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Biomedical subjects

I Ishikawa

Publications and source records attributed to I Ishikawa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Gender difference in the mean age at the induction of hemodialysis in patients with autosomal dominant polycystic kidney disease.

Male patients with autosomal dominant polycystic kidney disease (ADPKD) begin hemodialysis earlier than female patients. The rate of progression of many other renal diseases is also faster in men than women. In this study, gender difference in ADPKD was compared with that in other diseases, such as chronic glomerulonephritis, diabetic nephropathy, and nephrosclerosis, using the data obtained from an annual statistical survey of the Japanese Society for Dialysis Therapy. The male-female ratio in ADPKD (n = 8,176) was 1.17:1 and closer to 1.0:1 than the other diseases. Men with ADPKD started hemodialysis therapy 1.3 years earlier than women (male age, 55.9 +/- 12.4 years versus female age, 57.2 +/- 11.5 years), and the age difference was less than that in other diseases. These results suggest that the prognosis in women with ADPKD is relatively worse than that in men with ADPKD or that women are not well protected against the progression of this disease compared with other renal diseases. In conclusion, men with ADPKD are introduced to hemodialysis therapy earlier than women; however, the age difference was small compared with other common renal diseases.

Adolescent↗
PubMed2000

Acute glomerulonephritis after human parvovirus B19 infection.

We evaluated clinical and histological characteristics of four adult patients who presented with acute glomerulonephritic syndrome with serological confirmation of recent HPB19 infection. All patients had generalized edema with urinary abnormalities. Body weight gain ranged from 3 to 10 kg. Three of the patients had contact with erythema infectiosum simultaneously with or within 10 days before development of flu-like symptoms. Two patients had an erythematous rash, and one patient had lower-extremity purpura. Joint pain was present in three of the patients. All patients had proteinuria and hematuria. Renal functions were normal except in one patient who had a serum creatinine of 3.2 mg/dL. Three of the patients had hypocomplementemia. All renal biopsy specimens were characterized by glomerular leukocyte infiltration and endothelial cell swelling. Mesangiolysis was seen in three of the patients. C3 was deposited in a coarse granular pattern along the capillary walls in all cases. Electron microscopic examination showed marked expansion of the subendothelial space of glomerular capillaries in all patients. Subendothelial electron-dense deposits were present in all patients. Immunohistochemical analysis using monoclonal anti-HPB19 antibody showed that one of the four patients had positive staining in the glomeruli. DNA extracted from renal biopsy specimens contained HPB19 DNA, as shown by polymerase chain reaction (PCR) analysis in all patients. PCR amplification of the renal DNA generated a 104-bp product, which hybridized to an HPB19-specific probe. No control group subjects contained HPB19 DNA as determined by PCR. This circumstantial evidence indicates that HPB19 infection may be one of the causes of acute glomerulonephritis in normal individuals.

Acute Disease↗
PubMed2000

Digital glomerular reconstruction in a patient with a sporadic adult form of glomerulocystic kidney disease.

This study describes a sporadic adult form of glomerulocystic kidney disease in a 52-year-old man. To determine whether the aperture of the proximal tubule was stenosed or obstructed to clarify the pathogenesis of glomerular cyst development, 100 serial sections of the open biopsy specimen were made. Ten glomerular cysts were reconstructed using three-dimensional imaging analysis. Bowman's capsule (glomerular cyst) volume, the volume of glomerular tufts, and the area of the proximal tubular opening were estimated using imaging analysis. The volumes of Bowman's capsule and of glomerular tufts were 0.0098 +/- 0.0039 mm3 (mean +/- SD) (normal: 0.0041 to 0.0083 mm3) and 0.0026 +/- 0.0013 mm3, respectively. The area of the proximal tubular opening was 0.0017 +/- 0.0003 mm2 (normal: 0.0012 to 0.0028 mm2). There was neither obstruction nor stenosis of the opening of the renal tubule in this sporadic adult form of glomerulocystic kidney disease. After 4 years of hemodialysis, the glomerular cysts, as well as the kidneys, enlarged. This study shows that the main cause of glomerular cyst development is not glomerulotubular neck obstruction.

Adolescent↗
PubMed2000

Prostaglandins E2 and I2 downregulate tumor necrosis factor alpha-induced intercellular adhesion molecule-1 expression in human oral gingival epithelial cells.

In the present study, we examined whether prostaglandin (PG) E2 and PGI2 regulated intercellular adhesion molecule-1 (ICAM-1) expression in human oral gingival epithelial cells stimulated with tumor necrosis factor alpha (TNF alpha). TNF alpha potently induced ICAM-1 expression in a dose- and time-dependent fashion. PGE2 and carbacyclin (a stable analogue of PGI2) significantly decreased ICAM-1 expression in TNF alpha-challenged oral gingival epithelial cells. Next, of the four subtypes of PGE2 receptors (EP1, EP2, EP3 and EP4), we examined which subtype(s) mediated inhibition of TNF alpha-induced ICAM-1 expression by PGE2. 11-deoxy-PGE2, an EP2/EP4 agonist, significantly suppressed TNF alpha-induced ICAM-1 expression, whereas butaprost, an EP2 agonist, sulprostone, an EP1/EP3 agonist, and ONO-AP-324, an EP3 agonist, caused no effect on it. By reverse transcriptase-polymerase chain reaction, expression of EP4 mRNA was detected in oral gingival epithelial cells. Dibutyryl cAMP, a cAMP analogue, and forskolin, a direct activator of adenylate cyclase, significantly inhibited TNF alpha-induced ICAM-1 expression in oral gingival epithelial cells. From these results, we suggest that PGE2 and PGI2 inhibit TNF alpha-elicited ICAM-1 expression by cAMP-dependent pathways via EP4 receptors and IP receptors, respectively.

Acetates↗
PubMed2000

Prevalence of Bacteroides forsythus, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans in subgingival microflora of Japanese patients with adult and rapidly progressive periodontitis.

BACKGROUND, AIMS: This study investigated the prevalence of Bacteroides forsythus, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans among various periodontitis patients and healthy individuals in Japan, and correlated it with clinical parameters. METHOD: Subgingival plaque samples were collected from 21 patients with adult periodontitis (AP), 8 with rapidly progressive periodontitis (RPP) and 15 healthy individuals. RESULTS: The frequency detected in culture was as follows: B. forsythus was found in 47.6% of AP sites and in 37.5% of RPP sites. P. gingivalis was identified in 64.3% of AP and 59.4% of RPP sites. A. actinomycetemcomitans was detected in 4.8% of AP and 3.1% of RPP sites. The 3 species were detected in only 2 of the healthy individuals. The proportion of B. forsythus in the total microflora in culture was 0.07% in the healthy group, 4.1% in AP and 2.4% in RPP. The proportions of P. gingivalis were 0% in the healthy group, 18.8% in AP and 16.2% in RPP. The proportion of A. actinomycetemcomitans was very low in all 3 groups. A DNA probe detected B. forsythus in 78.6% of AP and 65.6% of RPP sites, as well as P.gingivalis in 58.3% of AP and 59.4% of RPP sites. A. actinomycetemcomitans was detected in only 1.2% of AP sites. The 3 species were undetectable in the healthy group. CONCLUSIONS: The prevalence and the proportion of B. forsythus and P. gingivalis were significantly correlated with clinical parameters, suggesting that B. forsythus and P. gingivalis are closely related to AP and RPP in the Japanese population.

Aggregatibacter actinomycetemcomitans↗
PubMed2000

In vitro evaluation of Er:YAG laser scaling of subgingival calculus in comparison with ultrasonic scaling.

The purpose of the present study was to evaluate the effectiveness of Er:YAG laser scaling and the morphological and histological changes of the laser-scaled root surface in comparison with the effectiveness and root surface changes produced by conventional ultrasonic scaling. Fifty-three periodontally involved human extracted teeth with a band of subgingival calculus were used. The teeth were divided randomly into 2 groups for laser scaling and ultrasonic scaling. Laser irradiation was performed at an energy output of 40 mJ/pulse and 10 pulses/s under water spray, with the probe tip contacted obliquely to the root surface. Ultrasonic scaling was performed at a clinically standard power setting. The time required for scaling, the scaled area and the temperature changes were determined using both methods of treatment. The features of the scaled surfaces were examined by histological and scanning electron microscope (s.e.m.) observations. The Er:YAG laser provided subgingival calculus removal on a level equivalent to that provided by the ultrasonic scaler, without major thermal elevation. Macroscopically, the laser-treated root surface was somewhat rougher than or similar to the ultrasonically scaled root. However, the efficiency of the laser scaling was lower than that of the ultrasonic scaling. In addition, histological examination revealed a thin deeply stained zone on the lased root surface, and s.e.m. analysis revealed a characteristic microroughness on the lased surface. The laser scaling provided a level of calculus removal that was similar to that provided by the ultrasonic scaling. However, the Er:YAG laser produced superficial, structural and thermal microchanges on the root cementum.

Dental Calculus↗
PubMed2000

Individual diversities in interferon gamma production by human peripheral blood mononuclear cells stimulated with periodontopathic bacteria.

Polarization of type 1 (Th1) or type 2 (Th2) immune responses determines the prognosis of many infectious diseases. Interferon gamma (IFN-gamma) and IL-4 are key cytokines for the development of type 1 and type 2 immune responses, respectively. The aim of this study was to examine individual diversities in the polarization of type 1 and type 2 responses against periodontopathic bacteria. Peripheral blood mononuclear cells (PBMCs) from adult periodontitis (AP) patients and healthy (H) subjects were stimulated with Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Bacteroides forsythus with or without polymyxin-B, CTLA-4 Ig and anti-IL-12 antibody. IFN-gamma, IL-4 and IL-12 in the culture supernatant were measured. IFN-gamma and IL-4 producing cells were also examined using a multiparameter flow cytometric assay. Bone resorption rate in AP patients was calculated using Schei's method, and the probing pocket depth was also measured. PBMCs from AP patients and H subjects produced IFN-gamma and IL-12, whereas the production of IL-4 was rarely observed. Among the bacteria tested, A. actinomycetemcomitans was the most potent inducer of IFN-gamma and IL-12, and the reaction was inhibited by polymyxin-B. IFN-gamma was found to be produced by T cells in the PBMCs, and the production was significantly reduced by CTLA-4 Ig and anti-IL-12 neutralizing antibody. The amount of IFN-gamma produced by the PBMCs of AP patients and H subjects varied among individuals, and was significantly correlated with the amount of IL-12 produced in a particular individual. The production of IFN-gamma was not related with periodontal condition which was evaluated using bone resorption and pocket depth. These results suggest that polarization of type 1 response against periodontopathic bacteria is dependent on the production of IL-12 by monocytes, and that IL-12 stimulates IFN-gamma production. However, individual diversities of IFN-gamma production might not be directly related to the severity of periodontitis.

Adult↗
PubMed2000

Comparison of the oral bacterial flora in saliva from a healthy subject and two periodontitis patients by sequence analysis of 16S rDNA libraries.

The oral bacterial flora in the saliva from two patients with periodontitis and from a periodontally healthy subject were compared using a sequence analysis of 16S rDNA libraries without cultivation. 16S rDNAs were amplified from salivary DNA by PCR and cloned. Randomly selected clones were partially sequenced. On the basis of sequence similarities, the clones were classified into several clusters corresponding to the major phylum of the domain Bacteria. The major phylum in the libraries was the low G+C Gram-positive bacteria. There was no clonal sequence affiliated with periodontopathic bacteria in the salivary sample from the healthy subject, while a number of periodontal pathogens such as Campylobacter rectus, Prevotella intermedia, Porphyromonas gingivalis and Treponema socranskii were detected in the salivary samples from the patients with periodontitis. In addition, a number of previously uncharacterized and uncultured microorganisms were recognized. These organisms may have some role in periodontal disease. This study reveals some potential for a molecular-biological technique to analyze the oral microflora associated with periodontal disease, including previously uncharacterized and uncultured microorganisms, without cultivation.

Adult↗
PubMed2000

Papillon-Lefèvre syndrome: analysis of HLA antigens.

OBJECTIVES: Papillon-Lefèvre syndrome (PLS) is a rare disease associated with prepubertal periodontitis. Our previous studies demonstrated that three unrelated patients with PLS showed the similar antigen-specific immune responses to Actinobacillus actinomycetemcomitans. The initiation of antigen-specific immune responses was involved with human leukocyte antigens (HLA) on antigen-presenting cells. The aim of this study was to examine HLA haplotypes in the three patients with PLS. SUBJECTS AND METHODS: The three PLS patients, their mothers and the father of one patient participated in this study. HLA class I and class II antigens were determined serologically and DNA typing for DRB1 and DQB1 was performed using the restriction fragment length polymorphism-polymerase chain reaction method. RESULTS: The distribution of serologic HLA haplotypes, in two of three patients, was found to be quite similar. The DNA typing revealed that DRB1*0406, DRB1*08032, DQB1*0302, DQB1*06011 genotypes were shared in the two patients. The probability of sharing these four DNA types in unrelated individuals was nearly 1:40,000 in the Japanese population. CONCLUSION: Our results suggest that HLA antigen may be included as a possible host factor in the pathogenesis of PLS and that a genetically controlled immune response may account for an increased susceptibility to periodontal infection.

Aggressive Periodontitis↗
PubMed2000

Novel apoptosis-inducing activity in Bacteroides forsythus: a comparative study with three serotypes of Actinobacillus actinomycetemcomitans.

Bacteroides forsythus, which has been reported to be associated with periodontitis but has not been recognized as a key pathogen, was found to induce cytolytic activity against HL-60 and other human leukemic cells. This cytolytic activity was demonstrated according to three different criteria: (i) loss of both mitochondrial membrane potential and membrane integrity in cells treated with bacterial extracts and then with Rh123 and propidium iodide, respectively, as demonstrated by flow cytometry; (ii) damage to cytoplasmic membrane, as revealed by scanning electron microscopy (SEM); and (iii) DNA ladder formation and activation of caspase-3. These results indicate that B. forsythus produced an apoptosis-inducing factor(s) found to be composed of protein as judged by heat and trypsin sensitivity. In addition to extracts from B. forsythus, the culture supernatant of this bacterium has the ability to induce a cytolytic effect against peripheral white blood cells, especially lymphocytes. For comparison with B. forsythus, the same analyses were applied to two strains with different serotypes of Actinobacillus actinomycetemcomitans, serotypes a (ATCC 43717) and c (ATCC 43719), in addition to previously reported apoptosis-inducing serotype b (ATCC 43718), which was used as a positive control. The strains of A. actinomycetemcomitans serotypes a and b induced apoptosis in HL-60 cells as judged by the above three criteria but to a slightly lesser extent than did B. forsythus, while the serotype c strain produced apoptosis to a negligible extent. Detailed SEM images showed that the A. actinomycetemcomitans serotype a strain induced large-pore formation and the serotype b strain produced small pores with typical blebbing, while B. forsythus induced severe membrane ruffling. Further DNA ladder formation and caspase-3 activation were observed in the serotype a and b strains but not in the serotype c strain. The present paper is the first report of a protein factor(s) from B. forsythus and the A. actinomycetemcomitans serotype a strain which induces apoptotic cell death.

Aggregatibacter actinomycetemcomitans↗
PubMed2000

Incidence of acquired renal cysts in biopsy specimens.

AIMS: This study investigated whether or not acquired renal cysts develop in patients with mild chronic renal failure. METHODS: A retrospective study was carried out using renal biopsy specimens from 720 patients. A renal cyst was defined as a tubule dilated >200 microm. RESULTS: Renal cysts were found in 21 of 720 renal biopsy specimens. Serum creatinine of 21 patients with renal cysts was significantly higher than that of 699 patients without cysts (2.59 +/- 2.64 vs. 1.09 +/- 0.79 mg/dl) (p < 0.0001). Poor renal function (serum creatinine >1.6 mg/dl) reveals more cyst formation on biopsy specimens than good renal function (serum creatinine <1.5 mg/dl). Cysts were observed in 11 of 607 (1.8%) patients less than 50 years of age and in 10 of 113 (8.8%) patients over 51 years. To exclude simple cysts which are commonly observed in older subjects, 11 patients under 50 years of age were extensively examined. Mean serum creatinine was 2.98 +/- 3.06 mg/dl (0.7-10.4 mg/dl). These 11 patients revealed low creatinine clearance of 47.5 +/- 25.6 ml/min (5-71 ml/min). Creatinine clearances in 7 patients were 52-71 ml/min (serum creatinine 0.7-2.0 mg/ dl). One of 11 biopsy specimens with cysts was examined by immunohistochemistry on lectin. This specimen was positive for tetragonolobus lectin and negative for peanut lectin, suggesting that the epithelial cells lining the cyst were derived from proximal tubules, unlike those of simple cysts. CONCLUSION: These results suggest that low normal renal function such as creatinine clearances 52-71 ml/min due to nephron loss is sufficient to induce acquired cyst development in various renal diseases.

Adolescent↗
PubMed2000

Hemolytic uremic syndrome associated with influenza A virus infection in an adult renal allograft recipient: case report and review of the literature.

Hemolytic uremic syndrome (HUS) is a rare but serious complication following renal transplantation. It usually develops early after transplantation, and ciclosporin treatment is the most common triggering factor. We report the case of a 35-year-old male with posttransplant HUS which developed 1 year after renal transplantation. He became febrile 4 days before the onset of HUS, and the significant rise in viral titer confirmed the diagnosis of influenza A virus infection. The association of ciclosporin treatment with HUS was unlikely, because of the late onset of HUS and the low ciclosporin trough levels. The patient was treated successfully without a dose reduction of ciclosporin. An etiologic relationship between influenza A virus and HUS was highly probable in our patient. We also review a total of 156 adult cases with HUS after renal transplantation described in the literature. The prognosis of posttransplant HUS differs according to the cause. The advent of ciclosporin has improved the graft survival rate and mortality of patients with rejection-induced HUS.

Adult↗
PubMed2000

Cyclooxygenase-2-dependent prostaglandin E2 down-regulates intercellular adhesion molecule-1 expression via EP2/EP4 receptors in interleukin-1beta-stimulated human gingival fibroblasts.

Prostaglandin E2 (PGE2), which exerts its actions via EP receptors (EP1, EP2, EP3, and EP4), is a bioactive metabolite of arachidonic acid produced by cyclooxygenase (COX)-1 and/or COX-2. We have previously demonstrated that PGE2 down-regulates intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1beta (IL-1beta)-stimulated human gingival fibroblasts (HGF). In the present study, we investigated which COX was involved in down-regulation of ICAM-1 expression by PGE2 in IL-1beta-stimulated HGF and which subtypes of EP receptors modulated the ICAM-1 expression. NS-398, a specific COX-2 inhibitor, completely inhibited PGE2 production by IL-1beta-stimulated HGF, as did indomethacin, a COX-1/COX-2 inhibitor. Northern blot analysis and immunocytochemical staining showed that mRNA and protein of COX-2 were expressed in IL-1beta-challenged HGF, but not in unstimulated HGF, and that the expression of mRNA and protein of COX-1 was similar both in unstimulated and in stimulated cells. NS-398 and indomethacin enhanced ICAM-1 expression in IL-1beta-challenged HGF. EP1, EP2, and EP4 receptor mRNA was expressed in HGF according to reverse-transcription/polymerase chain-reaction. PGE2, 11-deoxy-PGE1 (a selective EP2/EP4 agonist), and Butaprost (a selective EP2 agonist) attenuated IL-1beta-elicited ICAM-1 expression, although Butaprost was less potent than PGE2 and 11-deoxy-PGE1. AH-23848B, an EP4 antagonist, antagonized the inhibitory effect of IL-1beta-elicited ICAM-1 expression by PGE2. Sulprostone, an EP1/EP3 agonist, had no effect on IL-1beta-elicited ICAM-1 expression. Analysis of these data suggests that COX-2-derived PGE2 down-regulates ICAM-1 expression via EP2/EP4 receptors in IL-1beta-stimulated HGF.

Analysis of Variance↗
PubMed2000

Time-related changes of developing enamel crystals after exposure to the tissue fluid in vivo: analysis of a subcutaneously implanted rat incisor.

To investigate the effects of tissue fluid on the growth of enamel crystals, upper and lower incisors extracted from 3-week-old Wistar rats were removed of the enamel organ, implanted subcutaneously in the dorsal portion of animals from the same litter, and harvested at 72 h or 1 week after implantation. The grafts were chemically fixed with surrounding tissues and prepared for light and electron microscopy, X-ray microanalysis, or for the immunohistochemistry of amelogenin. Mineralization of implanted enamel layers was examined by contact X-ray microradiography. The immunoreactivities for 25 kD amelogenin in immature enamel decreased sequentially, starting from the surface to the deeper layers; by 1 week after implantation, no positive reactivities remained in the entire enamel layers at the stages of matrix formation and early maturation. In accordance with the loss of enamel proteins, immature enamel gained mineral density until it attained higher radio opacity than that of the adjacent dentin by 1 week. In contrast, the radio opacity of the full thickness of the enamel at early maturation remained low except for a superficial thin layer. Electron microscopy revealed no sign of growth of original enamel crystals, but showed heavy precipitation of electron-dense fine granules of calcium phosphate in all layers of the secretory enamel and the superficial layer of enamel at early maturation, which showed high radio opacity. The Ca/P ratio and electron diffraction patterns of the granular materials precipitated between intrinsic enamel crystals indicated the property of hydroxy apatite or octacalcium phosphate though a characteristic ribbon-like profile of enamel crystals was lacking. These data indicate that the enamel organ blocks exogenous mineral precipitates in growing enamel during the stage of matrix formation and plays an essential regulatory role for fine enamel crystallites to grow into large hexagonal crystals.

Amelogenin↗
PubMed2000

Cyclooxygenase-2-dependent prostaglandin production by peripheral blood monocytes stimulated with lipopolysaccharides isolated from periodontopathogenic bacteria.

BACKGROUND: Prostaglandin E2 (PGE2) plays important roles in the pathogenesis of periodontal disease. Recent studies have revealed the existence of 2 isozymes of cyclooxygenase (COX), called COX-1 and COX-2. The purpose of the present study was to investigate the contribution of COX-1 and COX-2 to PGE2 production by human peripheral blood monocytes that are stimulated with lipopolysaccharides (LPS) from periodontopathogenic bacteria. METHODS: LPS were isolated from Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) and Porphyromonas gingivalis (P. gingivalis) by the phenol-water method. Peripheral blood monocytes were stimulated with LPS for the indicated periods, and the levels of PGE2 or interleukin (IL)-1 beta in the culture media were measured by enzyme-linked immunosorbent assay. Expression of COX-1 and -2 proteins was studied by immunocytochemical staining, and COX-2 mRNA expression was examined by Northern blot analysis. RESULTS: Peripheral blood monocytes stimulated with A. actinomycetemcomitans- or P. gingivalis-LPS produced PGE2 in a time- and dose-dependent manner. Indomethacin, a non-selective COX-1/COX-2 inhibitor, and NS-398, a specific COX-2 inhibitor, completely inhibited PGE2 production. Immunocytochemical staining of COX-1 and COX-2 proteins showed that expression of COX-2 protein was increased in monocytes that were stimulated with A. actinomycetemcomitans- or P. gingivalis-LPS, compared with that in unstimulated monocytes, whereas expression of COX-1 protein was not altered. Northern blot analysis showed that monocytes stimulated with A. actinomycetemcomitans- or P. gingivalis-LPS expressed COX-2 mRNA, while COX-2 mRNA was not detectable in unstimulated cells. Treatment of A. actinomycetemcomitans-LPS-stimulated monocytes with NS-398 induced a significant increase of IL-1 beta production to the same extent as treatment with indomethacin. CONCLUSIONS: These results suggest that COX-2 is induced in monocytes stimulated with LPS derived from A. actinomycetemcomitans and P. gingivalis and that the COX-2 is primarily responsible for PGE2 production. COX-2 may be pivotal in PGE2 production in periodontal lesions and may be involved in inflammatory responses.

Aggregatibacter actinomycetemcomitans↗
PubMed1999

An activation-responsive element in single C motif-1/lymphotactin promoter is a site of constitutive and inducible DNA-protein interactions involving nuclear factor of activated T cell.

Single C motif-1 (SCM-1)/lymphotactin is a C-type chemokine whose expression is activation dependent, cyclosporin A sensitive and restricted to CD8+ T cells, double-negative thymocytes, gammadelta-type T cells, and NK cells. In humans, there are two highly homologous genes encoding SCM-1alpha and SCM-1beta. Here we examined the regulatory mechanism of the SCM-1 genes. The luciferase reporter gene under the control of the 5' flanking region of 0.7 kb was strongly induced upon activation with anti-CD3 or PHA plus PMA only in SCM-1-producer T cell lines through a cyclosporin A-sensitive mechanism. An element termed E1 located at -108 to -95 nt relative to the major transcription start site was found to be critical for the promoter activity. In electrophoretic mobility shift assays using the E1 oligonucleotide as probe, nuclear extracts from unstimulated T and B cell lines formed a constitutive complex termed complex I, while nuclear extracts from stimulated SCM-1-producer T cell lines formed a higher mobility complex termed complex II with a concomitant decrease in complex I. The shift from complex I to complex II seen only in SCM-1-producer T cell lines upon activation was completely suppressed by cyclosporin A. Both complexes were critically dependent on the NF-AT core sequence TTTCC in the E1 element and were partially supershifted by anti-NF-ATp. One-hybrid assays in yeast isolated NF-ATp as an E1 binding protein, and transfection of NF-ATp into T and B cell lines strongly enhanced the activation-dependent SCM-1 promoter activity. Collectively, a unique mechanism involving NF-ATp appears to regulate the cell type-specific and activation-dependent expression of the SCM-1 genes.

5' Untranslated Regions↗