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Biomedical subjects

H Takashima

Publications and source records attributed to H Takashima.

At least 91 records · Page 5Linked to original sources

High seroprevalence of anti-HTLV-I antibody in rheumatoid arthritis.

OBJECTIVE: To investigate the association between human T lymphotropic virus type I (HTLV-I) infection and rheumatoid arthritis (RA) in Nagasaki, an area highly endemic for HTLV-I infection. METHODS: Sera from 113 female patients with RA and 19,796 female blood donors were screened for anti-HTLV-I antibodies with a gelatin particle agglutination kit and confirmed using an immunoblotting kits. RESULTS: The age-adjusted summary odds ratio of HTLV-I infection among RA patients, as compared with blood donors, was 2.8 (95% confidence interval [95% CI] 1.8-4.6). The etiologic fraction, i.e., the proportion of RA in the study population that is attributable to HTLV-I infection, was estimated to be 13.2% (95% CI 5.1-21.2). There was no significant difference in the clinical and laboratory findings between HTLV-I- infected and HTLV-I-uninfected RA patients. CONCLUSION: These epidemiologic findings support the idea that HTLV-I infection is a risk factor for RA, and suggest that approximately 13 % of the cases of RA in females living in Nagasaki are associated with HTLV-I infection.

Adult↗

Accumulation of Tc-99m MIBI in breast lymphoma: comparison with Ga-67 citrate.

We report 2 cases of malignant lymphoma of the breast which were clearly shown on total body imaging as well as on SPECT with Ga-67 and Tc-99m MIBI. Tumor accumulation of Ga-67 was seen in all cases including a recurrent tumor. Ga-67 scintigraphy is useful for follow up in detecting relapse, as well as in predicting responses to therapy. Tc-99m MIBI was found to accumulate in the malignant lymphoma of the breast, and especially SPECT images of breast lesions provided better contrast than planar images, and Tc-99m MIBI SPECT could diagnose localization of the tumor because there was no uptake by the breast. But the Tc-99m MIBI accumulation of the tumor was lower than Ga-67.

Breast Neoplasms↗

Immunohistochemical demonstration of S-phase cells by anti-bromodeoxyuridine monoclonal antibody in cattle tissues.

Bromodeoxyuridine (BrdU), a non-radioactive thymidine analogue, was administered to 15 cattle at a dosage of 1-10 mg/kg intravenously or intraperitoneally to demonstrate S-phase cells in the tissues. The organs and tissues were fixed in 10% neutral buffered formalin or in 70% ethanol, sectioned, denatured with hydrochloric acid, and treated with monoclonal antibody against BrdU. Immunohistochemical methods were used to "visualize" BrdU-labelled nuclei. BrdU-positive cells were satisfactorily demonstrated in both formalin- and ethanol-fixed tissues of animals given doses of 2 mg/kg or over, by either route of administration. Large numbers of BrdU-positive cells indicative of active cell production were found in the basal region of the stratified squamous epithelium, the neck between gastric pits and gastric glands in the abomasum, and the crypts of Lieberkühn of the small and large intestines. Moderate numbers of positive cells were observed amongst inflammatory cells in cases of nephritis and in granulation tissue. Numerous positive cells were detected in leukaemia cells. The study showed that BrdU can be used to measure proliferative S-phase cells in cattle, as in human beings, mice and rats.

Animals↗

Septal structure of incomplete interlobar fissures of the lung.

RATIONALE AND OBJECTIVES: Some septal structures have been observed in the areas of incomplete interlobar fissures (IIFs) in resected lungs. We describe the anatomy of IIFs with or without the presence of septal structures. METHODS: Twenty fused areas from 16 autopsy cases were examined histologically. Other septal structures outside the areas of IIFs also were examined. RESULTS: In 10 of the 20 fused areas, there was a mixture of septal structures with and without defects. In the remaining 10, there were no septal structures. The septal structures consisted of two inner layers from both lobes. Other septal structures examined were the same as ones observed in the IIFs. CONCLUSION: Linear shadows seen at interlobar fissures and on computed tomography scans do not necessarily depict the presence of complete interlobar fissures. The absence of linear shadows does not necessarily imply the absence of septal structures.

Bronchi↗

Cytokine production by endothelial cells infected with human T cell lymphotropic virus type I.

OBJECTIVE: To investigate the ability of human T cell lymphotropic virus type I (HTLV-I) to infect endothelial cells and induce cytokine production by these cells. METHODS: Human umbilical vein endothelial cells (HUVEC) were cocultured with HTLV-I infected T cell line (MT-2 cells) or uninfected T cell line (CEM cells). RESULTS: Following coculture with MT-2 cells, endothelial cells expressed HTLV-I specific core antigens. Endothelial cells cocultured with MT-2 cells produced significant amounts of several cytokines, including interleukin (IL)-1 alpha, IL-6, granulocyte colony stimulating factor (G-CSF), and granulocyte/macrophage colony stimulating factor (GM-CSF), compared with endothelial cells cocultured with CEM cells. Coculturing of endothelial cells with MT-2 and CEM cells failed to produce detectable amounts of IL-1 beta and tumour necrosis factor alpha (TNF-alpha). The production of cytokines by endothelial cells cocultured with MT-2 cells was more persistent than that by endothelial cells cocultured with CEM cells after several passages. Furthermore, the production was blocked by cocultivation of endothelial cells and MT-2 cells using the Millicell system. Finally, after cocultivation of endothelial cells and MT-2 cells, endothelial cells positive for HTLV-I antigen were stained by anti-GM-CSF antibody. CONCLUSIONS: HTLV-I can infect endothelial cells, resulting in their active production of several cytokines, such as IL-1 alpha, IL-6, G-CSF, and GM-CSF. These findings strongly suggest that the excess production of these cytokines by HTLV-I infected endothelial cells may be involved in the pathogenesis of HTLV-I associated inflammatory diseases.

Cell Line↗

Cerebral vasospastic vessels: histologic changes after percutaneous transluminal angioplasty.

PURPOSE: To investigate histologic changes before and after percutaneous transluminal angioplasty (PTA) in experimental cerebral vasospasm in comparison with normal vessels. MATERIALS AND METHODS: In seven monkeys, vasospasm was induced in the subarachnoid space. After 7 days, PTA was performed. Microscopic studies were performed in vasospastic vessels. In two animals, vasospasm was induced but angioplasty was not performed. The controls were two animals without vasospasm who underwent only contralateral angioplasty. RESULTS: Angiography after vasospasm revealed marked narrowing but dilatation after PTA, without changes in distal spastic vessels. Specimens after PTA showed platelets that covered denuded endothelium, stretching, and focal dehiscence of internal elastic lamina and altered myocytes in media. Myocytes were deformed and arranged irregularly. These changes were not uniform. CONCLUSION: The prolonged effect of PTA may be caused by mechanical damage of myocytes and the nonuniformity of histologic changes in vascular walls.

Angioplasty, Balloon↗

[Comparative evaluation of 99mTc-MIBI (hexakis2-methoxy isobutyl isonitrile) and 201Tl-chloride in primary lung cancer].

We performed comparative study, using 99mTc-MIBI and 201Tl-chloride in patients with primary lung cancer. There were 42 patients with primary lung cancer. All patients underwent dual radionuclide imaging with 201Tl-chloride and 99mTc-MIBI. Regions of interest were placed over the tumor area (T) and contralateral normal lung area (N). A tumor to normal lung ratio (T/N ratio) and retention index were calculated by early and delayed ratios. In the SPECT images, the positive rate was 98% in both the early and delayed images for 201Tl-chloride and 95% in the early and 88% in the delayed images for 99mTc-MIBI. Both early and delayed T/N ratios of 201Tl-chloride were significantly higher than those of 99mTc-MIBI. The retention index of 201Tl-chloride was higher than that of 99mTc-MIBI. T/N ratio and retention index did not significantly correlated with reference to histological types. We conclude that 99mTc-MIBI SPECT can be helpful in localizing primary lung cancers. However, in our study the tumor accumulation of 99mTc-MIBI was significantly lower compared with 201Tl-chloride.

Adult↗

[Untoward effects of low dose methotrexate therapy in rheumatoid arthritis].

Sixty patients with rheumatoid arthritis who were administered weekly low dose methotrexate (MTX) were retrospectively analyzed for their untoward effects of MTX by interviewing to the patients and by the medical records. Cough and sputa were the most frequent symptoms (23.3%) and gastrointestinal symptoms were the next (20%). Five of 60 patients (8.2%) showed liver function test abnormalities, and four (6.7%) exhibited transient exacerbation of arthralgia for several hours to a few days after MTX administration. Three patients (5%) suffered from interstitial pneumonitis. Hair loss was seen in 3 patients (5%), and headache, leucocytepenia, fever, skin eruption, abnormal taste, hemorrhagic cystitis, and flashing were experienced in a patient, respectively. Three (5%) suffered from fungal infection, and herpes zoster, sepsis, and osteomyelitis were experienced in each one patient, respectively. MTX was withdrawn in three patients (5%) because of cough and sputa the drug was withdrawn in other three patients because of the interstitial pneumonia, and was drawn in another three patients because of transient exacerbation of arthralgia. The drug was withdrawn in each one patient, because of nausea and vomiting, skin eruption, osteomyelitis, and sepsis, respectively. Overall, MTX were withdrawn in 21 patients (35%), and, of those, 13 patients (21.7%) because of untoward effects and 8 patients (13.3%) because of the lack of efficacy.

Adult↗

[Second phase 99mTc-HMDP accumulation using three phase bone scintigraphy in a case of primary breast cancer].

Accumulation of 99mTc-HMDP was recognized by three-phase bone scintigraphy in a case of primary breast cancer. A 67-year-old female was found to have a 14 x 13 mm mass in the upper lateral area of the left breast. At operation the histopathological finding was a proven solid-tubular carcinoma. On the first phase images, there was no abnormal accumulation in the tumor. On the second phase images, there was abnormal accumulation in the tumor, however, abnormal accumulation was observed followed by a decrease in accumulation. The third phase image showed no abnormal extra-skeletal accumulation. Color Doppler ultrasound sonography showed an abundance of color signals within the breast tumor. Increased 99mTc-HMDP accumulation in the second phase image might reflect tumor hypervascularization. It is concluded that three-phase bone scintigraphy using 99mTc-HMDP has the ability of positive description in primary breast cancer.

Adenocarcinoma↗

Increased circulating serum amyloid A protein derivatives in rheumatoid arthritis patients with secondary amyloidosis.

Secondary amyloidosis, a serious complication of chronic inflammatory diseases, is caused by the deposition of amyloid fibrils in various organs. The major component of amyloid fibrils is derived from serum amyloid A protein (SAA) by proteolysis. To explore the mechanisms of amyloidogenesis, we measured SAA concentrations in the sera of 38 patients with rheumatoid arthritis (RA) without secondary amyloidosis and in the sera of 18 RA patients with secondary amyloidosis, using the latex agglutination immunoassay. We also determined whether SAA was present as a full-length protein in the sera of RA patients by immunoblotting. Although SAA concentrations were elevated in the sera, there were no significant differences in these concentrations between RA patients without amyloidosis (128.2 +/- 145.4 micrograms/ml) and RA patients with amyloidosis (165.0 +/- 162.9 micrograms/ml). To test for qualitative abnormalities of SAA, the isolated SAA proteins from individual RA patients were analyzed by anti-SAA immunoblot. In addition to full-length SAA protein, 6-kd and 4.5-kd SAA-derived fragments were detected in the sera of RA patients, and the ratio of these fragments to total SAA proteins was significantly higher in RA patients with amyloidosis (37.0% +/- 0.7%) compared with that of RA patients without amyloidosis (15.0% +/- 5.5%). Although a high serum level of SAA is a predisposing condition for amyloid formation in RA patients, our data suggest that the increased circulating proteolytic cleavage of SAA may potentially contribute to the development of AA-amyloid deposition.

Adult↗

[Evaluation of 99mTc-MIBI to predict chemotherapeutic response in patients with small cell lung carcinoma].

The purpose of this study was to evaluate the relationship between 99mTc-MIBI (MIBI) accumulation and the response to chemotherapy. Twelve patients with small cell lung carcinoma (SCLC) underwent MIBI SPECT before chemotherapy. SPECT data were acquired 15 minutes and 2 hours after the injection of 600MBq MIBI. The early ratio (ER), delayed ratio (DR) and retention index (RI) was measured. Tumor response were classified into complete remission (CR), partial remission (PR) and no change (NC) by follow-up CT examination. The mean +/- standard deviation of ER was 3.10 +/- 0.85 (n = 4) for CR, 2.72 +/- 0.46 (n = 5) for PR and 2.43 +/- 0.95 (n = 3) for NC. DR was 3.05 +/- 1.11 for CR, 2.64 +/- 0.30 for PR and 1.90 +/- 0.82 for NC. RI was -3.0 +/- 11.69 for CR, -1.84 +/- 11.03 for PR and -18.19 +/- 38.51 for NC. CR, DR and RI were not significantly correlated with tumor response (CR, PR, NC) MIBI has the potential to predict the response to chemotherapy in SCLC.

Adult↗

Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.

Several 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1; HEPT) were synthesized and evaluated for their anti-HIV-1 activity. LDA (lithium diisopropylamide) lithiation of 5-ethyluracil derivatives 7 and 8 and subsequent reaction with an aryl aldehyde gave 6-(arylhydroxymethyl)-5-ethyluracil derivatives 9-12. 6-(Arylhydroxymethyl)-5-isopropyluracil derivatives 15-18 were prepared from the 5-isopropyl-2-thiouracil derivatives 13 and 14 by the above procedure following oxidative hydrolysis of the thione. Preparation of the target 5-alkyl-1-(alkoxymethyl)-6-benzyluracil derivatives 27-34 was carried out by acetylation of 9-14 followed by Pd-catalyzed hydrogenolysis. The 1-butyl- (37 and 39) and 1-(2-methoxyl)- (38 and 40) 5-alkyl-6-benzyluracils were synthesized by 1-alkylation of the 3-phenacyl derivatives 35 and 36 with alkyl halides followed by deprotection of the 3-phenacyl group. Compounds synthesized in this study inhibited HIV-1 replication in MT-4 cells in the submicromolar to namomolar concentration range. From this series of compounds, 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (33) was selected for clinical evaluation.

Animals↗

Transforming growth factor beta 1 induces apoptotic cell death in cultured human umbilical vein endothelial cells with down-regulated expression of bcl-2.

Transforming growth factor beta 1 (TGF-beta 1) is a potent growth inhibitor of human umbilical vein endothelial cells (HUVEC). We investigated whether apoptosis is involved in the TGF-beta 1 mediated HUVEC growth inhibition. Using immunofluorescence microscopy and staining by propidium iodide, we showed HUVEC treated with TGF-beta 1 contained characteristic apoptotic nuclei with condensation of chromatin. FACS analysis demonstrated that the number of cells with hypodiploid DNA contents were increased in HUVEC treated with TGF-beta 1. The DNA fragmentation assay exhibited typical ladder formation in TGF-beta 1-treated HUVEC. Using Western blot analysis, the expression of bcl-2 on HUVEC was down-regulated by TGF-beta 1-treatment. These findings suggest that TGF-beta 1 regulates the growth of HUVEC by inducing apoptosis accompanied with down-regulation of bcl-2 expression.

Apoptosis↗

Intraoperative radiotherapy for gliomas.

Intraoperative radiotherapy (IORT) was performed in 20 of 36 patients with glioma; 11 glioblastomas, 7 malignant astrocytomas, 2 benign astrocytomas. Twenty or 25 Gy of irradiation was delivered in a single fraction intraoperatively, followed by external beam irradiation. The electron beam energy was selected so that the 80% isodose line fell at 2 or 3 cm below the residual tumor surface. Median survival time of IORT group was 14 months and that of the control group was 10 months. Difference of survival curve was significant. There were 6 incidences of complication caused by IORT; 1 radionecrosis, 1 convulsion, 1 abscess, and 3 severe brain edemas. IORT is suited for the treatment of malignant gliomas.

Adult↗