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Biomedical subjects

N Fujimoto

Publications and source records attributed to N Fujimoto.

At least 55 records · Page 3Linked to original sources
PubMed2001

Modulation of gene expression by (-)-epigallocatechin gallate in PC-9 cells using a cDNA expression array.

Green tea is the most effective cancer preventive beverage. In the light of this, the mechanisms of action of tea polyphenols were investigated on the molecular levels. We present here the effects of (-)-epigallocatechin gallate (EGCG) on expression of 588 genes in human lung cancer cell line PC-9 cells, using a human cancer cDNA expression array. The levels of gene expression in non-treated control cells, and cells treated with EGCG alone, with the tumor promoter okadaic acid alone, and with EGCG plus okadaic acid, were studied, and their expression levels were classified into down-regulation (under 0.5 fold) and up-regulation (over 2.0 fold) by comparing with the levels of control. Non-treated PC-9 cells expressed 163 genes out of 588, and EGCG-treated cells induced down-regulated expression of 12 genes and up-regulated expression of 4 other genes. From a comparison of gene expression in the cells treated with EGCG and in cells treated with EGCG plus okadaic acid, we found the following genes commonly affected by EGCG: down-regulation of four genes, NF-kappaB inducing kinase (NIK), death-associated protein kinase 1 (DAPK 1), rhoB and tyrosine-protein kinase (SKY); up-regulation of one gene, retinoic acid receptor alpha1. Among them, we think down-regulation of NIK gene expression is significant for cancer prevention, based on evidence that inhibition of NF-kappaB activation is a result of inhibition of NIK/IKK signalling complex.

Antimutagenic Agents↗
PubMed2001

[Efficiency improvement of dispensing of drugs for injection by a total automatic injection dispenser system including infusion fluids and its evaluation].

For the appropriate use of drugs for injection, injection dispensing by pharmacists has been initiated at various institutions. With this movement, automatic injection dispensers have actively been developed. In our hospital, an injection order system was connected with an automatic injection dispenser in November, 1997, and this integrated system has been operating in all wards. However, the efficiency of dispensing work was not satisfactory because there were limitations in the types and volume of drugs placed in the automatic injection dispenser. Therefore, we constructed an automatic injection dispenser system that allows us to use more than 100 ml infusion fluids and also to use drugs stored in a cool place, which could not be used in the conventional system. In the new system, two trays coming from an ampoulevial line and an infusion fluid line are automatically coordinated using a discharge lifter for each patient and transported into an injection cart. After the introduction of this system, the automatic dispenser utilization rate in terms of the number of used injections increased from 52.6% to 73.3%. In addition, since the dispensing time for infusion fluids and drugs stored in a cool place, which had been collected by man power, was reduced, it became possible to pay more attention to checking for prescription.

Drug Prescriptions↗
PubMed2001

Age-dependent exposure to radioactive iodine (131I) in the thyroid and total body of newborn, pubertal and adult fischer 344 rats.

Female rats of the Fischer 344 strain at ages of 1, 4 and 9 weeks were exposed to 131I intraperitoneally with activities of 0.38, 1.03 and 3.42 kBq per gram of body weight under the condition of iodine deficiency. The absorbed doses in the thyroid increased linearly depending on the injected activities. Irradiation at 1 week old caused heavier exposure than those at 4 and 9 weeks old by 7.5 and 7.7 times, respectively; however, damage of the thyroid tissue was more obvious in the 4-week-old groups than in the 1-week-old groups. The absorbed doses in the total body were proportional to the square root of the injected activities. The one-week-old groups were exposed more heavily than the 4- and 9-week-old groups by 3.6 and 4.7 times, respectively, shown by the slow excretion of 131I with the values of effective half-life of 131I activity (Teff). An IDD-treatment was not so effective to enhance the 131I absorption in the total body, as in the thyroid. No matter how the iodine concentration in the blood changed, the 1-week-old groups could not react to normalize the level. We drew standard curves, which enabled us to estimate the absorbed doses in the thyroid and the total body in the case of the injected activities of 131I for the newborn, pubertal and adult rats.

Age Factors↗
PubMed2001

Dose-threshold for thyroid tumor-promoting effects of orally administered kojic acid in rats after initiation with N-bis(2-hydroxypropyl) nitrosamine.

In order to evaluate the threshold dose of thyroid tumor-promoting effects of KA, male F344 rats were initiated with N-bis(2-hydroxypropyl) nitrosamine (DHPN; 2000 mg/kg body wt., single s.c. injection) and, starting 1 week later, received pulverized basal diet containing 0%, 0.002%, 0.008%, 0.03%, 0.125%, 0.5% or 2%KA for 20 weeks. Five rats each in the 0%, 0.125%, 0.5% and 2%KA groups were sacrificed at week 12, and 10 rats each in all groups at week 20. As an additional experiment, three groups without DHPN initiation received basal diet, a diet containing 0.5% or 2%KA for 20 weeks. The serum T4 levels were significantly decreased in the DHPN-initiated groups given 0.125%KA or more at week 12. No significant decreases in serum T3 levels were observed in the groups treated with DHPN + KA and a significant increase was evident in the 2%KA-alone group at week 20. Some rats in the DHPN + 2%KA group at weeks 12 and 20 and the 2%KA-alone group at week 20 showed pronounced elevation of serum TSH. Thyroid weights were significantly increased in the DHPN-initiated groups receiving 0.5% and 2%KA at weeks 12 and 20 and in the 2%KA-alone group at week 20. Histopathologically, the incidences of focal thyroid follicular cell hyperplasias in the DHPN-initiated groups treated with 0.125%, 0.5% and 2%KA at week 20 were 5/10, 10/10 and 8/8 rats, respectively. At week 20, adenomas were observed in 7/10 rats in the DHPN + 0.5%KA group and 8/8 rats in the DHPN + 2%KA group, and carcinomas were observed in 6/8 rats in the DHPN + 2%KA group. In the groups without DHPN initiation, only focal follicular cell hyperplasia was observed in 1/9 rats in the 2%KA-alone group. These results suggest that the no-observed-adverse effect for the thyroid tumor-promoting effect of KA is 0.03% (15.5 mg/kg/day) under the present experimental conditions, and that KA possesses weak tumorigenic activity in rats due to continuous serum TSH stimulation by a non-genotoxic mechanism.

Animals↗
PubMed2001

Roles of membrane type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinases 2 in invasion and dissemination of human malignant glioma.

OBJECT: Acquisition of invasive and metastatic potentials through proteinase expression is an essential event in tumor progression. Among proteinases, matrix metalloproteinases (MMPs) are thought to play a key role in tumor progression through the degradation of the extracellular matrix. In the present study, the authors examined the role of MMP-2 (gelatinase A) and membrane type 1 MMP (MT1-MMP), an activator of the zymogen of MMP-2, proMMP-2, together with tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in the invasion of astrocytic tumors in humans. METHODS: Analyses performed using sandwich enzyme immunoassays demonstrated that the production levels of pro-MMP-2 and TIMP-1, but not TIMP-2, are significantly higher in glioblastomas multiforme than in other grades of astrocytic tumors. Quantitative reverse transcription-polymerase chain reaction indicated that MT1-MMP is expressed predominantly in glioblastoma tissues, and its expression levels are significantly enhanced as tumor grade increases. In addition, the expression levels and proMMP-2 activation ratio were remarkably higher in glioblastomas associated with cerebrospinal fluid (CSF) dissemination than in those not associated with CSF dissemination. In contrast, an examination of TIMP-2 levels showed a reverse correlation. Like MT1-MMP, TIMP-1 and TIMP-2 were immunolocalized to neoplastic cells in glioblastoma samples. To study the roles of these molecules in the invasion of astrocytic tumors more fully, stable transfectants expressing the MT1-MMP gene were developed in a U251 human glioblastoma cell line. The MT1-MMP transfectants displayed prominent activation of proMMP-2 and invasive growth in three-dimensional collagen gel; however, mock transfectants and parental cells displayed noninvasive growth without the activation. The invasion and gelatinolytic activity of the transfectants were completely inhibited by addition of recombinant TIMP-2, but not recombinant TIMP-1. CONCLUSIONS: These results indicate that MT1-MMP may contribute to tumor invasion and CSF dissemination of glioblastoma cells on the basis of an imbalance of TIMP-2.

Astrocytoma↗
PubMed2001

Effect of myopia on frequency-doubling perimetry.

PURPOSE: To examine the effect of myopia, occasionally associated with glaucomatous eyes, on the results obtained by frequency-doubling perimetry (FDP). METHODS: Sixty emmetropic or myopic normal volunteers (mean age, 26.2 +/- 0.35 years, mean +/- SEM; range, 19-34) with good visual acuity and without glaucoma were divided into three groups. The groups were emmetropia to low-myopia (mean refractive error, -1.16 +/- 0.23 D), intermediate-myopia (-4.95 +/- 0.17 D), and high-myopia (-8.12 +/- 0.36 D; n = 20 each). All subjects were tested on the FDP full-threshold C-20 program and the Humphrey Field Analyzer (HFA; Humphrey, Dublin, CA) full-threshold program on one randomly selected eye. FDP and the HFA test were conducted with the subjects wearing their full distance correction and with their distance correction with appropriate additional correction for near, respectively. The calculated mean sensitivity (MS), mean deviation (MD), pattern standard deviation (PSD), and test durations for FDP and the HFA test for the three groups were compared using one-way analysis of variance. The relationship between the refractive error and MS, MD, or PSD was also analyzed by simple regression analysis. RESULTS: The MS and MD for the fields determined by the HFA decreased significantly as the refractive errors increased, but there were no significant differences in the MS, MD, and PSD for FDP between the three groups. There were no significant differences in the test durations between the three groups for both FDP and HFA testing. The refractive error was correlated with both MS and MD only for the fields determined by the HFA. CONCLUSIONS: The results showed that lens-corrected myopia does not alter the visual fields obtained by FDP, and FDP can therefore be used regardless of the presence of myopia.

Adult↗
PubMed2001

[A case of renal cell carcinoma arising in bilateral original kidneys after failure of transplant graft function].

We report a case of renal cell carcinoma arising in bilateral original kidneys after failure of transplant graft function. A 47-year-old man had received a living related renal transplantation on December 10, 1985. He had resumed hemodialysis (HD) therapy because of graft failure on January 8, 1996. Periodic computed tomography (CT), after resumption of HD, revealed multiple cystic change in bilateral original kidneys and a mass in the right kidney. He was referred to our hospital on August 4, 1998 for management of the increased right renal lesion. Abdominal angiography demonstrated a hypervascular and solid mass not only in the right kidney but also in the left kidney. He underwent transperitoneal bilateral nephrectomy. Histopathological examination revealed renal cell carcinoma, bilaterally, with alveolar type and granular cell subtype. He was free of evidence of recurrence and metastasis for 30 months after nephrectomy.

Carcinoma, Renal Cell↗
PubMed2000

Metabolic activation of the proestrogens trans-stilbene and trans-stilbene oxide by rat liver microsomes.

A liver microsome-mediated activation of the proestrogens trans-stilbene and trans-stilbene oxide was found in this study. trans-Stilbene and trans-stilbene oxide were negative in estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7 and growth assay in rat pituitary tumor cell line MtT/E-2. However, these compounds exhibited estrogenic activity after incubation with liver microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH. In contrast, cis-stilbene and cis-stilbene oxide did not show estrogenic activity after such incubation. When trans-stilbene was incubated with the liver microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH, two metabolites were detected by HPLC. They were identified unequivocally as trans-4-hydroxystilbene and trans-4, 4'-dihydroxystilbene by mass and UV spectral comparison with authentic samples. The oxidase activity of the liver microsomes toward trans-stilbene was inhibited by SKF 525-A and alpha -naphthoflavone. Minor activity was observed when liver microsomes of untreated or phenobarbital-treated rats were used instead of those from 3-methylcholanthrene-treated rats. trans-4-Hydroxystilbene and trans-4,4'-dihydroxystilbene exhibited significant estrogenic activities. These results suggest that the estrogenic activities of trans-stilbene and trans-stilbene oxide were due to formation of hydroxylated metabolites.

Animals↗
PubMed2000

Marked increase of matrix metalloproteinase 9 in cerebrospinal fluid of patients with fungal or tuberculous meningoencephalitis.

Matrix metalloproteinases (MMPs) are believed to play an essential role in the breakdown of the extracellular matrix macromolecules in the blood-cerebrospinal fluid barrier and blood-brain barrier (BBB). In this study, the levels of MMP-2 and MMP-9 and their common tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) from patients with various meningitides including aseptic, fungal and tuberculous ones. MMP-9 production level in CSF was more increased in subacute meningitis including fungal and tuberculous meningitis than in acute aseptic meningitis and non-inflammatory neurological diseases (NIDs). Enhanced production of MMP-9 was associated with high proteolytic activity detected by gelatin zymography. The MMP-2 and TIMP-1 levels in CSF of subacute meningitis were also higher than those of NIDs. In contrast, the TIMP-2 levels in CSF of either acute aseptic or subacute meningitis were not up-regulated compared with those of NIDs. The central nervous system (CNS) complications (i.e. disturbance of consciousness, psychiatric symptoms, urinary disturbance, etc.) during the course of meningitis showed good correlation with the enhanced production of MMP-9 in CSF. Immunohistochemical studies in tuberculous meningitis demonstrated that the infiltrating mononuclear cells in the meninges were immunoreactive for both MMP-2 and MMP-9. However, the infiltrating mononuclear cells into CNS parenchyma had immunoreactivity for MMP-9, but not for MMP-2. Taken together, those data suggest that MMP-9 in CSF may be a useful marker of encephalitogenecity during the course of subacute meningitis.

Adolescent↗
PubMed2000

Interrater reliability of the short-memory questionnaire in a variety of health professional representatives.

A study was performed to assess interrater reliability of the Japanese version of the Short-Memory Questionnaire (SMQ), which is an easily-administered, informant-based scale of cognitive function. The subjects were 18 consecutive patients with Alzheimer's disease who were outpatients of Department of Neuropsychiatry in Ehime University School of Medicine and their principal caregivers. One neuropsychiatrist (NP) administered the SMQ, and all sessions were videotaped. Then one nurse (Ns), one clinical psychologist (CP), one occupational therapist (OT), and one neurologist (NL) from another institution viewed the videotape and performed reassessments independently. Interrater reliability between the NP and Ns, CP, OT, or NL were all extremely good. Interrater reliability between the Ns and CP, between the Ns and OT, between the Ns and NL, between the CP and OT, between the CP and NL, and between the OT and NL were also extremely good. The SMQ is a convenient, quantitative scale, and in this study it showed good interrater reliability between personnel from different fields. Therefore, it is a very useful test for everyday medical consultations and for clinical research.

Aged↗
PubMed2000

Expression of microfibril-associated glycoprotein-1 (MAGP-1) in human epidermal keratinocytes.

Microfibril-associated glycoprotein (MAGP) is a major structural component of connective tissue microfibrils. We studied the expression of MAGP-1 in cultured human keratinocytes and its modulation during Ca(++)-induced differentiation. RT-PCR and Western blot assays demonstrated the presence of mRNA and the polypeptide of MAGP-1 in cultured keratinocytes. MAGP-1 mRNA levels in cultured keratinocytes during Ca(++)-induced differentiation were enhanced eightfold with a concomitant increase in involucrin (a marker of terminal differentiation) mRNA levels. Double immunofluorescence labeling of cultured keratinocytes demonstrated that both anti-MAGP-1 and anti-involucrin antibodies reacted with the identical cells. The population of MAGP-1-producing cells in cultured keratinocytes significantly increased during Ca(++)-induced differentiation. These results indicate that MAGP-1 expressed by cultured keratinocytes reaches maximum levels at the stage of terminal differentiation in vitro. Double immunostaining of normal human skin with anti-MAGP-1 and anti-elastin antibodies demonstrated the colocalization of MAGP-1-positive and elastin-positive fibers in the superficial and mid-dermis. MAGP-1 produced by keratinocytes may play some functional role in the formation of dermal matrix organization in the dermis.

Calcium Chloride↗
PubMed2000

Characterization of the Neurospora crassa mus-25 mutant: the gene encodes a protein which is homologous to the Saccharomyces cerevisiae Rad54 protein.

Characterization of the Neurospora crassa mus-25 mutant suggests that it is defective in recombination repair and belongs to the uvs-6 epistasis group. It shows a high sensitivity to the alkylating agents methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but not to UV radiation. It is barren (i.e. does not produce ascospores) in homozygous crosses. The frequency of MMS-induced mutations at the ad-3 loci is approximately three times higher than in the wild type. The ratio of homologous to nonhomologous integration of the pMTR::HYG plasmid is much lower than in wild type. The mus-25 mutant is epistatic to the mei-3 mutant for MMS sensitivity. mei-3, which is a homololog of the Saccharomyces cerevisiae gene RAD51, is a member of the uvs-6 epistasis group which contains several genes that are homologous to recombination repair genes in other organisms. The mus-25 gene was cloned by identifying a genomic DNA fragment which complements the MMS sensitivity of the mutant. The amino acid sequence deduced from the cloned DNA showed a high degree of homology to the Rad54 protein, which is involved in recombinational repair in S. cerevisiae. Comparison of the nucleotide sequences of the genomic and cDNAs of the mus-25 gene revealed an ORF of 2505 bp with a single 118-bp intron beginning immediately after the second nucleotide of the AUG start codon. The molecular weight of the deduced gene product was 93.5 kDa. The transcript level was raised within 60 min after UV irradiation or MMS treatment, as also observed for the expression of the other N. crassa recombinational repair genes, suggesting the existence of a common mechanism which induces expression of the recombinational repair genes in response to DNA damage.

Alkylating Agents↗
PubMed2000

Matrix metalloproteinase-9 and tensile strength of fetal membranes in uncomplicated labor.

OBJECTIVE: To analyze the relation between tensile strength and levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 at a number of sites in human fetal membranes. METHODS: Tensile strengths of fetal membranes from five women who delivered vaginally at term were measured by the method of modified force application. A piece of membrane at each measured site was then dissected, and the levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 were measured by sandwich enzyme immunoassay. The relationship between tensile strength and enzyme levels was evaluated by Scheffé F test at a total of 81 sites on the five membranes. RESULTS: The mean tensile strength of the membranes was 45.3 +/- 19.8 (mean +/- standard deviation) mmHg/0.3 mm(2) (n = 81). When the measured sites were divided according to tensile strength into four groups (<25, 25-49, 50-74, and >/=75 mmHg/0.3 mm(2)), the level of matrix metalloproteinase-9 (0.72 +/- 0.82 nmol/g protein, n = 12) in the less than 25 mmHg/0.3 mm(2) group was significantly higher than the other groups (0.35 +/- 0.22, 0.28 +/- 0.15, and 0.15 +/- 0.08 nmol/g protein; n = 39, 23, and 7, respectively). The significance level was still higher when the molar ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 was used for comparison. CONCLUSION: An increased molar ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 might be related to decreased tensile strength of human fetal membranes in uncomplicated labor.

Extraembryonic Membranes↗
PubMed2000

Intramedullary spinal cord recurrence after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation for limited-disease small cell lung cancer.

Intramedullary spinal cord metastasis is very rare in small-cell lung cancer (SCLC), and develops in only 2% of neurological disorders associated with SCLC according to previous reports. We describe here a patient with SCLC who developed intramedullary spinal cord recurrence after high-dose chemotherapy (HDCT) followed by autologous blood progenitor cell transplantation (ABPCT). A 59-year-old Japanese male was referred to us for diagnosis and treatment of an abnormal shadow on a chest radiograph. Based on transbronchial biopsy and staging procedures, he was diagnosed with limited-disease (LD)-SCLC. He received concurrent chemoradiotherapy followed by late intensification with HDCT supported by ABPCT. He achieved complete response and was discharged after receiving prophylactic cranial irradiation (PCI). However 6 months later, he noticed rapidly progressive weakness of the left lower extremity and bowel/bladder dysfunction. Magnetic resonance imaging (MRI) of the spinal cord disclosed an intramedullary tumor exhibiting an enhancement effect with Gd-DTPA at the 11-12th level of the thoracic vertebra. Immediately, radiotherapy to the spinal cord metastasis was given at a dose of 30 Gy, and his neurological disorders were completely resolved. At this time of reporting, he is doing well without recurrence. This case indicates that intramedullary spinal cord is one of the recurrence sites implicated after HDCT and PCI in LD-SCLC.

Carcinoma, Small Cell↗
PubMed2000

Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human oral squamous cell carcinomas: implications for lymph node metastasis.

We measured the production levels of seven different matrix metalloproteinases (MMP-1, 2, 3, 7, 8, 9 and 13) and two tissue inhibitors of metalloproteinases (TIMP-1 and 2) in the homogenates of human oral squamous cell carcinomas and control normal squamous epithelia by the corresponding sandwich enzyme immunoassay systems. The levels of MMP-1, 2, 3, 8, 9, 13 and TIMP-1 were significantly higher in the carcinoma samples than in the control. Among them, only the production level of MMP-2 was significantly higher in the carcinomas with cervical lymph node metastasis than in those without metastasis (P < 0.05). Gelatin zymography demonstrated that activation ratio of the zymogen of MMP-2 (proMMP-2) is significantly higher in the carcinomas with lymph node metastasis than in those without metastasis (P < 0.05) or normal control (P < 0.01). Quantitative RT-PCR for membrane-types 1, 2 and 3 MMPs (MT1, 2 and 3-MMPs), which activate proMMP-2 in vitro, demonstrated that MT1-MMP is predominantly expressed in the carcinoma tissues, and the expression level is significantly higher in the carcinomas with lymph node metastasis than in those without metastasis (P < 0.05) or the control samples (P < 0.05). Although MT2-MMP and MT3-MMP were detected in approximately 30% of the carcinoma cases, their expression levels were extremely lower compared with that of MT1-MMP. There was a direct correlation between the MT1-MMP expression level and proMMP-2 activation ratio (r = 0.62, P < 0.01). In situ hybridization and immunohistochemistry indicated that carcinoma cells and stromal cells adjacent to carcinoma cell nests express MT1-MMP transcripts and protein. MMP-2 and TIMP-2 were also immunolocalized to the carcinoma cells in the carcinoma samples. By in situ zymography, gelatinolytic activity was demonstrated in the carcinoma cell nests and abolished by the treatment with an MMP inhibitor, BB94. These results suggest that among seven different MMPs, the production of proMMP-2 and its activation mediated by MT1-MMP play an important role in the cervical lymph node metastasis of the human oral squamous cell carcinomas.

Base Sequence↗
PubMed2000

Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium.

In vitro, membrane-type matrix metalloproteinases (MT-MMP) are known to activate the zymogen of MMP-2 (proMMP-2, progelatinase A), which is one of the key MMP in joint destruction in rheumatoid arthritis. In the present study, we examined the production and activation of proMMP-2, and the expression of MT1-MMP, MT2-MMP, and MT3-MMP, their correlation with proMMP-2 activation, and their localization in rheumatoid synovial tissue. Using sandwich enzyme immunoassay and gelatin zymography techniques, proMMP-2 production levels and activation ratios were found to be significantly higher in rheumatoid synovium compared with normal synovium (p < 0.01). Quantitative RT-PCR analyses demonstrated that MT1-MMP and MT3-MMP were expressed in all rheumatoid synovial tissue (30 of 30 cases), but that the mean expression level of MT1-MMP was approximately 11-fold higher than MT3-MMP. Significant correlation was found between the mRNA expression level of MT1-MMP and the activation ratio of proMMP-2 (p < 0.01). In situ hybridization indicated that the hyperplastic lining cells of rheumatoid synovium expressed MT1-MMP. Immunohistochemistry demonstrated that MT1-MMP was co-localized with MMP-2 and with a tissue inhibitor of metalloproteinase-2, and was mainly located in the rheumatoid synovial lining cells. In situ zymography of rheumatoid synovium showed gelatinolytic activity, predominantly in the lining cell layer. This activity was blocked when incubated with BB94, a specific MMP inhibitor. These results demonstrate that MT1-MMP plays an important role in the activation of proMMP-2 in the rheumatoid synovial lining cell layer, and suggest that its activity may be involved in the cartilage destruction of rheumatoid arthritis.

Aged↗
PubMed2000

Elastin peptides induce migration and terminal differentiation of cultured keratinocytes via 67 kDa elastin receptor in vitro: 67 kDa elastin receptor is expressed in the keratinocytes eliminating elastic materials in elastosis perforans serpiginosa.

To delineate the molecular mechanism of transepidermal elimination of dermal elastic materials in elastosis perforans serpiginosa, the interaction between elastin and cultured keratinocytes was studied in vitro. Synthetic elastin peptide VGVAPG elicited chemotactic responses to the cultured keratinocytes at the dose of 10-9 M. Treatment of keratinocytes with 10-6 or 10-5 M elastin peptides resulted in the suppression of cell growth and the increased expression of involucrin and transglutaminase-1, markers of terminal differentiation. When cultured keratinocytes were treated with the elastin peptides, the expression of 67 kDa elastin receptor was increased. The induction of terminal differentiation by elastin peptides was attenuated by the treatment with the combination of anti-67 kDa elastin receptor antibody. The results indicate that elastin is a potent inducer of migration and terminal differentiation of cultured keratinocytes, which is mediated by the 67 kDa elastin receptor. In the lesional skins of patients with elastosis perforans serpiginosa, the 67 kDa elastin receptor was specifically expressed in the epidermis immediately surrounding the elastic materials that were being eliminated. The elastin receptor may be involved in the interaction between keratinocytes and elastin in elastosis perforans serpiginosa.

Cell Differentiation↗