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Biomedical subjects

N Fujimoto

Publications and source records attributed to N Fujimoto.

At least 145 records · Page 8Linked to original sources
PubMed1996

Determination of stromelysin-1, 72 and 92 kDa type IV collagenase, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in synovial fluid and serum from patients with rheumatoid arthritis.

OBJECTIVE: To investigate the correlation between serum and synovial fluid (SF) concentrations of stromelysin-1 (MMP-3), gelatinases (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in patients with rheumatoid arthritis (RA) and to assess the role of these proteins in cartilage destruction and their clinical value as indicators of disease activity. METHODS: Enzyme linked immunoassays (ELISA) were used. SF and serum samples were collected simultaneously from 55 patients with RA. Radiographic (Larsen grade) and clinical evaluations were also done. RESULTS: There was significant correlation between SF concentrations of MMP-3 and MMP-9. In addition, there was significant negative correlation between SF concentrations of TIMP-2 and MMP-2, 3, and 9. The only correlation observed among MMP and TIMP in serum was that of MMP-3 with MMP-2. Significant correlation was also found between MMP-3 concentrations in the serum and SF. There were no significant correlations between radiological grade and concentrations of these proteins. Patients with mild to moderate functional disability showed significantly higher serum TIMP-1 concentrations than patients with severe disability. CONCLUSION: Extremely high concentrations of MMP-3 in SF of the patients with RA may contribute to its elevation in serum. It would seem that regulation of TIMP production depends upon the disease state and not the concentration of MMP. Discrepancies between concentrations of TIMP and MMP in SF may be responsible for cartilage destruction in RA.

Aged↗
PubMed1996

[Tumor enucleation for intrapelvic schwannoma: a report of two cases].

A 65-year-old man and a 35-year-old woman were diagnosed with intrapelvic tumors originating from the sacral nerves by computed tomographic (CT) scan, magnetic resonance imaging (MRI) and angiography. These tumors were tightly adhered to the iliac arteries and veins and could not be resected completely. Since the cryostat sections revealed benign schwannomas histopathologically, we enucleated the tumors without the pseudocapsules. All of the 57 intrapelvic schwannomas previously reported in Japan were resected with pseudocapsules. Both of our patients showed improvement of subjective symptoms, but should be followed up and examined for the presence of regrowth of tumors.

Adult↗
PubMed1996

[Effect of FUT-187, oral serine protease inhibitor, on inflammation in the gastric remnant].

Excessive enterogastric reflux following partial gastrectomy is believed to be responsible for the cause of inflammation in the gastric remnant. We examined the effect of FUT-187, a synthetic serine protease inhibitor, on symptoms and endoscopic findings in 33 patients who were diagnosed endoscopically as postgastrectomy gastritis. Patients took 50 mg FUT-187 orally after each meal and at bedtime for 8 weeks. Before treatment, 30 patients (91%) suffered from several symptoms including regurgitation and/or bitter taste in the mouth (49%), epigastric pain (42%) and nausea (36%). From endoscopic observation, erythema was detected in 32 patients, edema in 23 patients and erosion and/or ulcer in 9 patients. After treatment the global improvement rating for subjective symptoms was 76.7% (23/30) and the improvement of endoscopic findings was 63.6% (21/33). Diarrhea was observed in one patient but could be easily controlled by discontinuation of the drug. Our results suggest that FUT-187 can be a useful drug for the treatment of postgastrectomy gastritis with its efficacy and safety.

Administration, Oral↗
PubMed1995

Determination of tissue inhibitor of metalloproteinases-2 (TIMP-2) in experimental animals using monoclonal antibodies against TIMP-2-specific oligopeptides.

We have developed a one-step sandwich enzyme immunoassay (EIA) using monoclonal antibodies against oligopeptides of the human tissue inhibitor of metalloproteinases-2 (TIMP-2) (Fujimoto et al. (1993) Clin. Chim. Acta 220, 31). The present studies further demonstrated that the antibodies cross-react with TIMP-2 species of experimental animals including mouse, rat, guinea pig and rabbit. The detection of the TIMP-2 species in our EIA system was verified using rat TIMP-2 and the EIA was subsequently used to measure the animal TIMP-2 in the sera. Using human TIMP-2 as a standard, TIMP-2 levels in the sera of mouse, rat, guinea pig and rabbit were approximately 80, 200, 270 and 25 ng/ml, respectively.

Animals↗
PubMed1995

Increased levels of stromelysin-1 and tissue inhibitor of metalloproteinases-1 in sera from patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the efficacy of stromelysin-1 (matrix metalloproteinase-3 [MMP-3]) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in serum as markers for joint inflammation in rheumatoid arthritis (RA). METHODS: Levels of both macromolecules in sera from 97 healthy controls, 109 patients with RA, and 47 patients with osteoarthritis (OA) were measured by respective 1-step sandwich enzyme immunoassays. In the patients with RA, serum levels of MMP-3 and TIMP-1 were investigated in relation to laboratory and clinical measures of disease activity. In addition, the relationships between serum and synovial fluid (SF) levels in paired samples from individual patients were examined. RESULTS: Serum levels of both MMP-3 and TIMP-1 in RA patients were significantly higher than those in OA patients and in healthy controls (P < 0.001), and were shown to correlate with traditional systemic markers of inflammation including the erythrocyte sedimentation rate and C-reactive protein level, and with the Lansbury articular index. In addition, it was noted that serum levels of MMP-3 correlated with the corresponding values in paired SF samples obtained concurrently from patients with RA (rs = 0.588, P < 0.001), while such correlations were not found for TIMP-1 levels. CONCLUSION: Our results support the notion that levels of both MMP-3 and TIMP-1 in RA patient sera are increased in association with inflammation. Furthermore, the level of MMP-3 in serum provides a particularly useful marker of inflammatory activity in the joints of patients with RA.

Adult↗
PubMed1995

Levels of circulating collagenase, stromelysin-1, and tissue inhibitor of matrix metalloproteinases 1 in patients with rheumatoid arthritis. Relationship to serum levels of antigenic keratan sulfate and systemic parameters of inflammation.

OBJECTIVE: To measure serum levels of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of MMP-1 (TIMP-1) in patients with rheumatoid arthritis (RA) and in age-matched control subjects, and to determine how these correlate with serum levels of antigenic keratan sulfate (KS) and other biochemical and clinical indicators of disease activity. METHODS: Immunoassays were used to measure levels of MMP-1, MMP-3, TIMP-1, and antigenic KS. Radiologic and functional joint scores were based upon Steinbrocker's criteria. Erythrocyte sedimentation rates (ESR) and levels of C-reactive proteins (CRP) were measured. RESULTS: In RA patients, levels of MMP-3 and TIMP-1 were significantly increased, and strongly correlated with the ESR and CRP levels but not with radiologic or functional joint scores. Levels of antigenic KS were significantly lower in RA patients and correlated negatively with systemic parameters of inflammation and serum levels of TIMP-1. CONCLUSIONS: The increase in serum levels of MMP-3 and TIMP-1 appears to reflect systemic inflammation in RA. The inverse correlation between serum levels of TIMP-1 and antigenic KS suggests that an upregulation of TIMP-1 synthesis might be responsible for the apparent suppression of cartilage aggrecan catabolism in patients with severe inflammatory changes.

Adult↗
PubMed1995

Delayed graft function does not influence long-term outcome in cadaver kidney transplants without mismatch for HLA-DRB1.

The currently study focused on the influence of delayed graft function on the long-term graft success rate in cadaver kidneys without any mismatches for HLA-DRB1. Donor-recipient HLA-DRB1 was determined by the significant two-locus linkages of HLA-B and -DRB1. The overall 5-year graft success rate was 88% in an HLA-DRB1-compatible group, significantly higher than the 69% in an HLA-DRB1 mismatch group (P < 0.05) and the 66% in an HLA-DR mismatch (P < 0.01). Delayed graft function was observed in 182 of 223 transplants. This high incidence of 82% is due to the fact that, in Japan, kidney procurement may only occur after cardiac arrest. The incidence did not differ in each group. The 5-year success rate for grafts with delayed function was 87% in the HLA-DRB1-compatible group, again significantly superior to the 68% in the HLA-DRB1 mismatch group and the 63% in the HLA-DR mismatch cases (P < 0.05). There was, thus, no difference in graft success rate for each group, with or without delayed graft function. Consequently, we feel that delayed graft function has no impact on the long-term outcome in transplants without mismatches for HLA-DRB1.

Adult↗
PubMed1995

Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines.

PURPOSE: The purpose of this study was the evaluation of various factors in the formulation of guidelines for treatment of early invasive colorectal cancer, in which malignant cells extend through the muscularis mucosa into the submucosa but do not deeply invade the muscularis propria. METHOD: A total of 182 patients were followed for at least five years or until death, with early invasive cancer diagnosed between 1982 and 1989. Patients were grouped according to the level of invasion, as follows: 64 patients with slight carcinoma invasion of the muscularis mucosa (200-300 microns; sm1), 82 with intermediate invasion (sm2), and 36 with carcinoma invasion extending to the inner surface of the muscularis propria (sm3). RESULT: The configuration, diameter, and histologic grade of adenocarcinoma and lymphovascular invasion were correlated with level of invasion. After endoscopic polypectomy or local resection, 4 patients showed local recurrence and 13 patients showed lymph node metastasis. None of these 17 patients had sm1 disease. The level of invasion, configuration, and location were significant risk factors for development of lymph node metastasis or local recurrence (P < 0.05), but lymphovascular invasion, histologic grade, and diameter were not risk factors. CONCLUSIONS: Preoperative assessment of the level of invasion using this classification, in which the submucosa is divided into three depths, may decrease the incidence of unnecessary surgery for sessile polyps. Assessment according to the level of invasion is useful in the formulation of appropriate guidelines for the treatment of early invasive cancer.

Adenocarcinoma↗
PubMed1995

Antiestrogens: mechanisms and actions in target cells.

Antiestrogens, acting via the estrogen receptor (ER) evoke conformational changes in the ER and inhibit the effects of estrogens as well as exerting anti-growth factor activities. Although the binding of estrogens and antiestrogens is mutually competitive, studies with ER mutants indicate that some of the contact sites of estrogens and antiestrogens are likely different. Some mutations in the hormone-binding domain of the ER and deletions of C-terminal regions result in ligand discrimination mutants, i.e. receptors that are differentially altered in their ability to bind and/or mediate the actions of estrogens vs antiestrogens. Studies in a variety of cell lines and with different promoters indicate marked cell context- and promoter-dependence in the actions of antiestrogens and variant ERs. In several cell systems, estrogens and protein kinase activators such as cAMP synergize to enhance the transcriptional activity of the ER in a promoter-specific manner. In addition, cAMP changes the agonist/antagonist balance of tamoxifen-like antiestrogens, increasing their agonistic activity and reducing their efficacy in reversing estrogen actions. Estrogens, and antiestrogens to a lesser extent, as well as protein kinase activators and growth factors increase phosphorylation of the ER and/or proteins involved in the ER-specific response pathway. These changes in phosphorylation alter the biological effectiveness of the ER. Multiple interactions among different cellular signal transduction systems are involved in the regulation of cell proliferation and gene expression by estrogens and antiestrogens.

Cyclic AMP↗
PubMed1995

Immunocytochemical localization of prostaglandin E2 receptor subtypes in porcine ocular tissues. I. Uveal tissues.

Polyclonal antibodies were raised against 15-residue sequences in the carboxyl terminal region of mouse EP1, EP2, and EP3 subtypes. The selected sequences are well conserved in different species. Using the antibodies, the localization of the receptor subtypes in porcine uveal tissues was investigated by immunoperoxidase reaction (by light microscopy) and immunogold labeling (by electron microscopy). EP1 immunoreactivity was found in ciliary nonpigmented epithelium and iris muscles (both sphincter and dilator). EP2 was localized to ciliary nonpigmented epithelium and muscle, iris sphincter muscle, and trabecular meshwork. EP3 immunoreactivity was detected in all uveal tissues examined.

Amino Acid Sequence↗
PubMed1995

Elevated serum growth hormone accelerates gastric tumorigenesis in F344 rats after treatment with N-methyl-N-nitrosourea in their drinking water.

We examined the effects of growth hormone on tumorigenesis in F344 rats treated with N-methyl-N-nitrosourea (MNU). Four-week-old male F344 rats were exposed to 100 ppm MNU in their drinking water for 15 weeks. Thereafter Group II animals received 100 microCi/100 g body weight of 131I (radiothyroidectomy, Tx) injected i.p. and Group III rats were implanted with pituitary tumors (MtT) secreting growth hormone while Group I received no further treatment after MNU. Non-carcinogen control animals received MtT, Tx or no treatment. Animals were killed at 39 weeks after starting MNU administration. Gastric tumors were present in 13 of 31 (43%), 15 of 32 (47%) and 17 of 32 (53%) rats in Groups I to III, respectively. All tumors were of well-differentiated type. Spinal cord tumors appeared in 15 of 31 (47%) in Group I, 10 of 32 (32%) in Group II and 10 of 32 (32%) in Group III, most being malignant schwannomas. Thymic lymphomas also appeared in 10 of 31 (32%), 5 of 32 (16%) and 6 of 32 (19%) animals in Groups I to III, respectively. There were no significant differences among the groups. However, tumors in Group III developed significantly earlier than in Groups I or II. This was mainly due to gastric tumors, and cumulative incidence curves for spinal cord tumors or thymic lymphomas were similar in all groups. The results indicate that gastric tumors induced by MNU in F344 male rats are influenced by elevated levels of growth hormone.

Animals↗
PubMed1995

Progesterone enhancement of stomach tumor development in SD rats treated with N-methyl-N'-nitro-N-nitrosoguanidine.

The effects of chronic progesterone treatment on gastric tumorigenesis were examined in 6-week-old male SD rats. The rats were castrated, progesterone or testosterone pellets were implanted, and, starting one week after the operation, 100 mg/liter of N-methyl-N'-nitro- N-nitrosoguanidine (MNNG) was administered in the drinking water for 16 weeks. Every 2 months the pellets were changed. Group 1 animals received castration plus MNNG while Groups 2 and 3 also received progesterone and testosterone, respectively. In the Group 4 case, progesterone and testosterone were administered alternately for 2-month periods and in Group 5 MNNG was given to intact animals. All survivors were killed one year after the start of MNNG treatment. In Group 1 the incidence of gastric tumors was significantly decreased as compared with the Group 5 value. The Group 2 incidence, in contrast, was similar to that in Group 5, and the size of the observed gastric tumors was massively increased. The area of the pyloric gland mucosa was also greater than in other groups. Testosterone treatment was associated with a less pronounced increase in tumor size and a recovery in incidence. The results indicate that progesterone may exert a promoting influence on gastric tumor development.

Animals↗
PubMed1995

Observations on the growth rate of renal cell carcinoma.

We retrospectively reviewed the records of 18 patients to investigate the growth rate of renal cell carcinoma (RCC). Growth rates were calculated from two or more gross measurements of neoplastic foci in the kidney (6 cases) and lung (12 cases). RCCs in primary sites grew slowly and the tumor volume doubling time (DT) raged from 372 to 579 days (468 +/- 84.6). Pulmonary metastases present in 12 cases grew rapidly, with a DT ranging from 20 to 154 days (89.4 +/- 43.0). Tumors in both the kidney and lung were composed of cancer cells with equal proliferative activity, as determined by immunohistochemical analysis of argyrophilic nucleolar organizer regions and proliferating cell nuclear antigen activity. Thus, our results suggest that, in addition to the proliferative activity of cancer cells, the microenvironment of the specific region is an important determinant of the growth rate of cancer cells.

Adult↗
PubMed1995

Characterization of leukocyte-derived neutrophil chemotactic factor-2 and its possible roles in neutrophil infiltration in allergic inflammation in rats.

This study sought to clarify the responsible chemotactic factor for neutrophils in allergic inflammation in rats. When the leukocytes collected from the pouch fluid 4 h after injection of the antigen solution into the air pouch were incubated, the neutrophil chemotactic activity in the conditioned medium increased time-dependently with higher levels for the leukocytes from the immunized rats than the nonimmunized ones. The chemotactic activity did not result from cytokine-induced neutrophil chemoattractant (CINC) because CINC concentrations in the conditioned medium were low. Neutrophil chemotactic factors in the conditioned medium were separated by isoelectric focusing into two factors, leukocyte-derived neutrophil chemotactic factor (LDNCF)-1 and LDNCF-2. The activity of LDNCF-2 was more than 75% of the total chemotactic activity in the conditioned medium. LDNCF-2 was purified by gel chromatography and reverse-phase HPLC. The N-terminal amino acid sequence (1-20) of the purified LDNCF-2 was identical to the 32-51 amino acid sequence of the pro-form of rat macrophage inflammatory protein (MIP)-2. Higher levels of MIP-2 mRNA in the leukocytes from the immunized rats than that from the non-immunized rats were proved by the reverse transcription-polymerase chain reaction. In vivo, concentrations of CINC in the pouch fluid were low, and did not represent the chemotactic activity in the pouch fluid. These results suggest that LDNCF-2 (MIP-2) is an important chemotactic factor for neutrophils in the allergic inflammation in rats.

Amino Acid Sequence↗
PubMed1995

The effects of prostaglandins E2 and F2 alpha on porcine ciliary muscle cells in culture.

The purpose of this work is to investigate the effect of prostaglandins (PGs) on the contraction of ciliary muscle cells. It has been proposed that PGs induce relaxation of ciliary muscle and facilitate uveoscleral outflow, and reduce intraocular pressure (IOP). The ocular response to PGs is complicated because the relative contributions of uveoscleral flow and the conventional outflow to lowering IOP and the type of PG receptors associated with ciliary muscle may vary depending on animal species. In order to obtain insights into prostaglandin receptors of ciliary muscle, ciliary muscle cells from porcine eye were grown in culture and characterized immunocytochemically with antibodies against smooth muscle-alpha-actin and PGE2 receptor subtypes. As in ciliary muscle tissues, positive immunostaining for alpha-actin and EP2 and EP3 subtypes was observed in cultured cells. Time-dependent contraction of cultured cells induced by 10(-4) M carbachol was recorded by taking sequential photographs and analyzed. Using this assay method, the effect of prostaglandins E2 and F2 alpha to inhibit the carbachol-induced contraction was studied. PGE2 showed potent inhibition of cell contraction; 10(-7) approximately 10(-8) M PGE2 inhibited 50% of full contraction in 15 min. PGF2 alpha at 10(-4) M neither caused cell contraction by itself nor blocked carbachol-induced contraction. The EP2 agonist 11-deoxy-16, 16-dimethyl PGE2 at 10(-4) M inhibited cell contraction but the EP3 agonist sulprostone had no effect. Dibutyryl cAMP at 3 x 10(-5) M inhibited contraction by 50%. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), less than 10(-7) M dibutyryl cAMP caused 50% inhibition. In support of the cAMP effect, the addition of 10(-4) M PGE2 to cultured cells in the presence of indomethacin and IBMX was shown to cause an 80% increase in intracellular cAMP concentration compared with the basal (i.e. unstimulated) level of cAMP. Stimulation of cells with 10(-4) M PGF2 alpha caused no increase in cellular cAMP. These results indicate that PGE2 receptor EP2 subtype, but not PGF2 alpha receptor, is involved in the inhibition (hence relaxation by inference) of carbachol-induced porcine ciliary muscle cell contraction. It awaits further studies to determine whether cultured ciliary muscle cells of other species respond similarly to different PGs.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Effects of rhG-CSF on infection complications and impaired function of neutrophils secondary to chemotherapy for non-Hodgkin's lymphoma. Hokkaido Study Group of Malignant Lymphoma, and rhG-CSF, Japan.

It has been previously demonstrated that the administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF) ameliorates the decrease of the polymorphonuclear neutrophils (PMNs) count after the cytotoxic chemotherapies, thereby reducing the infection complications associated with neutropenia. In this multi-center study, we studied the prophylaxtic effect of rhG-CSF administration on infection complications in patients with non-Hodgkin malignant lymphoma, who received cytotoxic chemotherapies (CHOP or ProMACE/CytaBOM). rhG-CSF administration reduced the frequency of infection complications, and there was no obvious difference in it's frequency between the CHOP-treated and the ProMACE/CytaBOM-treated groups when administered with rhG-CSF, thereby indicating that third generation therapy for NHL may be safely completed in Japanese in combination with rhG-CSF administration. Furthermore, we investigated both the in vitro and the in vivo effects of rhG-CSF on the function of PMNs in patients with NHL and healthy donors, and revealed that the administration of rhG-CSF for NHL patients receiving cytotoxic chemotherapy brought on an improvement of the production of active oxygen but did not affect serum levels of IFNs, IL-1-beta, and IL-6, inspite of a slight elevation of TNF-alpha. Consistent with these results, in vitro treatment of PMNs with rhG-CSF induced no significant production of these inflammatory cytokines and their mRNA expressions. Furthermore, rhG-CSF administration showed no significant effects in vivo on the expression of CD11a, CD11b and LECAM-1 on PMNs and integrins on platelets.

Adult↗