Inhibition of insulin production by FK 506 is caused at the transcriptional level in pancreatic beta cell when FK BP-12 content is relatively high.
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Animals↗
Biomedical subjects
T Fujimura
Publications and source records attributed to T Fujimura.
[A case of secondary valve replacement caused by pulmonary bioprosthetic valve endocarditis].
A 42-year-old male with pulmonary bioprosthetic valve endocarditis accompanied by residual minor leakage through a previously closed patch for ventricular septal defect (VSD), underwent reoperation with a Carpentier-Edwards bioprosthetic valve. The patient had a history of pulmonary valve replacement and VSD in 1973. A massive vegetation on the pulmonary valve was demonstrated by echocardiography. Five repeated blood cultures yielded Eikenella corrodens. After medical treatment, reoperation was performed. The patient was free of complications after the procedure. Although bioprosthetic valves have potential problems of dysfunction and calcification in long-term use, these problems develop at a significantly slower rate in right-sided positions compared with left-sided positions and bioprosthetic valve thrombosis in the pulmonary position has apparently not been reported. Mechanical prostheses for pulmonary valve replacement have a poor prognosis, with a high incidence of valve thrombosis despite adequate anticoagulant therapy. For the replacement of prosthetic valves in right-sided positions (tricuspid and pulmonary), bioprosthetic valves are now our first choice.
Adult↗
[Chemohyperthermic peritoneal perfusion and subtotal peritonectomy for peritonitis carcinomatosa in gastroenteric cancer].
A new operative procedure, called subtotal peritonectomy (SP), in combination with chemohyperthermic peritoneal perfusion, was developed for the treatment of peritonitis carcinomatosa in gastrointestinal cancer. SP includes resection of primary lesion, colon, small bowel, spleen, and gall bladder and parietal peritonectomy. Six patients with gastric cancer and two patients with colon cancer underwent these procedures. A great deal of discharge from the peritoneal cavity, an increase in systemic vascular resistance index, and a decrease in central venous pressure represented much decrease in circulatory volume on days 1 to 2 postoperatively. This state improved at 3 to 4 days after operation. Histopathological study revealed multiple peritoneal seedings with negative surgical margins in all patients. There were no related deaths though bleeding, perforation, and abscess occurred in two patients each. One patient died of peritoneal recurrence after one year, but the other have survived.
Adult↗
[Combination therapy of high dose 5'-DFUR+MMC for advanced or recurrent gastric cancer. 5'-DFUR Joint Research Group in the Osaka District for Gastric Cancer].
We conducted multi-center clinical trials of 'Treatment with high dose 5'-DFUR+MMC' in order to evaluate the effects, the possibility for outpatient treatment and the survival effects in patients with advanced or recurrent gastric cancer. The treatment schedule was as follow; 5'-DFUR 1,600 mg/body/day was given orally for five consecutive days every week and MMC 6 mg/m2 was injected intravenously once every four weeks. Forty-eight patients were enrolled and 34 cases were evaluated for anti-tumor responses. The overall response rate was 29.4% (10/34 cases). Side effects were mainly diarrhea, but outpatient treatment was possible in most cases. The median survival period was 249 days, which is longer than with other treatments. This result suggests that this combination chemotherapy is useful in patients with advanced or recurrent gastric cancers.
Adult↗
[Correlation between the expression of urokinase-type plasminogen activator, E-cadherin and malignancy in gastric cancer].
We aim to elucidate the correlation between clinicopathological parameters and uPA and ECD expression in gastric cancer. Some 125 patients with primary gastric cancer, who were treated at the Second Department of Surgery, Kanazawa University, between 1988 and 1993, were enrolled in this study. The expression of uPA and ECD was evaluated by immunohistochemical staining using a anti-uPA and an anti-ECD monoclonal antibody. The nuclear DNA contents were measured by flow cytometry. Among 125 tumors, 42 (34%) were found to have preserved ECD expression (ECD (+)), and 83 (66%) reduced ECD expression (ECD (-)). uPA immunoreactivity was observed in 82 (65%) of 125 tumors. According to the expression of uPA and ECD status, groups of 22 uPA (-)/ECD (+), 21 uPA (+)/ECD (+), 17 uPA (-)/ECD (-) and 65 uPA (+)/ECD (-) were identified. There was a significant correlation between uPA (+)/ECD (-) status and depth of invasion, liver metastasis, peritoneal dissemination, lymph node metastasis, and venous invasion. Patients with uPA (+)/ECD (-) tumors showed the poorest prognosis and the highest rate of recurrence, as compared with the other groups of patients. No significant correlations were found between uPA (+)/ECD (-) status and DNA ploidy patterns, and histological type. Immunohistochemical analysis of the combination of uPA and ECD expression could be a useful method for the evaluation of metastasis and prognosis in gastric cancer patients. Our results indicate that uPA may have an important role in cancer infiltration and ECD in cancer infiltration and metastasis.
Cadherins↗
Late appearance of a Philadelphia translocation with minor-BCR/ABL transcript in a t(7;11)(p15;p15) acute myeloid leukemia.
We describe a patient with a t(7;11)(p15;p15) acute myeloid leukemia who was subsequently found to harbor the Philadelphia (Ph) translocation, in addition to the t(7;11), at the second relapse. A BCR/ABL transcript was detected at the second relapse by reverse transcription-polymerase chain reaction assay; the leukemic cells had a BCR/ABL fusion gene involving the minor breakpoint cluster region (minor-BCR; situated in intron 1 of the BCR gene). Although the Ph translocation is commonly detected in de novo acute leukemia and chronic myeloid leukemia as the primary leukemia-specific chromosomal translocation, our case suggests that this cytogenetic change might occur as an additional chromosomal change in neoplastic cells. Moreover, minor-BCR/ABL rearrangements may also occur as a late appearance of Ph translocation.
Base Sequence↗
Lymph node metastasis and surgical management of gastric cancer invading the esophagus.
In 88 resected patients with esophagus-invading gastric cancer, the factors determining the prognosis of this disease were investigated by multivariate analysis. Neither, age, sex, macroscopic type, thoracotomy, nor histological type proved to be independent prognostic factors. The presence or absence of lymph node metastasis, serosal invasion, tumor size, and the extent of esophageal invasion were found to be significant independent prognostic factors. Among lymph node metastases, involvement of para-aortic lymph nodes was especially important. The prognosis was significantly better in cases in which these nodes were carefully dissected (R4 gastrectomy), than in cases in which selected dissection was performed (R2). However, no patient with mediastinal lymph node metastasis survived for any lengthy period, and thus the mediastinal lymph nodes seemed to be nodes, the dissection of which brought little effect. Postoperative results were very poor in cases in which the extent of the esophageal invasion was 3 cm or more. These patients should be treated with multi-modal therapy such as neoadjuvant chemotherapy.
Adenocarcinoma↗
Decreased E-cadherin expression correlates with poor survival in patients with gastric cancer.
E-cadherin, Ca(2+)-dependent intracellular adhesion molecule, is known to be an invasion suppressor gene. To elucidate the correlation between E-cadherin expression and invasion or metastasis in gastric cancer, we examined E-cadherin tissue status immunohistochemically. Ninety-eight primary gastric cancer, prepared by AMeX method, were retrospectively analyzed with anti-E-cadherin monoclonal antibody. In normal gastric epithelium, E-cadherin is expressed homogeneously with a typical membranous staining at cell-cell borders. Decreased and heterogeneous expression is found in 70 of 98 tumours. Tumours with decreased E-cadherin expression had a tendency to infiltrate more deeply in stomach wall, and metastasize in lymph nodes or peritoneal surface. More importantly, decreased E-cadherin expression correlates with shorter survival (z = 3.98, P = 0.00086). These results may indicate that E-cadherin tissue status is a powerful prognostic indicator in gastric cancer. The high malignant potential of tumours with decreased E-cadherin expression may be associated with high potential of lymph node metastasis and peritoneal dissemination.
Cadherins↗
[Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer].
Irinotecan (CPT-11) is a camptothecine derivative with antitumor activity and inhibitor of DNA topoisomerase I. CPT-11 showed a excellent and broad anticancer activity against several malignant tumors. In this study, as in the Japanese phase II study, CPT-11 was administered at 100 mg/m2 weekly by intravenous infusion against 10 patients with recurrent colorectal cancer. Median total dose was 513 mg. Partial responses were obtained in 4/10 patient (40%). Lung metastases showed a 33.3% response and lymphnode metastases showed a 60% response. However, liver metastases showed no response. The median duration to the onset of partial response was 20 days and the median overall response duration was 89 days. Adverse effects were leukopenia (40%), nausea, vomiting and diarrhea (80%), fever (20%), and general malaise (30%). These were generally well tolerated and reversible. From these results, CPT-11 seemed to become an effective drug for recurrent colorectal cancer. Further trials of combination chemotherapy utilizing CPT-11 seem to be warranted.
Adult↗
Improving workplace environments and working conditions at worksites providing school lunch service in Japan.
With the cooperation of All Japan Prefectural and Municipal Workers' Union, we have started an overall program on occupational safety and health from 1984. This program has several strategies aimed at preventing occupational injuries and work-related diseases. At first, we analyzed the relationship between work-related hazards and occupational factors, and to identify dangerous or hazardous factors in the workplace. Second, we have conducted a couple of intervention studies at worksites and evaluated these improvements. Third, we discussed the priority, feasibility and cost of improvements with Workers' Union members and school lunch workers. Fourth, during the last decade, Workers' Union and many researchers have demanded that regulations be implemented which would establish comprehensive safety and health programs. Fifth, we provided the workers with procedures on how to improve working environments and conditions. These education and training programs are provided for small-group working ("safety and health circle"), and demonstrate to workers their abilities to solve occupational safety and health problems and to empower them with respect to health-related issues. Finally, we discussed and evaluated the preventive effects of improving workplace environments and working conditions. The overall program on occupational safety and health at worksites is developing nationwide and is gradually taking effect.
Cooking↗
[Surgical treatment of acute aortic dissections--a clinical study using a ringed intraluminal graft].
From 1984 to 1994, surgery was performed using a ringed intraluminal graft (RIG) in 75 patients with acute aortic dissection (DeBakey's type I in 37 cases, type II in 10 cases and type III in 28 cases). The operative death rate was 24% for type I, 30% for type II and 21% for type III. The average time from onset to surgery was short (47 +/- 67 hours for type I, 34 +/- 36 hours for type II and 47 +/- 77 hours for type III). The outcome of these cases indicated that this technique was effective for saving the lives of patients in the acute early stage of aortic dissection. No characteristic complications developed after this surgery. The postoperative course of patients was followed by using CT scans, MRI, angiography. No patients developed aneurysmal formation in the ligated area or dislocation of the RIG. There were no deaths directly attributable to the RIG. Patients who were autopsied in the late postoperative period showed no aneurysm of the ligated area or necrosis of the aortic wall. In conclusion, RIG surgery effectively saved the life of patients with acute aortic dissection and the RIG could be used as prosthetic graft for long-term periods.
Acute Disease↗
Association of yeast viral 23 S RNA with its putative RNA-dependent RNA polymerase.
T double-stranded RNA (dsRNA) and its single-stranded RNA (ssRNA) counterpart, 23 S RNA, are present in some strains of the yeast Saccharomyces cerevisiae. 23 S RNA is identical with the T (+)-strand, and both are cytoplasmically inherited. The T (+)-strand encodes a protein of 104 kilodaltons (kDa) (p104) that has sequences diagnostic of RNA-dependent RNA polymerases from (+)-strand and double-stranded RNA viruses. Here we show that p104 is expressed only in yeast strains carrying T dsRNA (and 23 S RNA) and that the ability to produce p104 is co-transmitted from one strain to another by cytoplasmic mixing (cytoduction) along with T dsRNA. Neither T nor 23 S RNA is encapsidated into viral particles; however, the latter was found to be non-covalently associated with p104. This finding was based on the evidence that: (i) both 23 S RNA and p104 cosedimented in sucrose gradients and that (ii) 23 S RNA was immunoprecipitated by a p104-specific polyclonal antiserum. Consistent with this association, p104 shows single-stranded RNA-binding activity in Northwestern blots. We have localized the RNA-binding domain of p104 within its C terminus 234 amino acids.
Fungal Proteins↗
Essential RNA binding and packaging domains of the Gag-Pol fusion protein of the L-A double-stranded RNA virus of Saccharomyces cerevisiae.
The crucial process in the assembly of the L-A double-stranded RNA virus is the recognition of its (+) single-stranded RNA by the Gag-Pol protein. The Pol region of this protein has RNA binding activity and is necessary for RNA packaging. Here we show that there are actually two in vitro RNA-binding domains of Pol (residues 172-190 and 770-819), and both are necessary for viral propagation, (but not for particle assembly). Furthermore, the N-terminal RNA-binding domain is necessary for in vivo packaging of viral (+) single-stranded RNA. We precisely define the extent of the Pol packaging domain (residues 67-213), which includes the N-terminal RNA-binding domain. This suggests that the N-terminal RNA-binding domain is responsible for binding the genomic RNA in the process of packaging and that additional surrounding residues are responsible for the specificity of binding.
Amino Acid Sequence↗
Interaction of tacrolimus(FK506) and its metabolites with FKBP and calcineurin.
Tacrolimus(FK506) is a strong immuno-suppressant and shows its activity through inhibiting IL-2 mRNA transcription by forming pentameric complex with intracellular receptor(FK506 binding protein 12 kDa or FKBP12), Ca2+, calmodulin, and calcineurin. Here, we report the binding activity to FKBP12, the pentameric complex formation and Con-A response inhibiting activities of 7 metabolites. C15-demethylated metabolite(M-3) needed higher quantity to compete in Con-A assay and in pentamer formation assay, although it binds more strongly to FKBP12. The result suggests that the ability to form a pentameric complex is not a two step reaction with the first binding to FKBP12, but a single step reaction by components for the pentamer formation.
Animals↗
Telomere shortening associated with disease evolution patterns in myelodysplastic syndromes.
We identified the telomere length at different hematological phases in 16 patients with myelodysplastic syndromes (MDS), showing disease evolution with a conventional Southern blot hybridization using the (TTAGGG)4 probe. The MDS patients studied were classified into three groups according to the pattern of telomere length reduction. The first group had telomere shortening at the time of disease diagnosis. In four of the six MDS patients in this group, the disease progressed within 6 months postdiagnosis and each of them survived for less than 1 year. Moreover, in this group four patients showed a 5q anomaly with or without additional changes, and 50% of patients in this group had complex chromosome abnormalities. The patients in the second group showed reductions in telomere length after disease progression; two of these three patients showed gradual disease progression and had one or two chromosome abnormalities. The third group comprised the remaining seven MDS patients; they showed no telomere reduction by disease evolution. Two patients in this group experienced rapid disease progression. These results may indicate that telomere reduction is linked to disease evolution in some MDS patients, perhaps as a result of genomic instability because patients with complex chromosome abnormalities were clustered in the first group. However, because some MDS patients show disease progression without telomere reduction, genetic changes, including point mutations of certain gene(s), may also contribute to disease progression. We further noted that telomere shortening at the time of MDS diagnosis might indicate a poor MDS prognosis.
Acute Disease↗
Nucleotide sequence of the structural gene for the penicillin-binding protein 2 of Staphylococcus aureus and the presence of a homologous gene in other staphylococci.
The structural gene for penicillin-binding protein 2 (PBP2) of Staphylococcus aureus was cloned and sequenced. The nucleotide sequence of the 2,458-bp chromosomal fragment was determined, and the 2,148-bp coding region for PBP2 was identified. Determination of ten N-terminal amino acids of the PBP2 protein indicated that N-terminal methionine had been removed from the primary translational product. Thus, PBP2 is comprised of 715 amino acids with a molecular mass of 79,147. Nucleotide sequences having some homology with the PBP2 gene and proteins cross-reactive with anti-PBP2 antibody were detected in some other species of staphylococci by polymerase chain reaction and Western blot analysis, respectively.
Amino Acid Sequence↗
A unique sequence located downstream from the rice mitochondrial atp6 may cause male sterility.
Asymmetric cell-fusion of the japonica cultivar of Oryza sativa (rice) with cytoplasmic-male-sterile (CMS) plants bearing cytoplasm derived from Chinsurah Boro II, resulted in two classes of cytoplasmic hybrids (cybrids), fertile and CMS. Southern-blot analysis of the mitochondrial DNA (mtDNA) indicates recombination events around a number of genes; however, the appearance of the CMS character is tightly correlated to reorganization around the atp6 gene, suggesting recombination downstream from the atp6 gene is involved in CMS. The nucleotide sequence downstream from atp6 contains a pseudogene which was probably created by recombination of the mitochondrial genome. Sense and antisense transcripts of the downstream region of atp6 were found in CMS- and restored CMS (fertile)-lines, but not in the normal (fertile) line. In the CMS line, several antisense transcripts of the atp6 gene were also found. However, in the restored line which contains a nuclear-encoded gene, Rf-1, the levels of these transcripts were lower than in the CMS line. These results suggest abnormal transcripts of the atp6 gene produced in the antisense direction may be involved in CMS, and that products of the nuclear-encoded restorer gene may reduce abnormal transcription in this region of the mitochondrial genome.
Base Sequence↗
Surgical results of performing R4 gastrectomy for gastric cancer located in the upper third of the stomach.
Because gastric cancers located in the upper third of the stomach are difficult to detect at an early stage, the surgical results remain poor. We performed R4 gastrectomy as a radical procedure for 25 patients, involving complete resection of the latero-aortic and interaorticovenous lymph modes above and below the left renal vein, in combination with the ordinary R2 or R3 gastrectomy (the R4 group). These patients were compared with 156 others who underwent R2 gastrectomy alone (the R2 group). There were no significant differences in operation time, blood loss, or the incidence of complications between the two groups; however, when the survival rates of the patients with tumors invading beyond the subserosa were compared, the 5-year survival rate was found to be significantly higher in the R4 group than in the R2 group. Furthermore, in patients with para-aortic nodal involvement, a significant survival advantage was observed in the R4 group, as compared with the R2 group. These results suggest that the R4 gastrectomy is a rational approach for patients with advanced gastric cancer located in the upper third of the stomach.
Female↗