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Biomedical subjects

F Suzuki

Publications and source records attributed to F Suzuki.

At least 19 recordsLinked to original sources
PubMed1995

Purification of an angiogenesis inhibitor from culture medium conditioned by a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8.

We previously reported that a novel human chondrosarcoma-derived chondrocytic cell line, HCS-2/8, produced an anti-tumor angiogenesis factor and secreted it into the culture medium [Takigawa et al.: Anticancer Res., 10, 311-316, 1990]. In the present study, we purified the inhibitor by monitoring gelatinase inhibitory activity from the conditioned medium (CM) of HCS-2/8 cells. By a simple three-step procedure, gel filtration chromatography, ion-exchange chromtography, and reverse-phase HPLC, 200 micrograms of the inhibitor was obtained from 6 liters of CM with 239-fold enrichment. Purified inhibitor, named hCHIAMP (human chondrocyte-derived inhibitor of angiogenesis and metalloproteinase activity), showed a single protein band with a molecular mass (M(r)) of 24,000 (24K) under reducing conditions and M(r) 22K under nonreducing conditions on SDS-PAGE. On reverse-zymography, purified hCHIAMP showed a single band of 22K M(r) under nonreducing conditions. Its NH2-terminal amino acid sequence determined up to the 11th amino acid residue was identical with that of the tissue inhibitor of metalloproteinases-2 (TIMP-2). On Western blotting, anti-human TIMP-2 antibody cross-reacted with hCHIAMP, hCHIAMP at a dose of as little as 0.45 microgram significantly inhibited angiogenesis in the yolk sac of chick embryos induced by 0.25 mumol of spermine. Because HCS-2/8 is a clonal cell line, these findings clearly showed for the first time that chondrocytes themselves produce a potent inhibitor of angiogenesis, which is also an inhibitor of gelatinase. The findings also indicate that hCHIAMP is a TIMP-2-like molecule. Because the HCS-2/8 cells are an immortal cell line and of human origin, hCHIAMP could be useful for therapy of angiogenic diseases including solid tumors.

Chondrosarcoma↗
PubMed1995

Small amounts of exogenous IL-4 increase the severity of encephalitis induced in mice by the intranasal infection of herpes simplex virus type 1.

The effect of murine rIL-4 on the development of herpesvirus encephalitis (HSE) in mice infected intranasally with herpes simplex virus type 1 (HSV-1) was investigated. The mortality rates of mice infected with a 0.5 LD50 dose of HSV-1 were greatly increased after the administration of rIL-4 at doses ranging from 0.01 to 1.0 U/mouse 2 h before and 2, 4 and 6 days after the infection. In contrast, survival rates of mice exposed to a 5 LD50 dose of HSV-1 were clearly increased when these mice were treated with anti-IL-4 mAb. Cervical lymph node (CLN) cells and cerebrospinal fluid (CSF) cells from mice with HSE (HSE mice) produced IL-4 in their culture fluids when they were stimulated in vitro with HSV-1 Ag. Increased amounts of HSV-1 infection in mice resulted in the increased production of IL-4 in the culture fluids of local lymphocytes. However, significant amounts of IL-4 were not produced in serum specimens or in culture fluids of spleen cells from HSE mice. IL-4 production in culture fluids of CLN and CSF cells from HSE mice was clearly reduced after treatment of HSE mice with anti-IL-4 mAb. Furthermore, IL-4 production by CLN and CSF cells was greatly enhanced when the cells were prepared from HSE mice previously treated with rIL-4. The IL-4 was mainly produced from CD4+ T cells. These results demonstrate that small amounts of exogenous IL-4 increase the severity of HSE in HSV-1-infected mice through the increased production of IL-4 from local CD4+ T cells.

Administration, Intranasal↗
PubMed1995

CD4+ contrasuppressor T cells improve the resistance of thermally injured mice infected with HSV.

Modulation of burn-associated CD8+ CD11b+ T cell receptor gamma/delta+ suppressor T cells (BA2T cells) and improved resistance to herpesvirus infections was studied in thermally injured mice. The susceptibility of thermally injured mice to infection by herpes simplex virus (HSV) was approximately 100 times greater than it was in normal mice. The increased susceptibility of thermally injured mice to HSV infection was transferred to normal mice by BA2T cells, which appeared in spleens of mice 2-9 days after thermal injury. The suppressor cell activity of BA2T cells was effectively counteracted by CD4+ CD28+ T cell receptor alpha/beta+ Vicia villosa lectin adherent antisuppressor cells (designated as burn-induced contrasuppressor T cells; BCS cells), which were generated naturally in spleens of mice after the appearance of BA2T cells. The adoptive transfer of BCS cells to mice just after the injury improved the resistance of thermally injured mice to HSV infection to levels observed in normal mice. These results suggest that the increased susceptibility of thermally injured mice to HSV infection may be affected by BA2T suppressor cells and BCS cells may improve the resistance of thermally injured mice to HSV infection through the inhibition of BA2T suppressor cell activities.

Animals↗
PubMed1995

Demonstration of endothelin (ET) receptors on cultured rabbit chondrocytes and stimulation of DNA synthesis and calcium influx by ET-1 via its receptors.

Endothelin (ET) receptors on chondrocytes were demonstrated using cultured rabbit costal chondrocytes. After crosslinking the receptors on the cells with 125I-ET-1, two major bands of 43 kDa and 46 kDa were separated by SDS-PAGE. Scatchard analysis demonstrated two classes of ET receptors with Kd values of 1 x 10(-10) M and 5 x 10(-9) M. The numbers of high- and low-affinity receptors were 1 x 10(4) and 2 x 10(5) per cell, respectively. The binding of ET-1 to chondrocytes was increased by treatment with PTH, DBcAMP, TGF-beta 1, IL-1 beta, RA and EGF. ET-1 stimulated DNA synthesis in cultured rabbit chondrocytes. ET-1 also stimulated calcium incorporation through the cell membrane of chondrocytes. These findings indicate that ET-1 has a physiological effect on chondrocytes via its receptors on the cells.

Animals↗
PubMed1995

Glycyrrhizin (20 beta-carboxy-11-oxo-30-norolean-12-en-3 beta-yl-2-O-beta-D-glucopyranuronosyl-alpha-D-glucopyranosiduronic acid) improves the resistance of thermally injured mice to opportunistic infection of herpes simplex virus type 1.

The effect of glycyrrhizin (GR) on the resistance of thermally injured mice to opportunistic herpes simplex virus type 1 (HSV) infection was investigated. We have previously reported that the susceptibility of thermally injured mice or normal mice inoculated with T6S cells (a clone of burn-associated CD8+ CD11b+ TCR gamma/delta + type-2 suppressor T cells), to HSV infection was about 100 times greater than it was in normal mice. When thermally injured mice were treated i.p. with a 10 mg/kg dose of GR 2 and 4 days after infection of HSV, the resistance of these mice to HSV was improved to levels observed in normal mice. The adoptive transfer of splenic mononuclear cells (MNC) from normal mice treated with GR (GR-MNC) to thermally injured mice (recipients) resulted in the improved resistance of recipients to HSV infection. Normal mice inoculated with T6S cells and exposed to HSV had an 80% mortality rate, when given GR-MNC they had a 95% survival rate. The suppressor cell activity of T6S cells was clearly counteracted by GR-MNC in vitro in a mixed lymphocyte-tumor cell reaction. The type of cells responsible for anti-suppressor cells in GR-MNC was shown to be a CD4+ CD28+ TCR alpha/beta + Vicia villosa lectin-adherent T cell. These results suggest that GR may reverse the increased susceptibility of thermally injured mice to HSV infection through the induction of CD4+ contrasuppressor T cells.

Animals↗
PubMed1995

Morphogenetic effect of kainate on adult hippocampal neurons associated with a prolonged expression of brain-derived neurotrophic factor.

Intraperitoneal or intrahippocampal injections of kainate induce both hippocampal cell death and axonal remodeling of the dentate gyrus granular neurons. We report here that injection of kainate into the dorsal hippocampus of adult mice may also trigger a conspicuous and long-lasting global trophic response of granule cells. Morphological changes include somatic and dendritic growth and increased nuclear volume with ultrastructural features characteristic of neuronal development. The trophic response is correlated with a specific overexpression of brain-derived neurotrophic factor that is maintained for at least six months. This shows that plasticity in adult neurons can, in addition to axonal remodeling, extend to generalized cell growth. Our results further suggest that brain-derived neurotrophic factor could be involved in the activation and/or maintenance of this phenomenon.

Animals↗
PubMed1995

Synthesis and preliminary evaluation of [11C]KF15372, a selective adenosine A1 antagonist.

As a radioligand for mapping the presynaptic adenosine A1 receptors in the central nervous system by PET, [1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine ([11C]KF15372), a selective adenosine A1 antagonist, was prepared by the reaction of 8-dicyclopropylmethyl-3-propylxanthine and [11C]propyl iodide with decay-corrected radiochemical yield of 5% based on the [11C]propyl iodide, radiochemical purity of > 99%, sp. at. of 10-56 GBq/mumol and preparation time of 45-55 min. Another 11C-labeled A1 antagonist with much lower affinity for the A1 receptors, 7-[11C]methyl-KF15372 ([11C]KF17109), was also prepared using [11C]methyl iodide with a decay-corrected radiochemical yield of > 50%. In mice, the brain uptake of [11C]KF15372 (1.91% ID/g at 5 min) decreased gradually with time. Carrier KF15372 competitively reduced the brain uptake to a level (43% of the control) comparable to the brain uptake of [11C]KF17109. On the other hand, an A2 antagonist 3,7-dimethyl-1-propargylxanthine showed no effect on the brain uptake of [11C]KF15372. The results show that [11C]KF15372 has potential as a PET radioligand for mapping the adenosine A1 receptors and that [11C]KF17109 may be a reference compound reflecting the non-specific uptake of the [11C]KF15372.

Animals↗
PubMed1995

Bradycardia-dependent activation delay of the atrial tissue in a patient with sick sinus syndrome.

Bradycardia-dependent block or activation delay of the atrial tissue has not been documented in the literature. A patient with sick sinus syndrome in whom bradycardia-dependent, as well as tachycardia-dependent, activation delay in the atria was elucidated is reported on. The phenomenon of bradycardia-dependent activation delay was reproducibly demonstrated, both during atrial extrastimulation and incremental atrial pacing from the high right atrium, in the setting of an abnormally prolonged activation interval from the distal stimulating electrodes to the proximal recording electrodes of a quadripolar catheter, which was localized in the high right atrial region. Supernormal conduction seemed to be an unlikely explanation for the observed phenomenon.

Aged↗
PubMed1995

A specific chromosome change and distinctive transforming genes are necessary for malignant progression of spontaneous transformation in cultured Chinese hamster embryo cells.

Chinese hamster embryo (CHE) cell strains, each initiated from a separate cell stock obtained from different mothers, were transferred successively at intervals of 3 days and the changes in growth properties and karyotypes at various passages were examined. All nine cell strains proliferated at varying growth rates for 60 passages but only 2 (designated CHE A1 and CHE A2) of them expressed malignant phenotypes. The acquisition of tumorigenicity in nude mice was observed in CHE A1 and CHE A2 cells at passages 40 and 10, respectively. After 5 passages, 8 of 9 cell strains contained one or two common additional chromosomes, chromosome 3q and/or chromosome 5, although one cell strain (designated CHE A3) maintained a normal diploid karyotype for 60 passages. Trisomy of chromosome 3q was observed in all tumorigenic CHE A1 and A2 cells. One or two 3q chromosomes were detected in all tumor-derived cell lines established from tumors produced by these tumorigenic cells. DNA from tumorigenic cells and tumor-derived cell lines exhibited a high ability to transform mouse NIH3T3 cells, but we could not detect any activation of Ha-ras, Ki-ras, hst, erbB-2, mos, met or raf in any of the transformed NIH3T3 cells. These results suggest that even though cultured CHE cells can transform spontaneously, without any specific chromosome change, to immortal cells, activation of unknown oncogene(s) in addition to a specific chromosome change may be required for their malignant progression. Our results suggest that trisomy of chromosome 3q is this specific chromosome change.

3T3 Cells↗
PubMed1995

Selective A1 adenosine receptor antagonism augments beta-adrenergic-induced renin release in vivo.

This study determines, in vivo, whether endogenous adenosine/A1 receptor interactions at juxtaglomerular cells restrain the release of renin induced by receptor-mediated activation of the adenosine 3',5'-cyclic monophosphate pathway and whether endogenous adenosine/A2 receptor interactions diminish this restraining response. The following four pharmacological probes were employed: 1) 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and 2) FK-453, both selective A1 receptor antagonists; 3) FR-113452, a nearly inactive enantiomer of FK-453; and 4) KF-17837, a selective A2 receptor blocker. Adult Sprague-Dawley rats were prepared (adrenalectomized, renal denervated, uninephrectomized, and treated with indomethacin, aldosterone, and hydrocortisone) to minimize endogenous stimulation of renin release and received either vehicle (control group) or one of the four drugs. Intrarenal infusions of isoproterenol (3, 30, and 100 ng.kg-1.min-1) caused dose-related increases in plasma renin activity (PRA). This PRA response was significantly augmented in the groups receiving DPCPX (P = 0.0010) or FK-453 (P = 0.0001) but was not altered in the groups treated with FR-113452 (P = 0.3422) or KF-17837 (P = 0.2155). Systemic and renal hemodynamics and renal electrolyte excretions were monitored and could not account for the PRA augmentation caused by the A1 antagonists. This study clearly demonstrates that endogenous adenosine acts on the A1 receptor to restrain the renin release induced by activation of intrarenal beta-adrenoceptors and is not counteracted by endogenous activation of the A2 receptor.

Animals↗
PubMed1995

[Clinical assessment for prognostic factors related to recurrence and progression in superficial bladder cancer].

PURPOSE: The objective of this assessment is to identify prognostic factors of recurrence and disease progression of primary superficial transitional cell carcinoma of the bladder. PATIENTS AND METHODS: TUR-Bt was performed in 150 patients with initial superficial bladder cancer, of which pathological diagnosis was pTa or pT1 transitional cell carcinoma. The recurrence and progression free survival was examined. The clinicopathological factors analyzed were as follows: grade, pT, tumor size, tumor number and tumor form. RESULTS: Median follow-up period was 39 months (range 3-184). The age distribution was from 25 to 98 years old with the average of 67. The patients were 122 males and 28 females. Recurrence was observed in 72 patients. The 5-year recurrence free rate for all cases were 41.6%. The factors found to be of significance for the prognosis for recurrence were tumor size (1 cm <) and tumor multiplicity (p < 0.01). Progression was seen in 15 patients; 8 invasive tumors, 2 lymph node metastases and 5 distant metastases. Twelve cases of those died of cancer. The 5-year progression free rate for all cases were 87.0%. The prognostic factors related to progression found in this study were G3, pT1 and sessile form (p < 0.01). There was no significant difference in recurrence free rate between cases with and without postoperative therapy; UFT p.o., ADM i.i. (intravesical instillation), ADM + Ara-C i.i. and PEP + 5-FU + Ara-C i.i. CONCLUSION: Tumor size more than 1 cm and tumor multiplicity were the high risk factors about recurrence. So were G3, pT1 and sessile form about progression.

Adult↗
PubMed1995

[HPV infection of the uterine cervix by cytodiagnosis, histodiagnosis and dot blot hybridization method].

Human papilloma virus (HPV) infection is diagnosed by morphological methods (including cytodiagnosis, histodiagnosis and electron microscopy) and DNA diagnostic methods. One of the DNA diagnostic methods, Dot blot hybridization (DBH), is generally regarded to be superior to the morphological methods in terms of specificity and sensitivity. There have recently been reports showing that such morphological methods as cytodiagnosis [for koilocytotic atypia (KC) or koilocytosis] and histodiagnosis are best for HPV detection in laboratories because they have better sensitivity, and are cheaper, and procedurally simpler than the DBH method. We compared detection rates by morphological methods (cytodiagnosis and histodiagnosis) and the DBH method. (Materials and Methods) The subjects were 377 patients who came to the Department of Obstetrics and Gynecology of Juntendo University Urayasu Hospital and had abnormal findings in the uterine cervix by cytodiagnosis of colposcopy. Uterine cervix swabs were scraped during colposcopic examination, and specimens for Papanicolaou and Giemsa staining were prepared on 2 slides. Scraping was again performed for the DBH (Vira pap. and type, Toray Industries, Inc.) method using swabs specified for the kit, and cells were obtained in a collection kit. At the same time, at least 3 sites including, possible atypical conversion zones, were biopsied, followed by paraffin embedding and hematoxylin-eosin staining of the specimens. (Results) 1) Comparison of detection rates by cytodiagnosis and the DBH method The positive rates by the DBH method were determined according to cytodiagnostic category in 377 patients. HPV-DNA was detected in every category and in 86 (22.8%) of all of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[A case of a ureteral polyp resected transurethrally].

We report a case of fibroepithelial polyp of right ureter. The patient was a 36-year-old man, complaining of macrohematuria. An excretory urogram and retrograde pyelogram revealed a filling defect of the middle third of ureter, but it did not show hydronephrosis. We observed the ureter by transurethral ureteroscopy and found a ureter polyp with a slender stalk. We resected the polyp transurethrally. The pathological diagnosis was a fibroepithelial polyp. This suggests that the endourological technique is a useful method for diagnosis and treatment in patients with a urinary tract filling defect.

Adult↗
PubMed1994

Decreased pentylenetetrazol-induced expression of zif/268 in NGF-transgenic mice.

Expression of the proto-oncogene zif/268 was investigated by in situ hybridization in the hippocampus and cerebral cortex of nerve growth factor (NGF)-transgenic mice during pentylenetetrazol (PTZ)-induced seizures. NGF-transgenic mice displayed normal basal levels of zif/268 mRNA in cortex and hippocampal formation except for the dentate gyrus which contained significantly reduced levels. PTZ induced a similar transient increase of zif/268 mRNA in cortex and Ammon's horn of normal and NGF-transgenic mice. On the other hand, increase of zif/268 mRNA in the dentate gyrus was significantly lower in transgenic mice. Reduced PTZ-induced activation of zif268 may reflect a decreased sensitivity of NGF-transgenic animals to epilepsy by direct or indirect interaction of NGF with immediate early genes.

Animals↗
PubMed1994

Expression of the linear DNA plasmid pRS64 in the plant pathogenic fungus Rhizoctonia solani.

The plant pathogenic isolate RI-64 of anastomosis group 4 of Rhizoctonia solani possesses three linear DNA plasmids (pRS64-1, -2, and -3). Unique poly(A)- RNA, 0.5 kb in length and hybridizable with the pRS64 DNAs was found in mycelial cells of the isolate RI-64. The overall homology at the nucleotide level between pRS64-1, -2, and -3, and the cDNA prepared from the poly(A)- RNA was 100%, 73%, and 84%, respectively. The open reading frames found in pRS64-1, -2, and -3 (ORF1-1, ORF2-1, and ORF3-1) are 68 amino acids long. The amino acids sequence showed no significant homology with known proteins. Extracts from Escherichia coli cells expressing ORF1-1 contain a specific protein of 7 kDa. Antisera raised against the ORF1-1 product obtained from E. coli cells cross-reacted with the specific proteins found in the mycelia. The results indicate that the DNA plasmids found in R. solani contain a sequence that encodes a specific protein which may be involved in determination of plant pathogenicity.

Amino Acid Sequence↗