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J Varga

Publications and source records attributed to J Varga.

At least 73 records · Page 4Linked to original sources
PubMed2000

Urinary N-acetyl-beta-D-glucosaminidase in epileptic children treated with antiepileptic drugs.

AIM: To investigate the effect of prolonged use of antiepileptic drugs on renal function in children. METHODS: Prospective study of 72 children (aged 3-18 years) with epilepsy, on either monotherapy (n = 44) or combined therapy (n = 28). The length of treatment varied from 1 to 13 years. Drugs used were valproic acid, carbamazepine, ethosuximide, clonazepam, clobazepam, and vigabatrin. RESULTS: In 65 patients plasma concentrations of the drugs were in the therapeutic range. In the remaining seven, plasma concentrations were slightly high. In 33 patients urinary N-acetyl-beta-D-glucosaminidase (NAG) activity was raised. The incidence of pathological NAG indices was significantly higher in the combined therapy group than in the monotherapy group. There were also significant differences in the NAG indices of patients depending on the duration of therapy. CONCLUSIONS: Results suggest that chronic use of some antiepileptic drugs-in spite of normal blood concentrations-may alter tubular function, and the dysfunction may result in clinical symptoms. Therefore, we recommend screening of tubular function in these patients.

Acetylglucosaminidase↗
PubMed2000

Molecular analysis of variability within the toxigenic Aspergillus ochraceus species.

Genetic variability of Aspergillus ochraceus was examined at the DNA level. Based on the HaeIII-Bg/II generated mitochondrial DNA restriction profiles, most isolates could be classified into two distinct groups. These two groups could also be distinguished by the random amplified polymorphic DNA technique, and with telomeric PCR amplifications. Phylogenetic analysis of sequences of the intergenic transcribed spacer region of some of the strains resulted in a dendrogram with the same topology as that based on mitochondrial DNA and amplified DNA data. None of the isolates with type 2 mtDNA profiles produce ochratoxins. Some strains (e.g., A. ochraceus ICMP 939) displayed strain-specific mitochondrial DNA patterns, and their amplified DNA profiles were also different from all other A. ochraceus strains examined.

Aspergillus↗
PubMed2000

Clinical study of the disease of calves associated with Mycoplasma bovis infection.

Clinical, bacteriological and serological examination of 35 calves from the age of 5 to 26 days was performed in a Holstein-Friesian dairy herd endemically infected with Mycoplasma bovis. M. bovis was isolated from 48.6% of nasal swabs taken from the calves at the age of 5 days, and from 91.4% of the same calves at the age of 26 days, indicating the gradual spread of infection. The isolation rate of Pasteurella multocida did not change much, and varied from 28.6 to 25.7%. No P. haemolytica could be detected. In addition to M. bovis and P. multocida, the herd was also infected with different viruses (including bovine viral diarrhoea virus, infectious bovine rhinotracheitis virus, bovine adenoviruses, parainfluenza-3 virus, and bovine respiratory syncytial virus) as a large proportion of the sera of newborn calves contained colostral antibodies against these viruses. In most of the newborn calves severe clinical signs (fever, depression, inappetence, hyperventilation, dyspnoea, nasal discharge and coughing) due to M. bovis infection developed. The clinical signs appeared already on the fifth day of life, and their incidence was the highest at the age of 10 to 15 days. Three calves (8.6%) died as a result of severe serofibrinous pneumonia. The surviving calves showed very poor weight gain (ranging from 1.5 to 3.5 kg) during the first two weeks of life.

Aging↗
PubMed2000

Circulating anticentromere CENP-A and CENP-B antibodies in patients with diffuse and limited systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.

OBJECTIVE: To determine the disease sensitivity and specificity of testing for autoantibodies against 2 of the 3 main human centromere antigenic components, CENP-A and CENP-B (recombinant, expressed in baculovirus). METHODS: ELISA with CENP-A and CENP-B antigens were used to test 45 sera showing a centromere pattern by immunofluorescence (IFA) and sera from 96 patients with systemic sclerosis (SSc), subdivided into diffuse (dSSc) and limited (lSSc) forms. For controls, the same tests were performed on sera from 100 patients with rheumatoid arthritis (RA), 100 with systemic lupus erythematosus (SLE), and 50 random blood donors. Sera from all the patients with SSc were also tested for the presence of anti-Scl70 antibody by ELISA (bovine antigen), and for pattern and titer by IFA (HEp-2 cells). RESULTS: Of the 45 IFA positive sera, 93% were positive for anti-CENP-A and 91% for anti-CENP-B. There was a very good quantitative correlation between the antibody levels against these 2 centromere components (r = 0.597; p<0.001). Anti-CENP-A and B were found in 48% of patients with lSSc, and in 11% and 9%, respectively, of those with dSSc. The difference in the frequency of anti-CENP-A between the 2 patient groups was significant (chi-squared, p<0.001). Similar levels of anticentromere staining pattern by IFA were observed for these 2 groups. Anti-Scl70 was elevated in 8% of lSSc and 25% of dSSc patients; this difference was also significant (chi-squared, p = 0.02). Neither CENP-A nor CENP-B reacted with IgG from SSc patients containing anti-Scl70. The frequency of abnormal levels in patients with SLE and RA was, respectively, 11% and 3% for anti-CENP-A and 4% and 3% for anti-CENP-B. The reaction of IgG from SLE and RA patients with CENP-A was not inhibited by histone H3, i.e., it was not due to recognition of the histone-like domain in CENP-A. Thus, when 96 SSc patients were compared to 200 patients with RA and SLE, the disease specificity of anti-CENP-A and B was 93% and 96.5%, respectively. CONCLUSION: In addition to IFA, ELISA tests for CENP-A and CENP-B yield results with similar sensitivity and specificity for the diagnosis of SSc. CENP-A and CENP-B are primarily associated with lSSc. In SSc the autoantibody response is directed simultaneously and with similar amplitude against these 2 components of the centromere structure, whereas in other autoimmune diseases the response is directed mainly against one of the 2 components.

Adult↗
PubMed2000

Exciton coupling in the CD spectra of chiral spiro-lambda 4-sulfanes and related sulfonium salts.

Enantiomers of spiro-lambda 4-sulfanes 2-7 and related cyclic sulfonium salts 2c-7c have been obtained by stereospecific synthesis. Exciton splitting was observed in the CD spectra of spiro-lambda 4-sulfanes and sulfonium salts having both benzene and naphthalene-benzene rings. The absolute configurations were deduced from the sign of the couplet. Exciton couplets in the CD spectra of sulfonium salts and their parent lambda 4-sulfanes show the same sign which follows from the same orientation of the coupled electric transition moments due to their similar trigonal bipyramidal geometry. Based on the known stereomechanism of the formation of spiro-lambda 4-sulfanes and sulfonium salts as well as of their hydrolysis leading to the corresponding sulfoxides (2a-7a and 2b-7b), the absolute configurations of sulfoxides could also be deduced from the sign of exciton couplet in the CD spectra of related lambda 4-sulfanes and sulfonium salts.

Journal Article↗
PubMed2000

Characterisation of Rhodococcus equi strains isolated from foals and from immunocompromised human patients.

The cultural, morphological, biochemical, serological characteristics and antibiotic susceptibility of 25 Rhodococcus equi strains isolated from lungs and lung abscesses of pneumonic foals and 5 R. equi strains isolated from immuno-compromised human patients were examined. All R. equi strains showed common cultural, morphological and biochemical characteristics both with conventional tests and on the basis of their enzyme profile. The R. equi strains examined were resistant to penicillins with the exception of ampicillin, to sulphamethazine and several strains also to sulphamethoxazole-trimethoprim. All strains were susceptible to erythromycin and rifampicin. The strains isolated from humans showed somewhat higher rate of antibiotic resistance to penicillin, cefotaxime, kanamycin, streptomycin, lincomycin, and oxytetracycline. The overwhelming majority (96%) of the equine isolates belonged to serotype 1 in Prescott's serotyping system, while the human isolates could not be serotyped.

Animals↗
PubMed1999

Negative modulation of alpha1(I) procollagen gene expression in human skin fibroblasts: transcriptional inhibition by interferon-gamma.

Interferon-gamma (IFN-gamma), a multifunctional cytokine produced by activated Th1 lymphocytes, exerts potent effects on the extracellular matrix by regulating fibroblast function. In this study, we examined the modulation of alpha1(I) procollagen gene (COL1A1) expression by recombinant IFN-gamma. The results showed that IFN-gamma stimulated the rapid accumulation of interferon regulated factor (IRF)-1 mRNA, followed by a delayed and dose-dependent inhibition of alpha1(I) procollagen mRNA expression in skin fibroblasts from several different donors. The inhibitory response was abrogated in fibroblasts stably expressing IRF-1 in the antisense orientation. A marked decrease in the amount of heterogeneous nuclear pre-mRNA preceded the inhibition of COL1A1 mRNA expression. In fibroblasts transiently transfected with COL1A1 promoter-chloramphenicol acetyltransferase reporter gene plasmids, IFN-gamma selectively inhibited promoter activity and abrogated its stimulation induced by TGF-beta. The inhibition by IFN-gamma was not due to downregulation of TGF-beta receptor mRNA expression in the fibroblasts or decreased ligand binding to the receptor. IFN-alpha and IFN-beta by themselves had little effect on promoter activity, but IFN-alpha augmented the inhibitory effect of IFN-gamma. Using a series of 5' deletion constructs, a proximal region of the COL1A1 promoter was shown to function as an IFN-gamma response element. This region of the gene harbors overlapping binding sites for transcription factors Sp1, Sp3, and NF-1 but no homologs of previously characterized IFN-gamma response elements. The putative IFN-gamma response region was sufficient to confer inhibition of reporter gene expression by treatment with IFN-gamma. Gel mobility shift analysis showed that two distinct and specific DNA-protein complexes were formed when fibroblast nuclear extracts were incubated with oligonucleotides spanning the IFN-gamma response region. IFN-gamma did not modify the ability of nuclear proteins to bind to this region. The results indicate that IFN-gamma inhibits COL1A1 expression in fibroblasts principally at the level of gene transcription. Inhibition involves IRF-1 and is mediated through a short proximal promoter segment but without an apparent change in promoter occupancy. The findings provide novel insight into the mechanism of IFN-gamma regulation of fibroblast function.

Adult↗
PubMed1999

High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial.

OBJECTIVE: To test the hypothesis that systemic sclerosis (SSc) patients taking high-dose D-penicillamine (D-Pen) would have greater softening of skin, lower frequency of renal crisis, and better survival than patients taking low-dose D-Pen. METHODS: Seventeen centers enrolled 134 SSc patients with early (< or =18 months) diffuse cutaneous scleroderma into a 2-year, double-blind, randomized comparison of high-dose D-Pen (750-1,000 mg/day) versus low-dose D-Pen (125 mg every other day). All 134 patients were followed up for a mean+/-SD of 4.0+/-1.1 years to assess the frequencies of new-onset scleroderma renal crisis (SRC) and mortality. RESULTS: Sixty-eight patients completed 24 months of drug treatment. The course of the modified Rodnan skin thickness score in the 32 high-dose and the 36 low-dose D-Pen completers was not different at 24 months: the skin score dropped 4.8+/-10.3 (mean+/-SD) units in the high-dose group and 6.9+/-8.4 units in the low-dose group (P = 0.384 by t-test; favoring low-dose D-Pen) from 20.4+/-10.3 in the high-dose and 19.9+/-6.6 in the low-dose D-Pen group at study entry. The incidences of SRC and mortality were not different (P > 0.38 by Cox proportional hazards and by chi-square test) in the 66 high-dose patients (8 developed SRC and 8 died) compared with the 68 low-dose patients (10 developed SRC and 12 died). Of the 20 adverse event-related withdrawals, 80% occurred in the high-dose D-Pen group. CONCLUSION: The course of the skin score and the frequencies of SRC and mortality in the high-dose D-Pen group were not different from those in the low-dose D-Pen group. Eighty percent of the adverse event-related withdrawals occurred in the high-dose D-Pen patients. Although this study cannot answer the question of whether low-dose D-Pen is effective, it does suggest that there is no advantage to using D-Pen in doses higher than 125 every other day.

Adult↗
PubMed1999

Correlates of the disability index of the health assessment questionnaire: a measure of functional impairment in systemic sclerosis.

OBJECTIVE: To evaluate functional impairment in systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma at the time of entry into a trial of a therapeutic intervention (D-penicillamine). METHODS: The 20-item Disability Index of the Health Assessment Questionnaire (HAQ-DI) was administered to 134 patients as they entered a multicenter trial of high-dose versus low-dose D-penicillamine. All patients had diffuse SSc of < 18 months' duration. SSc patients who had severe organ system involvement and recent renal crisis and who were receiving prednisone > 10 mg/day were excluded from entry. Logistic regression modeling was used to examine the relationship of HAQ-DI scores to SSc skin and organ system involvement. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to estimate effects. RESULTS: The mean (+/-SD) HAQ-DI score at entry was 1.04 +/- 0.67. Fifty-three percent of patients had HAQ-DI scores > or = 1.0 (signifying moderate-to-severe functional impairment). Multivariate logistic regression demonstrated that impaired fist closure > or = 23 mm (OR 4.24, 95% CI 1.68-10.70), reduced handspread < or = 175 mm (OR 4.5, 95% CI 1.80-11.24), joint tenderness count > or = 1.0 (OR 2.93, 95% CI 1.16-7.40), age > or = 43 years (OR 2.44, 95% CI 1.01-5.95), platelet count > or = 330,000/mm3 (OR 2.30, 95% CI 0.96-5.57), and female sex (OR 2.43, 95% CI 0.77-7.73) were the most important correlates of HAQ-DI scores > or = 1.0. CONCLUSION: Increased HAQ-DI scores at baseline were correlated with reduced fist closure, reduced hand-spread, elevated platelet count, presence of tender joints, older age, and female sex. The most important contributor to functional impairment was hand dysfunction. Even within the first 18 months after SSc onset, moderate-severe functional impairment (HAQ-DI scores > or = 1.0) was frequent (53%) in this group of diffuse SSc patients. In early diffuse SSc, the self-administered HAQ-DI is therefore a valuable assessment of function that correlates with objective physical and laboratory measures of SSc disease involvement. Abnormal HAQ-DI scores may support patient claims of functional impairment, help to focus physician attention on implementing measures to reduce functional impairment, and be useful in reflecting the disease course over time.

Adolescent↗
PubMed1999

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the differential diagnosis of cold thyroid nodules.

Various diagnostic techniques have been successfully used in the clinical management of cold nodules; however, the decision on whether to employ surgery or a conservative treatment is not always easy. This study was designed to appraise the diagnostic value of technetium-99m methoxyisobutylisonitrile (MIBI) scintigraphy in the assessment of cold nodules detected using (99m)Tc-pertechnetate. Fifty-two patients were included in the study. All had already been selected for surgery, based on their clinical and laboratory findings, including fine-needle aspiration biopsy. The total number of cold nodules on (99m)Tc-pertechnetate scans was 59. The thyroid scan was performed 20-40 min after i.v. injection of 400 MBq of (99m)Tc-MIBI. Uptake of MIBI in thyroid nodules was compared with that in the surrounding normal thyroid tissue, and a score of between 0 and 3 was assigned to each nodule as follows: 0, cold; 1, decreased; 2, equal; 3, hot. Definitive histology revealed nodular goitre in 24 cases, adenoma in 19, thyroiditis in 1, differentiated cancer in 12, medullary cancer in 2, and anaplastic cancer in 1. None of the degenerative nodules were hot on MIBI scan, while the adenomas showed a variety of MIBI imaging patterns, most frequently the score 3 pattern. In the diagnosis of differentiated thyroid cancer the sensitivities of score 3 and score 2+3 MIBI uptake patterns were 83% (10/12) and 100%, respectively. The score 3 MIBI uptake pattern had a specificity of 100% and a positive predictive value of 100% with respect to thyroid (benign and malignant) neoplastic diseases, whereas a specificity of 72% and a positive predictive value of 43% were observed in the detection of differentiated cancer. After a cold nodule had been detected using (99m)Tc-pertechnetate, a second scan with high MIBI uptake increased by 7.8 times the probability that this nodule would be a differentiated cancer. In conclusion, (99m)Tc-MIBI scintigraphy is a useful method in the differential diagnosis of cold thyroid nodules if the primary aim is to differentiate degenerative from neoplastic diseases rather than to differentiate benign from malignant nodules. High MIBI uptake considerably increases the probability of a differentiated thyroid cancer and facilitates immediate surgical removal, while decreased uptake actually excludes it. We suggest a combination of fine-needle aspiration biopsy and MIBI scan as a routine diagnostic approach to cold thyroid nodules.

Biopsy, Needle↗
PubMed1999

Stimulation of type I collagen transcription in human skin fibroblasts by TGF-beta: involvement of Smad 3.

Transforming growth factor-beta (TGF-beta) stimulates the transcription of the alpha2(I) procollagen gene (COL1A2). The intracellular mediators involved in this response remain poorly understood. In this study, we demonstrate that primary human skin fibroblasts express Smads, a novel family of signaling molecules, in vitro in the absence of TGF-beta. The levels of Smad 7 mRNA was rapidly and transiently increased by TGF-beta. Transient overexpression of Smad 3 and Smad 4, but not Smad 1 or Smad 2, caused trans-activation of a CAT reporter gene driven by a 772 bp segment of the human COL1A2 promoter containing putative TGF-beta response elements. Smad stimulation of promoter activity was ligand independent, but was further enhanced by TGF-beta. Overexpression of a phosphorylation-deficient Smad 3 mutant or wild-type Smad 7, which lacks the carboxy-terminal phosphorylation motif, specifically inhibited TGF-beta-induced activation of COL1A2 promoter. A CAGACA sequence shown to be a functional Smad-binding element in the plasminogen activator inhibitor-1 gene promoter was found within the TGF-beta-response region of the proximal COL1A2 promoter. Gel mobility shift assays showed protein phosphorylation-dependent binding activity in fibroblast nuclear extracts specific for this sequence; TGF-beta treatment strongly stimulated the formation of this DNA-protein complex. Smad was identified as a component of the CAGACA-binding transcription complex in TGF-beta-treated fibroblasts by antibody supershifting. These results demonstrate that (i) Smad 3 transmits TGF-beta signals from the receptor to the COL1A2 promoter in human fibroblasts, and is likely to play an important role in stimulation of COL1A2 promoter activity elicited by TGF-beta; (ii) in fibroblasts, Smads appear to function as inducible DNA-binding transcription factors; and (iii) Smad 7 may be involved in autocrine negative feedback in the regulation of COL1A2 promoter activity by TGF-beta.

Cells, Cultured↗
PubMed1999

Calculation of the radioiodine dose for the treatment of Graves' hyperthyroidism: is more than seven-thousand rad target dose necessary?

Some authors recently suggested a significant increase in the target dose of radioiodine treatment in Graves' disease. The aim of the present study was to investigate the impact of thyroid gland mass on the success rate of radioiodine treatment. For this purpose, the thyroid function of 105 consecutive Graves' patients was assessed 6 and 12 months after a 131I treatment and correlated to the gland mass. The patients were categorized according to the gland mass into small (< or = 30 g; 19 patients), medium size (31-50 g; 40 patients), and large size (> 50 g; 46 patients) groups (S, M, L groups, respectively). None of the patients received more than a 10,000-rad (100-Gy) target dose. During the calculation of administered 131I activity, late uptake measurement has also been routinely used, in addition to the usual maximal uptake parameter. The established effective half-life of 131I was highly variable (5 +/- 1.2 days; range: 2-7.6 days) and could not be predicted based on other clinical data without measuring an extended radioiodine uptake curve of the given patient. However, the correlation between the administered activity calculated from the complete set of uptake values and that of only a single late one was excellent (r = 0.99). Six months after the 131I treatment, hyperthyroidism was cured in 81% of patients with small and medium size thyroid glands, with 62% euthyroid and 19% hypothyroid ratios respectively. In the early phase of study for large goiters, the same linear mass activity function was used during calculation as in smaller glands. In these 17 patients the nonhyperthyroid result was comparable to the results of treatment of the small and medium size gland groups only after 1 year (77%), but the 6-month success rate was significantly lower (53%; p < 0.05). After obtaining these results, the usual 7000-rad target dose was increased to 8000-10,000 rad (depending on the gland mass) in another group of 29 patients with large thyroid glands that result in an acceptable 6-month success rate of 72%. In conclusion, instead of the "mCi 131I/g gland mass/maximal uptake" dose calculation, we suggest a method in which (1) the late 131I uptake measurement is taken into account and (2) for large goiters there is an additional dose adjustment, ie, increase is needed over the usual linear, size driven calculation. No overall increase of target dose over 10,000 rad is necessary if no antithyroid medication is given shortly before 131I treatment.

Adult↗
PubMed1999

Serotypes of Pasteurella haemolytica and Pasteurella trehalosi isolated from farm animals in Hungary.

The biochemical and serological characteristics of 486 P. haemolytica and 31 P. trehalosi strains (517 in total) isolated from different lesions of cattle, sheep, goats, pigs and poultry were examined. A total of 476 P. haemolytica strains (97.9%) showed the characteristics typical of the former biotype A of P. haemolytica, while 10 isolates (2.1%), all from poultry, could not be biotyped. A total of 481 strains (93.0%) could be assigned to one of the 17 serotypes of P. haemolytica-P. trehalosi and 36 strains (7.0%) could not. The majority (83.6%) of the cattle isolates were serotypes A1 and A2. Among strains isolated from sheep all serotypes of P. haemolytica could be identified with the exception of A14, but serotypes A1, A2, A6, A8 and A5 were the most frequent. The overwhelming majority (94%) of the caprine isolates were A2, other serotypes occurred only sporadically. The pig isolates, which could be isolated only very rarely, represented different serotypes, while none of the 10 strains isolated from poultry could be biotyped or serotyped.

Animals↗
PubMed1998

[Study of the contractility of the gallbladder by ceruletide infusion cholescintigraphy after litholysis].

Twenty-six randomly selected patients 2-6 years (mean: 3.5) after rapid percutaneous catheteric litholysis at the Radiological Department were investigated by quantitative Ceruletide cholescintigraphy in this pilot study. The average EF of the patients with recurrent gallstones (Group II) was lower (55 +/- 23%) than that of the patients without stones (69 +/- 23%) (Group I). The authors conclude that this scintigraphic method could help not only to select the best method to make patient stonefree but has an important role in forecasting the prognosis of gallstone recovery after litholytic therapy.

Ceruletide↗
PubMed1998

Beta-amyloid (1-42) peptide impairs blood-brain barrier function after intracarotid infusion in rats.

The effects of intracarotid infusions of beta-amyloid (1-42) peptide was studied on the permeability of brain vessels. Using a quantitative Evans blue method a dose-dependent increase of brain tissue albumin content was established following intracarotid injections of the peptide. Cerebral vessels of increased permeability were also demonstrated with a vital 'staining' technique. Lectin histochemistry revealed an almost complete abolition of specific lectin binding sites of affected endothelial cells. The findings indicate a significant deterioration by beta-amyloid (1-42) peptide of blood-brain barrier function and suggest that this may result from endothelial damage. It is assumed that altered permeability of cerebral vessels may be involved in the development of brain pathologies associated with Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed1998

Modulation of human alpha1(I) procollagen gene activity by interaction with Sp1 and Sp3 transcription factors in vitro.

In previous work, we delineated a proximal region of the human alpha1(I) collagen gene (COL1A1) promoter necessary to direct its basal transcription in fibroblasts. This region has potential recognition sites for a variety of DNA-binding proteins. Here, we show that the -129/-107-bp sequence in this region of the promoter, which harbors an inverted CCAAT motif closely linked to a GC-rich direct repeat and is perfectly conserved between mouse and human, specifically bound the transcription factors Sp1, Sp3, and CTF/NF-1 in nuclear extracts from human skin and lung fibroblasts. Drosophila Schneider L2 cells lacking endogenous Sp activity were used to investigate the effect of expression of Sp or CTF/NF-1 transcription factors on COLlAl promoter activity. Expression of Sp1 caused potent trans-activation of a COL1A1 promoter (-174 to +42bp). In contrast, expression of Sp3, which binds to the same recognition sites as Sp1, and CTF/NF-1 stimulated COL1A1 promoter activity only at higher concentrations, and Sp2 did not transactivate. Expression of a 10-fold excess of Sp3, but not CTF/NF-1 or Sp2, abrogated the stimulation of COL1A1 promoter activity induced by Sp1. TGF-beta at concentrations previously shown to increase COL1A1 transcription caused a decrease in the relative amount of Sp3 in fibroblast nuclear extracts. These results suggest that both Sp1 and Sp3 bind to the proximal COL1A1 promoter and stimulate its activity; however, their interaction with each other may result in repression of Sp1-induced COL1A1 transcription. Alterations in the relative amounts or DNA-binding activities of these transcription factors in a cell- or signal-specific manner may contribute to the control of transcription from the COL1A1 promoter. The present findings, and recent observations implicating Sp1 and its homologs in regulating the expression of several collagen genes, suggest that the family of Sp1 transcription factors play a role in physiological and pathological modulation of connective tissue accumulation.

Animals↗