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Biomedical subjects

K Ishida

Publications and source records attributed to K Ishida.

At least 253 records · Page 14Linked to original sources
PubMed1996

Drug sensitivity testing for clinical samples from oesophageal cancer using adhesive tumour cell culture system.

A total of 83 specimens of surgically resected tumours from 78 patients with oesophageal cancer were assayed for drug sensitivity using an adhesive tumour cell culture system (LifeTrac CSA assay). Seventyone of 83 specimens had a sufficient number of cells to permit growth in culture and 57 of 71 (80%) were evaluable for drug response. Cells (3 x 10(3) ml-1 well-1) were cultured for 14 days and exposed to drugs on days 3-8. Growing cells were confirmed as cancer cells by immunohistochemical staining. IC90 values against several anti-cancer drugs were determined and population distributions of IC90 for each drug served as the basis for judging sensitivity. The 10th percentiles of IC90 (microgram ml-1) for CDDP, 5-FU, DOX, CPM, MTX, VP16, IFOS, VDS, BLM and CDDP + 5-FU were 0.3, 0.16, 0.005, 0.9, 0.006, 0.09, 0.8, 0.006, 0.04 and 0.15 + 0.09 respectively. The population distribution of IC90 against each drug showed a specific pattern that was very similar among histopathological gradings and stages of the disease. This system appeared to be a clinically applicable drug sensitivity test for human oesophageal cancer.

Antineoplastic Agents↗
PubMed1996

Common deleted region on the long arm of chromosome 5 in esophageal carcinoma.

BACKGROUND & AIMS: The existence of an unknown tumor-suppressor gene on 5q for esophageal carcinoma other than the APC gene has been suggested. The location of the putative tumor-suppressor gene on 5q, distinct from the APC gene, was examined. METHODS: Sixty-one primary esophageal carcinomas were examined for nine microsatellite loci by the polymerase chain reaction followed by polyacrylamide gel electorophoresis. Loss of heterozygosity at the APC gene locus also was examined by the polymerase chain reaction-restriction fragment length polymorphisms. RESULTS: Thirty-five of 61 esophageal carcinomas (57%) showed loss of heterozygosity at single or multiple loci on 5q, and the smallest common deleted region was identified at 5q31.1, the location of the IRF-1 gene locus. All tumors showing loss of heterozygosity at the APC gene locus showed complete or large interstitial deletions on 5q. CONCLUSIONS: Deletion at the APC gene locus may just be the result of large deletions on 5q and may not be important in esophageal carcinogenesis, and the IRF-1 gene or other gene(s) on 5q31.1 may be the true target of frequent deletions on 5q that may play an important role in the pathogenesis of the majority of esophageal carcinomas.

Carcinoma↗
PubMed1996

Elevated serum interleukin-6 and decreased thyroid hormone levels in postoperative patients and effects of IL-6 on thyroid cell function in vitro.

We studied a wide variety of surgical patients to determine whether serum levels of interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) correlate with the changes in serum thyroid hormone levels of the postoperative period. Surgical procedures were divided into minor surgery (cholecystectomy, n = 12), moderate surgery (colorectal cancer and stomach cancer, n = 54), and extensive surgery (esophageal cancer or pancreatic cancer, n = 6). One day after surgery, serum free T3 levels decreased in all 3 groups when compared to the preoperative values; serum free T4 levels did not change regardless of surgical procedure. Serum TSH levels decreased significantly 1 day after surgery in the groups of moderate and extensive surgery. Serum levels of IL-6 increased 12 h after surgery and began to decrease gradually thereafter. There was no change in serum levels of TNF-alpha before and after surgery. The increment of serum IL-6 was dependent on the surgical procedures: the more extensive the surgery, the greater the increase in serum IL-6. Serum free T3 and free T4 levels were inversely correlated with the serum levels of IL-6. To further examine whether IL-6 is responsible for alteration of thyroid hormone production, cultured porcine thyroid follicles were exposed to 0 to 20 ng/ml of recombinant human IL-6 for 24 to 48 h. Then, type 1 5'-deiodinase activity (T4 to T3 converting enzyme), iodide uptake, and thyroid peroxidase (TPO) activity were measured. Our in vitro experiments showed no effect of IL-6 on these parameters. In summary, surgical procedure can cause elevation of serum IL-6 and decrease in serum free T3 levels. However, IL-6 alone does not appear to be a strong candidate for alteration of thyroid hormone production including T3 generation from T4.

Aged↗
PubMed1996

Phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus: nine Japanese institutions trial.

A phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus was carried out cooperatively by nine Japanese institutions. Forty-five patients with thoracic advanced squamous cell carcinoma, who had T4 tumor or distant lymph node metastasis (M1(LYM)), were enrolled in the study for treatment with cisplatin (70 mg/m2) on days 1 and 36, and 5-fluorouracil infusion (700 mg/m2) on days 1-4 and 36-39 sandwiched around external beam irradiation (60 Gy over 6 weeks). Of the 45 evaluable patients, 37 (84.1%) completed the treatment. The overall response rate was 64.4%, and the complete response rate 8.9%. The median duration of response was 125.0 days for patients who achieved complete and partial response. The 50% median survival time was 215 days. There was one toxicity-related death due to radiation pneumonitis. The major form of toxicity exceeding grade 2 was myelosuppression and anorexia, but grade 4 toxicity was also observed (2 pulmonary, 1 severe hypoxemia, 1 severe cardiac failure and 1 mental disturbance). The results showed that this form of chemoradiotherapy had a satisfactory effect and might be useful for treatment of inoperable advanced esophageal cancer.

Adult↗
PubMed1996

Evaluation of a novel osteogenic factor, bone cell stimulating substance, in a rabbit cranial defect model.

A novel osteogenic factor, bone cell stimulating substance (BCSS), was recently isolated from bovine bone. Unlike the bone morphogenetic proteins, which are generally 20- to 40-kDa glycoproteins belonging to the transforming growth factor-beta superfamily, BCSS is a 2.5-kDa, water-soluble polypeptide. This study evaluated the osteogenic potential of BCSS in combination with coralline-derived porous hydroxyapatite to reconstruct a large, nonhealing cranial defect in the rabbit. Twenty-four rabbits underwent a 16 x 20 mm full-thickness (extradural) excision of the parietal bones and were divided into six groups of four rabbits each. Group 1 through 5 were reconstructed with 16 x 20 x 1.5 mm hydroxyapatite implants treated with: (1) 20 osteogenic units (424 micrograms) BCSS, (2) 8 osteogenic units (170 micrograms) BCSS, (3) 4 osteogenic units (85 micrograms) BCSS, (4) 0 osteogenic units (424 micrograms) inactive BCSS analog, or (5) left untreated. Group 6 was left unreconstructed. Implants were harvested at 12 weeks and analyzed for percentage of lamellar bone formation by a computerized microscope video image analysis system. Groups reconstructed with BCSS-treated hydroxyapatite implants demonstrated more bone ingrowth than did the control hydroxyapatite groups not treated with BCSS (inactive BCSS analog or untreated). Linear regression dose-response analysis indicated an average 3.2 percent increase in bone ingrowth for a 10-U increase in BCSS (p = 0.043). The unreconstructed control group demonstrated no healing. With a molecular mass of only 2.5 kDa and its identity not completely known, BCSS is a novel factor that seems to possess osteogenic potential similar to that of previously investigated osteogenic proteins.

Animals↗
PubMed1996

Case report: hippocratic digital and Crohn's disease.

A case of Hippocratic digital associated with secondary hypertrophic osteoarthropathy complicating Crohn's disease in a 29 year old Japanese male is reported. Hippocratic digital, or finger clubbing, complicating inflammatory bowel disease has been frequently reported in the Western hemisphere. However, its association with secondary hypertrophic osteoarthropathy has been very rarely found in that disease. In Japan, Hippocratic digital has not been described previously. With regard to the pathogenesis of Hippocratic digital and secondary hypertrophic osteoarthropathy, the theory that both entities belong to the same pathological spectrum and that megakaryocytes or platelet clumps may play the most important role, is discussed.

Adult↗
PubMed1996

Pharmaceutical studies for gene therapy: expression of human Cu, Zn-superoxide dismutase gene transfected by lipofection in rat skin fibroblasts.

To evaluate whether lipofection using Lipofectin is suitable for delivering foreign genes into skin fibroblasts as target cells, we performed experiments using human superoxide dismutase (hSOD) and neomycin-resistance (Neo) genes as models in rat skin fibroblasts (FR and primary cells) in vitro. The amounts of DNA used in the lipofection procedure significantly affected the transfection efficiencies, and the optimal amounts were determined for all cells used. However, the efficiencies in rat skin fibroblasts were about 20-fold higher than that in rat lung epithelial-like cells (L2 cells). The differences in plasmid vectors (pRc/RSV-SOD and pRc/CMV-SOD) hardly affected the transfection efficiencies. The amounts of Lipofectin significantly affected the transfection efficiencies, and the optimal amounts were determined for both types of skin fibroblasts. However, cytotoxic effects in both skin fibroblasts were observed with high doses of Lipofectin. On the other hand, with optimal amounts of DNA and Lipofectin, the reporter gene (NeoT) introduced into cells was mainly integrated into the host cell chromosome. Western blot analysis showed the continuous expression of hSOD protein for at least 45 d in skin fibroblasts transfected with the expression plasmid for hSOD by Lipofectin under the optimal conditions, and the cellular SOD activity fluctuated in parallel with the expression of hSOD protein. Differences in the type of cells also affected the expression of hSOD. These results indicate that it is necessary to set up optimal conditions for transfection using Lipofectin for each cell type, and that transfection with Lipofectin under optimal conditions may be an efficient method for introduction of foreign genes into skin fibroblasts for use as a clinical delivery system of therapeutic protein.

Animals↗
PubMed1996

Cytolytic activity induced by intramuscular injection of plasmid DNA expressing the nucleocapsid protein of the JHM strain of mouse hepatitis virus into C57BL/6 mice.

We constructed plasmids expressing mRNA7 coding the nucleocapsid (N) protein of JHM strain of MHV (JHMV) under the control of Rous sarcoma virus (RSV) LTR or human elongation factor (EF) 1a promoter, referred to as pRSV-mRNA7 and pEF-mRNA7, respectively. Although only a slight level of cytolysis was observed by the spleen cells from C57BL/6 mice injected intramuscularly with pEF-mRNA7, the spleen cells from the mice administered with pRSV-mRNA7 showed a significant level of cytolytic activities against the cells expressing the viral N protein. The difference in the level of specific cytolysis might have been mainly due to a difference in the expression levels of the N protein in the muscles between the mice injected with pEF-mRNA7 and pRSV-mRNA7, since the specific activity of chloramphenicol acetyltransferase (CAT) in muscles from the mice injected with plasmid DNA expressing CAT gene directed by RSV LTR was significantly higher than that in those administered by the plasmid DNA directed by EF-1a promoter.

Animals↗
PubMed1996

[Diagnosis of superficial-type early carcinoma of the gallbladder by endoscopic ultrasonography--comparison with ultrasonography].

The detectability of superficial-type carcinoma of the gallbladder by ultrasonography (US) and endoscopic ultrasonography (EUS) were investigated. Eight patients with such carcinoma of the gallbladder were reviewed. They had undergone both US and EUS previous to surgery. The tumor was detected in 3 patients by US, 2 patients with IIa + IIb-type carcinoma and 1 patient with IIa-type carcinoma. Those lesions were visualized as localized thickening of the gallbladder wall or as broad-based tumor. In 2 patients, lesions were not initially detected by US, but were shown by US after the examination by EUS. The tumor was detected by EUS also in 1 case of IIb + IIa-type carcinoma besides those 3 patients mentioned above. All four of these lesions were visualized as broad-based tumor by EUS. It was difficult to detect pure IIb-type or small IIa-type carcinoma even by EUS. In patients with concomitant acute cholecystitis or gallbladder stone, it was difficult to evaluate the abnormal findings of the gallbladder wall.

Aged↗
PubMed1996

The largest isoform of platelet membrane glycoprotein Ib alpha is commonly distributed in eastern Asian populations.

Platelet membrane glycoprotein Ib alpha has at least two polymorphisms which affect phenotype. One is the dimorphism at codon 145, and the other is a molecular weight polymorphism due to variable numbers of tandem repeats (TR) in the macroglycopeptide region. These two polymorphisms are in linkage disequilibrium. The frequencies of these polymorphisms differ considerably depending on race, and the largest variant with four TR is almost exclusively present in the Japanese population. We examined the genotypes of HPA-2 and TR polymorphism in three different races from Eastern Asia; the Japanese (n = 103), Korean (n = 101) and Chinese population (n = 177). The gene frequency of HPA-2 differed significantly among these three populations. Among HPA-2b-positive individuals, the A isoform with four TR and B with three TR were present in all three populations and A dominated over B. Individuals homozygous for the A isoform were found in both Japanese and Korean populations. These findings indicate that the largest haplotype is common in the Eastern Asian region.

Antigens, Human Platelet↗
PubMed1996

[Ultrasonographic study of rectal carcinoid tumors].

To compare intraluminal ultrasonographic (ILUS) findings with histological findings of rectal carcinoid tumors, 35 patients with rectal carcinoid tumors were reviewed. The results were as follows: 1) The rectal wall was visualized as a seven- or nine-layer structure by means of ILUS in 81% of the patients. 2) The possibility that the thin hyperechoic third layer above the tumor on ILUS corresponds to the muscularis mucosae and fibrointerstitium above the tumor histologically. 3) In cases with relatively high internal echoes, the amount of fibrointerstitium exceeded that of tumor cells histologically. 4) In cases with nonuniform internal echo patterns, tumor cells were separated by thick fibrointerstitium forming nodular nests.

Carcinoid Tumor↗
PubMed1995

The largest variant of platelet glycoprotein Ib alpha has four tandem repeats of 13 amino acids in the macroglycopeptide region and a genetic linkage with methionine145.

Platelet membrane glycoprotein Ib alpha (GPIb alpha) bears the human platelet alloantigen (HPA)-2 and molecular weight (MW) polymorphisms on sodium dodecyl sulfate-polyacrylamide gels. HPA-2 arises from a threonine/methionine dimorphism at residue 145 of the GPIb alpha sequence, whereas different numbers of tandem repeats of a 39-bp sequence encoding 13-amino acids corresponding to a region between serine399 and threonine411 of the GPIb alpha account for the latter. To identify the genetic basis of the MW polymorphism among Japanese, we counted the tandem repeats in 103 individuals. In addition to the reported three variants with one, two, or three tandem repeats, we identified a new variant with four perfect tandem repeats of the 39-bp sequence that corresponded to the largest phenotype. Phenotypic analysis of the MW polymorphism on 12 individuals including all four phenotypes completely accorded in the genotype. We also determined the genotype of HPA-2 and found that methionine145 was in complete linkage disequilibrium, with the larger variants containing three or four tandem repeats. These results imply a model of evolutionary steps in the gene encoding GPIb alpha.

Alleles↗
PubMed1995

Is there a critical gestational age in neutrophil superoxide production activity?

We studied superoxide (O2-) production in neutrophils from 78 normal pregnant women at 7 to 39 weeks' gestation to determine whether there is a critical gestational age in O2- production activity of maternal neutrophils. The O2- production was measured by determining the rate of superoxide dismutase-inhibitable reduction of ferricytochrome c at 550 to 540 nm. A scattergram of neutrophil O2- production value versus gestational age was analyzed using the least median of squares regression, leading to a statistical stratification in which the median values of O2- production for outlying and nonoutlying points were 6.60 nmol/10(6) cells and 2.72 nmol/10(6) cells, respectively. All of the outlying points were concentrated at 19 to 22 gestational weeks. There was the significant difference in FMLP-induced O2- production in neutrophils of nonpregnant subjects when incubated with the sera from 10 cases (selected among 60 cases with nonoutlying points) (3.86 +/- 0.77 nmol/10(6) cells) compared with 5 cases with outlying points (5.62 +/- 1.19 nmol/10(6) cells) (P < .05) These results suggest that during the normal course of pregnancy, the production of O2- from the function of circulating neutrophils can be dissociated from such neutrophil functions as adherence, chemotaxis, and phagocytosis.

Adult↗
PubMed1995

Inhibition of viral multiplication in acute and chronic stages of infection by ribozymes targeted against the polymerase gene of mouse hepatitis virus.

Two hammerhead ribozymes targeted against the polymerase gene of mouse hepatitis virus (MHV), which consisted of 22-nucleotide (nt) ribozyme core sequences and antisense sequences of different lengths, 243-nt (S-ribozyme) and 926-nt (L-ribozyme), were tested for their++ inhibitory effects on viral multiplication. Vectors that expressed the ribozymes were transfected into mouse DBT cells and several resulting cell lines constitutively expressing the ribozymes were selected and examined for intracellular MHV multiplication in acute and chronic stages of infection. The production of infectious progeny viral particles was significantly reduced in the transfected cell lines expressing either the S-ribozyme or L-ribozyme in acute infection. Although the in vitro cleavage process of the L-ribozyme was slower than that of the S-ribozyme, no difference was observed in inhibitory effects on MHV multiplication between S- and L-ribozymes in the transfected cells. In the transfected cells expressing L-ribozymes, production of viral particles was also inhibited in the chronic stage of MHV infection.

Animals↗