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Biomedical subjects

Y Koyanagi

Publications and source records attributed to Y Koyanagi.

At least 109 records · Page 6Linked to original sources

[Development of quality of life questionnaire for patients with colorectal cancer in surgical area--a study of reliability and validity of Tokyo Yamabuki Forum Version].

We developed a new questionnaire in the surgical area based on a core quality of life (QOL) questionnaire for patients with gastrointestinal cancer. In this study, we investigated the validity and reliability of a QOL questionnaire (Tokyo Yamabuki Forum Version) for patients with colorectal cancer. The questionnaire was composed of 17 items including 5 scales (basic sensory scale, psychological scale, physiological scale, defection-related scale and active scale) and a face scale as an global scale. The time needed to answer questionnaires was expected to be around 7 minutes and the questionnaires should basically be answered by the patients themselves everyday in the hospital. The study was performed in 10 hospitals in the Tokyo area, and 394 samples collected from 21 patients with rectal and colonic cancers were analyzed. A number of respondents failed to answer the question "Do you feel your foods tasty?", so we judged this item inappropriate and deleted it from the analysis. Fifteen items, including 5 scales showed satisfactory internal consistency and construct validity in correlation and factor analyses. Performance status showed a low correlation between each item, each scale and the global scale, while SDS and STAI showed an inordinately negative correlation with the fundamental and physical scales. Especially, SDS revealed an extremely close correlation with the active scale, and STAI showed an excessive correlation with the psychological scale. In the time course of QOL under chemotherapy, reductions (aggravations) were observed in both the total score of 15 items and global scale within one week postoperatively, but after that recovered to preoperative levels at 2 weeks postoperatively. A tendency to QOL improvement was observed 2 weeks after starting chemotherapy or chemoimmunotherapy. QOL of 13 patients was measured over 3 months, and the longest term was 8 months. The results suggested that this QOL questionnaire has sufficient reliability and validity to be usable for patients with colorectal cancer in the surgical area and that this model is applicable for long-term QOL surveys and frequent measurement.

Adult↗

[Comparison between the mammographic extent of microcalcifications and the virtual extent of breast carcinoma, and observation of changes in mammographic features with time].

In 26 nonpalpable breast carcinoma cases showing microcalcifications not accompanied by any associated mass on mammograms, the maximum diameter of the area of microcalcifications was measured and then compared with the histological extent of carcinoma. The extent of carcinoma was larger than the diameter of the area of microcalcifications in 14 cases (53.8%) and almost equal in five cases. When the maximum diameter of the area of microcalcifications was less than 2.5cm, carcinoma extended no more than 1.5cm beyond the diameter of the microcalcifications. Employing 24 cases subjected to excision biopsy, the extent of carcinoma was compared with the diameter of the area of microcalcifications on sectioned material containing microcalcifications, and it was found that carcinoma tended to extend further than the extent of calcifications (62.5%). Mammographic microcalcifications obtained from 37 breast cancer cases not accompanied by any associated mass were analyzed in contrast to their previous survey films. Twelve cases were found to have shown several extremely faint calcifications on the previous survey films. Follow-up study that focused on such faint calcifications had been performed in 43 cases from 1990 to 1992, resulting in the successful detection of four cases of breast cancer.

Adult↗

Sequence heterogeneity of HTLV-I proviral DNA in the central nervous system of patients with HTLV-I-associated myelopathy.

The nucleotide sequence of human T-lymphotropic virus type I (HTLV-I) in central nervous system tissue was determined in 3 autopsy cases with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) and 1 seropositive carrier without HAM/TSP but with multiple sclerosis. All HAM/TSP samples (3 spinal cords and 2 brains) and the sample from the seropositive carrier without HAM/TSP (brain) were positive for HTLV-I env (5146-6681), pX5' (6549-7494), and pX3' (7354-8276) regions by the two-step polymerase chain reaction method. A nucleotide sequence analysis of the pX5' and pX3' polymerase chain reaction products from nucleotides 6631 to 8259 revealed heterogeneity of the HTLV-I genome in all cases. It is notable that 13 of 50 clones derived from the pX3' polymerase chain reaction products were defective in the tax open reading frame while 7 were defective in the rex open reading frame in the HAM/TSP samples. All 17 clones from 1 HAM/TSP case were defective in the pX open reading frame II. One nucleotide insertion at 7784 creating a frame shift in both tax and rex was seen in all 3 HAM/TSP cases but not in the HTLV-I carrier without HAM/TSP. The pX-defective mutants found frequently in the central nervous system may contribute to the neural damage, since the pX gene products are essential for the transactivation of various cellular genes as well as for viral replication.

Aged↗

Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism.

To detect transcripts encoding the interleukin-6 receptor (IL-6R) molecule lacking the transmembrane (TM) domain, in various cell lines and peripheral blood mononuclear cells (PBMC), we used the polymerase chain reaction (PCR) with primer pairs that flank the TM domain and which were selected to generate a 398-bp fragment. We detected 398-bp and 304-bp DNA molecules in the PCR products of the U1, J22HL60, MT-2, MT-4, U937 and HL60 cell lines and of PBMC isolated from several individuals. The sequencing analysis of both DNA molecules showed that a 94-bp region consisting of the TM domain of IL-6R was deleted in the 304-bp molecule. Moreover, we detected a soluble (s) IL-6R protein of 45 kDa in culture supernatants of the MT-2, MT-4 and U937 cell lines by radioimmunoprecipitation using specific antibodies against sIL-6R. Our results indicate that active deletion of the TM domain by alternative splicing of mRNA represents one mechanism for release of sIL-6R into the culture supernatants of cells, or into serum or urine.

Alternative Splicing↗

Pertussis toxin inhibits induction of human immunodeficiency virus type 1 in infected monocytes.

Tumor necrosis factor alpha (TNF-alpha) and 12-0-tetradecanoyl phorbol-13-acetate (TPA) activate human immunodeficiency virus type 1 (HIV-1) in U1 cells that are latently infected with HIV-1 to produce viral particles. Pertussis toxin, which inactivates several members of the G protein family of signaling components, including Gi, Go, and transducin, was found to inhibit either TPA or TNF-alpha induction of HIV-1 in U1 cells at the concentration of 1-10 ng/ml. Chloramphenicol acetyl transferase (CAT) assay revealed that pertussis toxin could inhibit HIV-1 gene expression. B-oligomer, the mitogenic and non-ADP-ribosylating component of pertussis toxin, did not show any effect on HIV-1 replication alone or in combination with TNF in the same concentration range. It was of particular interest to note that a single protein (Gi) with a molecular weight of 40 kDa was dose-dependently ADP-ribosylated after treatment with pertussis toxin in U1 cells. The degree of ADP ribosylation of Gi corresponded well to that of inhibition of HIV-1 upon treatment with pertussis toxin. These results strongly support the contention that TPA and TNF-alpha induction of HIV-1 is mediated by a Gi-like receptor-effector coupling protein in the membrane of U1 cells. On the basis of these findings, we propose a model for signal transduction of HIV-1 expression through c-kinase-dependent (TPA) and c-kinase-independent (TNF-alpha) pathways in the U1 cell to determine the point at which Gi-like protein is involved.

Cell Line↗

Cell type-specific heterogeneity of the HIV-1 V3 loop in infected individuals: selection of virus in macrophages and plasma.

The primary targets for infection of HIV-1 are CD4+ T cells and monocyte/macrophage cells. We investigated the genotype heterogeneity of HIV-1 in distinct blood compartments, CD4+ T cells, monocytes, and plasma. Nucleotide sequences of proviral DNA from CD4+ T cells, monocyte cells, and cell-free virion RNA from plasma were determined in three HIV-1 infected individuals. We found that the heterogeneity in proviral DNA from CD4+ T cells was much higher than that found in monocyte cells or in virion RNA from plasma. These data showed that different swarms of HIV-1 exist in individually infected cells and plasma. Furthermore, predicted V3 amino acid sequences in the infected monocytes were very similar to the reported sequence of prototypic macrophage-tropic HIV-1 isolates. Our results show that macrophage-tropic virus is quite homogeneous in monocytes/macrophages and has a common V3 structure in contrast to T-cell-tropic virus in vivo.

Acquired Immunodeficiency Syndrome↗

Mycoplasma stimulates HIV-1 expression from acutely- and dormantly-infected promonocyte/monoblastoid cell lines.

Treatment of a myelo-monocyte cell line, J22HL-60, dormantly infected with human immunodeficiency virus type 1 (HIV-1) with heat-inactivated extracts of Acholeplasma (A) laidlawii (250 micrograms/ml) enhanced virus production more than 45-fold as assessed by p24 viral core antigen assay. When treated with a suboptimal dose of TPA or TNF-alpha, Acholeplasma extracts further augmented virus production in J22HL-60 cells. H7, an inhibitor of protein kinase C(PKC), almost completely abrogated HIV-1-inducing ability of Acholeplasma extracts in the cells. A. laidlawii and several other mycoplasmas also enhanced acute infection of U937 cells as shown by increased virus-positive cells and augmentation of HIV-1 production in the culture supernatant independent of their pathogenicity to humans.

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

Induction of antibody responses that neutralize human T-cell leukemia virus type I infection in vitro and in vivo by peptide immunization.

In order to define neutralization regions on the envelope antigen of human T-cell leukemia virus type I (HTLV-I), we have generated a number of new anti-envelope gp46 monoclonal antibodies from rats and mice. Epitopes recognized by new monoclonal antibodies which could neutralize HTLV-I in syncytium and transformation inhibition assays were localized to sequences in gp46 from amino acids 186 to 193, 190 to 195, 191 to 195, 191 to 196, and 194 to 199. Ovalbumin-conjugated synthetic gp46 peptides containing these neutralization epitopes, pep190-199 (a synthetic gp46 peptide containing amino acids 190 to 199) and pep180-204, but not pep185-194 or pep194-203, could give rise to HTLV-I-neutralizing antibody responses in rabbits. These immune or nonimmune rabbits were then challenged with HTLV-I by intravenous inoculation with 5 x 10(7) live HTLV-I-producing ILT-8M2 cells. By a PCR assay, it was revealed that HTLV-I provirus was detected in peripheral blood lymphocytes from nonimmune and pep288-312-immunized rabbits, whereas the provirus was not detected in peripheral blood lymphocytes from pep190-199- and pep180-204-immunized rabbits over an extended period. These results suggest that the induction of anti-gp46 neutralizing antibody responses by immunization with synthetic peptides has the potential to protect animals against HTLV-I infection in vivo.

Amino Acid Sequence↗

[A study of various complications in arterial infusion chemotherapy].

Complications of arterial infusion chemotherapy were analyzed in 261 cases from December 1983 to December 1993 in our department. Their complications involved nausea and vomiting (40.6%), bone marrow suppression (33.3%), liver dysfunction (20.3%), gastric and duodenal ulcer (9.6%) and so on. Complications involving an implantable device were hepatic arterial obstruction (29.1%), reservoir obstruction (5.7%), dislocation of catheter (4.6%), infection of catheter (3.8%), and obstruction of catheter (1.9%). In another cases with hepatic arterial obstruction, we performed arterial infusion in another artery as a bypass or stopped the infusion. In cases with obstruction of catheter not able to be reopened, we reinserted the catheter. An obstructed and/or infected reservoir was removed or replaced. Nausea and vomiting were found in 46.3% of FAM arterial infusion method (FAM) cases, in 53.3% of 5-FU persistent arterial method (5-FU) + FAM cases, and in 40.5% of intermittently persistent arterial method (IP) cases. Gastric and duodenal ulcer were noted in 9.8% of FAM, 13.3% of 5-FU + FAM, and 8.1% of IP cases. There were no significantly statistical differences between the methods. Hepatic arterial obstruction predominantly occurred in 32.4% of IP and 26.7% of 5-FU + FAM and bone marrow suppression was predominant in cases in which ADM was used. The duration of obstruction after administration was 154.0 +/- 117.4 days on average (21-455 days). Complications of hepatic arterial infusion chemotherapy are based on various causes which can be managed for prevention. We intend to enhance safety and assure the greater effectiveness of hepatic arterial chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of peritoneal metastasis of breast cancer successfully treated by multidisciplinary therapy with hyperthermia therapy].

A 53-year-old female with peritoneal metastasis of breast cancer was treated with hyperthermia with chemotherapy. One course consisted of THP 60 mg and FT 400 mg/iv (day 1), CPM 100 mg and MPA 800 mg/daily/po) with RF heating of hyperthermia monthly. After completion of 10 courses of this regimen, ascites completely disappeared and peritoneal metastases were not found observed in any peritoneal cavity with abdominal CT and ultrasound. Peritoneal metastasis of breast cancer was one of the worst reactions with any therapy. The patient has been living for about four years without any signs of recurrence, with the tumor markers within the normal range after surgery. Thermochemotherapy seems a very promising treatment modality for peritoneal metastasis of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of inflammatory breast cancer successfully treated with 5'-DFUR and MPA].

A 67-year-old female with extensive inflammatory breast cancer was treated with oral chemoendocrine therapy using 5'-deoxy-5-fluorouridine (5'-DFUR) 1,200 mg and medroxyprogesterone acetate (MPA) 1,200 mg before intra-arterial infusion chemotherapy, which made the extensive inflammatory skin lesion improve remarkably. Sequential intra-arterial infusion made the skin lesion completely disappear. But the main tumor remained, so extended mastectomy was performed. These findings suggested that this therapy was effective for the prevention of extension of the skin lesion on the inflammatory breast cancer, and also served as induction therapy for this modality.

Administration, Oral↗

cAMP stimulates human immunodeficiency virus (HIV-1) from latently infected cells of monocyte-macrophage lineage: synergism with TNF-alpha.

The present experiments were designed to study whether GTP binding protein activation and the resulting cAMP plays any role in HIV replication. The results showed that cholera toxin (CT) enhanced HIV replication dose dependently in myelo-monocytic cell lines latently infected with HIV-1, U1 and J22HL-60. Three- to 4-fold enhancement of virus production was observed in U1 cells and 4- to 11-fold enhancement in J22HL-60 cells 4 days after treatment with 100 ng/ml of CT. The increment of intracellular cAMP accumulation was parallel with HIV augmentation by CT in both cells. Even at the low concentration 0.1 ng/ml, TNF enhanced virus production to about an 80-fold higher level than the untreated U1 control cells as described previously (11). However, a synergistic effect (80- to 238-fold enhancement) was observed, when TNF-alpha and CT were added together to U1 cells. Similar synergism was seen in J22HL-60 cells. HIV antigen positive cells and gp120 expression were also increased to a similar degree. Phosphodiesterase inhibitor IBMX had no effect on HIV production alone, but potentiated HIV induction by CT and TNF. Adenylate cyclase activator, forskolin (FK), at 100 microM also significantly augmented HIV production (> 4-fold) and potentiated TNF induction in J22HL-60 and U1 cells. On the other hand, CT did not show any effect on HIV replication as well as TNF induction in HIV-1-infected T cell line. Northern blot experiment confirmed that this enhancement was mediated through the activation of HIV transcription. These data suggest that cAMP augments HIV replication and potentiates TNF induction in a particular monocyte-macrophage system.

1-Methyl-3-isobutylxanthine↗

In vivo infection of human T-cell leukemia virus type I in non-T cells.

Using three different procedures, immunomagnetic isolation, FACS and panning, each of the T4 cell, T8 cell, monocyte, and B cell population was fractionated from peripheral blood mononuclear cells (PBMC) obtained from 10 human T cell leukemia virus type I (HTLV-I)-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) cases, 3 adult T cell leukemia and lymphoma (ATLL) cases and 9 HTLV-I-infected healthy carriers. DNA from each fraction was then subjected to the quantitative polymerase chain reaction. Although T4 cells possessed the highest copy number of HTLV-I in general, we also detected a significant amount of HTLV-I provirus in T8 cells, monocytes, and B cells. To confirm virus infection of the non-T cell populations, especially the monocyte fraction, we performed further experiments and the following results were obtained: (1) HTLV-I tax RNA expression was confirmed simultaneously in the RNA of monocytes that were negative for T cell receptor beta chain (TCR beta) expression in vivo. (2) We cultured these monocytes for a short period of time and detected HTLV-I antigen expression in non-specific esterase-positive monocyte/macrophage cells. Our data indicate that HTLV-I has a broad host range in vivo and that monocytes or cells of monocyte lineage such as tissue macrophages might comprise a virus reservoir in vivo.

B-Lymphocytes↗

Dual infection of HIV-1 and HTLV-I in south India: a study on a patient with AIDS-related complex.

A dually HIV- and HTLV-infected ARC patient was found by serological studies in South India. These viruses were isolated and molecular study showed that the patient had both HIV-1 and HTLV-I but not HIV-2 and HTLV-II. In addition to this, 9 other dually infected persons which include another full-blown AIDS case have been identified as on July 1993 in South India. Our findings provide an opportunity to clarify geographical distribution of these human retroviruses.

AIDS-Related Complex↗

[A case of advanced gastric cancer responding well by preoperative chemotherapy with CDDP and MMC].

A 35-year-old female who suffered advanced gastric cancer (classified Borrmann type 3) with para-aortic lymph nodes swelling received chemotherapy preoperatively. These lymph nodes, which could be detected by abdominal CT scan, were highly suspected of metastasis from gastric cancer. The regimens of neoadjuvant chemotherapy were Mitomycin C (MMC) 8 mg/m2 and Cis-platinum (CDDP) 75 mg/m2, administered intravenously as one course. After she was given these two courses, we performed total gastrectomy, pancreatico-splenectomy, and lymph-adenectomy curatively. The patient has been maintained in an outpatient clinic for one and half years without any evidence of recurrence.

Adult↗

[A case of external supravesical hernia].

The first report of external supravesical hernia was made by Astley Cooper in 1804, but it is so rare that we could not find any case reported in Japan. Here we report a case of external supravesical hernia in a male who had bladder cancer. This hernia was reported to be caused by fragility induced by operation or radiotherapy. It can be confused with inguinal direct hernia because it is not considered in the differential diagnosis. Findings such as a palpable hernia sack and the orifice can enable correct diagnosis. Surgical treatment is the only treatment of choice for this disorder.

Aged↗

[A case report of atypical Fabry's disease with colon cancer].

An atypical case of Fabry's disease, a rare congenital disorder of glyco-lipid metabolism, associated with sigmoid cancer was reported. A 50-year-old man who had been diagnosed as having atypical form of Fabry's disease complained of lower abdominal pain and difficult defection. A barium enema and an endoscopic examination disclosed sigmoid colon cancer. The cancer was curatively resected. Fabry's disease is often associated with intestinal disease, but the patient with Fabry's disease associated with intestinal malignancy has not been reported.

Adenocarcinoma↗