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Biomedical subjects

Y Koyanagi

Publications and source records attributed to Y Koyanagi.

At least 55 records · Page 3Linked to original sources
PubMed2000

Role of human telomerase reverse transcriptase and telomeric-repeat binding factor proteins 1 and 2 in human hematopoietic cells.

Telomerase, an enzyme that adds hexameric repeats of 5'-TTAGGG-3', termed telomeres, to the ends of chromosomal DNA, has been implicated in cellular immortalization and cellular senescence. Recently several relevant genes have been cloned, including those encoding three major components of human telomerase: human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase-associated protein-1 (TEP1). Also important are genes encoding human telomeric-repeat binding factor proteins (TRF) 1 and 2. We compared 10 human malignant hematopoietic cell lines, 19 samples from patients with acute leukemia and normal granulocytes and monocytes to study telomerase activity and expression of these various genes using a reverse transcription-polymerase chain reaction (RT-PCR). In all 10 malignant cell lines with telomerase activity, hTR, hTERT mRNA, and TEP1 mRNA were expressed, while in normal monocytes and granulocytes without telomerase activity, expression of hTR, but not hTERT mRNA was detected. TEP1 mRNA was expressed in normal monocytes, but not granulocytes. Expression of TRF1 and TRF2 mRNAs was greater in the normal cells than in human malignant hematopoietic cell lines and in 16 samples of patients with acute leukemia. When differentiation of the malignant hematopoietic cell line HL-60 was induced using tumor-necrosis-factor 471 and all-trans retinoic acid (ATRA), telomerase activity decreased gradually during differentiation. Of the three telomerase components, only hTERT mRNA expression showed changes paralleling telomerase activity, becoming undetectable with differentiation. In contrast, initially low expression of TRF1 and TRF2 mRNAs increased during differentiation. Not only hTERT, but also TRF1 and TRF2 are important regulators of telomerase activity that represent potential targets for gene therapy against cancer.

Adolescent↗
PubMed2000

[Efficient replication of human immunodeficiency virus type 1 in cytokine induced CD 4+ T helper 1 (Th 1)- and Th 2-type conditions].

Potent stimuli for CD 4+ T cell differentiation are cytokines. Among them, IL-12 or IL-4 induce naive CD 4+ T cells to Th 1 or Th 2 cells, respectively. In this study we found that macrophage-tropic (M-tropic) HIV-1 strains more efficiently replicated in interleukin 12 (IL-12) induced T helper 1 (Th 1)-type culture derived from normal CD 4+ T cells than T-cell-line-tropic (T-tropic) strains did. In contrast, T-tropic strains preferentially infected IL-4 induced Th 2-type culture derived from same donor CD 4+ T cells. Additional studies using chimeric viruses demonstrated that the V 3 region of gp 120 was the principle determinant for this efficient replication. It was also isolated T-tropic viruses from an acutely infected patient who had been evidenced as severe CD 4 depletion during short time course. These results indicate that HIV-1 isolates exhibit differences in the ability to infect CD 4+ T cell subset such as Th 1 or Th 2 cells, and that this difference may partly correlate with the viral pathogenesis. The findings suggest that immunological condition is one of the factors responsible for inducing selection of HIV-1 strains.

Cells, Cultured↗
PubMed2000

[Two cases of recurrent gastric cancer for which combination chemotherapy with pirarubicin, cis-platinum and 5-fluorouracil were markedly effective].

In the treatment of 2 patients with recurrent gastric cancer who showed bone metastasis and lymph node recurrence, we administered 30 mg/body of pirarubicin (THP) on the first day of treatment, and 30 mg/body of cis-platinum (CDDP) and 500 mg/m2 of 5-fluorouracil (5-FU) for 3 days (FP therapy). Marked effects were achieved. Gastric cancer of Borrmann IV type was diagnosed in Case 1, and total gastrectomy was performed. The histological type was poorly differentiated adenocarcinoma, and the histological classification was II. A bone metastasis was found three years after operation. The patient was CR after three courses of treatment, and has survived for 2 years. In Case 2, advanced gastric cancer was treated with neoadjuvant chemotherapy and distal gastrectomy. The histological type was moderately differentiated adenocarcinoma, and the histological classification was IIIa. Obstructive jaundice due to lymph node recurrence developed 6 years after operation. Two courses of treatment were provided after PTCD, and PR was observed. The patient has survived for 3 months. Both patients exhibited mild side effects such as anemia and leukocytopenia, but no serious complications were observed. Although various dosage regimens of FP therapy have been investigated, there has been a certain limit to the response rate achieved by this therapy, and new protocols have been explored. We achieved marked effects in 2 patients by adding THP to FP therapy. These cases are reported here together with some discussion of cases reported in the literature.

Adenocarcinoma↗
PubMed2000

[Two cases of malignancy-associated hypercalcemia from bone metastases of breast cancer successfully treated with combination therapy using pamidronate and calcitonin].

Two patients with malignancy-associated hypercalcemia from bone metastases of breast cancer, accompanied by consciousness disturbance, were treated by a combination therapy of pamidronate and salmon calcitonin. The cause of the hypercalcemia in both cases was thought to be expanded bone metastases, which induced a local osteolytic hypercalcemia (LOH). In the end, this regimen could not control the growth of the metastatic tumor, but it produced a more rapid and prolonged decrease in serum calcium level than a single agent, and resulted in lessened consciousness disturbance without adverse effects. Hypercalcemia is a life-threatening paraneoplastic syndrome which requires urgent medical treatment, since malignant hypercalcemia progresses very rapidly and induces several severe complications. In conclusion, this combination therapy was extremely effective for consciousness disturbance accompanying hypercalcemia due to widespread bone metastases of cancer.

Antineoplastic Agents↗
PubMed2000

[The indications for autonomic nerve-sparing surgery in rectal cancer patients].

Although extended lymph node dissection was developed to improve the therapeutic result in advanced rectal cancer in the 1970s, postoperative dysfunction remained problematic. Informed consent of cancer is generalized at present. The balance between complete cure and functional preservation is important. Therefore the autonomic nerve-sparing surgical technique for rectal cancer was introduce din the 1980s. The success of nerve-sparing surgery depends on a thorough knowledge of pelvic anatomy, especially the anatomic relationship between the pelvic plexus and internal intestinal vessels. Further investigation is required to clarify the indications for autonomic nerve-sparing surgery in rectal cancer patients.

Autonomic Nervous System↗
PubMed2000

[Significance of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) activity in breast cancer tissue].

TS, DPD, uridine phosphorylase and thymidine phosphorylase are enzymes involved in the metabolism of the anticancer drug pyrimidine fluoride. In this study, levels of these enzymes were measured in 47 women with primary breast cancer. These enzyme levels were then compared to levels determined from breast cancer patients who received either preoperative chemotherapy or nothing, in order to determine whether they might predict clinical outcome. The TS inhibition rate was significantly higher (p < 0.05) in patients receiving preoperative chemotherapy (20.4 +/- 13.3%) than in the untreated group (11.4 +/- 9.8%). No other significant differences in activity were noted between the treated and untreated groups for any of the other enzymes studied. The activity of each enzyme at the tumor site and the tumor/normal (T/N) ratio were also compared between patients with and without recurrence. The TS inhibition rate at the tumor site was lower in recurring cases than in non-recurring cases, and the T/N ratio tended to be higher for DPD in patients with recurrences. These findings indicate that the TS inhibition rate and DPD activity may be useful predictors for early recurrence of breast cancer following surgery.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[Analysis of the salvage synthesis within biosynthesis of nucleic acid route in colon cancer].

Orotate phosphoribosyl transferase (OPRT), thymidine phosphorylase (TP), uridine phosphorylase (UP), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthetase (TS) are enzymes which analyze the salvage synthesis within the biosynthesis of the nucleic acid route of colon cancer. These enzymes were measured in carcinoma and normal tissue. OPRT was 0.065 +/- 0.041 nmol/min/mg protein, TP 4.04 +/- 2.81 nmol/min/mg protein, UP 1.79 +/- 1.19 nmol/min/mg protein, DPD 23.8 +/- 12.0 pmol/min/mg protein, and TS 6.1 +/- 4.4 pmol/g tissue in the normal tissue, and OPRT was 0.199 +/- 0.146 nmol/min/mg protein, TP 13.63 +/- 6.04 nmol/min/mg protein, UP 5.84 +/- 2.37 nmol/min/mg protein, DPD 22.0 +/- 13.4 pmol/min/mg protein, TS 16.9 +/- 7.8 pmol/g tissue in the carcinoma. OPRT, TP, and UP in the carcinoma mainly existed about 3.06-3.37 times that in normal tissue and TS at about 2.77 times. No significant difference was seen in DPD. A correlation was found between OPRT in normal tissue and carcinoma. Biosynthesis of nucleic acid via salvage synthesis is actively stimulated. Enzymatic activity related to uracil was high, and was thought to be closely connected to the growth of the cancer.

Aged↗
PubMed2000

[A case of postoperative lung and pleural recurrence after 20 years in a breast cancer patient with marked response to orally administered UFT and cyclophosphamide].

A 62-year-old woman who underwent standard radical mastectomy for left breast cancer developed pleural and pulmonary metastases 16 years later. She complained of slight dyspnea, and computed tomography of the chest revealed a tumor with marked pleural effusion. Her serum level of carcinoembryonic antigen was also increased (49 ng/ml). Systemic chemotherapy with cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) was performed, but she did not show a marked response to CAF therapy. Therefore, she was orally administered UFT and CPA for 5 consecutive days followed by 2 drug-free days. Pleural disseminated foci and a lung tumor were reduced in size on chest CT and the CEA level was decreased within the normal limit. Recently, it was reported that UFT demonstrated significant antiangiogenic activity. This effect may play an important role in the efficacy seen in this patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[A case of breast cancer with multiple metastases successfully treated by medroxyprogesterone acetate with intermittent intra-arterial infusion low-dose chemotherapy to hepatic metastasis].

A 48-year-old woman who underwent breast-conserving therapy for left breast cancer developed bone, pleural, and liver metastases with local recurrence. The result was an improvement in each image with a marked improvement as seen by elevated tumor marker levels, with treatment by MPA (800 mg/day p.o.) and intermittent low-dose chemotherapy with hepatic arterial infusion. The side effects were acceptable. Normalization of imagings and an improvement in tumor markers continued for two years. Thus, in spite of being a palliative treatment, hepatic arterial infusion chemotherapy for liver metastasis from breast cancer might lead to prolongation of survival because of the improvement of other metastases due to the increased passage effect with MPA.

Antineoplastic Agents, Hormonal↗
PubMed1999

Acquisition of HIV type 1 resistance by beta-chemokine-producing CD4+ T cells.

The CD4+ T cell is a major target cell type for human immunodeficiency virus type 1 (HIV-1) infection. In this study, we provide evidence that the susceptibility to HIV-1 infection is variable in individual CD4+ T cells. Five CD4+ T cell clones were isolated from an HIV-1-seronegative donor and were investigated for their susceptibility to HIV-1 infection. Four CD4+ T cell clones were resistant to infection by a macrophage-tropic (R5) HIV-1 isolate whereas one clone was fully permissive. The level of susceptibility to HIV-1 correlated inversely with beta-chemokine production, including RANTES (regulated on activation, normally T cell expressed and secreted), macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-1beta. Resistance to HIV-1 infection was abrogated by the combined use of neutralizing antibodies against these three beta-chemokines. Interestingly, a complete inhibition of HIV-1 infection was observed in peripheral blood mononuclear cells on infection induced by adding the culture supernatant or a small number of HIV-1-resistant cell clones. Our results suggest the presence of a clonal self-defense mechanism within the CD4+ T cell population in vivo that involves the secretion of beta-chemokines.

CD4-Positive T-Lymphocytes↗
PubMed1999

Malignant paraganglioma metachronously recurring at short duration in different paraganglions: report of a case.

We report the rare case of a 57-year-old man with retroperitoneal malignant paraganglioma. He was referred to our hospital complaining of left lower abdominal dull pain. Computer tomography (CT), magnetic resonance imaging, and aortography showed a mass measuring 5 x 4 cm in size on the left side of the abdominal aorta below the renal artery. The resected tumor was confirmed histologically to be malignant paraganglioma. Irradiation of the resected area was performed. Four months after the operation, an abdominal CT scan showed a 5.5 x 3.0 cm mass on the right side of the aorta below the diaphragm. This tumor was thereafter also resected. Three months after the second operation, a soft subcutaneous nodule measuring 4.5 x 2.0 cm in size was palpable above the left clavicle and was visible on a CT scan. A resection was again performed. All tumors showed the same histological findings. This is the first case reported in the Japanese literature with such a short-term demonstration of multiple metachronous recurrences in different paraganglions.

Humans↗
PubMed1999

Pancreatic arteriovenous malformation observed to bleed from the bile duct and a duodenal ulcer: report of a case.

A 48-year-old man with recurrent episodes of biliary colic and subsequent pancreatitis was admitted to undergo a cholecystectomy. A gastroduodenal fiberscopic examination was performed because of massive melena on the seventh day after admission. It revealed a shallow ulcer on the posterior wall of a duodenal bulbus with rubor and an exposed vessel, which was clipped endoscopically to stop the bleeding. Further observations showed the papilla of Vater to be bleeding from the papilla. A contrast-enhanced abdominal computed tomography scan demonstrated a dilatation of the common bile duct and several dilated vasculatures around the portal vein, some of which drained into the portal vein. Based on the angiography findings, a diagnosis of arteriovenous malformation in the pancreas head was obtained and an embolization of the gastroduodenal artery was performed. Although the melena subsided, he underwent a pylorus-preserving pancreatoduodenectomy to prevent the recurrence of hemorrhaging. The histopathological findings of the bile duct revealed inflammatory cell infiltration and a detachment of the epithelium, except in a small part of the bile duct. A rupture of a damaged vessel inside the bile duct was observed, which was thought to be the cause of hemobilia. Sections of the pancreatic head demonstrated an inflammatory lesion with fibrosis and saponification as well as a large degree of arteriovenous anastomosis. The patient was discharged on the 35th day after the operation following an uneventful postoperative course.

Arteriovenous Malformations↗
PubMed1999

Epitope mapping of rat neutralizing monoclonal antibody against human immunodeficiency virus type-1 by a phage peptide library: comparison with ELISA using synthetic peptides.

We generated a rat monoclonal antibody (mAb W#10) with the ability to neutralize human immunodeficiency virus type 1IIIB (HIV-1IIIB) infection. The epitope recognized by mAb W#10 was defined as R-I-Q-R-G-P-G by enzyme-linked immunosorbent assay (ELISA) with the use of synthetic peptides. The filamentous phage clones displaying random 15-amino-acid peptides on the amino terminus of the pIII coat protein reacting with mAb W#10 were identified with affinity and immunological selection procedures. Thirteen out of 16 selected phage clones contained the G-X-G-R-X-F sequence in the coat protein region representing significant homology to a part of conserved G-P-G-R-A-F sequence in the V3 loop of various HIV-1 strains. In addition, the phage clones included the G-X-G sequence in the sequence detected by synthetic peptides as the recognition site. The selected phage clones were stained by mAb W#10 specifically and were able to compete with mAb binding to cells expressing viral antigens.

Amino Acid Sequence↗
PubMed1999

Determinant in human immunodeficiency virus type 1 for efficient replication under cytokine-induced CD4(+) T-helper 1 (Th1)- and Th2-type conditions.

Cytokines are potent stimuli for CD4(+)-T-cell differentiation. Among them, interleukin-12 (IL-12) and IL-4 induce naive CD4(+) T cells to become T-helper 1 (Th1) or Th2 cells, respectively. In this study we found that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains replicated more efficiently in IL-12-induced Th1-type cultures derived from normal CD4(+) T cells than did T-cell-line-tropic (T-tropic) strains. In contrast, T-tropic strains preferentially infected IL-4-induced Th2-type cultures derived from the same donor CD4(+) T cells. Additional studies using chimeric viruses demonstrated that the V3 region of HIV-1 gp120 was the principal determinant for efficiency of replication. Cell fusion analysis showed that cells expressing envelope protein from a T-tropic strain effectively fused with IL-4-induced Th2-type culture cells. Flow cytometric analysis showed that the level of CCR5 expression was higher on IL-12-induced Th1-type culture cells, whereas CXCR4 was highly expressed on IL-4-induced Th2-type culture cells, although a low level of CXCR4 expression was observed on IL-12-induced Th1-type culture cells. These results indicate that HIV-1 isolates exhibit differences in the ability to infect CD4(+)-T-cell subsets such as Th1 or Th2 cells and that this difference may partly correlate with the expression of particular chemokine receptors on these cells. The findings suggest that immunological conditions are one of the factors responsible for inducing selection of HIV-1 strains.

Cell Fusion↗
PubMed1999

Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 infection.

We recently reported that a cationic peptide, T22 ([Tyr(5,12), Lys(7)]-polyphemusin II), specifically inhibits human immunodeficiency virus type 1 (HIV-1) infection mediated by CXCR4 (T. Murakami et al., J. Exp. Med. 186:1389-1393, 1997). Here we demonstrate that T22 effectively inhibits replication of T-tropic HIV-1, including primary isolates, but not of non-T-tropic strains. By using a panel of chimeric viruses between T- and M-tropic HIV-1 strains, viral determinants for T22 susceptibility were mapped to the V3 loop region of gp120. T22 bound to CXCR4 and interfered with stromal-cell-derived factor-1alpha-CXCR4 interactions in a competitive manner. Blocking of anti-CXCR4 monoclonal antibodies by T22 suggested that the peptide interacts with the N terminus and two of the extracellular loops of CXCR4. Furthermore, the inhibition of cell-cell fusion in cells expressing CXCR4/CXCR2 chimeric receptors suggested that determinants for sensitivity of CXCR4 to T22 include the three extracellular loops of the coreceptor.

Amino Acid Sequence↗
PubMed1999

Coxsackievirus B4 myocarditis in an orangutan.

A 37-year-old female orangutan died at the zoological garden. Autopsy examination demonstrated severe coxsackievirus B4 myocarditis immunohistochemically as a cause of the death. Apoptosis of the cardiac muscle cells was observed using the TdT-mediated dUTP-biotin nick endo labeling method and was considered to play a role in the myocarditis. Congestion of the liver and both lungs due to cardiac failure was also observed. Coxsackievirus infection is found frequently in the Okinawan human population. The present orangutan's infection might have come from visitors who were allowed to go near the orangutan. Malignant tumors, severe suppurative infections, and intestinal parasite infections were not observed. Epstein-Barr virus DNA was detected in lymph nodes, but there was no Burkitt's lymphoma.

Animals↗