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Biomedical subjects

T Sekine

Publications and source records attributed to T Sekine.

At least 127 records · Page 7Linked to original sources

Guanidinoacetic acid (GAA) synthesis in rat tubular suspension as a system for evaluating gentamicin (GM) nephrotoxicity.

Since guanidinoacetic acid (GAA), a precursor of creatine, is synthesized mainly in the proximal tubule of the kidney where gentamicin (GM) nephrotoxicity often occurs, GM-induced renal cell damage was investigated using GAA synthesis in tubular suspension as an indicator. Results obtained were as follows: (1) GAA synthesis was significantly suppressed with 1 mM GM; (2) GM-induced decrease in GAA synthesis was recognized during incubation longer than 15 min; (3) furosemide significantly enhanced the suppression of GAA synthesis by GM. The results obtained parallel with those in the whole animal thus making GAA synthesis in tubular suspension a valid system for evaluating the GM-induced proximal tubular damage.

Animals↗

Clinical and Histological Prognostic Factors in Axillary Node-Negative BreastCancer: Univariate and Multivariate Analysis with Relation to 5-Year Recurrence.

In the recent years several studies have shown that about 30% of cases with axillary node-nagative breast cancer suffer relapse of the disease. Our attempt was made to evaluate the most significant prognostic factors to predict this high risk group which may be benefited from adjuvant treatment. For this purpose, we selected 9 patients out of 80 cases of node-negative breast cancer who had been followed up at least for 5 years and had the recurrence of the disease. For comparison, 16 patients from the same group who did not have relapse were selected on a random basis. Histology, receptor status, AgNOR, DNA flow cytometry and various immunohistochemical parameters were compared between the groups with recurrence and that without recurrence. On univariate analysis, tumor size, immunohistochemical expressions of PCNA, MIB-1, c-erbB-2 and S-phase fraction were significantly different between the above two groups. By multivariate analysis, immunohistochemical c-erbB-2 expression (more than 50% of cancer cells) was an independent parameter. As a summary from our studies, c-erbB-2 immunohistochemical staining on paraffin sections might be the best independent prognostic factor in axillary node-negative breast cancers.

Journal Article↗

Demethylation of a repetitive DNA sequence in human cancers.

To detect DNA alterations in unknown regions in human cancers, we have performed restriction landmark genomic scanning (RLGS) analysis of DNA isolated from cancer and normal cells. One spot with a highly intensified signal was detected in DNA from all six malignant melanoma cell lines, two of five colon cancer cell lines and one of six pancreatic cancer cell lines analyzed. In DNA from normal cells, two placentas and seven cultured lymphocytes, the signal of this spot was not intense. The DNA fragment corresponding to the spot was cloned. By nucleotide sequence analysis, the DNA fragment was revealed to be a part of a repeating unit of a 13 kbp nucleotide sequence of which 200 copies were located in chromosome 8q21. Southern blotting analysis using the cloned fragment as a probe demonstrated that the intensified signal for the DNA fragment observed in cancer cells was due to demethylation in the recognition sequence of the NotI restriction enzyme. The results suggest that marked demethylation in the repeating units might be associated with the genesis or progression of some types of cancers.

Base Sequence↗

Colonic and peritoneal tuberculosis associated with coloduodenal fistula.

We report a very rare case of tuberculous colitis that showed relatively long-segment involvement of the colon near the hepatic flexure with coloduodenal fistula that caused severe malnutrition. The formation of fistula in abdominal tuberculosis is very rare. This is the eighth reported case of abdominal tuberculosis with fistula and the first reported case with a coloduodenal fistula.

Adult↗

Cytotoxic activity of CD4+ T cells against autologous tumor cells.

The 51Cr-release assay is mostly applied to detecting the cytotoxic activity of CD8+ T cells, and little is known about the activity of CD4+ T cells. Therefore, the correlation between the cytotoxic activity of CD4+ or CD8+ T cells and the incubation period with autologous tumor cells was analyzed by two methods. The incubation periods were 4 and 20 h (4 h and 20 h assay) for the 51Cr-release assay. Eight pairs of tumor cells and T cells were assayed. T cells were fractionated into CD4+ and CD8+ T cells by using magnetic beads and panning methods, and those cells were activated by culture with recombinant interleukin-2 and immobilized anti-CD3 monoclonal antibody. In 6 out of 8 cases, no cytotoxic activity of CD4+ T cells was detected by the 4 h assay, whereas cytotoxic activity was detected in all cases in the 20 h assay. The cytotoxic activities in 20 h assay of CD4+ T cells were increased 67-fold in comparison with the activities in 4 h assay (range: 5-197). In the case of CD8+ T cells, cytotoxic activities were detected in 6 out of 8 cases in the 4 h assay. The lytic unit ratio of CD4+ and CD8+ T cells was calculated as 1.5 in the 20 h assay (range: 0.2- > 7.2) versus 0.4 in the 4 h assay (range: < 0.1-1.3). Cytotoxic activities in colorimetric assay using Crystal Violet with a 24 h incubation were similar to those in the 20 h 51Cr-release assay in all eight cases. These results indicate that CD4+ T cells have cytotoxic activity as strong as that of CD8+ T cells towards autologous tumor cells.

Adult↗

Synthesis of [5'-11C]ribonucleoside and -2'-deoyribonucleoside derivatives from D-ribose.

An approach to the synthesis of 2'-deoxy[5'-13C]ribonucleosides was achieved by the coupling reaction of a nucleic acid base derivative with D-[5-13C]ribose derivative (8). Compound 8 was derived from D-ribose (1) by way of methyl 2,3-di-O-benzyl(Bn)-D-ribofuranoside (2), 2,3-di-O-Bn-D-ribose diethyl dithioacetal (3), 2,3-di-O-Bn-D-ribose dibenzyl acetal (4), and 4-aldehydo-2,3-di-O-Bn-D-erythrose dibenzyl acetal (5), which was then successively subjected to Wittig reaction using Ph3P13CH3I-BuLi, highly stereoselective hydroxylation with OsO4 to give 2,3-di-O-Bn-D-ribose dibenzyl acetal (7), debenzylation with H2-Pd/C. The resulting 8 was subjected to coupling reaction with a nucleic acid base to give [5'-13C]ribonucleosides. The products were derived into the corresponding 2'-deoxy[5'-13C]ribonucleoside derivatives by the established manner.

Carbon Isotopes↗

Alpha-fetoprotein-producing rectal cancer: calculated tumor marker doubling time.

alpha-fetoprotein (AFP) production by rectal cancer is very rare. In the English literature there are only a few reported cases in which serum AFP level was > 1,000 ng/ml. A 43-year-old Japanese man with rectal cancer and liver metastases had a high serum AFP level (941 ng/ml) when first evaluated. Three weeks later, the serum AFP level was extremely elevated (7,060 ng/ml). He underwent abdominoperineal excision of the rectum and biopsy of liver metastases. The placement of an intrahepatic-arterial infusion catheter into the proper hepatic artery via the right gastroepiploic artery was also performed. Immunohistochemically, AFP-positive cells were identified in both the rectal and liver tumors. Nine days postoperatively, the serum AFP level was 2,000 ng/ml. In spite of intensive chemoimmunotherapy, serum AFP level was increased and 14 weeks after surgery was extremely elevated (267,300 ng/ml). The patient succumbed to cancer 3 months after surgery. To our knowledge, this is the first case of an AFP-producing rectal cancer in which AFP doubling time could be calculated as 12.8 days.

Adenocarcinoma↗

Fully mechanized latex immunoassay for serum lipoprotein(a).

We have developed a fully automated system to quantify lipoprotein(a) (Lp(a)) in human serum, based on the latex-enhanced turbidimetric immunoassay by application of the Immuno Chemistry Analyzer 501X. This assay was carried out with undiluted serum and was able to detect at Lp(a) levels higher than 4.0 mg/l. When judged to be out of range of the calibration (> 600 mg/l), the sample was automatically re-tested after automatic 10-fold dilution. Within-run C.V.s ranged from 1.9 to 2.1% and between-run C.V.s from 2.7 to 3.9%. Results by the present method were in good agreement with those by the in-house ELISA (r = 0.978) and the commercial ELISA (r = 0.990). The distribution of Lp(a) levels in sera from 508 healthy donors was highly skewed; the mean and median were 158 mg/l and 105 mg/l, respectively.

Adolescent↗

[A prospective study of septic episodes due to Staphylococcus aureus and the background of the patients].

From January 1983 to December 1991, 94 cases of Staphylococcus aureus septicemia were identified at Matsue Red Cross Hospital and were evaluated. Methicillin-resistant Staphylococci aureus counted 49%. Seventy two percent of the patients were 60 years or over in age. Intravascular catheters were the most common foci (33%), respiratory infections in 25% and so on. Administration of antibiotics before isolation of Staphylococcus aureus were thought to be the most significant factor in producing the methicillin-resistant septicemia, used in 41% of MSSA and 91.3% of MRSA cases. Especially, the trend of unproper usage of the 3rd generation cephems derivative antibiotics had a major role in producing multi-drug resistant bacteria. No significance was seen in the clinical background, underlying diseases, primary site of infection in between the two groups of methicillin resistant and sensitive cases. Mortality due to septicemia was 47.9% in the MSSA group of patients, while it was much higher in cases of MRSA (73.9%). In conclusion, as the administration of antibiotics even in non-infectious episodes is common in daily clinical activities in some out-patient clinics, the indications should be restricted, in order to prevent the further MRSA infections.

Adolescent↗

Successful continuous treatment with all-trans retinoic acid for acute promyelocytic leukemia; secondary malignancy after the treatment of osteosarcoma.

We report a rare case of complete remission for 32 months with continuous treatment with all-trans retinoic acid (ATRA) alone in a patient with acute promyelocytic leukemia which developed as a second malignancy after the treatment of osteosarcoma after failure of conventional chemotherapy. The adverse effects of ATRA were apparently tolerable.

Adolescent↗

[Prevention of cancer recurrence by infusion of activated autologous lymphocytes].

Activated and expanded autologous peripheral blood lymphocytes by cultivation with immobilized anti-CD3 antibody and IL-2 have been infused to the patients with hepatocellular carcinoma after culative operation as a randomized clinical trial. This study is on-going and primary efficacy endpoints of this study were disease-free survival and overall survival, and the sample size for the study was designed as a minimum of 146 patients. From interim analysis at the second year from start of the study, Eligible cases were 101, 49 cases in treated group and 52 cases in control. Recurrences were confirmed 13 cases from treated group and 22 cases from control group. Minor adverse reaction were observed in 28 cases (57%).

Antibodies, Monoclonal↗

[Randomized controlled trial of MMC + UFT and MMC + 5-FU therapy in advanced gastric cancer].

To compare the effects of MMC + UFT (A) with MMC + 5-FU (B) therapy on the response rate, survival time and changes with time in quality of life (QOL) in unresectable or recurrent gastric cancer, we carried out a study by a multicenter, randomized controlled trial from June 1990 to August 1992. 39 patients were randomly divided into A group and B group, including 6 incompletely evaluated cases and 3 in eligible cases. Responses were recognized in 3 out of 13 evaluable cases (23.1%) treated with regimen A and in one out of 15 evaluable cases (6.7%) treated with regimen B. Mean survival time was 150 days (A) and 116 days (B), respectively. These results suggested that MMC + UFT therapy is one of the effective regimens for advanced gastric cancer and as useful as MMC + 5-FU therapy. Moreover, it showed that regimen A was superior to B on QOL.

Antineoplastic Combined Chemotherapy Protocols↗

Identification of a new serine kinase that activates NF kappa B by direct phosphorylation.

A novel serine kinase, named nuclear factor kappa B (NF kappa B) kinase, has been shown to be associated with the NF kappa B.I kappa B complex in the cytosol of human primary T lymphocytes. It activates the DNA binding activity of NF kappa B by directly phosphorylating its p65 and p50 subunits. There is no evidence that it phosphorylates I kappa B. Experiments with inhibitors and antisera showed that it is distinct from other known serine kinases such as mitogen-activated protein kinase or Mos. It has an apparent molecular size of 43 kDa determined by the substrate binding assay. This kinase might have a central role in mediating various signals to NF kappa B.

Adenosine Triphosphate↗

Biologic characteristics of acute leukemia after myelodysplastic syndrome.

Ten patients with acute leukemia after primary myelodysplastic syndrome (MDS-AL) were examined to clarify the biologic nature of the leukemic cells in comparison with that of de novo acute myelocytic leukemia (AML). The morphologic and cytochemical features of the leukemic cells from all these patients corresponded well to those of de novo AML, and they were diagnosed with MDS-AML. Phenotypically, the frequent expression of the lymphocyte activation antigens, CD25 and CD30, was characteristic in MDS-AML. The in vitro response of MDS-AML cells to various growth factors was similar to that of de novo AML cells. Transforming growth factor beta 1 (TGF beta 1) suppressed growth factor-dependent colony formation by normal bone marrow cells, MDS bone marrow cells, and de novo AML cells, but did not inhibit colony formation by MDS-AML cells. The number of TGF beta 1 high-affinity binding sites of MDS-AML samples (< 5 to 47 sites/cell) was markedly lower than that in de novo AML samples (120 to 221 sites/cell). Our results indicate that the reduced TGF beta 1 may represent disregulation of the proliferation system in MDS-AML cells. This is thought to occur during the MDS phase, and may be related to the poorer response shown to conventional chemotherapy of AML.

Adult↗

Three-dimensional cytoarchitecture of complex branched fibers in soleus muscle from mdx mutant mice.

Three-dimensional cytoarchitecture and types and features of muscle fibers were examined in soleus muscles from mdx mutant mice at different stages of development. In the 2-week-old mice, no abnormal muscle fibers were observed light microscopically, whereas in the 4-week-old animals, disrupted fibers were frequent in light microscopy and scanning electron microscopy. Muscle fibers fused with several short fiber branches appeared at the sixth week after birth and increased in number until the tenth week. In the 1-year-old mice, approximately ten or more muscle fibers were seen fused together. They had many complex branches forming an "anastomosing syncytial reticulum." Muscle fibers with irregular diameters and aggregations of the same type fibers were also observed. Our results demonstrated that these complex branched fibers might be formed by long term repetition of the degeneration and regeneration cycle during the development of soleus muscles, indicating that the characteristic features of muscle fibers with irregular diameters and aggregations of the same type fibers are certainly dependent on the existence of the complex branched fibers.

Animals↗

Acute renal failure after exercise in a child with renal hypouricaemia.

We describe a 12-year-old boy with renal hypouricaemia who presented with acute renal failure after a 6-h sports training session. Back and loin pain were noted at presentation. Although serum creatinine and blood urea nitrogen were elevated, the serum uric acid concentration was normal (2.6 mg/dl). This decreased to 0.3 mg/dl after recovery. The pyrazinamide and probenecid tests revealed that the cause of renal hypouricaemia in this patient was totally defective uric acid reabsorption. Acute renal failure after exercise is a rare but serious complication in paediatric patients with renal hypouricaemia.

Acute Kidney Injury↗