Basal level glucose-6-phosphatase gene transcription requires binding sites for Sp family proteins within the gene promoter.

The significance of two regions (SpA: -19 to -11 and SpB: -63 to -55) within the human glucose-6-phosphatase (G6Pase) gene promoter for gene expression was examined. The mutation of SpA and SpB together, but not alone, decreased G6Pase promoter activity. Electromobility shift assays showed that SpA and SpB were able to bind the transcription factors Sp1 and Sp3.

Identification of a cAMP response element within the glucose- 6-phosphatase hydrolytic subunit gene promoter which is involved in the transcriptional regulation by cAMP and glucocorticoids in H4IIE hepatoma cells.

The expression of a luciferase reporter gene under the control of the human glucose 6-phosphatase gene promoter was stimulated by both dexamethasone and dibutyryl cAMP in H4IIE hepatoma cells. A cis-active element located between nucleotides -161 and -152 in the glucose 6-phosphatase gene promoter was identified and found to be necessary for both basal reporter-gene expression and induction of expression by both dibutyryl cAMP and dexamethasone. Nucleotides -161 to -152 were functionally replaced by the consensus sequence for a cAMP response element. An antibody against the cAMP response element-binding protein caused a supershift in gel-electrophoretic-mobility-shift assays using an oligonucleotide probe representing the glucose 6-phosphatase gene promoter from nucleotides -161 to -152. These results strongly indicate that in H4IIE cells the glucose 6-phosphatase gene-promoter sequence from -161 to -152 is a cAMP response element which is important for the regulation of transcription of the glucose 6-phosphatase gene by both cAMP and glucocorticoids.

Glucose induces glucose 6-phosphatase hydrolytic subunit gene transcription in an insulinoma cell line (INS-1).

Primer extension analysis and RNase protection assays revealed the identity of glucose 6-phosphatase gene transcripts in both the insulinoma cell line INS-1 and hepatic cells. In transient transfection assays of INS-1 cells, using constructs between the human glucose 6-phosphatase gene promoter and a luciferase reporter gene, the reporter gene activity was induced by dexamethasone and dibutyryl cAMP. Furthermore, the promoter was regulated by the glucose concentration in the medium. This effect was dependent on glucose metabolism. The data indicated that glucose 6-phosphatase gene transcription is regulated in a similar way in the insulinoma cell line and in liver.

The art of unproven remedies.

Dealing with unproven treatments involves more than analyzing the available scientific data. The patient-physician relationship--the foundation of medical practice--is challenged and threatened by unproven treatments. To understand the problem, we need to understand ourselves as well as the patient and the disease. Handling the problem effectively can strengthen the patient-physician bond.

Unproven arthritis remedies. How to approach the problem.

The traditional medical model (ie, history taking, physical examination, diagnosis, and treatment) is not sufficient in the management of chronic diseases such as arthritis. The complex social interactions that lead patients toward and away from traditional medical treatment must be recognized and addressed. Physicians need to acknowledge the likelihood that their patients may use unproven arthritis remedies and to make an effort to reduce the problem. Clinical research on the use of unproven remedies is needed, especially as it relates to complex physician-patient interactions. A good patient-physician relationship remains the basis of good clinical medicine and increases the likelihood of patient compliance.

DR antigens in systemic sclerosis: lack of clinical correlations.

The information available in the literature is controversial as to the association between HLA-DR and systemic sclerosis (SS). We studied 44 Caucasians with SS and found DR1 (P = 0.025; RR = 2.4) and DR5 (P = 0.05; RR = 3.8) to be increased whereas DR3 was not found to be increased when compared to local controls. The possible influence of a DR specificity in the clinical manifestations of SS was also investigated but not found.

A controlled trial of antihypertensive therapy in systemic sclerosis (scleroderma).

Antihypertensive treatment may be life saving in scleroderma renal crisis. Patients surviving such crises frequently have had dramatic improvement in the dermal manifestations of their scleroderma. To investigate the potential role of antihypertensive treatment in nonhypertensive patients we randomly assigned 28 patients with systemic sclerosis into drug (14) and placebo (14) groups, using blocked randomisation , and followed them up in a prospective, double-blind clinical trial for 24 months. Overall, both groups improved slightly, with both subjective and objective markers. There were no statistically significant differences and no clinically meaningful trends between the 2 groups, except that the blood pressure was reduced in the group on the active drug.

Patients, physicians, and unproven remedies.

Chronic arthritis management is complicated by patient administered unproven treatments. Disease, patient, and physician characteristics all contribute to this problem. Physicians must understand the complex cultural, sociological and psychological variables which encourage the use of unproven treatments. Part of any therapeutic regimen for chronic arthritis should include physician awareness and patient education regarding unproven treatments.

A multicenter study of outcome in systemic lupus erythematosus. I. Entry variables as predictors of prognosis.

A retrospective study of factors influencing survival in 1,103 patients with systemic lupus erythematosus (SLE) was carried out at 9 university centers diverse in geographic, socioeconomic, and racial characteristics. The mortality and disease characteristics of the patients at study entry varied widely among centers. The survival rates from the time patients with a diagnosis of SLE were first evaluated at the participating center was 90% at 1 year, 77% at 5 years, and 71% at 10 years. Patients with a serum creatinine greater than 3 mg/dl at study entry had the lowest survival rates: 48%, 29%, and 12% at 1, 5, and 10 years, respectively. Survival rate also correlated independently with the entry hematocrit, degree of proteinuria, number of preliminary American Rheumatism Association criteria for SLE satisfied, and source of funding of medical care. When data were corrected for socioeconomic status, race/ethnic origin did not significantly influence survival. Survival rates varied widely at different participating institutions, generally due to differences in disease severity. Place of treatment was independently associated with survival only in the second year after study entry. Disease duration before study entry did not account for the differences in disease severity.

A multicenter study of outcome in systemic lupus erythematosus. II. Causes of death.

Causes of death were examined for 1,103 systemic lupus erythematosus patients who were followed from 1965 to 1978 at 9 centers that participated in the Lupus Survival Study Group. A total of 222 patients (20%) died. Lupus-related organ system involvement (mainly active nephritis) and infection were the most frequent primary causes of death. Causes of death were similar throughout the followup period. Hemodialysis had little impact on the length of survival for patients with nephritis. Active central nervous system disease and myocardial infarction were infrequent causes of death. There were no deaths from malignancy.

The use of unorthodox therapies and marginal practitioners.

This study examines the extent of utilization of unorthodox therapies and marginal practitioners among patients with one broad category of chronic disease, rheumatic disorders. Almost all respondents (94%) had tried some unorthodox remedy or practitioner, and several had used 13 different unorthodox remedies or practitioners. There was no relationship between age, sex, race, geographic location and magnitude of usage of treatments. There was no statistically significant relationship between education and income and amount of usage, although there was some variation by income group in which unorthodox remedies were employed. Thus, this study provides evidence that some elements of folk medicine practice continue to exist among most segments of the American population and this issue deserves further research. An important role for medical sociologists is to examine disease and disease treatment from the perspectives of the lay culture, as well as that of the medical community.

Nonsteroidal anti-inflammatory agents in rheumatoid arthritis and ankylosing spondylitis.

The relative effectiveness of six nonsteroidal anti-inflammatory agents was studied in 33 patients with rheumatoid arthritis and 32 patients with ankylosing spondylitis in a double-blind, randomized, prospective study employing a six-way multiple crossover design with six-week trials of each agent. In ankylosing spondylitis, naproxen, indomethacin, and fenoprofen calcium were the most effective agents. In rheumatoid arthritis, relatively little mean difference between drugs was found. Most of this difference could be attributed to compliance factors, which favored drugs that required only a small number of pills daily. Despite the small differences in effect, patients had strong preferences. More than 85% of patients were still taking their preferred medication after a mean follow-up period of one year.

Scleroderma. Current understanding of pathogenesis and management.

Scleroderma is no longer the diagnostic or therapeutic dilemma it previously was. New diagnostic techniques facilitate earlier diagnosis, and many symptoms are amenable to treatment.

Treatment decisions in systemic lupus erythematosus.

Rheumatologists and nephrologists were surveyed, by the use of specifically designed case histories, regarding their management of selected aspects of systemic lupus erythematosus (SLE). Treatment was individualized on a case by case basis by the vast majority of respondents. There was agreement on the initial treatment of SLE involving mild arthritis, active nephritis, or central nervous system disease and on steroid tapering practices. There was disagreement about treatment of a "serologic flare" and the management of late-stage nephropathy. Academic centers were more selective and less aggressive than practicing subspecialists. Areas of concordance document current standard treatment practices but sometimes show dissociation between the degree of consensus and the level of available medical knowledge.

Ibuprofen, meningitis, and systemic lupus erythematosus.

A 33 year old female with systemic lupus erythematosus developed an aseptic meningitis with a polymorphonuclear CSF pleocytosis temporally correlated with ibuprofen. Several weeks later after one ibuprofen tablet this syndrome recurred. This represents the second report of this unusual manifestation and suggest an adverse reaction to ibuprofen in SLE patients.