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T T Provost

Publications and source records attributed to T T Provost.

At least 19 recordsLinked to original sources

Significance of the anti-Ro (SS-A) antibody in evaluation of patients with cutaneous manifestations of a connective tissue disease.

The anti-Ro(SS-A) antibody is arguably the most important antibody determination except for antinuclear antibodies in evaluation of patients suspected of having lupus erythematosus. During the past 25 years, studies have established the importance of this antibody in the evaluation of patients with atypical lupus erythematosus, who have a photosensitive dermatitis as the presenting sign. The purpose of this review is to demonstrate the utility and the necessity of this antibody determination in the evaluation of all patients with cutaneous manifestations who are suspected of having a connective tissue disease.

Antibodies, Antinuclear

One hundred anti-Ro (SS-A) antibody positive patients: a 10-year follow-up.

To explore further the varied clinical expression of anti-Ro(SS-A) antibody positive patients and to determine the outcomes of these patients, we followed 100 anti-Ro(SS-A) antibody positive patients, originally seen at the Johns Hopkins Medical Institutions in 1982 and 1983, over a 10-year period. The results of this study indicate that anti-Ro(SS-A) antibody positive patients have a diverse clinical presentation and that the anti-Ro(SS-A) antibody response generally persists for years. Some of these patients appear to have a static disease process for years. However, 65% (51, including 13 deaths, of 78 patients) of the patients for whom we had follow-up data had a chronic (10 years or greater) progressive disease process. Black patients, in general, have an earlier onset of disease and may have a more severe disease than white patients. At least 25% of our anti-Ro(SS-A) antibody positive patients demonstrated a dynamic change in clinical presentation with the development of Sjögren syndrome and/or a progressive "rheumatoid-like" arthritis. Interstitial pulmonary disease, central nervous system disease, and vasculitic insults occur frequently in these patients. Renal disease occurred in 19 anti-Ro(SS-A) positive patients, and in 47% of these renal disease patients, no anti-DNA antibodies (dsDNA or ssDNA) were detected. Cutaneous manifestations are prominent in anti-Ro(SS-A) antibody positive patients with lupus. Photosensitivity and a malar dermatitis were the most common features. Twenty percent of lupus patients had discoid lesions, and 20% had SCLE lesions. Based on this study, we believe that anti-Ro(SS-A) antibody positive patients should be routinely evaluated for the emergence of systemic features. Since these systemic features are at least in part, if not solely, the result of inflammation, early treatment with steroids and/or immunosuppressive agents may minimize the damage and influence in a positive manner the significant morbidity and mortality observed in some anti-Ro(SS-A) antibody positive patients.

Adolescent

Ovarian cancer in patients with dermatomyositis.

A consensus regarding adequate screening to detect early malignancy in the setting of dermatomyositis (DMM) has yet to be reached. This issue is particularly relevant with regard to ovarian cancer, as early detection with routine examinations, ultrasound, and abdominal CT may not be successful. Four of 15 women diagnosed with and seen in our department for DMM between 1986 and 1993 were subsequently diagnosed with metastatic papillary serous ovarian carcinoma. One additional patient developed metastatic pelvic papillary adenocarcinoma, believed to be of ovarian origin. These diagnoses of advanced cancer were unexpected, as all women had undergone repeated cancer screenings beyond what is normally recommended for patients with DMM. The 5 women were strikingly similar in their initial presentations and subsequent courses. In each, the diagnosis of DMM was delayed from 2 to 10 months, as they were initially misdiagnosed with a photoinduced or contact dermatitis. All except 1 had severe, recalcitrant skin disease despite attempted therapy with antimalarial and immunosuppressive agents. All 4 patients who survived the postoperative period after tumor debulking showed either improvement or resolution of their DMM. It appears that women with DMM have an increased incidence of ovarian cancer, which is usually diagnosed months to a few years (range, 0 d to 6 y) after DMM has been diagnosed. Although recommendations have been made regarding cancer screening in these individuals, recommendations for initial and surveillance examinations vary from routine history and physical examination to evaluations including extensive radiologic evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Age of Onset

Neonatal lupus erythematosus. Report of serological and immunogenetic studies in twins discordant for congenital heart block.

Autoantibody, HLA studies and C4 phenotypes were performed on twins discordant for isolated congenital heart block. Serum from the mother and cord blood from the infants revealed Ro(SSA) and La(SSB) antibodies in all three sera. No significant difference in Ro(SSA) antibody titre was noted in the cord blood of either twin when compared with maternal titres, as detected by a sensitive ELISA assay. The infants' mother was HLA-DR3 positive. Both infants had identical HLA and C4 phenotypes. Immunoblot analysis revealed that sera from both mother and infants reacted with the 52-kDa Ro(SSA) macromolecule. Quantitative cord blood IgM levels were not elevated in either twin. This study indicates that placental transfer of anti-Ro(SSA) or anti-La(SSB) alone to the fetus is not sufficient for the expression of congenital complete heart block. We conclude from this experiment of Nature that there must be a second event determining which infant develops complete heart block, but this is unknown at present.

Adult

Cutaneous manifestations of lupus erythematosus.

Lupus erythematosus is an autoimmune disease that demonstrates cutaneous, systemic, or both cutaneous and systemic manifestations. This article reviews the cutaneous manifestations of lupus erythematosus.

Alopecia

Anti-Ro(SS-A) HLA-DR3-positive women: the interrelationship between some ANA negative, SS, SCLE, and NLE mothers and SS/LE overlap female patients.

During the past 15 years, the clinical spectrum associated with the anti-Ro(SS-A) antibody response has been defined. Various clinical presentations, including subacute cutaneous lupus erythematosus, the neonatal lupus syndrome, the Sjögren's syndrome/lupus erythematous overlap syndrome, and primary Sjögren's syndrome, have been detected in association with the anti-Ro(SS-A) response. The anti-Ro(SS-A) antibody response is associated with the HLA-DR2 and HLA-DR3 phenotypes. There is now a good deal of evidence to suggest that many anti-Ro(SS-A)-positive HLA-DR3 women are genetically closely related, sharing in common an enriched frequency of the HLA-DR3-linked B8, DQw2, and DRW52 phenotypes. DNA sequence studies have confirmed this genetic relationship. These studies have led us to the following conclusions. 1) The HLA-DR2 and HLA-DR3 associations with systemic lupus erythematosus and the HLA-DR3 association with Sjögren's syndrome are related to the anti-Ro(SS-A) antibody response and not to the clinical disease expression. 2) HLA-DR3 anti Ro-positive female patients with first-degree Sjögren's syndrome, subacute cutaneous lupus erythematosus, or Sjögren's syndrome, or who are asymptomatic, are immunogenetically closely related even though the clinical presentations are strikingly different. All these HLA-DR3 anti-Ro(SS-A) antibody-positive women are at risk to give birth to a child with the neonatal lupus syndrome.

Adult

Anti-Ro/SS-A antibodies in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro electrophysiologic and immunocytochemical studies.

OBJECTIVE: To determine whether anti-Ro/SS-A antibodies selectively bind to neonatal cardiac cells and alter membrane repolarization. METHODS: An in vitro electrophysiologic and immunocytochemical experimental model contrasting neonatal and rabbit cardiac tissue was employed. RESULTS: Sera and IgG-enriched fractions from anti-Ro/SS-A antibody-positive mothers of infants with neonatal lupus erythematosus and congenital heart block bind to neonatal, rather than adult, rabbit cardiac tissue and alter the transmembrane action potential (i.e., inhibit repolarization). The additional presence of anti-La/SS-B antibodies was not additive or synergistic for these immunocytochemical and electrophysiologic features. Sera containing other antibody specificities (i.e., anti-native DNA, cardiolipin, Sm, and nuclear RNP) failed to stain the neonatal cardiac tissue or produced alterations in membrane repolarization. CONCLUSION: Anti-Ro/SS-A antibodies may play a pathophysiologic role in the development of congenital heart block in neonatal lupus.

Action Potentials

Cutaneous manifestations of Sjögren's syndrome.

The major mucous membrane and cutaneous manifestation of Sjögren's syndrome (SS) is xerosis. Severe dryness of the eyes, mouth, nasal passage, and vagina produce many annoying symptoms, including photophobia, burning and itching of the eyes, alterations in taste and smell, recurring nonallergic bacterial sinusitis rhinitis, and dysparunia. SS patients frequently complain of dryness of lips and soreness and a burning sensation of the tongue and oral mucosa. SS patients also complain of dryness of their hair and note a decrease in luster, and severe dryness of the skin is frequently accompanied by pruritus.

Humans

Cerebral vasculopathy associated with collateralization resembling moya moya phenomenon and with anti-Ro/SS-A and anti-La/SS-B antibodies.

We describe a 48-year-old, previously healthy, anti-Ro/SS-A and anti-La/SS-B antibody positive black woman with negative risk factors for atherosclerosis, who developed mental status and personality changes over a 6-12-month period, and progressive cortical blindness over a 2-week period. Angiographic and computed axial tomographic studies of the brain demonstrated multiple large areas of infarction correlating with stenosis and occlusions of the internal carotid and posterior cerebral arteries. Moya moya-like findings were prominent radiographically. Results of angiographic, computed tomographic, and magnetic resonance imaging studies were interpreted as being compatible with large, medium, and small vessel disease, most likely a vasculitis.

Angiography

Subacute cutaneous lupus erythematosus-immunogenetic associations.

Thirty-two patients who fulfilled criteria for subacute cutaneous lupus erythematosus (SCLE) were examined for their immunogenetic associations. Our results confirm the previously reported association of HLA-DR3 (15/31 48% P less than 0.01) and also demonstrate an increase in HLA-DR2 (14/31, 45%, P = less than 0.05). These findings indicate there are two distinct immunogenetic (HLA) populations of Ro(SS-A) antibody-positive SCLE patients. The increased frequency of HLA-DR2 and DR3 appears to be associated with expression of the Ro(SS-A) antibody, since no HLA associations were seen in Ro(SS-A)-negative SCLE patients when compared with normal population controls. Furthermore, these data indicate that the distinctive cutaneous lesions of SCLE are not associated with one specific HLA allele, as previously suspected. These findings contrast with the relatively homogeneous immunogenetic background seen in other lupus erythematosus subsets with a high frequency of Ro(SS-A) antibody, i.e., neonatal lupus erythematosus and Sjögren's syndrome/lupus erythematosus overlap (increased frequency of HLA-DR3, DQw2 and DRW52).

Adult

Detection of anti-Ro(SSA) antibodies by gel double diffusion and a 'sandwich' ELISA in systemic and subacute cutaneous lupus erythematosus and Sjögren's syndrome.

A newly described Ro 'sandwich' ELISA was compared to the gel double diffusion technique to detect anti-Ro(SSA) antibodies in Sjögren's syndrome, systemic and subacute cutaneous lupus erythematosus patients. This study demonstrates that the ELISA assay increased the frequency of detection of anti-Ro(SSA) antibodies in these well defined connective tissue disease patients by approximately 5-10% compared to the gel double diffusion anti-Ro(SSA) antibody assay. The study also confirms that some patients make anti-Ro(SSA) antibodies directed solely at unique human Ro(SSA) antigen epitopes. We also detected the existence of a significant Sjögren's syndrome patient population failing to make significant anti-Ro(SSA) antibodies. We conclude from our study that the gel double-diffusion technique employing human spleen extract as a source of the Ro(SSA) antigen is, at present, the most cost-effective test to detect anti-Ro(SSA) antibodies.

Antibodies, Antinuclear

Israel Zeligman.

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Baltimore

Anti-Ro(SSA) and anti-La(SSB) antibodies in lupus erythematosus and Sjögren's syndrome.

Anti-Ro(SSA) and La(SSB) antibody determinations have become important serologic tests in the evaluation of lupus erythematosus and Sjögren's syndrome patients. These antibodies appear to identify a group of lupus patients with prominent skin diseases. Although much of the initial investigations regarding the value of these antibodies has been performed in the United States and Europe, preliminary studies suggest that the frequency of these antibodies in Japanese and other Oriental patients may be double that seen in American patients. This article will briefly review our knowledge of the molecular, immunogenetic and clinical features of the anti-Ro(SSA) and anti-La(SSB) antibody responses.

Antibodies, Antinuclear