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Biomedical subjects

K Ishikawa

Publications and source records attributed to K Ishikawa.

At least 19 recordsLinked to original sources

Laparoscopic sentinel node navigation achieved by infrared ray electronic endoscopy system in patients with gastric cancer.

BACKGROUND: The sentinel node (SN) concept has attracted considerable attention recently for the treatment of patients with early gastric cancer (EGC). This study evaluated the feasibility of laparoscopic SN navigation achieved by means of an infrared ray electronic endoscopy (IREE) system with indocyanine green (ICG) injection in patients with EGC. METHODS: Laparoscopic SN navigation was performed for 16 patients with preoperatively diagnosed EGC. After identification of SNs, routine laparoscopically assisted distal gastrectomy with lymphadenectomy was performed. Lymph nodes were examined histologically for metastasis by hematoxylin and eosin staining on one section of each node. RESULTS: One or more SNs and lymphatic basins were detected in all 16 patients. The average number of SNs detected was 2.9. Lymph node metastasis was found in 2 of the 16 patients (13%). In one of these two patients, lymph node metastasis was found in SNs. In the other patient, metastasis was found in a non-SN rather than a SN, but in the same lymphatic basin. The accuracy of this detection method was 94%, and there was one false-negative case. No adverse events occurred after injection of ICG. CONCLUSION: Laparoscopic SN navigation by means of IREE combined with ICG injection is feasible for patients undergoing laparoscopic surgery for EGC.

Adult↗

Seasonal variations of acute massive submacular haemorrhage associated with age-related macular degeneration.

AIMS: To determine whether there is a seasonal variation in the onset of acute, massive submacular haemorrhage associated with age-related macular degeneration. METHODS: Sixty eyes of 59 patients diagnosed between April 1998 and March 2005, were studied retrospectively. For each patient, the month and season of onset of the submacular haemorrhage and the mean monthly ambient temperature in Nagoya were analysed. Any history of systemic hypertension was also recorded, and the seasonal variations were also investigated in hypertensive and non-hypertensive groups. RESULTS: The number of cases peaked in winter with a trough in summer, and this seasonal variation was significant (Roger's R = 12.03, p<0.01). The monthly incidence was inversely correlated with the temperature (Spearman's rank correlation coefficient r = 0.89, p<0.01). The seasonal variations were significant in the hypertensive group but not in the non-hypertensive group. CONCLUSION: The considerable seasonal variations suggests that the mechanism for the haemorrhage is strongly correlated with the systemic blood pressure.

Acute Disease↗

16q-linked autosomal dominant cerebellar ataxia: a clinical and genetic study.

The autosomal dominant cerebellar ataxias (ADCAs) comprise a genetically and clinically heterogenous group of neurodegenerative disorders. Very recently, a C-to-T single nucleotide substitution in the puratrophin-1 gene was found to be strongly associated with a form of ADCA linked to chromosome 16q22.1 (16q-linked ADCA; OMIM 600223). We found the C-to-T substitution in the puratrophin-1 gene in 20 patients with ataxia (16 heterozygotes and four homozygotes) and four asymptomatic carriers in 9 of 24 families with an unknown type of ADCA. We also found two cases with 16q-linked ADCA among 43 sporadic patients with late-onset cortical cerebellar atrophy (LCCA). The mean age at onset in the 22 patients was 61.8 years, and that of homozygous patients was lower than that of heterozygous ones in one family. Neurological examination revealed that the majority of our patients showed exaggerated deep tendon reflexes in addition to the cardinal symptom of cerebellar ataxia (100%), and 37.5% of them had sensorineural hearing impairment, whereas sensory axonal neuropathy was absent. The frequency of 16q-linked ADCA was about 1/10 of our series of 110 ADCA families, making it the third most frequent ADCA in Japan.

Age of Onset↗

Reduced tau expression in gastric cancer can identify candidates for successful Paclitaxel treatment.

A recent study disclosed that breast cancer cases with low 'tau' expression can predict susceptibility to Paclitaxel administration. In the current study, the clinical significance of tau expression in gastric cancer cases was established by identifying candidates with Paclitaxel administration. Tissue specimens from 20 cases of in-operable or noncuratively resected gastric cancer were examined. Subsequent to the administration of 80 mg m(-2) of Paclitaxel in six 3-h intravenous infusions, the clinical effectiveness of Paclitaxel was evaluated by the size of metastatic lesions with computed tomography. The status of the tau expression was determined by immunohistochemistry. Based on a previously reported classification scheme, six were classified as tau-negative expression (0, 1+) cases and 14 were classified as tau-positive expression (2+, 3+) cases. All six (100%) cases of tau-negative expression showed a favourable response (partial response or minor response) to Paclitaxel administration. However, 12 (86%) of the 14 cases of tau-positive expression showed progressive disease (n = 11) or no change (n = 1) after Paclitaxel administration. The serum carcinoembryonic antigen values of the six cases of tau-negative expression were markedly decreased in comparison to the 14 tau-positive cases. These data indicate that tau-negative expression can be used to select gastric cancer patients, which will favourably respond to Paclitaxel treatment.

Adenocarcinoma↗

Engineering of Escherichia coli L-serine O-acetyltransferase on the basis of crystal structure: desensitization to feedback inhibition by L-cysteine.

L-Serine O-acetyltransferase (SAT) from Escherichia coli catalyzes the first step of L-cysteine synthesis in E.coli and is strictly inhibited by the second step product, L-cysteine. To establish a fermentation process to produce L-cysteine, we embarked on a mutational study of E.coli SAT to desensitize the feedback inhibition by L-cysteine. The crystal structure and the reaction mechanism of SAT from E.coli have shown that the substrate L-serine and the inhibitor L-cysteine bind to the identical region in the SAT protein. To decrease the affinity for only L-cysteine, we first built the structure model of L-serine-binding SAT on the basis of the crystal structure with bound L-cysteine and compared these two structures. The comparison showed that the Calpha of Asp92 underwent a substantial positional change upon the replacement of L-cysteine by L-serine. We then introduced various amino acid substitutions at positions 89-96 around Asp92 by randomized, fragment-directed mutagenesis to change the position of the Asp92. As a result, we successfully obtained mutant SATs which have both extreme insensitivity to an inhibition by L-cysteine (the concentration that inhibits 50% activity; IC(50) = 1,100 micromol/l, the inhibition constant; K(i) = 950.0 micromol/l) and extremely high emzymatic activities.

Amino Acid Substitution↗

Extranodal metastasis is an indicator of poor prognosis in patients with gastric carcinoma.

BACKGROUND: The aim of this study was to determine the clinical significance and prognostic impact of extranodal metastasis (EM) in gastric carcinoma. METHODS: The study included 1023 patients who underwent gastrectomy with lymphadenectomy for primary gastric carcinoma between January 1993 and December 1996. EM was defined as the presence of tumour cells in extramural soft tissue that was discontinuous with either the primary lesion or locoregional lymph nodes. RESULTS: EM was detected in 146 (14.3 per cent) of the 1023 patients and in 1060 (3.0 per cent) of the 35 811 nodules that were retrieved as 'lymph nodes' from adipose connective tissues. The incidence of EM was significantly higher in patients with tumours that were large (diameter 10 cm or more), infiltrative, deeply invading or undifferentiated and in those with lymph node, peritoneal or liver metastases, or lymphatic or vascular involvement. After curative operation overall survival was significantly worse for patients with EM than those without (P < 0.001). Multivariate analysis identified EM as an independent prognostic factor (hazard ratio 1.82 (95 per cent confidence interval 1.23 to 2.71); P = 0.003). CONCLUSION: EM is an independent prognostic factor and should therefore be included in the tumour node metastasis (TNM) staging system.

Aged↗

Subcutaneous fat modulates insulin sensitivity in mice by regulating TNF-alpha expression in visceral fat.

The distribution of fat in obese persons is related to the risk of developing various metabolic disorders, such as glucose intolerance, dyslipidemia and hypertension, and the combination of these conditions is known as the metabolic syndrome. The aim of this study was to investigate the role of subcutaneous fat in regulating insulin resistance and its influence on TNF-alpha expression in visceral fat, by using mice that were subjected to subcutaneous lipectomy with or without subsequent fat transplantation. After partial subcutaneous lipectomy, mice showed significantly greater accumulation of visceral fat compared with sham-operated control mice. Lipectomy led to higher plasma insulin and lower plasma glucose levels after loading with glucose and insulin, respectively, compared with the levels in control mice. Insulin-induced phosphorylation of IRS-1 was decreased in the skeletal muscles of lipectomized mice. Subcutaneous transplantation of fat pads into lipectomized mice reversed the above-mentioned changes indicating insulin resistance in these animals. The fat storage area of adipocytes and TNF- alpha expression by adipocytes in visceral fat were significantly higher in the lipectomized mice than in controls, while subcutaneous transplantation of fat reduced both the fat storage area and TNF-alpha expression. The insulin resistance of lipectomized mice was also ameliorated by systemic neutralization of TNF-alpha activity using a specific antibody. These findings obtained in mice subjected to subcutaneous lipectomy with/without subsequent fat transplantation indicate that subcutaneous fat regulates systemic insulin sensitivity, possibly through altering fat storage and the expression of TNF-alpha by adipocytes in visceral fat. The balance between accumulation of subcutaneous fat and visceral fat may be important with respect to the occurrence of systemic insulin resistance in the metabolic syndrome.

Animals↗

Roles of TGF-beta1 and apoptosis in the progression of glomerulosclerosis in human IgA nephropathy.

Apoptotic glomerular cells have been detected in the severely damaged glomeruli that are a consequence of human IgA nephropathy. Transforming growth factor-(TGF) beta1 is known to induce apoptosis in cultured mesangial cells. To clarify whether TGF-beta1 contributes to the progression of IgA nephropathy by activating apoptosis in glomerular cells, we examined the expression of TGF-beta1 gene and apoptotic changes in kidney biopsy samples, and assessed those relations to the severity of nephropathy. 32 patients with IgA nephropathy, showing proteinuria (> 1 g/day) and serum creatinine less than 1.5 mg/dl were classified according to glomerular sclerosis index (GSI) into 3 groups (Group I: GSI < 0.3,Group 11: 0.3 < or = GSI < 1.0, Group: III GSI > or = 1.0). Computer-aided morphometry of glomeruli and arteries, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling of fragmented DNA (TUNEL) staining were performed. Expression of TGF-beta1 and caspase-3 mRNAs in renal biopsy samples was analyzed by real-time PCR (Taq Man method). Increased glomerular area, interstitial fibrosis, lymphocytic infiltration, and tubulointerstitial changes were observed to accompany increased severity of GSI. TUNEL index was higher in Group III. The levels of TGF-beta1 and caspase-3 mRNAs were significantly increased in Group III (183 and 190%, respectively). Furthermore, caspase-3 mRNA levels were tightly associated with TGF-beta1 mRNA expression (r = 0.677, p < 0.0001). The present study suggests that the activation of TGF-beta1 plays a role in the progression of IgA nephropathy even in the moderate degree of glomerular injury, in part via activation of apoptosis of glomerular cells.

Adult↗

A clinical, genetic, and neuropathologic study in a family with 16q-linked ADCA type III.

Presented is the new kindred with autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 (16q-ADCA type III) associated with progressive hearing loss. By haplotype analysis, the critical interval was slightly narrowed to three megabase regions between GATA01 and D16S3095. Neuropathologic study of 16q-ADCA type III demonstrated characteristic shrinkage of Purkinje cell bodies surrounded by synaptophysin-immunoreactive amorphous material containing calbindin- and ubiquitin-positive granules.

Adolescent↗

Usefulness of transanal endoscopic surgery for carcinoid tumor in the upper and middle rectum.

BACKGROUND: This study evaluated the indications and outcome for transanal endoscopic surgery (TES) used to manage rectal carcinoid tumor as compared with those of conventional transanal local resection (TAR). METHODS: The retrospective study subjects were 28 patients with rectal carcinoid tumor treated by TES (n = 17) or TAR (n = 11) between January 1995 and December 2001. Patient and tumor characteristics, operative results, and postoperative outcomes were compared between the two groups. RESULTS: The distance from the anal verge to the distal tumor margin in the TES group (range, 4-12 cm; median, 6.8 cm) was significantly greater than in the TAR group (range, 3-6 cm; median, 4.5 cm) (p = 0.001). The median tumor diameter was 5.5 mm (range, 3-11 mm) in the TES group and 5.0 mm (range, 3-8 mm) in the TAR group, showing no statistical difference. Microscopically, resected specimens in both groups were typical carcinoid tumors restricted to the submucosal layer. No recurrence was noted in either group. CONCLUSION: Whereas TES is useful for patients with small rectal carcinoid tumor of typical histology within the submucosal layer in the upper and middle rectum, TAR is effective for accessing the lower rectum.

Adult↗

Liver metastasis and ICAM-1 mRNA expression in the liver after carbon dioxide pneumoperitoneum in a murine model.

BACKGROUND: Liver metastasis of colorectal malignancies is an important prognostic factor. Several studies have demonstrated that carbon dioxide (CO2) pneumoperitoneum enhances liver metastasis in animal models. Little is known about intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha (TNF-(alpha) mRNA expression in the liver after CO2 pneumoperitoneum. METHODS: Forty-five male BALB/c mice were randomly divided into three groups after intra-splenic tumor cell (colon 26) inoculation and the following procedures were performed: CO2 pneumoperitoneum (n = 15), open laparotomy (n = 15), and anesthesia alone (n = 15). On day 7 after each procedure, the livers were excised and the number and diameter of the tumor nodules and the cancer index score were determined. Another 90 male BALB/c mice were randomly divided into three groups as described above, and they underwent each procedure (n = 30 each). After each procedure, the livers were excised on days 0, 1, 3, and ICAM-1 and TNF-alpha mRNA expression were examined by real-time RT-PCR using SYBR Green I. RESULTS: The number of tumor nodules and the cancer index score were larger in the CO2 pneumoperitoneum group than in the control group (p < 0.05). The mean diameter of the tumor nodules was not different among the three groups. The expression of ICAM-1 in the CO2 pneumoperitoneum group was higher than that in the other groups on day 1 (p < 0.05), and the TNF-alpha mRNA was higher than that in the control group on day 1 (p < 0.05). CONCLUSIONS: CO2 pneumoperitoneum enhances liver metastasis compared with anesthesia alone, and ICAM-1 expression in the liver after the pneumoperitoneum plays an important role in establishing liver metastasis in a murine model.

Animals↗

Morphological changes in hepatic vascular endothelium after carbon dioxide pneumoperitoneum in a murine model.

BACKGROUND: Liver metastasis is an important prognostic factor in advanced colorectal cancer. Several studies have demonstrated that carbon dioxide (CO2) pneumoperitonem enhances liver metastasis in an animal model. In the present study, we used scanning electron microscopy (SEM) to investigate morphological changes in hepatic vascular endothelium after CO2 pneumoperitoneum in a murine model. METHODS: Thirty-three male BALB/c mice were randomized to undergo pneumoperitoneum (CO2, air, or helium), open laparotomy, and anesthesia alone. After each procedure, the animals' livers were excised at days 0, 1, and 3 and examined by SEM. RESULTS: In the CO2 pneumoperitoneum group, we observed rough surface and derangement of the hepatic vascular endothelial cells and intercellular clefts on day 1. In the other groups, no major morphologic changes were observed at any time. CONCLUSIONS: Hepatic vascular endothelium changes after CO2 pneumoperitoneum. Such characteristic changes may play an important role in establishing liver metastasis after CO2 pneumoperitoneum.

Acidosis↗

Molecular analysis of coat protein coding region of tobacco stunt virus shows that it is a strain of Lettuce big-vein virus in the genus Varicosavirus.

To evaluate the relationship between tobacco stunt virus (TStV) and Lettuce big-vein virus (LBVV), we determined nucleotide sequences of the coat protein (CP) coding region of five TStV and three LBVV isolates and compared them with those of one Japanese and four Spanish isolates of LBVV. CP coding regions were identical in size and the nucleotide and amino acid sequence identities between TStV and LBVV were 95.6-96.5% and 97.2-98.7%, respectively. Phylogenetic analysis of nucleotide sequences indicated that TStV was very closely related to LBVV and a strain of LBVV rather than a distinct species.

Amino Acid Sequence↗

Effects of hydrothermal treatment with CaCl(2) solution on surface property and cell response of titanium implants.

In order to obtain early and good osteointegration after implantation of a titanium implant in the human body, the surface modified treatments using NaOH or H(2)O(2) etc. were reported. In this study, titanium was hydrothermally treated with CaCl(2) solutions at 200 degrees C for 24hr (CaCl(2)-HT). Scanning electron microscope (SEM) observation clearly showed apatite deposition on the surface of CaCl(2) HT treated titanium faster than other chemical treated titanium immersion in simulated body fluid. X-ray photoelectron spectroscopy (XPS) analysis demonstrated that Ti--O--Ca bonding was formed on titanium surface by hydrothermal treatment with CaCl(2) solution. And it was revealed that thickness of TiO(2), which was known to play important roles for the formation of bone-like apatite, became approximately three times thicker than as-polished titanium. The amount of initial attached MC3T3-E1 cells on as-polished and NaOH, H(2)O(2) and this CaCl(2) HT treated titanium were almost the same values. After 5 days incubation, the growth rate of MC3T3-E1 cells on CaCl(2)-HT treated titanium was significantly higher than that on other chemical treated titanium. The hydrothermal treatment with 10-20 mmol/L CaCl(2) solution at 200 degrees C was an effective method for the fabrication of titanium implant with good bioactivity and osteoconductivity.

3T3 Cells↗

Ammonium hexafluorosilicate increased acid resistance of bovine enamel and dentine.

Although diamine silver fluoride (AgF: (NH3)2AgF) stains teeth black, it is known as a very effective agent to prevent the dental caries progress. In order to find another fluoride that has a similar anticariogenic effect without changing tooth color, we prepared ammonium hexafluorosilicate (SiF: (NH4)2SiF6), in which the silver of AgF is replaced with silicon. In this study, the anticariogenic effect of SiF was evaluated using bovine teeth. Fluoride solutions, SiF, AgF, acidulated phosphate fluoride (APF), and sodium fluoride (NaF), were applied to bovine enamel and dentine blocks, and the depth of demineralization was measured after exposure to a demineralizing solution for 24 h. Also, fluoride was applied to a simulated dentine caries specimen to evaluate the caries progress-preventing ability. For the dentine specimens, mineral loss (Delta Z) was also measured with microradiography. We found that SiF treated enamel showed better acid resistance than specimens treated with NaF or APF. AgF treated enamel also showed similar acid resistance, but was stained black. SiF and AgF treated caries-affected dentine showed reduced demineralization when exposed to a demineralization solution for 24 h. Mineral loss (Delta Z) was reduced to 85% and 75%, respectively. Although the acid resistance of the SiF treated teeth was inferior to that of the AgF treated teeth, we consider that SiF has good potential as anticariogenic agent, since it increased acid resistance without changing tooth color.

Acids↗

The effect of Pt and Pd alloying additions on the corrosion behavior of titanium in fluoride-containing environments.

In this study, we examined the corrosion behaviors of pure titanium, the alloys Ti-6Al-4V and Ti-6Al-7Nb, and the new experimental alloys Ti-Pt and Ti-Pd using anodic polarization and corrosion potential measurements in an environment containing fluoride. Before and after immersion in the test solutions, we made observations using a scanning electron microscope. The test solutions included an artificial saliva containing 0.2% NaF (corresponding to 905 ppm F) and an artificial saliva with a low concentration of oxygen. Although the surfaces of the Ti-Pt and Ti-Pd alloys were not affected by an acidic environment containing fluoride, the surfaces of the pure titanium, the Ti-6Al-4V alloy, and the Ti-6Al-7Nb alloy were markedly roughened by corrosion. The surfaces of the pure titanium, the Ti-6Al-4V alloy, and the Ti-6Al-7Nb alloy were microscopically damaged by corrosion when they were immersed in the solution containing a low concentration of dissolved oxygen, even with a fluoride concentration included in the commercial dentifrices. In this situation, however, the surfaces of the new Ti-Pt and Ti-Pd alloys were not affected. These alloys are expected to be of use in dental work as new titanium alloys with high corrosion resistances.

Alloys↗