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Biomedical subjects

T Fujimura

Publications and source records attributed to T Fujimura.

At least 163 records · Page 9Linked to original sources

[Chemohyperthermic peritoneal perfusion and high-dose chemotherapy followed by peripheral blood stem cell transplantation in advanced colon cancer--a case report].

A 49-year-old woman who suffered from caecal cancer in 1988 underwent chemohyperthermic peritoneal perfusion for peritoneal and ovarian metastases in 1990, and high dose chemotherapy (HDC) with peripheral blood stem cell transplantation (PBSCT) for lung metastases in 1995. Heated saline containing anticancer drugs such as cisplatin, mitomycin C, etoposide (ETP), and pirarubicin, was intraperitoneally perfused at 43 degrees C for 60 minutes. The CD34 positive cells were mobilized by intravenous 500 micrograms G-CSF administration on five consecutive days. These cells were transplanted three days after the last day in the course of HDC, which included intravenous administration of 475 mg carboplatin, 2,020 mg cyclophosphamide, and 540 mg etoposide. The patient has survived with no sign of the disease.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical usefulness of serum CYFRA21-1 in colorectal cancer].

Serum CYFRA21-1 levels were studied in 127 cases of colorectal cancer. The positive rates for serum CYFRA21-1 were 34.6% in primary colorectal cancer. There was a significant correlation between the positive rates of serum CYFRA21-1 and liver metastases, peritoneal dissemination, lymph node metastases, or clinical stage. The survival rate for patients in the CYFRA21-1 positive group was lower than those with CYFRA21-1 negative group. Among patients who underwent curative operation, patients is the CYFRA21-1 positive group gave a recurrence rate of 26.6%, against 9.4% in the CYFRA21-1 negative group. There was no correlation between serum CYFRA21-1 levels and serum CEA levels. These findings suggest that Serum CYFRA21-1 levels may be a useful indicator in estimating the prognosis for colorectal cancer.

Adenocarcinoma↗

Infected aneurysms--clinical study of 5 cases.

The infected aneurysm has been assumed to be a disease with a poor prognosis due to the occurrence of aneurysmal ruptures and sepsis, in contrast to the outcome of atherosclerotic aneurysms. In the present study, we conducted surgical treatment on five patients with infected aneurysms (infected abdominal aortic aneurysm in three cases and iliac artery aneurysm in two cases). In particular, two of the three patients suffering from infected abdominal aortic aneurysms underwent extra-anatomic bypass and the remaining one case underwent vascular graft replacement in situ. In the two patients who underwent an extra-anatomic bypass, an aneurysm was found at the site of aortic stump closure. In the patient who underwent in situ replacement, wrapping was carried out using the omentum after vascular graft replacement, and the postoperative course was uneventful. Accordingly, we consider that the optimum primary therapeutic intervention for infected aneurysms is in situ revascularization followed by wrapping with the omentum after removal of the aneurysm and debridement of the surrounding infected tissue to the maximum extent possible.

Adult↗

The expression pattern of erythrocyte/megakaryocyte-related transcription factors GATA-1 and the stem cell leukemia gene correlates with hematopoietic differentiation and is associated with outcome of acute myeloid leukemia.

To understand the clinical implications of transcription factors and their biologic roles during cellular differentiation in the hematopoietic system, we examined the expression of GATA-1, GATA-2, and stem cell leukemia (SCL) gene in human leukemia cell lines and various leukemia patients using the reverse transcriptase-polymerase chain reaction. Cell lines exhibiting megakaryocytic or erythrocytic phenotypes had GATA-1, GATA-2, and SCL gene transcripts, while monocytic cell lines had no detectable GATA-1, GATA-2, or SCL gene mRNA. In some myeloid cell lines, GATA-1 expression, but not SCL gene expression, was detected; GATA-1 expression in HL-60 cells was downregulated during the process of monocytic differentiation. We next examined GATA-1, GATA-2, and SCL gene expression in 110 leukemia samples obtained from 76 patients with acute myeloid leukemia (AML), 19 with acute lymphoblastic leukemia (ALL), and 15 with chronic myeloid leukemia in blast crisis (CML-BC). SCL gene expression was usually accompanied by GATA-1 expression and was preferentially detected in patients with leukemia exhibiting megakaryocytic or erythrocytic phenotypes, while patients with monocytic leukemia were clustered in the group with no detectable GATA-1 expression. None of the patients with ALL or CML-lymphoid-BC expressed SCL. De novo AML patients with SCL gene expression had a lower complete remission (CR) rate and had a significantly poorer prognosis. Among the patients with AML not expressing SCL, a high percentage of patients with CD7+ AML and CD19+ AML had detectable GATA-1, while patients with GATA-1-negative AML had the best CR rate (87.5%). Our results suggest that the expression pattern of transcription factors reflects the lineage potential of leukemia cells, and GATA-1 and SCL gene expression may have prognostic value for the outcome of patients with AML.

Acute Disease↗

E-cadherin and urokinase-type plasminogen activator tissue status in gastric carcinoma.

BACKGROUND: E-cadherin (ECD) is known to be an invasion suppressor gene, and urokinase-type plasminogen activator (uPA) plays a central role in infiltration of solid cancers. METHODS: To elucidate the relationship between expression of these factors and metastasis in patients with gastric cancer, the authors examined immunohistochemically a combination analysis of uPA and E-cadherin expression in 98 primary tumors, and the results were correlated with several parameters related to metastasis. RESULTS: Among 125 tumors, 42 (34%) were evaluated as having E-cadherin expression (E-cadherin-positive), and the other 83 (66%) were defined as having reduced E-cadherin expression (E-cadherin-negative). uPA immunoreactivity was observed in 82 tumors (66%). There were four subtypes of patterns of uPA and E-cadherin expression: 22 uPA-negative/E-cadherin-positive, 17 uPA-negative/E-cadherin-negative, 21 uPA-positive/E-cadherin-positive, and 65 uPA-positive/E-cadherin-negative, uPA overexpression and reduced E-cadherin expression were associated with lymph node metastasis, vessel invasion, serosal involvement, and poor prognosis. In addition, uPA-positive/E-cadherin-negative tumors were associated significantly with large tumors, positive serosal invasion, lymph node involvement, and poor prognosis. Patients with uPA-positive/E-cadherin-negative expression had the poorest prognoses, compared with the three other groups of patients uPA-positive/E-cadherin-negative tumors had a fourfold relative risk of death when compared with uPA-negative/E-cadherin-positive tumors. A Cox proportional hazard model projected lymph node status as the strongest of the prognostic variables followed by DNA ploidy patterns and uPA/E-cadherin tissue status. CONCLUSIONS: These results indicate that immunohistochemical combination analysis of uPA and E-cadherin expression may be a powerful aid in evaluating metastatic potential or the prognosis of patients with gastric cancer.

Adult↗

Yeast viral 20 S RNA is associated with its cognate RNA-dependent RNA polymerase.

Most Saccharomyces cerevisiae strains carry in their cytoplasm 20 S RNA, a linear single-stranded RNA molecule of 2.5 kilobases in size. 20 S RNA copy number is greatly induced in stress conditions such as starvation, with up to 100,000 copies per cell. 20 S RNA has coding capacity for a protein of 91 kDa (p91) with sequences diagnostic of RNA-dependent RNA polymerases of (+) strand and double-stranded RNA viruses. We detected p91 in 20 S RNA-carrying strains with specific antisera. The amount of p91 in growing cells is higher than that of stationary cells and similar to the one in 20 S RNA-induced cells. Although 20 S RNA is not encapsidated into viral particles, p91 non-covalently forms a ribonucleoprotein complex with 20 S RNA. This suggests a role of p91 in the RNA to RNA synthesis processes required for 20 S RNA replication. Although the strain analyzed also harbors 23 S RNA, a closely related single-stranded RNA, 23 S RNA is not associated with p91 but with its putative RNA polymerase, p104. Similarly, 20 S RNA is not associated with p104 but with p91. These results suggest that 20 S RNA and 23 S RNA replicate independently using their respective cognate RNA polymerases.

Fungal Proteins↗

Transcriptional inhibition of insulin by FK506 and possible involvement of FK506 binding protein-12 in pancreatic beta-cell.

FK506 (tacrolimus) is a strong immunosuppressant: it has been approved as a drug for liver transplantation in Japan, the United States, and the United Kingdom. One of its main adverse effects is hyperglycemia. Thus, in this study, we investigated the mechanism and the reversibility of the hyperglycemia caused by FK506. FK506 did not affect the glucose uptake by insulin into rat strio-muscle cell line, but suppressed insulin production in rat insulinoma cells. Two-week oral administration of FK506 at 10 mg/kg/day suppressed insulin production time-dependently at the transcriptional step in pancreatic beta-cells, while glucagon content in pancreatic alpha-cells was not affected. When FK506 administration was stopped in these rats, insulin mRNA transcription and insulin production returned to normal. This recovery indicates that the adverse effect of FK506 on the pancreas is reversible. A high content of FK506 binding protein-12 (FKBP-12) in the pancreatic beta-cells was confirmed by immunostaining with anti-human FKBP-12 mAb, but the content was less in the pancreatic alpha-cells and almost negligible in the acinar cells. In contrast, a high content of calcineurin in the pancreatic alpha-cells was confirmed by using anti-calcineurin polyclonal antibody, but this content was less in the pancreatic beta-cells and not found in the acinar cells. Thus, as in the case with NF-AT in T cells, these findings point to the reduction of unidentified nuclear factors for insulin mRNA transcription caused by the binding of FK506 to FKBP-12 and a subsequent inhibition of calcineurin in the beta-cells.

Animals↗

Ecotropic virus integration site-1 gene preferentially expressed in post-myelodysplasia acute myeloid leukemia: possible association with GATA-1, GATA-2, and stem cell leukemia gene expression.

We investigated expression of the human ecotropic virus integration site-1 (EVI1) gene in patients with leukemia and myelodysplastic syndrome (MDS) using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. The EVI1 transcripts were detected in 5 (10.0%) of 50 patients with de novo acute myeloid leukemia (AML), including two AML patients with trilineage myelodysplasia, and in 8 (34.8%) of 23 patients with post-myelodysplastic syndrome AML (post-MDS AML). EVI1 expression was also detected in 6 (35.3%) of 17 MDS patients and three of six patients with chronic myeloid leukemia (CML) in myelomegakaryoblast crisis. No EVI1 transcripts were detected in patients with acute lymphoid leukemia (n = 15) or CML in lymphoid blast crisis (n = 4). Chromosomal abnormalities at the 3q26 region, where the EVI1 gene is located, were found in one patient with MDS and two patients with CML myelomegakaryoblast crisis who had EVI1 expression. Our results showed that EVI1 expression was frequent in patients with post-MDS AML and AML with trilineage myelodysplasia, regardless of the presence or absence of 3q26 abnormalities. EVI1 expression was accompanied by expression of GATA-1 and GATA-2, and often by stem cell leukemia (SCL) gene expression. In patients with post-MDS AML, EVI1 expression was not always associated with a 3q26 abnormality, whereas EVI1 expression in CML myelomegakaryoblast crisis was often linked to a 3q26 abnormality. Our results suggest that the leukemogenic role of EVI1 expression may differ between post-MDS AML and leukemia, with EVI1 expression associated with a 3q26 abnormality.

Adult↗

High-level production, chemical modification and site-directed mutagenesis of a cephalosporin C acylase from Pseudomonas strain N176.

A cephalosporin acylase from Pseudomonas strain N176 hydrolyses both 7-beta-(4-carboxybutanamido)-cephalosporanic acid (glutarylcephalosporanic acid) and cephalosporin C to 7-amino-cephalosporanic acid. However, its productivity in the original host was low and its activity against cephalosporin C was not sufficient for direct large-scale production of 7-amino-cephalosporanic acid. In order to overcome these problems, we established a high-level expression system for the acylase in Escherichia coli. Tyr270 in the acylase is reported to play an important role in the interaction with glutarylcephalosporanic acid, as determined from the reaction with an affinity-label reagent, 7 beta-(6-bromohexanoylamido) cephalosporanic acid [Ishii, Y., Saito, Y., Sasaki, H., Uchiyama, F., Hayashi, M., Nakamura, S. & Niwa, M. (1994) J. Ferment. Bioeng. 77, 598-603] and modification with tetranitromethane [Nobbs, T. J., Ishii, Y., Fujimura, T., Saito, Y. & Niwa, M. (1994) J. Ferment. Bioeng. 77, 604-609]. From carbamoylation with potassium cyanate and site-directed point mutagenesis of the cephalosporin C acylase, we have deduced that Tyr270 exists at a position where it can interact with a residue (possibly Ser239) corresponding to inactivation by carbamoylation. We mutated Met269 and Ala271 of the acylase and found that mutation of Met269 to Tyr or Phe caused a 1.6-fold and 1.7-fold increase, respectively, of specific activity against cephalosporin C as compared to that of the wild-type enzyme. Kinetic studies of these mutants revealed that their kcat values increased, although their Km values against cephalosporin C were not changed. These data indicate that the mutation of Met269 near Tyr270 induces a minor conformational change to increase the stability of the activated complex with the enzyme and cephalosporin C. In particular, a mutant in which Met269 was replaced by Tyr was 2.5-fold more efficient in converting cephalosporin C to 7-amino-cephalosporanic acid than the wild-type enzyme under conditions similar to those in a bio-reactor system.

Amino Acid Sequence↗

High-frequency inter-parental recombination between mitochondrial genomes of rice cybrids.

Analyzing more than 100 independent rice cybrids, we found evidence for inter-molecular recombination between parental mitochondrial genomes occurring at high frequency soon after protoplast fusion. The structure of the region around the atp6 gene showed extensive polymorphism among Indica (MTC-5A), Japonica (Nipponbare), and wild abortive (IR58024A) mitochondrial genomes. Recombination between the mitochondrial genomes of IR58024A and MTC-5A around the atp6 gene was detected by Southern-blot analysis of cybrid plants. Such recombinant mitochondrial molecules were also cloned from IR58024A/Nipponbare cybrid callus. PCR analysis around the atp6 gene demonstrated that inter-parental recombination occurs in practically all cybrid calli within 2 weeks after protoplast fusion. At this point, parental and recombinant mitochondrial genomes co-existed within the callus. Over the course of further cultivation, however, mitochondrial genome diversity decreased as parental and/or recombinant genomes segregated out.

Base Sequence↗

Double-minute chromosomes appearing in a patient with myelodysplastic syndrome with disease evolution.

We present the first case of a myelodysplastic syndrome (MDS) demonstrating an association between the appearance of double-minute chromosomes (dmin) and disease progression. This 59-year-old Japanese woman showed a deletion of the long arm of chromosome 5 [del(5)(q21q34)] and monosomy 9, when she was diagnosed as having refractory anemia with an excess of blasts (RAEB). Subsequential cytogenetic analyses demonstrated that the neoplastic cells in the peripheral blood had six copies of dmin, when the disease progressed into RAEB in transformation (RAEBt). This cytogenetic change was consistently observed when the patient developed the leukemia phase. The findings in this case suggest that the appearance of dmin may be linked to progression of the disease.

Chromosome Aberrations↗

Rationale for extensive lymphadenectomy in early gastric carcinoma.

The incidence of nodal metastasis in early gastric carcinoma (EGC) is 10-20%. However, the optimal nodal dissection for early gastric carcinoma has not been established. A retrospective study was conducted in 392 consecutive patients who underwent potentially curative distal gastrectomy for EGC between 1962 and 1990. Of these 295 patients treated after September 1972 were prospectively entered into an extensive lymphadenectomy protocol. These patients were compared with 97 patients with simple gastrectomy in respect of the causes of death after surgery and the 10 year disease-specific survival rate. The incidence of nodal metastasis in early gastric carcinoma patients was 13.0%. Operative mortality from extensive lymphadenectomy was almost the same as from simple gastrectomy (2.0% and 2.1% respectively). Extensive lymphadenectomy provided a significantly higher 10 year survival rate than limited lymph node dissection (97.9% vs 88.1% respectively; P < 0.005). Among patients with nodal metastasis, the survival rate following extensive lymphadenectomy was significantly higher than that after simple gastrectomy (87.5% vs 55.6%; P = 0.018). Among patients without nodal metastasis, there was no difference between the two groups in the survival rate (99.4% and 96.7% respectively; P = 0.12). Multivariate analysis using the Cox proportional hazards model disclosed two significant independent prognostic factors on disease-specific survival, the nodal involvement (risk ratio: 8.4; P < 0.0001) and the extent of lymph node dissection (risk ratio: 5.8; P < 0.005). Extensive nodel dissection appears to prevent recurrence and to improve the cancer-specific survival in EGC patients with nodal metastasis.

Adult↗

Involvement of annexin-I in glucose-induced insulin secretion in rat pancreatic islets.

Annexin-I was demonstrated to specifically present in islets and not in exocrine tissues of the rat pancreas and to have a diffuse and homogeneous distribution in all islet cells in our previous study. In the present report, to clarify the functions of annexin-I in rat pancreatic islets, especially in beta-cells, we investigated the role of annexin-I in insulin secretion. Immunoelectron microscopic analysis of pancreatic beta-cells demonstrated that immunogold particles reactive to annexin-I were almost exclusively observed on most of the insulin-containing granules (approximately 90%) and less frequently located in cytosol and other organelles, such as the endoplasmic reticulum and mitochondria. The number of annexin-I gold particles located on insulin granules after oral glucose administration was significantly increased compared with that observed in fasted rats. Moreover, when the isolated islets were stimulated by a high concentration of glucose (20 mM), the phosphorylation of annexin-I was markedly enhanced, and it was synchronized to insulin secretion. This phosphorylation mainly occurred on serine residues. H-7 (100 microM), a potent inhibitor of protein kinase-C, inhibited the phosphorylation to about 90%. These findings suggest that annexin-I might be involved in the regulatory mechanism of glucose-induced insulin secretion in rat pancreatic islets via phosphorylation-dephosphorylation processes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Life satisfaction and its related factors among institutionalized patients at a Hansen's disease sanatorium].

We conducted a questionnaire survey on life styles and health status for 293 patients with Hansen's disease. They were admitted to the wards for disabled and physically able patients of Ohshima Seishoen, in Kagawa prefecture, in 1991. This institution is one of Japan's national leprosy sanitarians. We measured patients' life satisfaction with the Delighted-Terrible Scale. In this report, the distribution of life satisfaction and its associated factors were examined for 210(71.7%) respondents. Factors examined were length of treatment, physical health, and social aspects of life at the sanatorium. The major findings were as follows; 1. The patients aged under 60 had lower proportions of being satisfied with life than those aged 60 or older. The proportions of life satisfaction of the 40-59 age group were 17% for men and 22% for women, while for the 60 or older age groups were 33-44% for men and 41-45% for women. The proportions of life satisfaction in the 60 or older age groups were lower than those of community dwelling elderly persons. 2. We examined factors associated with life satisfaction for the respondents aged 60 or older. Dependence on activities of daily living (ADL) was associated with life satisfaction in some ADL items. Care and aid provided by the staff of the sanatorium may modify the relationship between ADL impairment and life satisfaction. For social aspects of life at the sanatorium, both having networks with family members and having resources other than family were associated with life satisfaction. Going out and positively spending their daily lives were associated with life satisfaction, too. These associations were significant for men. Similar patterns of association were observed for women, but were insignificant. This finding suggests that it is important for the health and medical care staff to pay attention to the social aspects of the life of elderly patients with Hansen's disease.

Activities of Daily Living↗

Work-related factors of low back pain among nursing aides in nursing homes for the elderly.

This survey was performed in December 1991 on 555 nursing aides (NAs) in 32 Special Nursing Homes for the Elderly (SNHs) in Kochi Prefecture, Japan. The purpose of the survey was to establish the relationship between low back pain among NAs in SNHs, and the degree of dependency in the activities of daily living (ADL) of the patients under their care. In order to investigate the work-related factors of low back pain, a questionnaire was sent to the NAs, requesting information on the NAs' low back pain condition. Another questionnaire was sent to the 32 SNHs, concerning the status of patients in the respective SNHs. Of the 463 NAs questionnaires which were returned, 443 female NAs' responses were analyzed. The following findings were observed. The prevalence of low back pain among the NAs was high (the one month prevalence was 77.0%), and of the afflicted NAs, 98 (24.5%) were visiting a health care provider. The NAs with low back pain experienced difficulty in completing their care-giving tasks, and complained about their working conditions and working environment more often than the NAs without low back pain. In addition, this study showed that, at SNHs where the proportions of dependence in patients' ADL were high, the prevalence of low back pain among their NAs was high. This fact was also confirmed by multiple logistic regression. We, therefore, suggest in this study that patients' care needs are associated with low back pain among NAs.

Activities of Daily Living↗

Quantitative evaluation of the cutting quality and abrasive resistance of scalers.

An automatic scaling apparatus that simulated the scaling process of hand instrumentation was developed to quantitatively analyze the cutting quality and abrasive resistance of scalers. We first tested 4 synthetic resins as the abraded material. Of the 4 synthetic resins tested, polycarbonate resin proved most similar to dentin. The effects of lateral scaling forces (700, 500, and 300 dyne) and scaler angles (70 degrees to 95 degrees) on the cutting quality and abrasive resistance of scalers were evaluated quantitatively by the amount of the abraded material worn away in 1,000 strokes. Comparison of the 3 scaling forces showed a greater amount of abrasion at higher force than that at lower force. This suggests that the decrease in the amount due to abrasion could be compensated by increasing the lateral scaling force. Regarding the scaler angle, results indicated that the amount of material removed increased with an increase of the scaler angle up to 70 degrees, but then rapidly decreased at an angle of 90 degrees or more. The most effective scaling angle was 87 degrees, and this was not affected by scaling force. These results suggest that a greater amount of removal could be obtained at a scaling angle of 87 degrees and a scaling force of 700 dyne. The present findings suggested the automatic scaling apparatus could be a useful tool for quantitatively evaluating the cutting quality and abrasive resistance of scalers.

Analysis of Variance↗

A newly-developed electrodeposited diamond scaler with high abrasive resistance.

A diamond scaler on which blade diamond particles were coated by electrodeposition was developed to improve the abrasive resistance of scaler blades. The electrodeposited coating was tested with diamond particles of four different sizes, designated D-4000 with 2 to 4 microns diameter of the particles; D-800 with 12 to 25 microns; D-600 with 20 to 30 microns; and D-400 with 30 to 40 microns. The abrasive resistance of the scalers was examined quantitatively using a recently-developed automatic scaling apparatus that simulated the scaling process of hand instrumentation, as well as SEM observation of the blades. A series of abrasion tests suggested that all the diamond scalers except D-4000 showed better abrasive resistance than the control (D-0), and that D-600 showed the highest abrasive resistance and cutting quality. The SEM observation also suggested that D-600 and D-400 might have higher abrasive resistance. Furthermore, the profilometric evaluation of the surface roughness of the scaled natural dentin after hand instrumentation indicated that the average surface roughness increased in the order of D-4000, D-800, D-600, and D-400, although no marked differences were observed among D-4000, D-800, D-600 and D-0, but not D-400. These results suggested that the electrodeposited diamond scaler with 20 to 30 microns diamond particles (D-600) might have marked abrasive resistance as well as cutting quality without remarkable damage to the tooth surface after conventional scaling procedure.

Adult↗