Biomedical subjects

F Tanaka

Publications and source records attributed to F Tanaka.

At least 127 records · Page 7Linked to original sources

PubMed1997

Chemotactic factors released in culture by intact developing and healing skin lesions produced in rabbits by the irritant sulfur mustard.

Development, peak and healing lesions were induced in the skin of rabbits by topical applications (on different days) of the chemical irritant sulfur mustard (SM). Immediately after the rabbits were euthanized, the intact lesions were excised and organ-cultured for 17 to 20 hours. The culture fluids from early, peak and healing SM lesions all showed high chemotactic activity for both PMN and MN. This finding suggests that the PMN and MN, seen microscopically in tissue sections of the lesions, were entering continuously, even during the healing process. The chemotaxins identified were the eicosanoid LTB4, the chemokine IL-8, and proteases producing the complement fragment C5a. Other studies from our laboratory showed that the number of cells containing IL-1, IL-8, MCP-1, and GRO mRNAs was increased in SM lesions. Chemotactic activity was released by both live and dead (frozen and thawed) cell suspensions of PMN, MN, and fibroblasts, suggesting that these cells were major sources of the chemotaxins produced by the SM lesion explants. Explants of normal skin produced considerable chemotactic activity for MN, but not for PMN. Chemotactic activity for PMN, and the release of LTB4, IL-8 and proteases cleaving C5 to C5a, occurred only in explants infiltrated by leukocytes.

Animals↗

PubMed1997

Effects of pulmonary surfactant on macrophage migration: suppression of chemokinesis by surfactant phospholipid and enhancement of chemotaxis by surfactant protein.

We fractionated the bronchoalveolar lavage fluid (BALF) from normal rabbit lungs into several fractions by high speed centrifugation and ethanol-ether extraction. Random migration, chemokinesis and chemotaxis of freshly harvested alveolar macrophages (AM), 24 h cultured AM, and peritoneal exudate cells (PEC) were assayed in vitro using a modified, under agarose method and a blind well chemotactic chamber method. Freshly harvested AM demonstrated little random migration compared with PEC. However, when freshly harvested AM were pre-incubated in surfactant free medium for 24 h, the cells showed the same rate of migration as PEC. The increased migration of the 24 h cultured AM was partially suppressed by the presence of all BALF fractions containing high proportions of phospholipid. The inhibition by Fr-L (a fraction enriched in phospholipids) was reversed by normal serum, but not by heat-inactivated serum, cholesterol, synthetic dipalmitoyl phosphatidyl choline, or indomethacin. Fr-L markedly suppressed macrophage chemokinesis but did not affect on macrophage chemotaxis. Alternatively, Fr-P, a delipidated preparation of surfactant consisting mainly of protein, had no effect on macrophage chemokinesis but increased the chemotaxis of PEC to zymosan-activated serum. We conclude that surfactant phospholipid suppresses AM migration, while surfactant protein increases macrophage chemotaxis.

Animals↗

PubMed1997

GFAP gene expression during development of astrocyte.

Glial fibrillary acidic protein (GFAP) is expressed exclusively in astrocytes in the central nervous system. In order to characterize individual cultured cells in which the GFAP promoter is active and to identify the regulatory mechanisms of GFAP expression in these cells, we have developed a unique assay system for promoter activity using retrovirus vectors. Retrovirus containing the mouse GFAP promoter fused to the lacZ gene were used to infect mixed glial cultures. The infected cells, in which the GFAP promoter was active, were visualized by X-Gal staining. From these experiments, we found that a 256 bp fragment 5' of the transcription initiation site was sufficient to confer astrocyte-specific expression of GFAP. The GFAP promoter became active about 3 days before GFAP protein can be detected immunohistochemically, which indicates that detection of GFAP promoter activity can be used to identify astrocyte progenitors. We have also established immortalized astrocyte cell lines in which we detect GFAP promoter activity. Immorto mouse is a transgenic mouse generated by the introduction of thermolabile SV40 T Ag, tsA58. A mixed glial culture prepared from 2-day-old Immorto mouse brain was incubated at 32 degrees C, at which temperature most of the cells expressed T Ag. The culture was then infected with retrovirus containing GFAP promoter-lacZ, and the infected cells were selected. Using the fluorescence-activated cell sorter with fluorescein di-beta-D-galactopyranoside as a substrate (FDG-FACS), these cells were separated into two groups: FDG(+), in which the GFAP promoter was active, and FDG(-), in which it was inactive. Mature astrocyte cell lines were established from the FDG(+) cells by colony isolation. The FDG(-) cells were cloned by colony isolation and cultured at 32 or 39 degrees C. At the latter temperature the expression of T Ag was suppressed and cell differentiation was induced in most cells. The cells which became positive for X-Gal staining only after switching to 39 degrees C were collected as immature astrocyte cell lines. These immortalized cell lines should be useful to investigate the molecular mechanisms of astrocyte differentiation.

Animals↗

PubMed1997

UCE6, a new antitumor antibiotic with topoisomerase I-mediated DNA cleavage activity produced by actinomycetes: producing organism, fermentation, isolation and biological activity.

A novel antitumor antibiotic, UCE6 (1,3,8,10,11-pentahydroxy-2-methyl-10-(2-oxo-4-hydroxypentyl)na phthacene-5, 12-dione) with topoisomerase I-mediated DNA cleavage activity, was isolated from the culture broth of actinomycetes strain UOE6. Addition of silicone oil antifoam agent, KS69 (2%), to the fermentation enhanced the production of UCE6 by approximately 3 fold. A total of 1.15 g of UCE6 was recovered as reddish orange crystals from a 100 liter fermentation supplemented with 2% KS69. UCE6 exhibited growth inhibitory activity against HeLa S3, HCT116 and Lu-65 cells comparable to that of camptothecin.

Actinomyces↗

PubMed1997

GE3, a novel hexadepsipeptide antitumor antibiotic, produced by Streptomyces sp. I. Taxonomy, production, isolation, physico-chemical properties, and biological activities.

GE3, a novel cyclic hexadepsipeptide antibiotic, was isolated from the culture broth of Streptomyces sp. GE3. GE3 was weakly active against some Gram-positive and Gram-negative bacteria and showed potent cytotoxicity against human tumor cell lines. GE3 also exhibited antitumor activity against human pancreatic carcinoma, PSN-1, in vivo. GE3B, a linear peptide form of GE3, which was isolated from the same culture broth with GE3, showed no antibiotic and cytotoxic activities, suggesting the necessity of the cyclic structure of GE3 for its biological activities.

Animals↗

PubMed1997

Polymorphism of alcohol-metabolizing genes affects drinking behavior and alcoholic liver disease in Japanese men.

Alcohol is known to be mainly metabolized in the liver by alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2), and cytochrome P-450IIEI. The purpose of this study was to clarify the role of polymorphism of these ethanol-metabolizing enzymes in drinking behavior and the progression of alcoholic liver disease among Japanese men. Polymorphism of the ADH2, ALDH2, and P-45IIEI genes were determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis in 189 normal Japanese men and 26 male patients with alcoholic liver disease. Drinking behavior was estimated by self-assessment according to DSM-III-R criteria. Facial flushing was reported in 91 subjects heterozygous for ALDH2*1/*2 and in two subjects homozygous for ALDH2*2/*2, but was not found in 96 subjects homozygous for ALDH2*1/*1. In contrast, polymorphism of ADH2 and P-450IIEI did not differ between flushers and nonflushers. Although the flushers only drank a small amount of alcohol (< 20 g of ethanol/day), the nonflushers were divided into a group of moderate drinkers (20 to 80 g/day; n = 54) and a group of heavy drinkers (> 80 g/day; n = 42). A high preponderance of heterozygosity for the ADH2*1/*2 genes (20/42; 60%) and a high frequency of the ADH2*1 allele were found in heavy drinkers, compared with moderate drinkers. However, cytochrome P-45IIEI gene polymorphism was similar among the moderate and heavy drinkers. Not only a high frequency of the ALDH2*1 and ADH2*1 alleles, but also a high frequency of the P-450IIEI c2 allele was found in the patients with alcoholic liver disease. From these results, the drinking behavior of Japanese men is strongly influenced by the ALDH2*1 allele, and the level of alcohol intake is affected by the ADH2*1 allele, but not by cytochrome P-45IIEI. However, progression to alcoholic liver disease among heavy drinkers may be affected by the cytochrome P-450IIEI c2 allele.

Adult↗

PubMed1997

[Adjuvant chemotherapy for non-small cell lung cancer].

Surgery is the first choice for patients in the early stage of non-small cell lung cancer (NSC-LC). But, even for pathologic stage I patients, the post-operative survival remains unsatisfactory; the five-year survival rate is around 70 percent, in spite of potential curative resections. Therefore, post-operative adjuvant chemotherapy is considered to be necessary to improve the survival. Although many prospective randomized studies of post-operative adjuvant chemotherapy have been conducted, the efficacy of post-operative chemotherapy for NSCLC has not been proved (a consensus report of post-operative adjuvant treatment for NSCLC, 3rd IASLC Workshop, Bruges, August 1993). It has been recently reported by the West Japan Study Group for Lung Cancer Surgery (WJSG) that oral administration of UFT (a mixture of tegafur and uracil) as a post-operative adjuvant chemotherapy is effective for patients with complete resected NSCLC (stage I to III) and that UFT administration is tolerable with mild adverse effects in most patients. In order to improve postoperative survival of patients with more advanced stage NSCLC (e.g., bulky N2, III b), we has introduced biochemical modulation therapy using 5-FU, UFT combined with CDDP.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Postoperative adjuvant chemotherapy for non-small-cell lung cancer. West Japan Study Group for Lung Cancer Surgery. The Japan Lung Cancer Research Group on Postsurgical Adjuvant Chemotherapy.

Given that no therapeutic methods of postoperative adjuvant chemotherapy for non-small-cell lung cancer have been established, we selected UFT (tegafur and uracil) for investigation because UFT is less injurious to the host than intensive chemotherapies. The second study of the West Japan Study Group for Lung Cancer Surgery showed that the 5-year survival rates were 64.1% in the UFT group (UFT 400 mg/day for 1 year after surgery) and 49.1% in the control group (surgery alone). Thus, the survival rate for all patients was improved significantly in the UFT group as compared with the control group (log rank test, P = .033; generalized Wilcoxon test, P = .019). To establish the usefulness of long-term oral administration of UFT as an adjuvant therapy for completely resected non-small-cell lung cancer, the nationwide Japan Lung Cancer Research Group on Postsurgical Adjuvant Chemotherapy is now conducting a comparative study of surgery alone versus surgery and UFT in patients with pathologic stage I adenocarcinoma.

Antineoplastic Agents↗

PubMed1997

Tumor angiogenesis in pulmonary adenocarcinomas: relationship with basic fibroblast growth factor, its receptor, and survival.

Tumor angiogenesis was examined in tissue specimens from 120 patients with a pulmonary adenocarcinoma. The microvascular density (MVD) was determined by the factor 8-related antigen (F8RA), and the basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1 (FGFR1) protein expressions were immunologically studied with the MVD. Patients with over 30 counts of the MVD showed significantly poorer prognosis than those with less than 30 counts. bFGF and FGFR1 expressions correlated with tumor angiogenesis and prognosis. Univariate analysis showed that the MVD, bFGF, and FGFR1 had a significant effect on prognosis, and multivariate analysis of three prognostic factors revealed the MVD correlated with survival. Our findings suggest that bFGF and FGFR1 expressions play an important role in tumor angiogenesis and that the bFGF and FGFR1 expressions promote angiogenesis and metastasis in pulmonary adenocarcinoma, and that the MVD is a useful prognostic marker for assessing the outcome of a pulmonary adenocarcinoma.

Adenocarcinoma↗

PubMed1997

Induction of antitumor cytotoxic T lymphocytes from the peripheral blood mononuclear cells of cancer patients using HLA-A2-restricted MAGE-3 peptide in vitro.

As the basis for the application of MAGE antigens to therapeutic use, the induction of peptide-specific CTLs has been investigated by the stimulation of peripheral blood mononuclear cells (PBMCs) with antigenic peptides derived from MAGE genes. However, the cross-reactivity of the peptide-induced CTLs to the target cells endogenously presenting the MAGE epitope, especially in cancer patients, remains controversial, despite the use of complicated manipulations. Because we recently developed a new simplified method to induce peptide-specific CTLs that killed MAGE expressing tumor cells from the PBMCs of a healthy donor, we examined the induction of specific CTLs by stimulation of PBMCs with HLA-A2-restricted MAGE-3 peptide in HLA-A2(+) cancer patients whose tumors expressed MAGE-3 by using the simple method. The CTL responses could thus be induced from unseparated PBMCs by stimulation with freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells and by using interleukin 7 and keyhole limpet hemocyanin for the primary culture. All CTLs induced from the PBMCs of four cancer patients tested could thus lyse the HLA-A2 target cells pulsed with the peptide, and moreover, two of the CTLs were also able to kill HLA-A2 tumor cells expressing MAGE-3 in a HLA class I and A2-restricted manner. Therefore, these findings seem to indicate that HLA-A2-restricted MAGE-3 peptide may be potentially useful for specific immunotherapy in cancer patients.

Antigens, Neoplasm↗

PubMed1996

In vitro senescence enhances IL-6 production in human gingival fibroblasts induced by lipopolysaccharide from Campylobacter rectus.

The production of interleukin-6 (IL-6) in human gingival fibroblasts (Gin cells) is increased by lipopolysaccharide (LPS) from Campylobacter rectus (C. rectus), which is associated with adult periodontitis; however, the age-related changes in the susceptibility of Gin cells to C. rectus LPS remain unclear. We examined the influence of in vitro senescence on C. rectus LPS-stimulated IL-6 production in Gin cells. LPS was prepared from C. rectus ATCC 33238 using hot phenol-water. The Gin cells were established from healthy gingival tissue removed from three patients, aged 10-12 years. The cells were cultured until confluence then stimulated with LPS (0.01, 0.1, 1.0 and 10.0 micrograms/ml). Levels of IL-6 released in the medium were measured after incubation for 3, 6, 9, 12, and 24 h. In both young (5-6 population doublings) and senescent (17-20 population doublings) cells, LPS stimulated IL-6 production in a dose- and time-dependent manner. In response to 0.01-10.0 micrograms/ml of LPS, IL-6 production in the senescent cells was higher than that in the young cells. Using cells from each of the three donors, we found that this phenomenon of higher LPS-stimulated IL-6 production in senescent cells was reproducible. The greater capacity of the senescent cells to synthesize IL-6 in response to LPS was a higher production of mRNA for IL-6. This increase of IL-6 production induced by C. rectus LPS in senescent Gin cells could help to explain the increased susceptibility to periodontal diseases shown by aged individuals.

Adult↗

PubMed1996

Solubility of artificial proteins with random sequences.

A library of artificial random proteins of 141 amino acid residues of which 95 are random and which includes the 20 kinds of amino acids was prepared. Out of the 25 identified random proteins, 5 were soluble in the cell lysate, indicating that about 20% of the random proteins expressed in Escherichia coli are expected to be soluble. The soluble random proteins RP3-42 and RP3-45 and insoluble RP3-70 were purified. The solubility of the purified form is the same as that in the cell lysate.

Amino Acid Sequence↗

PubMed1996

Delayed image of iodine-123 iomazenil as a relative map of benzodiazepine receptor binding: the optimal scan time.

"Delayed" single-photon emission tomograpic (SPET) images after an intravenous bolus injection of iodine-123 iomazenil have been used as a relative map of benzodiazepine receptor binding. We determined the optimal scan time for obtaining such a map and assessed the errors of the map. SPET and blood data from six healthy volunteers and five patients were used. A three-compartment kinetic model was employed in simulation studies and analyses of actual data. The simulation studies suggested that, in the normal brain, the scan time at which a single SPET image best represented the relative receptor binding was 3.0-3.5 h post-injection. This finding was supported by actual data from the volunteers. The simulation studies also suggested that the optimal scan time was not greatly changed by the variability of the input functions, and that the error in the SPET image contrast in the vicinity of the optimal scan time was not increased by changes in the tracer kinetics in the entire brain. The SPET image contrast in the patients at 3.0 h post-injection agreed well with the reference receptor binding estimated by kinetic analysis, with a mean error of 3.6%. These findings support the use of a single SPET image after bolus injection of [123I]iomazenil as a relative map of benzodiazepine receptor binding. For this purpose, a SPET scan time of 3.0-3.5 h post-injection is recommended.

Alzheimer Disease↗

PubMed1996

Simplified quantification of regional cerebral blood flow with 99mTc-ECD SPECT and continuous arterial blood sampling.

The goal of this study was to develop a simple method for quantification of regional cerebral blood flow (rCBF) with 99mTc-ethyl cysteinate dimer (ECD) SPECT. Following an intravenous constant infusion of ECD for one minute, serial dynamic SPECT imaging was performed for 40 minutes in 6 healthy male volunteers with intermittent arterial blood sampling. PET scan with 15O-water was performed on the same day before the SPECT study for measurement of rCBF. Arterial blood data demonstrated rapid conversion of ECD to the hydrophilic metabolites, and most of the arterial input to the brain was completed within 5 minutes after the injection. Brain activity reached a peak value soon after the cessation of infusion, and was stable thereafter with very little washout. Net extraction of ECD in the brain calculated by arterial input of ECD and rCBF demonstrated a rapid decrease within a few minutes, reaching 42.7% at 5 minutes. The simulation study suggested that the arterial blood activity obtained by continuous drawing for 5 minutes and a single SPECT scan would provide a reasonable estimate of rCBF under the assumption of constant net extraction in the brain.

Adult↗

PubMed1996

Differential pattern in tissue-specific somatic mosaicism of expanded CAG trinucleotide repeats in dentatorubral-pallidoluysian atrophy, Machado-Joseph disease, and X-linked recessive spinal and bulbar muscular atrophy.

We investigated the somatic mosaicism of trinucleotide repeat expansion in the neural and nonneural tissues of a dentatorubral-pallidoluysian atrophy (DRPLA), Machado-Joseph disease (MJD), and spinal and bulbar muscular atrophy (SBMA) patient and their correlation to the topographical distribution of the pathological involvement. The spatial pattern of tissue-specific somatic mosaicism in the CAG repeat size was significantly different among the DRPLA, MJD and SBMA patients. The size of the major bands of the mutant CAG repeat allele was significantly smaller in the cerebellar cortex in both DRPLA and MJD patients by 6 and 2 repeat units respectively and larger in the colon and liver of DRPLA by 5 repeats or more. There were also 1-2 repeat-sized small variations of major band size among the neural tissues in DRPLA. In contrast, there was no tissue-specific variation of major bands of CAG repeats and diversity of extra bands among the examined tissues including the cerebellum in the SBMA patient. There was no parallel occurrence of tissue-specific CAG instability and severity of neuropathological involvement in the neural and nonneural tissues of DRPLA, MJD and SBMA patients. Lack of significant tissue-specific somatic mosaicism in SBMA including the cerebellar cortex may suggest that CAG repeat expansion in the mutant androgen receptor gene is far more stable compared with that in DRPLA and MJD as well as those reported in Huntington's disease.

Adult↗

PubMed1996

The basic fibroblast growth factor and its receptor in pulmonary adenocarcinomas: an investigation of their expression as prognostic markers.

The expression of basic fibroblast growth factor (bFGF) and its receptor, the high-affinity type I basic fibroblast growth factor receptor (FGFR-1): were immunohistologically studied in tissues specimens from 167 patients with a pulmonary adenocarcinoma. Of the 167 specimens, 82 (49%) expressed bFGF and 104 (62%) expressed FGFR-1, bFGF and FGFR-1 were simultaneously expressed in 72 (43%). It was also found that many patients who showed intensely positive staining for bFGF were also positive for FGFR-1, and that the expression of bFGF or FGFR-1 or both was associated with p-stage, T and N factors. The overall prognosis was significantly poorer in the bFGF-positive or FGFR-1-positive patients than in negative patients (P < 0.01). The prognosis was also significantly poorer in all patients positive for both bFGF and FGFR-1 than in those negative for both (P < 0.01); this was also true for stage I patients (P < 0.05). Multivariate analysis showed that bFGF had a significant affect on prognosis, whereas FGFR-1 did not. As FGFR-1 is significantly linked with the bFGF expression, it may be that FGFR-1 interferes with the bFGF effect on survival. These findings suggest that bFGF and FGFR-1 play important roles in tumour progression, and that bFGF expression may be a useful prognostic marker for pulmonary adenocarcinomas.

Adenocarcinoma↗

PubMed1996

Time trends and survival after operations for primary lung cancer from 1976 through 1990.

To assess the time trends and survivals after operations for primary lung cancer, the cases of 845 consecutive patients who underwent thoracotomy between 1976 and 1990 were retrospectively reviewed by groups corresponding to year of the operation (the early period was 1976 to 1980, n = 208; the middle period was 1981 to 1985, n = 291, and the late period was 1986 to 1990, n = 346). The 5-year survivals at the early, the middle, and the late periods were 31.5%, 39.0%, and 54.0%, respectively, with significant improvement particularly at the late period (p < 0.05 for the early period vs the middle period, p < 0.01 for the early or middle period vs the late period); the improvement was caused by increase in the ratio of patients with stage I disease (20.7% at the early period, 32.0% at the middle period, 44.2% at the late period), increase in the rates of complete tumor resection with lymph node dissection (57.2%, 68.0%, 74.3%, respectively), and decrease in the rates of operation-related death (3.8%, 3.4%, 0.9%, respectively). The postoperative prognosis of patients with stage II disease at the late period (5-year survival 74.8%) showed significant improvement compared with the other periods. Moreover, the prognosis of patients with stage IIIa, pN2 disease (5-year survival 41.5%) showed significant improvement, which was caused by the significant decrease in patients with pT3 N2 M0 disease and poor prognosis.

Adenocarcinoma↗

PubMed1996

A case of giant cell tumor of the rib with magnetic resonance imaging.

A surgical case of giant cell tumor originating from the right seventh rib in a 51-year-old Japanese man is reported. Surgical resection without radiation therapy is preferable, because radiation may cause malignant transformation of this kind of tumor. Magnetic resonance imaging (MRI) of the tumor, reported for the first time in the English literature, was useful in planning complete resection, because both the excellent soft-tissue contrast resolution and the multiplanar images could demonstrate accurately the tumor extent both in the bone marrow and to the surrounding soft tissue.

Bone Neoplasms↗