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H Shimada

Publications and source records attributed to H Shimada.

At least 163 records · Page 9Linked to original sources
PubMed2000

A feasibility study of chemosensitivity assay by adhesive tumor cell culture system using biopsy specimens for gastric cancer.

BACKGROUND AND OBJECTIVES: The adhesive tumor cell culture system (ATCCS) is known to produce high colony-forming efficiency. We, therefore, studied the feasibility of ATCCS for gastric cancer by use of biopsy specimens and the relationship between the results of ATCCS and histological effects of anticancer drugs. METHODS: Tumor specimens extracted by gastroendoscopic biopsy were sufficient for obtaining the result of sensitivity to at least one drug in 24 out of 30 (80%) patients. Twenty patients were administered 5-fluorouracil (5-FU) for 14 days prior to surgery, and the results of ATCCS were compared with histological changes of the resected specimens. RESULTS: The histological response rate was found to be 100% (4/4) when the 90% inhibition concentration (IC90) of 5-FU was less than 0.24 microg/ml (sensitive) and was 0% (0/3) when IC90 was greater than 0.40 microg/ml (resistant). CONCLUSIONS: Although lacking in statistical significance, the results suggest that the drug to which the tumor revealed sensitivity in the ATCCS would produce histological effects and the drug to which the tumor was resistant would have no histological effect.

Aged↗
PubMed2000

A patient with rectal ulcer with severe stenosis presenting with perforated peritonitis.

We report a patient with rectal ulcer with severe stenosis, who underwent urgent surgical treatment for perforated peritonitis. The 54-year-old man suddenly developed cramping abdominal pain and fever while hospitalized, with signs of peritoneal irritation. An emergency laparotomy was performed, and severe stenosis of the rectum and a perforated lesion on the oral side approximately 10 cm distant from the stenosis were found, with massive abdominal purulent fluid. He was treated by rectosigmoid colon resection with transverse colon loop colostomy. Histopathologically, the stenosis was caused by ulceration extending to all muscular layers of the rectum, with inflammatory changes. Benign rectal stenosis is so rare that differential diagnosis from malignancy may be difficult when there are inflammatory changes in the surrounding tissues. However, it is necessary to keep in mind the likelihood of this disease in differentiation from rectal cancer.

Constriction, Pathologic↗
PubMed2000

Propofol improves recovery from paraquat acute toxicity in vitro and in vivo.

OBJECTIVE: To investigate whether the antioxidative sedatives propofol and thiopental can improve recovery from acute paraquat toxicity in A549 cells and in mice. DESIGN: Prospective, controlled, dose-response, in vitro study and prospective, controlled animal study. SETTING: A university animal research laboratory. SUBJECTS: Established human lung cultured cells and male SPF ICR mice. INTERVENTIONS: Paraquat-treated (0.2 mM) A549 cells were incubated either with the antioxidative sedatives propofol (0-0.56 mM) or thiopental (0-2.0 mM), or the nonantioxidative sedatives diazepam (0-3.0 mM), midazolam (0-3.0 mM) and ketamine (0-9.0 mM), as well as the antioxidative drugs, trolox (0-2.0 mM), alpha-tocopherol (0-4.4 mM), antioxidative-processed food (AOB; 0-1.0 mg/ml), superoxide dismutase (SOD; 0 and 3,000 U/ml) and ulinastatin (0 and 50,000 U/ml), for 48 h. Paraquat-treated mice received i.v. injections of 10 mg/kg propofol, 5 mg/kg thiopental, 4.0 mg/kg trolox, 100 mg/kg alpha-tocopherol, 10 mg/kg AOB or 5,000 U/kg SOD, b.i.d. for 4 days (n = 10 each). MEASUREMENTS AND RESULTS: Post-administered propofol and thiopental, as well as the antioxidative drugs, trolox, alpha-tocopherol and AOB, improved A549 cell survival in vitro. The non-antioxidative sedatives SOD and ulinastatin were not protective. An i.p. injection of 50 mg/kg of paraquat resulted in a survival rate of 40% in mice at day 6. Propofol, trolox, alpha-tocopherol and AOB significantly lowered the mortality rate (80% survival), while thiopental did not. CONCLUSION: Post i.v. injection of propofol is protective against paraquat-induced damage. Propofol can be given during mechanical ventilatory support after paraquat poisoning.

Anesthetics, Intravenous↗
PubMed2000

Feasibility of a novel weekday-on/weekend-off oral UFT schedule as postoperative adjuvant chemotherapy for colorectal cancer. UFT Compliance Study Group, Kanagawa, Japan.

PURPOSE: When oral anticancer agents are used for adjuvant chemotherapy of colorectal cancer, compliance and feasibility become issues because of the long treatment time. Appropriate studies of these issues are lacking. We investigated compliance and feasibility during a weekday-on/weekend-off schedule of oral UFT (uracil-tegafur) over a period of 1 year administered as adjuvant chemotherapy to patients with colorectal cancer. PATIENTS AND METHODS: A UFT dose of 600 mg/day was prescribed according to a weekday-on/weekend-off schedule to 87 patients after potentially curative resection. Compliance was investigated in three ways: physician interview, patient self-report, and chemical analysis of urine. The results were compared with the dose prescribed. Feasibility was evaluated on the basis of two indices: relative performance (RP), which was the ratio of the actual total dose taken to the total dose planned, and individual dose intensity (IDI), which was the ratio of the actual dose taken to the dose planned during a given period. RESULTS: The compliance assessed by physician interview and by patient self-report conformed well with the prescribed dose, the rate of agreement among the three compliance measures being more than 94%. Chemical analysis of urine in 38 of the patients revealed that they were actually taking the drug. The RP was 0.72, and the IDI was 0.8. CONCLUSION: From these results, the feasibility of the weekday-on/weekend-off schedule was judged to be good. It is suggested that the feasibility would be even better if the dose of UFT was set according to body surface area.

Administration, Oral↗
PubMed2000

Appraisal of surgical resection of gallbladder cancer with special reference to lymph node dissection.

BACKGROUND: Radical lymph node dissection in surgery for advanced gallbladder cancer is controversial. The purpose of this study is to evaluate the role of lymph node dissection based on the clinico-pathologic results. PATIENTS: Seventy-three patients who underwent radical surgery including systematic dissection of the N1+N2 region lymph node plus some of the para-aortic nodes were reviewed. RESULTS: pT1 patients had no lymph node metastasis, but pT2 and pT3/pT4 patients had lymph node metastasis at a rate of 50.0% (13/26) and 83.3% (25/30), respectively. As infiltration of the hepatoduodenal ligament (Binf) became severe, the rate and extent of lymph node metastasis increased. There were four 5-year survivors with lymph node involvement. The 5-year survival rates are 77.0% in pN0 cases and 27.3% in pN1 cases (P<0.01). There was no difference in survival between pN1 and pN2 patients. However, significant differences in survival were observed between pN0/1 and pN2/3 patients when these patients were limited to Binf0/1. Examination of the recurrence pattern showed that most patients with pN0/1/2 had no regional lymph node recurrence, but there was para-aortic lymph node recurrence in patients with pN3 outside the dissected region. Significant prognostic factors influencing survival after surgery by multivariate analysis were pN2/3, pT, and residual tumor. CONCLUSION: Systematic lymph node dissection of N1, N2, and part of the para-aortic region improves survival in advanced gallbladder cancer patients, especially in those without either para-aortic lymph node metastases or Binf2/3.

Adult↗
PubMed2000

CAAT sites are required for the activation of the H. pulcherrimus Ars gene by Otx.

A product of sea urchin homologues of the Drosophila orthodenticle gene, HpOtxL has been implicated as a transcription activator of the aboral ectoderm-specific arylsulfatase (Ars) gene during early development of the sea urchin embryo. Using an in vivo transactivation system, we present evidence that HpOtxL activates the target gene by interacting with co-factors. Otx binding sites alone have little effect on the activity of an Ars promoter, but when both Otx binding sites and CAAT sequences are present in the enhancer region of Ars, the fragment shows a high enhancer activity. A gel mobility shift assay reveals that a nuclear protein binds to the CAAT sequences present near the Otx binding sites in the enhancer region of Ars. The activation domain of HpOtxL resides in the C terminal region between amino acids 218 and 238. The N-terminal region is responsible for the enhancement of transactivation of the Ars promoter, although the region itself does not function as an activation domain. HpOtxE, which possesses an N-terminal region different from HpOtxL, does not activate the Ars promoter even in the presence of CAAT sequences. Together with previous findings, our results suggest that Otx regulates different genes by interacting with different co-factors in sea urchin development.

Animals↗
PubMed2000

Gene therapy for cancer.

The basic strategies for gene therapy that have been explored include immunogene therapy such as cytokine gene transfer, selective prodrug activation, so-called suicide genes, transfer of a tumor suppressor gene, and inhibition of activated oncogenes by antisense mechanisms. Many therapeutic protocols have so far been registered in the office of the Recombinant DNA Advisory Committee, NIH, as of June 1999. Regarding the basic research in gene therapy, we planned a clinical application of gene therapy for an esophageal cancer patient at our institution. We review herein the present status of gene therapy for cancer overseas, and describe a protocol of clinical trials for gene therapy for esophageal cancer at our institution.

Clinical Protocols↗
PubMed2000

Comparison between indocyanine green angiography and outcome of surgical removal of choroidal neovascular membrane in age-related macular degeneration

Purpose: To review the outcome of surgical removal of choroidal neovascular membranes in age-related macular degeneration as classified by indocyanine green angiographic findings.Subjects and Method: Surgery was performed in 42 eyes. They were divided into four types by indocyanine green angiographic findings prior to surgery. Type I comprised 29 eyes showing hyperfluorescence throughout the angiographic phases. Type II comprised 3 eyes showing hyperfluorescence during the early phase only. Type III comprised 5 eyes showing hyperfluorescence in the late phase only. Type IV comprised 5 eyes without hyperfluorescence throughout the angiographic phases. The results were evaluated according to the visual acuity expressed as log MAR before and after surgery.Results: Visual acuity improved significantly in Types I, II, and III after surgery. Visual acuity did not improve in Type IV.Conclusion: The findings of indocyanine green angiography are thought to reflect the histological characteristics of the choroidal neovascular membrane. Neovascular membranes of Type IV may contain a smaller number of vessels and abundant fibrous tissue. Eyes of Type IV will have atrophies in the neurosensory retina, retinal pigment epithelium, and choriocapillaris. Surgical removal of the choroidal neovascular membrane in Type IV is not effective in improving visual acuity.

Journal Article↗
PubMed2000

NADPH-protochlorophyllide oxidoreductase in cucumber is encoded by a single gene and its expression is transcriptionally enhanced by illumination.

NADPH-protochlorophyllide oxidoreductase (POR) catalyzes the photoreduction of protochlorophyllide a in the chlorophyll biosynthetic pathway. Recently, two POR genes, the expressions of which were differently regulated by light, were isolated in barley and Arabidopsis, and it is suggested that in angiosperms, the chlorophyll synthesis is controlled by the differential action of the two distinct POR isozymes. Meanwhile, we have isolated POR cDNA from cucumber, and reported that its expression was enhanced by illumination. In this study, we analyzed the gene expression and organization of cucumber POR in more detail. Northern blot analysis with 5'- or 3'-noncoding gene-specific and full length probes and RNase protection assay revealed that cucumber POR mRNA is transcribed from a single gene. Run-on assay revealed that the transcript level of isolated nuclei from illuminated cotyledons was 6-fold that of dark control, indicating that the light-enhanced expression of cucumber POR is caused by transcriptional activation. Using degenerated primers and the genomic DNA of cucumber as template, PCR showed the presence of only one type of fragment encoding cucumber POR. The PCR product was hybridized with the genomic Southern blot from cucumber and only one band was detected under low stringency conditions. From these results, we conclude that there is a single POR gene in cucumber and PORs are organized by different gene families among higher plants, and in cucumber the single POR may play the roles of two POR genes, which are present in other higher plants such as Arabidopsis and barley.

Journal Article↗
PubMed2000

Survival efficacy of the combination of the methioninase gene and methioninase in a lung cancer orthotopic model.

We have previously demonstrated the antitumor efficacy of recombinant methioninase (rMETase) derived from Pseudomonas putida. To enhance the efficacy of rMETase, we have constructed the pLGFP-METSN retrovirus encoding the P. putida methioninase (MET) gene fused with the green fluorescent protein (GFP) gene. pLGFP-METSN or control vector pLGFPSN was introduced into the human lung cancer cell line H460. The methionine level of H460-GFP-MET cells was reduced to 33% of that of H460-GFP cells. rMETase (0.08 U/mL) in the medium resulted in 10% survival of H460-GFP-MET cells compared with untreated cells in vitro. In contrast, rMETase-treated H460-GFP cells survived at 90% of control. Tissue fragments harvested from subcutaneous tumors of H460-GFP-MET or H460-MET were implanted by surgical orthotopic implantation into the lungs of nude mice. A suboptimal dose of rMETase was administered intraperitoneally daily to mice in each group. Overall survival of rMETase-treated animals with H460-GFP-MET tumors was significantly longer than either rMETase-treated or -untreated animals with H460-GFP tumors (P < .05 in log-rank test). In two repeat experiments, rMETase-treated animals with H460-GFP-MET tumors had a 30-day survival of 80% and 83%, respectively. Untreated animals with H460-GFP-MET tumors had a 30-day survival of 40% and 58%, respectively. rMETase-treated animals with H460-GFP tumors had a 30-day survival of 0% and 33%, respectively. Untreated animals with H460-GFP tumors had a 30-day survival of 0% and 33%, respectively. The retrovirus-mediated gene transfer of METase decreased the intracellular methionine level of tumor cells and consequently enhanced the efficacy of treatment with the rMETase protein. We have thus demonstrated a new strategy of combination tumor therapy with the gene and gene product of MET.

Animals↗
PubMed2000

In vivo tumor delivery of the green fluorescent protein gene to report future occurrence of metastasis.

The green fluorescent protein (GFP) gene was administered to intraperitoneally (i.p.) growing human stomach cancer in nude mice to visualize future regional and distant metastases. GFP retroviral supernatants were injected i.p. from day 4 to day 10 after i.p. implantation of the cancer cells. Tumor and metastasis fluorescence was visualized every other week with the use of fluorescence optics via a laparotomy on the tumor-bearing animals. At 2 weeks after retroviral GFP delivery, GFP-expressing tumor cells were observed in gonadal fat, greater omentum, and intestine, indicating that these primary i.p. growing tumors were efficiently transduced by the GFP gene and could be visualized by its expression. At the second and third laparotomies, GFP-expressing tumor cells were observed to have spread to lymph nodes in the mesentery and other regional sites. At the fourth laparotomy, widespread tumor growth was visualized by GFP expression, inducing liver metastasis. No normal tissues were found to be transduced by the GFP retrovirus. Thus, reporter gene transduction of the primary tumor enabled detection of its subsequent metastasis. This gene therapy model could be applied to primary tumors before resection or other treatment to have a fluorescent early detection system for metastasis and recurrence.

3T3 Cells↗
PubMed2000

Generation of the NUP98-HOXD13 fusion transcript by a rare translocation, t(2;11)(q31;p15), in a case of infant leukaemia.

We report a case of de novo acute myelomonocytic leukaemia with the t(2;11)(q31;p15) translocation in a Japanese female infant. The NUP98-HOXD13 fusion transcript generated by the translocation was detected in the patient's bone marrow cells by reverse transcription-polymerase chain reaction (RT-PCR). Additionally, ectopic expression of the normal allele of the HOXD13 gene was observed in this patient, suggesting that it might be associated with leukaemogenic development. This case is the third report of t(2;11) leukaemia with NUP98-HOXD13 and the first report showing that NUP98 rearrangements are associated with infant leukaemia, as well as therapy-related acute myelogenous leukaemia or myelodysplastic syndrome.

Aged↗
PubMed2000

Sox regulates transcription of the sea urchin arylsulfatase gene.

A 50 bp region from -194 bp to -144 bp of the arylsulfatase gene (HpArs) of the sea urchin, Hemicentrotus pulcherrimus, is related to the temporally regulated expression of this gene. This region contains a Sox (Sry-related HMG box)-binding site, and the introduction of sequence mutations to this site significantly reduced the activity of the HpArs promoter, even in the presence of the C15 enhancer, which consists of HpOtx and CAAT motifs. A protein that binds to the Sox-binding site in the 50 bp region of the HpArs gene was detected in nuclear extracts of mesenchyme blastulae and a protein synthesized in vitro using SoxB1 cDNA of another sea urchin, Strongylocentrotus purpuratus, also bound to this Sox site. These results suggest that HpSox, which is maternally expressed and remains abundant by the pluteus stage, is clearly implicated in regulation of the HpArs gene. The presence of a negatively acting cis element in this 50 bp region has also been detected.

Animals↗