Dehydrogenase↗

Binding characteristics of an anti-Siaalpha2-6GalNAcalpha-Ser/Thr (sialyl Tn) monoclonal antibody (MLS 132).

To determine the epitopic structure for an anti-Siaalpha2-6GalNAcalpha-Ser/Thr (anti-sialyl Tn) monoclonal antibody, MLS 132, ovine submaxillary mucin (OSM) was digested with the combination of trypsin and thermolysin and the digest fractionated by immunoaffinity column chromatography and HPLC. From tryptic digest, a major glycopeptide designated as T3 was obtained as an immunoaffinity column-bound fraction. On solid-phase radioimmunoassay, it was found that T3 exhibited strong immunoreactivity with MLS 132. On treatment with thermolysin, T3 was converted into about 50 fragments, as found on fractionation by HPLC. Several of them were strongly immunoreactive and had the same amino acid sequence, i.e. Phe-Ser*-Gly-Glu-Thr*-Ser*-Thr*-Thr*-Val-Ile-Ser*-Gly-Thr*-Asn-Val, where asterisks denote the sites of attachment of carbohydrate. Of these, one was fully sialylated, the others having one Ser or Thr with unsialylated GalNAc attached. Results of analyses of the carbohydrate attached in these glycopeptides led us to postulate that a cluster composed of four sialyl Tn antigens is the essential epitopic structure for MLS 132.

Amino Acid Sequence↗

Plasma levels of mevalonate and 7alpha-hydroxy-4-cholesten-3-one in chronic liver disease.

BACKGROUND AND AIMS: Cholesterol levels in blood tend to be preserved despite hepatic impairment, in contrast to albumin levels and other markers of liver function in patients with liver cirrhosis (LC). We reported previously that the levels of plasma mevalonate (MVA) and 7alpha-hydroxy-4-cholesten-3-one (7alpha3one) closely reflect hepatic synthetic rates of cholesterol and bile acids. The aim of this study was to examine the association between hepatic cholesterogenesis and bile acid synthesis in hepatocellular impairment using these indices. METHODS: The plasma indices were measured in patients with LC (n = 38) or chronic hepatitis (CH; n = 11) and in normal controls (n = 22). The severity of LC was assessed by the Child-Pugh score. RESULTS: There were no significant differences in plasma MVA levels between CH, LC and control groups. However, plasma 7alpha3one levels were significantly lower in LC than in CH and control groups (P< 0.01). While MVA levels did not correlate with the Child-Pugh score, there was a significant correlation between 7alpha3one level and Child-Pugh score (P< 0.005). The plasma 7alpha3one level in controls correlated positively with MVA levels (P< 0.01); however, there was no significant correlation between these indices in CH and LC. CONCLUSION: In chronic liver disease, there was a tendency for hepatic cholesterogenesis to be sustained in the face of hepatocellular impairment, while bile acid synthesis declined in parallel with the severity of impairment.

Bile Acids and Salts↗

Diagnostic usefulness of endorectal magnetic resonance imaging with dynamic contrast-enhancement in patients with localized prostate cancer: mapping studies with biopsy specimens.

BACKGROUND: New diagnostic criteria for dynamic magnetic resonance (MR) imaging in prostate cancer are presented. The diagnostic usefulness of endorectal MR imaging with dynamic contrast-enhancement in localized prostate cancer and the validity of these criteria were evaluated. METHODS: Eighteen untreated patients who were suspected of localized prostate cancer were included in the study. They received endorectal dynamic MR imaging before systematic sextant needle biopsy. First. a mapping study with the findings of MR images and histopathology of biopsy specimens was performed in eight patients out of 18 to compare the difference in T2-weighted images with the endorectal coil and the body coil in the same individuals. Second, another mapping study was performed in all 18 patients by analyzing the findings of endorectal dynamic MR images. For the diagnosis of prostate cancer in MR imaging, we offered diagnostic criteria from our experience in addition to those in plain T2-weighted images from the literature. RESULTS: The overall diagnostic rates of endorectal dynamic MR imaging were 88.9% in accuracy, 100% in sensitivity, and 81.8% in specificity. In the comparison of the endorectal and body coils in T2-weighted images in eight patients, there was no difference in the diagnostic rates except for one more histopathologic false positive portion in endorectal MR imaging. In the second mapping study in 18 patients, the diagnostic rates were 92.6% in accuracy, 88.9% in sensitivity and 93.3% in specificity. Endorectal dynamic imaging raised the diagnostic sensitivity from 77.8 to 88.9%. CONCLUSION: The data demonstrated the validity of this diagnostic criteria and the diagnostic usefulness of endorectal dynamic MR imaging in localized prostate cancer.

Aged↗

Pretreatment antimicrobial susceptibilities of paired gastric Helicobacter pylori isolates: antrum versus corpus.

BACKGROUND: Antimicrobial susceptibility testing of Helicobacter pylori isolates is the most useful tool for guiding specific therapy, especially when primary resistance is suspected. However, the most informative gastric biopsy site for detection of resistant H. pylori isolates is uncertain. We sought to determine whether susceptibilities to commonly used antimicrobials (amoxicillin, clarithromycin, minocycline, and metronidazole) were related to biopsy site. METHODS: H. pylori isolates were obtained from patients who had duodenal ulcer and had not received any therapy directed against H. pylori. Agar-dilution minimum inhibitory concentrations of each antimicrobial were compared between paired H. pylori isolates from the antrum and the proximal corpus. RESULTS: Differences in minimum inhibitory concentrations exceeding twofold were observed within the pairs of H. pylori isolates in 5 of the 40 patients tested. In three patients with clarithromycin-resistant isolates and two with metronidazole-resistant isolates, both antral and corporeal specimens revealed resistance. However, no patient had pairs of isolates categorized as resistant at one site and sensitive at the other. CONCLUSIONS: While we found that an individual may have a mixed H. pylori infection with respect to differing antimicrobial susceptibility in different parts of the stomach, a single biopsy specimen from either the antrum or the corpus should provide reliable detection of H. pylori isolates with primary resistance.

Adolescent↗

Lymphovascular and neural invasion in low-lying rectal carcinoma.

We have previously demonstrated that lymphovascular infiltration was correlated with an increased risk for developing lymph node metastasis in rectal adenocarcinomas confined within the submucosal layer. In another study, lymphovascular infiltration was also correlated with poor prognosis for patients with advanced rectal cancers. Considerations that low rectal tumors have an increased risk to develop recurrence and neural invasion have been recently implicated with a more localized pattern of tumor spread. We therefore assessed the lymphovascular and neural invasion in 65 specimens from patients with low rectal cancers who underwent curative operation to determine its implications in the treatment and prognosis. Lymphovascular invasion was noted in 60%, and neural invasion was found in 27% of the cases. Five-year survival rates (Kaplan-Meier method) were significantly decreased in patients with lymphovascular invasion (31 vs. 67%; p < 0.01) or neural invasion (30 vs. 58%; p < 0.01). Neither lymphovascular nor neural invasion was noted in Dukes' stage A tumors. There was no recurrence or distant metastasis in these patients. However, lymphovascular and neural invasion increased with tumor stage. Local recurrence and distant metastasis occurred respectively in three and four, and five and five patients with Dukes' B and C tumors, respectively. Both Dukes' B and C cases with local recurrence had a higher incidence of neural invasion as compared with the disease-free group. These results suggest that postoperative assessment of venous and neural invasion may provide valuable information to better determine which patients with low rectal cancers would benefit from adjuvant treatment.

Adenocarcinoma↗

The effect of electrolyzed strong acid aqueous solution on hemodialysis equipment.

We reported the high effectiveness of electrolyzed strong acid aqueous solution (ESAAS) in cleaning hemodialysis lines. Although ESAAS has a strong bactericidal action, one concern is its strong acidity. It has a pH of 2.3-2.7, more than 1,000 mV in oxidation-reduction potential (ORP), and 10-50 ppm of available chlorine. The possibility of metal corrosion, degradation of synthetic resins, chorine gas emission, or dissolving calcium carbonate (CaCO3) deposits due to ESAAS's acidity was tested using in vitro experiments. The bactericidal and antiviral effects of various ESAAS's were also tested. Metal corrosion and synthetic resin degradation, although they occurred, were not serious. There were no problems with chlorine gas emission and dissolving of CaCO3 deposits. Each type of ESAAS showed almost the same bactericidal and antiviral effect, but in some cases differences were observed.

Acetic Acid↗

The cleaning and disinfecting of hemodialysis equipment using electrolyzed strong acid aqueous solution.

In general, sodium hypochlorite, formalin, and Dialox (Teijin Gambro Medical, Ltd., Tokyo, Japan [main ingredients: H2O2, CH3CHOOOH, CH3COOH, H2O]) are used to clean and disinfect hemodialysis pipelines. In this study, the suitability of electrolyzed strong acid aqueous solution (ESAAS), which has attracted considerable interest in Japan because of its strong disinfecting properties, was examined. The crossover method was used to investigate the effectiveness of ESAAS in disinfecting the dialysis pipelines in comparison to that of sodium hypochlorite (200 ppm) used alternately with 1% acetic acid. The number of bacteria and the concentration of endotoxin (Et) were measured over an approximately 3 year period, starting in September 1994. Until then, 200 ppm sodium hypochlorite had been used alternately with 1% acetic acid, and the contamination of the pipeline had been marked. However, after switching to the ESAAS disinfection method, the dialysis pipelines very rapidly became cleaner. Therefore, the decision to develop an automated ESAAS cleaning system for long-term use was made. During the development period, the original disinfectants (200 ppm sodium hypochlorite used alternately with 1% acetic acid) were used as a stopgap. After confirmation of its performance and safety, the automated ESAAS cleaning system was introduced. To find out whether the decrease in bacteria secondarily caused a decrease in the Et concentration or whether the ESAAS directly inactivated the Et, an in vitro experiment was carried out. Highly concentrated Et, which had been left in the reverse osmosis (RO) drainage pipeline, was used as a sample to investigate the effects of ESAAS on Et at various concentrations and temperatures and on the recovery test. The results showed that ESAAS directly inactivated Et. This paper reports the results of the crossover test. The results of parallel tests carried out over an approximately 4 year period have already been reported. No significant problems occurred in the dialysis. The automated ESAAS cleaning system that was developed proved to be more economical than the conventional disinfecting method.

Acetic Acid↗

Ondine's curse and Hirschsprung's disease: neurocristopathic syndrome.

We report a female newborn with Ondine's curse and Hirschsprung's disease--neurocristopathic syndrome. The female infant required endotracheal intubation and mechanical ventilation due to apnea which developed soon after birth. She had abdominal distension with bilious vomiting. A barium enema revealed a caliber change at the rectum and rectal biopsies showed no ganglion cells. Colostomy was performed at the age of 17 days. Hypoxemia with hypercapnia was noted during her sleep, and tracheostomy was performed at the age of 55 days. In addition, deafness and pupillary autonomic dysfunction were observed. The definitive surgery for Hirschsprung's disease was performed at the age of 4 months. She is now 2 years old with normal growth but needs ventilator support at home. In this case, we detected no mutation in the RET gene and EDNRB gene.

DNA Mutational Analysis↗