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Biomedical subjects

N Fujimoto

Publications and source records attributed to N Fujimoto.

At least 181 records · Page 10Linked to original sources
PubMed1994

Extracorporeal shock wave lithotripsy for ureteral stones using the Dornier lithotriptor MFL5000.

A total of 157 ureteral stones in 150 patients were treated by extracorporeal shock wave lithotripsy (ESWL) using the Dornier lithotriptor MFL5000. Stones were treated in situ in 149 cases and with a double-J ureteral stent bypass in 8 cases due to large stone burden or failure of the preceding in situ ESWL. The average number of ESWL sessions and shock waves were 1.6 and 4,446, respectively. Multiple sessions were required in 58 cases (36.9%) for satisfactory fragmentation. At a 3-month follow-up, 91.7% of the cases treated by in situ ESWL and 50% of those treated with a stent bypass were rendered stone-free, achieving an overall stone-free rate of 89.4%. Ureteroscopic extraction or open ureterolithotomy was performed in 4 cases with an impacted stone for the removal of the residual fragments. No serious complications related to ESWL were observed. In situ ESWL is an effective and noninvasive method of treating ureteral stones. Large and/or impacted stones can also be successfully treated by ESWL with or without a stent bypass, but ureteroscopic or surgical procedures may be necessary to salvage fragments packed in the ureteral edema.

Adult↗
PubMed1994

Alteration in the agonist/antagonist balance of antiestrogens by activation of protein kinase A signaling pathways in breast cancer cells: antiestrogen selectivity and promoter dependence.

We find that stimulation of the protein kinase A (PKA) signaling pathway in MCF-7 human breast cancer cells changes the agonist/antagonist activity of tamoxifen and related antiestrogens; it activates or enhances their estrogen agonist activity and reduces their ability to antagonize the effects of estradiol (E2). In MCF-7 human breast cancer cells which contain high levels of endogenous estrogen receptor (ER), the antiestrogen trans-hydroxy-tamoxifen (TOT) fails to stimulate transcription of the estrogen-responsive promoter-reporter constructs estrogen response element (ERE)-TATA-chloramphenicol acetyl transferase (CAT), (ERE)2-TATA-CAT, and pS2-CAT. However, when cells are treated with isobutyl methylxanthine plus cholera toxin (which increases intracellular cAMP approximately 10-fold), or with 8-bromo-cAMP, or are transfected with expression vectors for the PKA catalytic subunits, the transcriptional activity of the antiestrogen-ER complex is now increased, to levels 20-75% that of E2, and TOT also becomes much less effective in antagonizing the stimulation of transcription by E2. Although this alteration in the agonist and antagonist activity of TOT is observed with three promoter-reporter constructs, containing a simple TATA promoter or a more complex, pS2 promoter, elevation of cAMP did not enhance the transcription by either TOT or E2 of the reporter plasmid ERE-thymidine kinase-CAT. Thus, this phenomenon is promoter specific. The maximal stimulatory effects of isobutylmethylxanthine plus cholera toxin and PKA catalytic subunits on TOT and E2 transcriptional enhancement were not additive, consistent with the hypothesis that they are both acting via stimulation of the same signal transduction pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1994

Hemichorea in hyperglycemia associated with increased blood flow in the contralateral striatum and thalamus.

We studied a patient with hyperglycemia who developed choreic involuntary movements in the right extremities using single photon emission computed tomography (SPECT) with 123I-N-isopropyl-p-iodoamphetamine. SPECT revealed an increased blood flow in the left striatum and thalamus. Through the control of blood glucose and the administration of haloperidol, the hemichorea was resolved, and the increased blood flow in the striatum and thalamus disappeared. These findings suggest that the increased blood flow, which probably indicates increased neuron activity in the striatum and thalamus, is an underlying pathophysiological state in hemichorea.

Aged↗
PubMed1994

[Theoretical analysis about an optimal screening interval for renal cell carcinoma].

In recent years the number of incidentally detected renal cell carcinoma (RCC) has increased. It is undoubtedly true that ultrasonography is the most useful tool to detect RCC in small size. However, the optimal interval of ultrasound examination is unknown. To elucidate this, we investigated the growth rate of RCC during the period of non-treatment in 6 patients. Their growth was slow and the tumor volume doubling time ranged 372 to 579 (468 +/- 84.6) days. Based on this growth rate, we conclude that we can detect the majority of RCC ranging from 1.5 to 3 cm in diameter if ultrasonography is repeated every 3 years and that the age of subjects for screening is over 40 years.

Adult↗
PubMed1994

[Expression of integrin molecule in urological tumor cell lines by using RT-PCR method].

Integrins are heterodimer molecule that are composed of one alpha subunit and one beta subunit. Integrins appear to be the major receptors by which cells attach to extracellular matrices, and some integrins also mediate important cell-cell adhesion event. In recent years signaling pathway via beta subunit of integrin molecule has been clarified, and 8 kinds of integrin beta subunit are known to exist. And so we investigated the expression of integrin beta subunit in various urological tumor cell lines by using RT-PCR method. Materials are composed of 8 renal cell carcinoma cell lines, 2 urinary bladder carcinoma cell lines, a testicular tumor cell line and a prostate tumor cell line. All 12 cell lines express integrin beta 1 subunit. The expression rate of beta 4 subunit in renal cell carcinoma lines are lower than that in other urological tumor cell lines. The expression of beta 6 subunit was observed in renal cell carcinoma cell lines and testicular tumor line. In testicular tumor cell line we also found the expression of beta 2 subunit which expression had been believed to be specific in leukocyte.

Base Sequence↗
PubMed1994

[Extracorporeal shock wave lithotripsy monotherapy for upper urinary tract stones using the Dornier lithotriptor MFL5000].

A total of 345 cases of upper urinary tract stones (188 renal and 157 ureteral stones) were treated by extracorporeal shock wave lithotripsy (ESWL) monotherapy using the Dornier lithotriptor MFL5000. Of these cases 294 (85.2%) had stones less than 20 mm in length. A double-J ureteral stent was placed in 40 cases of renal stones and 8 ureteral stones due to large stone burden or failure of in situ ESWL for impacted stones. Epidural or spinal anesthesia was necessary in 32 cases to maximize the generator voltage or to prevent intractable pain. The number of ESWL sessions and shock waves increased in accordance with the stone size, with an average of 1.6 and 4442, respectively. Multiple sessions were required in 68 cases of renal stones (36.2%) and 59 of ureteral stones (37.6%). With a 3-month follow-up, the stone-free rate was 60.5% for renal stones and 89.4% for ureteral stones, with the overall stone-free rate of 74.7%. Including the cases with residual fragments less than 4 mm, ESWL monotherapy was successful for 86.4% of renal stones and 93.6% of ureteral stones, achieving the overall success rate of 89.9%. No serious complications related to ESWL were observed. Four cases of impacted ureteral stones underwent ureteroscopic extraction or open ureterolithotomy for fragment removal. ESWL monotherapy using the Dornier MFL5000 is an effective and noninvasive method of treating upper urinary tract stones. Satisfactory fragmentation and clearance can be achieved with multiple sessions even for large or impacted stones, but alternative procedures may be necessary to salvage fragments of impacted stones.

Adolescent↗
PubMed1994

Excess of metalloproteases over tissue inhibitor of metalloprotease may contribute to cartilage degradation in osteoarthritis and rheumatoid arthritis.

BACKGROUND: In an attempt to identify the factor(s) involved in the modulation of the degradative pathway of articular cartilage, we previously reported a possible imbalance between the levels of biologically active forms of metalloproteases and tissue inhibitor of metalloprotease (TIMP) in osteoarthritis (OA) cartilage. EXPERIMENTAL DESIGN: We extended our analysis on the protein level and the synthesis of stromelysin-1, collagenase, TIMP-1, and TIMP-2 in normal, OA, and RA cartilages, and provided information on the synthesis pattern of these proteins in respect to the action of interleukin-1 (IL-1). These protein concentrations were determined by specific sandwich EIA assays. RESULTS: This study allowed us to establish that the concentration of stromelysin-1 and collagenase is elevated in both OA and rheumatoid arthritis (RA) cartilages when compared with normal, with significantly higher levels of collagenase found in OA (p < 0.0003) and RA (p < 0.0001), and of stromelysin-1 in RA (p < 0.02). In all cases, the level of stromelysin-1 significantly exceeded (a few 100-fold) the collagenase level. The cartilage TIMP-1 level was notably enhanced only in RA, whereas TIMP-2 was increased in both OA and RA cartilage. RA patients with active disease had a higher level of metalloproteases and TIMP than those patients with inactive disease. Moreover, patients taking steroids alone or in combination with methotrexate had a markedly lower metalloprotease level without any changes in the TIMP-1 level. In culture cartilage explants, the synthesis of stromelysin-1 was enhanced in RA cartilage, whereas the level of collagenase was increased both in OA and RA explants. When compared with normal patients, the TIMP-1 synthesis was essentially unchanged in arthritic explants, whereas the level of TIMP-2 was decreased in RA explants when compared to OA. IL-1 induced a statistically significant increased synthesis of metalloproteases with the highest level found in arthritic explants. IL-1 also significantly decreased the TIMP-1 synthesis in OA and RA explants, and the TIMP-2 synthesis in OA. CONCLUSIONS: This study demonstrates that stromelysin-1 is the predominant metalloprotease synthesized in human articular cartilage and that both TIMP-1 and TIMP-2 are present in this tissue. The differential regulation of metalloprotease and TIMP syntheses by IL-1 suggests that this cytokine, during inflammatory conditions, may promote cartilage degradation by creating an imbalance between the level of these enzymes and their inhibitors.

Aged↗
PubMed1994

Prostaglandins E2 and E1 inhibit cytokine-induced metalloprotease expression in human synovial fibroblasts. Mediation by cyclic-AMP signalling pathway.

BACKGROUND: Cytokine modulated matrix metalloprotease (MMP, i.e., collagenase and stromelysin) synthesis may be associated etiologically with osteoarthritic diseases. The aim of this study was to investigate the mode of action by which interleukin-1 beta (IL-1 beta) induced collagenase and stromelysin mRNA expression and synthesis in normal human synoviocytes and to explore mechanisms of suppression of these proteolytic enzymes by prostaglandins (PG). EXPERIMENTAL DESIGN: Collagenase and stromelysin expression and synthesis were induced in cultured human synoviocytes with rhIL-1 beta in the absence or presence of either chemical inhibitors of protein kinase (PK) A and C, PGE2 or PGE1, or cAMP mimetics. We used enzyme immunoassays to determine MMP antigen levels in spent culture medium and Northern hybridization to measure steady-state MMP mRNA expression. RESULTS: Dose-response experiments revealed that 10 pg/ml of interleukin-1 beta was an effective sub-saturating concentration for the induction of collagenase and stromelysin expression in normal human synovial fibroblasts. The rate of collagenase synthesis and expression peaked at 18 to 24 hours after rhIL-1 beta stimulation, whereas stromelysin output increased steadily within the experimental time frame (72 hours). Protein kinase C inhibitors, H-7 and staurosporine, prevented the rhIL-1 beta induction of MMP mRNA expression and protein synthesis. Pretreatment of synoviocytes with phorbol myristate acetate for 18 hours abrogated the ability of rhIL-1 beta to induce MMP synthesis. Prostaglandins E2 and E1 potently inhibited in a dose-dependent fashion rhIL-1 beta induced MMP synthesis: PGE2, IC50, collagenase, 2.3 ng/ml; stromelysin, 21.2 ng/ml; PGE1, IC50, collagenase, 2.5 ng/ml; stromelysin, 13.4 ng/ml. MMP mRNA steady-state levels were suppressed in a fashion similar to that of the protein synthesis. Forskolin, dibutyryl cAMP, and 3-isobutyl-1-methyl xanthine mimicked the effects of the prostaglandins (PGs). [N-(2-methyl-amino)-5-isoquinoline-sulfonamide dihydrochloride] (H-8), an inhibitor of PKA activity, could reverse to a large extent, the suppressive effects of the PGs as did cycloheximide when preincubated with PGE2 before rhIL-1 beta activation of synoviocytes. CONCLUSIONS: We conclude that IL-1 beta stimulates MMP synthesis by activating PKC but not PKA, and that the synthesis of collagenase and stromelysin is discoordinate on a temporal and quantitative basis. PGs inhibit rhIL-1 beta-induced MMP expression and synthesis by virtue of their ability to increase cAMP intracellular levels and subsequent activation of signal transduction mechanisms involving PKA. Homeostasis may be maintained in acute episodes of joint inflammation through feedback processes involving locally produced eicosanoids.

Alprostadil↗
PubMed1993

A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 2 (72-kDa gelatinase/type IV collagenase) using monoclonal antibodies.

A one-step sandwich enzyme immunoassay (EIA) for human matrix metalloproteinase 2 (MMP-2, 72-kDa gelatinase/type IV collagenase, EC 3.4.24.24) was established with a pair of monoclonal antibodies prepared against the precursor form of MMP-2 (proMMP-2) purified from the conditioned medium of human skin fibroblasts or against a synthetic peptide corresponding to the N-terminal domain of proMMP-2. ProMMP-2 in samples was allowed to simultaneously react with both solid-phase and peroxidase-labeled antibodies. Sensitivity of this EIA system was 2.4 pg/assay (0.24 microgram/l) and linearity was obtained between 10 and 5,000 pg/assay (1.0-500 micrograms/l). The EIA system recognized both the free form of proMMP-2 and its complex form with TIMP-2 with the same degree of immunoreactivity. ProMMP-2 levels in human sera from patients in various disease states were analyzed. In sera from patients with hyperthyroidism (12), primary biliary cirrhosis (8) and hepatocellular carcinoma (11), 749 +/- 166, 716 +/- 135 and 686 +/- 236 micrograms/l of proMMP-2 were detected, respectively and these were significantly higher than that observed in 213 normal human sera (570 +/- 118 micrograms/l). In contrast, the levels in sera from 33 patients with osteoarthritis (449 +/- 72 micrograms/l), 45 with rheumatoid arthritis (408 +/- 139 micrograms/l), 13 with stomach cancer (427 +/- 103 micrograms/l) and 10 with pancreatic cancer (422 +/- 130 micrograms/l) were significantly lower than that found in normal sera. Immunoblot and gel filtration analyses showed that human sera contain several MMP-2 species in addition to proMMP-2 which exist in a complex form with TIMP-2.

Amino Acid Sequence↗
PubMed1993

A one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases-2 using monoclonal antibodies.

A one-step sandwich enzyme immunoassay system was developed with a pair of monoclonal antibodies against two individual oligopeptides prepared from the amino acid sequence of the human tissue inhibitor of metalloproteinases-2 (TIMP-2). The assay system consisting of two simultaneous immunoreactions used a solid phase monoclonal antibody and a horse-radish peroxidase-labeled monoclonal antibody. The system detected a free form of TIMP-2 and that complexed with active forms of matrix metalloproteinases (MMPs) giving a different sensitivity for each MMP but not TIMP-2 complexed with the precursor of 72 kDa gelatinase/type IV collagenase (MMP-2). The sensitivity of the system was 1.6 microgram/l (16 pg/assay) and linearity was obtained between 6.3 and 50 micrograms/l (63-500 pg/assay). TIMP-2 levels in the sera of 20 patients with rheumatoid arthritis (68 +/- 25 micrograms/l, mean +/- S.D.) and 13 patients with hepatocellular carcinoma (76 +/- 46 micrograms/l) were significantly higher (P < 0.05) than those of 18 normal subjects (5.6 +/- 7.4 micrograms/l). In contrast, the levels in the sera of 10 patients with gastric cancer (45 +/- 18 micrograms/l) and 7 patients with cancer of the uterus (36 +/- 13 micrograms/l) were significantly lower (P < 0.05 or P < 0.01) than those of normal subjects. Immunoreactivity analyses suggested that the precursor of MMP-2 in normal sera exists in a complexed form with TIMP-2 by interacting with the C-terminal domain of TIMP-2.

Amino Acid Sequence↗
PubMed1993

A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 1 (interstitial collagenase) using monoclonal antibodies.

Interstitial collagenase (EC 3.4.24.7, matrix metalloproteinase-1, MMP-1) is synthesized and secreted by many cells, and plays an important role in a wide variety of pathophysiological degradation processes of extracellular matrices. The activity of MMP-1 is regulated by tissue inhibitors of metalloproteinases, TIMP-1 or TIMP-2, which form a non-covalent complex with the active enzyme. We raised monoclonal antibodies against zymogen of MMP-1, proMMP-1 purified from human skin fibroblasts. The antibodies recognized both precursor and active forms of MMP-1, but did not cross-react with 72-kDa and 92-kDa gelatinase/type IV collagenases or stromelysin-1. A specific and sensitive one-step sandwich enzyme immunoassay for human MMP-1 was developed using a solid phase monoclonal antibody and a horseradish peroxidase-labeled monoclonal antibody (Fab'). The assay can be completed within 1 h (30 min for immunoreaction and 15 min for color development) and the sensitivity is 0.12 microgram/l with the linearity between 0.12 and 10 micrograms/l. Active MMP-1 shows 1.3-fold higher absorption at 492 nm than proMMP-1. However, the recognition rate of MMP-1 is decreased to approximately 50% and < 3% for the MMP-1-TIMP-1 and MMP-1-TIMP-2 complex forms, respectively. The MMP-1 levels in human sera from 120 healthy subjects are shown to be in the range of 8.5 +/- 5.2 micrograms/l (mean +/- S.D.) and the levels of 95% of the samples range from 0 to 20 micrograms/l.

Amino Acid Sequence↗
PubMed1993

The significant effect of HLA-DRB1 matching on long-term kidney graft outcome.

Serotyping and genotyping (polymerase chain reaction with sequence-specific oligonucleotide probes method) were conducted on 520 unrelated individuals to determine the linkage disequilibrium of HLA-B and HLA-DRB1. Analyses of 511 kidney transplants (300 related and 211 cadaver recipients) were carried out at 4 transplant centers using the linkage disequilibrium of HLA-B and HLA-DRB1 established previously. All transplant recipients received CsA immunosuppression and were transplanted from June 1983 to December 1991. There were 51 significant linkages formed between HLA-B and HLA-DRB1 alleles (P < 0.05). DRB1-compatible transplants experienced a comparable 5-year graft success rate of 94% as did the HLA-identical recipients with a 100% 5-year success rate. However DRB1-incompatible recipients displayed a significantly reduced 5-year graft survival rate of 73% (73% vs. 94% P < 0.01). The 5-year graft survival rate of HLA-DR-incompatible recipients of 71% was compatible to the 73% for HLA-DRB1-incompatible recipients. No variation of rejection rate for DRB1-compatible grafts was seen in any of the 4 transplant centers. The results also indicated that HLA-DRB1 compatibility was essential for optimal success rate, regardless of HLA class I mismatches. The overall conclusion was that matching for HLA-DR was important to achieve optimal kidney graft survival on the molecular level but not on the serotyping level.

Alleles↗
PubMed1993

A case of xeroderma pigmentosum complementation group F with neurological abnormalities.

We report a 48-year-old Japanese man suffering from xeroderma pigmentosum associated with mental retardation, cerebral atrophy and cerebellar ataxia. Cultured fibroblasts from an unexposed area of skin had reduced DNA repair capacity after UV irradiation, with higher sensitivity to UV than normal cells in colony-forming ability and host cell reactivation using herpes simplex virus. Genetic complementation tests by cell fusion with polyethylene glycol revealed that the patient belonged to group F. He died of bile duct cancer at the age of 50. This is the first report of an XP-F patient with neurological abnormalities.

Brain Diseases↗