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Biomedical subjects

F Tanaka

Publications and source records attributed to F Tanaka.

At least 109 records · Page 6Linked to original sources
PubMed1998

Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients and clinical characterization of spinocerebellar ataxia type 6.

Using a molecular diagnostic approach, we investigated 101 kindreds with autosomal dominant cerebellar ataxias (ADCAs) from the central Honshu island of Japan, including spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2), Machado-Joseph disease (MJD), dentatorubral and pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 6 (SCA6). In our unselected series, MJD was the most common type of ADCA, accounting for 33.7% followed by DRPLA (19.8%), SCA2 (5.9%) and SCA6 (5.9%). No SCA1 mutations were identified. We analysed the clinical features of six molecular confirmed SCA6 kindreds: in each family, there was an expanded allele in the alpha1A-voltage dependent calcium channel comprising between 23 and 25 CAG repeats. The mean age at onset of symptoms was 43+/-13 years. The clinical features consisted predominantly of cerebellar ataxia, dysarthria and horizontal nystagmus, which was generally consistent with ADCA type 3. However several new clinical features were found in some patients: dramatic anticipation, rapid disease progression, severe ataxia associated with action tremor or action myoclonus, and very early onset, which are not described as the classical features of ADCA type 3.

Adult↗
PubMed1998

Streptomyces turgidiscabies sp. nov.

A new bacterial species is described, for which the name Streptomyces turgidiscabies is proposed. This organism causes potato (Solanum tuberosum) scab in eastern Hokkaido, Japan; the lesions caused are distinctly erumpent. In culture, S. turgidiscabies is distinct from other scab-causing Streptomyces species, having flexuous spore chains and grey mass colour. The spores of this organism are cylindrical and smooth. Its cell walls contain the LL-diaminopimelic acid isomer, and its DNA G + C content is 71 mol%. S. turgidiscabies does not produce melanin or other diffusible pigments, does not grow on agar media at pH 4.0 or 37 degrees C, is positive for utilization of raffinose and inulin as a carbon source, and is sensitive to streptomycin (20 micrograms ml-1), penicillin G (10 IU ml-1), polymyxin B (15 micrograms ml-1), and thallium acetate (10 micrograms ml-1). The levels of DNA relatedness within S. turgidiscabies strains are high but relatedness between strains of this species and strains of S. acidiscabies, S. scabies, S. caviscabies, S. griseus, S. setonii and S. tendae are low. The type strain is SY9113T (= ATCC 700248T = IFO 16080T).

DNA, Bacterial↗
PubMed1998

Autocrine motility factor in pulmonary adenocarcinomas: results of an immunohistochemical study.

Autocrine motility factors (AMF) have been shown to play an important role in tumor cell migration and metastasis. We have detected AMF expression in tissue specimens from 119 patients with pulmonary adenocarcinoma and examined the relationship between AMF expression, clinicopathological factors and prognosis. AMF expression was correlated with lymph node metastasis and stage. The prognosis of AMF-positive patients was poorer than that of AMF-negative patients. The expression of AMF correlated with more tumor aggressiveness and worse prognosis in pulmonary adenocarcinomas.

Adenocarcinoma↗
PubMed1998

CAG repeat number correlates with the rate of brainstem and cerebellar atrophy in Machado-Joseph disease.

We compared the CAG repeat length and the severity of the brainstem and cerebellar atrophy visualized by MRI in 30 patients with Machado-Joseph disease. We found a strong correlation between the CAG repeat number and the quotient of the degree of atrophy divided by age at examination. These results suggest that the rate of disease progression is dependent on the CAG repeat size and disease progression may commence at birth.

Adult↗
PubMed1998

[Therapy for non-small cell lung cancer: new concepts based on molecular biology].

Recent advances in molecular biology have broadened our knowledge of the biological characteristics of cancer. In the present paper, we review and discuss new modalities of therapy for non-small cell lung cancer (NSCLC) based on biological findings. These modalities include: 1) diagnosis of cancer based on gene abnormalities: 2) decision making on chemo-/radiotherapy based on new biological findings: 3) gene therapy: and 4) new chemotherapeutic agents. Mutation of the p53 gene, which occurs most frequently in NSCLC, is a well-documented molecular target in these modalities. The development of polymerase chain reaction technology has enabled early diagnosis of NSCLC by detection of p53 gene abnormalities in sputum. Transfer of the wild-type p53 gene using a retrovirus vector to cancer tissues with mutant p53 gene has already been tested clinically. Inhibition of tumor neovascularization has been studied extensively in attempts to develop noveal chemotherapeutic agents. Angiostatin or endostatin, an inhibitor of tumor neovascularization is in clinical use. Matrix metalloprotease inhibitions (MMPs) also inhibit neovascularization of tumors. Marimastat, an oral MMP, is expected to prevent cancer metastasis.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Age-related changes in D2 receptor binding with iodine-123-iodobenzofuran SPECT.

UNLABELLED: The purpose of this study was to evaluate the effects of age on D2 receptor binding with 123I-iodobenzofuran (IBF) SPECT. METHODS: Subjects were 40 healthy volunteers (age 19-83 yr), including 6 who had test/retest studies. Scans were acquired with a triple-head SPECT camera 3 hr postinjection of IBF (300 MBq). Striatal regions (caudate and putamen) were defined by two different region-of-interest (ROI) sets consisting of large volumes [(CLVs), 2.2 and 6.6 m] and small volumes [(SVs), 0.6 and 1.3 ml]. D2 binding (Rv=V3/V2) was quantified using our previously proposed multilinear regression technique. Effects of age on D2 binding were evaluated by fitting linear, exponential and logarithmic models. RESULTS: The mean Rvs were 26% lower than LV for both putamen and caudate than the corresponding values from the SV due to the partial-volume effect. Although the identifiability of Rv using SV deteriorated slightly, the test/retest reproducibility of Rv measurements was equally excellent for LV and SV. The mean Rvs were 11% higher for putamen compared with those for caudate. D2 binding declined significantly with age (p < 10(-5)) for all three models. The nonlinear models were slightly superior to the linear model in describing the relationship between Rv and age. In these models, D2 binding declined with age, equally for caudate and putamen at 7%-13% per decade; the decline was progressively smaller with age. CONCLUSION: IBF SPECT permitted reliable measurements of D2 binding in the caudate or putamen separately using small ROI volumes that significantly improved the quantitation loss from the partial-volume effect. Our results agreed with previous PET and postmortem findings of D2 binding losses with age. However, these age effects may be nonlinear. Age-related changes in D2 binding must be taken into consideration in clinical IBF SPECT investigations.

Adult↗
PubMed1998

[Two cases of spontaneous hemopeumothorax].

We experienced two cases of spontaneous hemopeumothorax. One case was a 17-year-old male with a complaint of back pain. A chest tube for rapid pleural evacuation disclosed hemorrhage as much as 3,000 ml, with drainage volume being gradually decreased. He needed about two month's admission because of complication of pyothorax. The other case was a 46-year-old male with a complaint of chest pain. Chest X-P gave the diagnosis of right hemopeumothorax. Thirty minutes later, he became shock, and five hours later, we performed an emergency intervention of video-assisted thoracoscopic surgery (VATS). Bleeding site of a funicular structure from the parietal pleura was stopped by clipping, with excellent postoperative results. Spontaneous hemopeumothorax is often indicated for early surgical intervention because of association with a high risk of hemorrhagic shock. In such a case, VATS is very helpful.

Adolescent↗
PubMed1997

Induction of antitumor cytotoxic T lymphocytes with a MAGE-3-encoded synthetic peptide presented by human leukocytes antigen-A24.

For the development of immunotherapy using MAGE peptides, the identification of additional tumor antigens is required. Because HLA-A24 is the most common allele in Japanese and is also frequently present in Caucasians, MAGE-3-encoded synthetic peptides with binding affinity for HLA-A24 were thus tested for the induction of specific CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A24 healthy donors using a simplified method. By using a peptide with a sequence of IMPKAGLLI (amino acid position in MAGE-3 195-203), the CTL responses could thus be induced from unseparated PBMCs by stimulation with freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and by also using interleukin 7 and keyhole limpet hemocyanin for a primary culture. The induced CTLs could lyse HLA-A24 carcinoma cells expressing MAGE-3, as well as the peptide-pulsed target cells, in an HLA class-I restricted manner. The identification of the MAGE-3/HLA-A24 peptide, IMPKAGLLI, may thus potentially offer the opportunities to design peptide-based immunotherapeutic approaches that might prove to be effective in treating patients with MAGE-3-positive malignant tumors.

Alleles↗
PubMed1997

The anti-human tumor effect and generation of human cytotoxic T cells in SCID mice given human peripheral blood lymphocytes by the in vivo transfer of the Interleukin-6 gene using adenovirus vector.

Interleukin-6 (IL-6) was found to function as a late-acting killer helper factor in the differentiation of CTLs. In the model of tumor-bearing mice, the systemic administration of recombinant IL-6 was found to mediate the antitumor effect on the immunogenic murine tumors via the in vivo induction of murine CTLs but not on the poorly immunogenic murine tumors in our previous study. However, an in vivo experimental model capable of analyzing the anti-human tumor effect via the in vivo induction of human CTLs has not yet been established. Therefore, in the present study, severe combined immunodeficient mice were given human peripheral blood lymphocytes (SCID-PBL/hu), and thereafter human tumor cells were administered i.p. into these SCID-PBL/hu mice as a model of human patients with cancer. When these SCID-PBL/hu mice bearing allogeneic human CESS B blastoid tumor cells were treated in vivo with recombinant adenovirus vector expressing IL-6 cDNA, both the induction of CD8+ human CTLs against CESS cells in the spleen cells and peritoneal exudate cells and a prolongation in the survival of these mice were observed. Furthermore, SCID-PBL/hu mice were given peripheral blood lymphocytes from patients with cancer (gastric or rectal cancers) and autologous human tumor cells. The in vivo administration of recombinant adenovirus vector expressing IL-6 cDNA induced CD8+ human CTLs specific for autologous human tumor cells from human precursor T cells. The in vivo injection of the IL-6 gene also inhibited growth and metastasis in autologous human cancers. Based on the above findings, the experimental model using SCID-PBL/hu mice and the IL-6 gene delivered in vivo by an adenovirus vector might therefore provide a new strategy capable of analyzing an anti-human tumor effect and the in vivo induction of human CTLs by cytokine gene therapy without using the human body.

Adenoviridae↗
PubMed1997

Roles of the transforming growth factor beta 1 and its type I and II receptors in the development of a pulmonary adenocarcinoma: results of an immunohistochemical study.

BACKGROUND: In the United States, pulmonary adenocarcinomas have recently replaced squamous cell carcinomas as the most frequent type of lung cancer encountered. The incidence of pulmonary adenocarcinoma continued to increase worldwide. METHOD: To determine the roles of the transforming growth factor-beta 1 (TGF-beta 1), and TGF-beta type I receptor (T beta R-I), and the TGF-beta type II receptor (T beta R-II) in the progression of a pulmonary adenocarcinoma, their respective expressions have been immunohistologically studied in specimens from 120 pulmonary adenocarcinoma patients. RESULT: The overall prognosis was significantly poorer for patients showing positive TGF-beta 1, T beta R-I, T beta R-II expressions than for patients who were negative to all three immunostainings (P < 0.01). Our multivariate analysis also revealed that a positive TGF-beta 1 response significantly affect prognosis (P < 0.05). CONCLUSIONS: TGF-beta 1, T beta R-I, and T beta R-II play important roles in tumor progression, and a positive TGF-beta 1 expression can serve as a pulmonary adenocarcinoma marker. T beta R-I and T beta R-II expressions are necessary for TGF-beta signal transduction.

Activin Receptors, Type I↗
PubMed1997

Presurgical identification of epileptic foci with iodine-123 iomazenil SPET: comparison with brain perfusion SPET and FDG PET.

Iodine-123 iomazenil (IMZ) has excellent characteristics for the quantification of central benzodiazepine receptor (BZR) binding with single-photon emission tomography (SPET). In order to evaluate the clinical value of IMZ SPET for presurgical identification of epileptic foci in patients with medically intractable seizures, we measured the binding potential (BP) of BZR using two IMZ SPET scans and compared the results with brain perfusion SPET and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). A total of ten patients with intractable partial epilepsy were examined by electroencephalography, magnetic resonance imaging, FDG PET, brain perfusion SPET and IMZ SPET. After neuroimaging examinations, five patients underwent selective surgery, and all of them have since been free of seizures. Two SPET scans were performed at 15 min (early) and 3 h (late) after intravenous injection of 123I-IMZ (167 MBq). Parametric images of the ligand transport (K1) and binding potential (BP) were calculated by the table look-up method, which is based on a three-compartment two-parameter model, using the standard arterial input function obtained by averaging of six normal volunteers' input functions. BP images delineated the epileptic foci more precisely than either FDG PET or ictal perfusion SPET. FDG PET showed widespread reduction, including the area surrounding the focus, and ictal increase in the cerebral blood flow was seen in possibly activated areas spread from the focus. In four epilepsy cases which originated from the mesial temporal lobe without lateral temporal abnormality, there was no significant decrease in the BP images in the lateral temporal structures, which showed decreased uptake of FDG. It is concluded that parametric images of BP with IMZ are valuable for precise presurgical localization of epileptic foci.

Adult↗
PubMed1997

Efficient induction of antitumor cytotoxic T lymphocytes from a healthy donor using HLA-A2-restricted MAGE-3 peptide in vitro.

The antigenic peptides encoded by tumor-rejection antigen genes, MAGE-1 and -3, have been identified, and various methods have been utilized for the in vitro induction of MAGE-specific, cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) using synthetic peptides. However, all of these methods are technically demanding and thus have a relatively limited usefulness. We herein report a simple and efficient method for the vitro induction of specific CTL by using the HLA-A2-restricted MAGE-3 peptide from the PBMC of a healthy donor. CTL responses could thus be efficiently induced from unseparated PBMC by stimulation with freshly isolated, peptide-pulsed PBMC as antigen-presenting cells and by using interleukin-7 and keyhole limpet hemocyanin for the primary culture. The induced CTL could thus recognize and lyse not only HLA-A2 target cells pulsed with the peptide but also HLA-A2 tumor cells expressing MAGE-3, in an HLA-class-I-restricted manner. This simple method may, therefore, become a useful tool for investigating the potential peptides for tumor antigens as well as for developing various immunotherapeutic approaches for human malignant tumors.

Antigens, Neoplasm↗
PubMed1997

The lateral corticospinal tract and spinal ventral horn in X-linked recessive spinal and bulbar muscular atrophy: a quantitative study.

A quantitative study was performed on spinal cord lesions in seven patients with X-linked recessive spinal and bulbar muscular atrophy. The myelinated fiber density of the lateral corticospinal tracts at the T7 cord level was well preserved for both large and small myelinated fibers. On the other hand, neurons in the L4 ventral horn were markedly depleted; marked loss was noted of the large alpha and medium-sized gamma motor neurons located in the lateral and medial nuclei as well as the small neurons in the intermediate zones of the ventral horn. These results suggest that myelinated fiber density and fiber-size distribution in the corticospinal tract are well preserved and that neuronal loss in the ventral horns is not restricted to alpha and gamma motoneurons but also involves small interneurons.

Aged↗
PubMed1997

Stimulation of plasminogen activator/plasmin system in gingival fibroblast cells by oxygen radicals.

The effect of extracellular oxygen radicals on cultured gingival fibroblast cells (Gin cells) was investigated in the plasminogen activator (PA)/plasmin system. The activation of the PA/plasmin system in Gin cells exposed to a sublethal oxygen radical [hypoxanthine (HX) 0.1 mg ml-1/xanthine oxidase (XOD) 5 munit ml-1] system was examined. Following a 1 h exposure, washed cells were cultured for up to 24 h in fresh medium containing 2% fetal calf serum. The exogenous addition of superoxide dismutase, an oxygen radical scavenger, abolished the PA/plasmin activity enhanced by the HX/XOD system. The PA produced by Gin cells was found to be urokinase-type PA (uPA), as preincubation of Gin cell-conditioned medium with anti-uPa serum completely inhibited PA activity. These findings suggest that extracellular oxidant targetting to Gin cells may be involved in the progression of inflammation and the invasion of periodontium through stimulation of the PA/plasmin system.

Cells, Cultured↗
PubMed1997

Prognosis of ipsilateral intrapulmonary metastases in resected nonsmall cell lung cancer.

OBJECTIVE: According to the new classification of intrapulmonary metastasis (pm) of lung cancer by the American Joint Committee on Cancer (AJCC), ipsilateral pm is classified as a T factor. We evaluated the prognostic factors of ipsilateral pm after surgical treatment, and validity of the new classification. METHODS: From January 1977 to December 1994, 41 patients (24 males and 17 females) with lung cancer had a postoperative diagnosis of intrapulmonary pm. The histologic type consisted of 27 adenocarcinoma. 12 squamous cell carcinoma, and 1 large cell carcinoma. Twenty patients had pm in the same lobe in which the primary lesion was located, and 21 patients had pm in ipsilateral different lobe(s). Thirty patients underwent lobectomy, 5 bilobectomy and 6 pneumonectomy. Survival was calculated by the Kaplan Meier method, and Cox proportional hazards model was used for multivariate analysis. RESULTS: The overall survival was 25.8% at 5 years (median survival time (MST), 26 months). The 3-year survival of patients with pm in the same lobe was 49% (MST, 33 months), and that of patients with different lobe was 21% (MST, 16 months) (P = 0.237). There were no significant differences in survival in relation to age, sex, histology, pathological N factor, or number of pm. Multivariate analysis identified a significant correlation between survival and T factor proposed by AJCC (P = 0.022). CONCLUSIONS: The new classification seems useful for estimating postoperative prognosis of the resected patients with lung cancer accompanied by ipsilateral pm.

Aged↗
PubMed1997

Time trends and survival after surgery for p-stage IIIa, pN2 non-small cell lung cancer (NSCLC).

OBJECTIVE: To evaluate the role of surgery for p-stage IIIa, pN2 non-small cell lung cancer (NSCLC), time trends and survival after surgery and the prognostic factors were investigated retrospectively. METHODS: Consecutive patients, 155, with p-stage IIIa, pN2 NSCLC who underwent thoracotomy at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between January 1976 and December 1990 were divided into three groups by the period of operation (the earlier period: 1976-1980, n = 49; the middle period: 1981-1985, n = 55; and the later period: 1986-1990, n = 51), and were reviewed. Of the 155 patients, 84 (54.2%) were preoperatively evaluated to have mediastinal lymph nodes metastases (cN2 disease). RESULTS: The 5 year survival rates in the earlier, middle and later periods were 12.1, 18.6, and 43.8%, respectively, showing significant improvement in the later period (P < 0.001, for the later period versus the earlier period or the middle period). The improvement was caused by decrease in the rate of operation-related death (4.1, 1.8, and 0.0%, in the earlier, the middle, and the later period, respectively), increase in the rate of complete tumor resection (59.1, 76.4, and 96.1%, respectively), and decrease in the ratio of pT3N2M0 patients (44.9, 34.5, and 17.6%, respectively) having poor prognosis compared with pT1-2N2M0 patients. Decrease in the ratio of cT3N2M0 patients and for increase in the rate of complete resection could be realized by accurate preoperative diagnosis with introduction of chest computed tomography (CT). Based on the preoperative evaluation, the 5 year survival rates of cT1N2M0, cT2N2M0, and cT3N2M0 patients were 39.4, 30.5, and 10.2%, respectively, showing significant poor prognosis in cT3N2M0 patients. CONCLUSION: In cT1-2N2M0 or pT1-2N2M0 patients, a good prognosis can be realized by complete tumor resection with mediastinal lymph nodes dissection. In contrast, surgical treatment should not be justified in cT3N2M0 or pT3N2M0 patients.

Adult↗