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Biomedical subjects

M Pras

Publications and source records attributed to M Pras.

At least 55 records · Page 3Linked to original sources
PubMed1998

Outcome of pregnancy in three patients with primary antiphospholipid syndrome after stroke.

OBJECTIVE: Ischemic stroke is the most common neurological manifestation in patients with antiphospholipid syndrome (APS). Pregnancy in APS patients markedly increases the risk of thrombosis. There is no data on pregnancy outcome in patients with APS with a history of an ischemic stroke. We report our experience with three APS patients with a history of stroke who had successful pregnancies and deliveries. PATIENTS: Three patients with APS and previous stroke were treated with small doses of aspirin and anticoagulants during pregnancy. RESULTS: The patients remained free of attacks of cerebral ischemia during their pregnancies and at follow-up periods of 1 to 4 years. CONCLUSIONS: Successful pregnancy and delivery is possible in APS patients with a history of stroke, treated with low-dose aspirin and anticoagulants. A previous episode of cerebral ischemia should not be considered an absolute contraindication for an APS patient to become pregnant.

Adult↗
PubMed1998

Familial Mediterranean fever: from the clinical syndrome to the cloning of the pyrin gene.

Familial Mediterranean fever (FMF) is a genetic disorder, restricted to peoples originating in the Middle East. The clinical syndrome is characterized by shortlived febrile episodes, accompanied by inflammation in one of the serous membranes, resulting in peritonitis pleuritis or synovitis. In many untreated FMF patients, systemic amyloidosis developed. The clinical presentation of amyloidosis in FMF is nephropathic, progressing from proteinuria, nephrosis to renal failure and end stage renal disease. Continuous colchicine treatment, which was introduced in 1972, prevents most febrile-inflammatory attacks of FMF, and inhibits the development of amyloidosis in this otherwise fatal disease. Recently, the gene that causes FMF was cloned. It is called the pyrin gene and encodes the pyrin protein. Five missense mutations were found so far in the gene. These give rise to 5 amino acid substitutions, all of them in the carboxyterminal part of the pyrin protein. The pyrin protein is expressed solely in neutrophiles white blood cells which are found in large numbers in the inflammatory sites during FMF attacks. It seems that the role of the wild type of the pyrin protein is to inhibit inflammation that can be provoked by a minor insult. The mutated pyrin protein in FMF is probably unable to inhibit these unnecessary inflammatory events. Preliminary studies of phenotype genotype correlation are reported.

Adult↗
PubMed1997

Isolation and purification of two major serum amyloid A isotypes SAA1 and SAA2 from the acute phase plasma of mice.

A new procedure was developed for isolation of two major serum amyloid A (SAA) isotypes SAA1 and SAA2 from acute-phase plasma of mice. The procedure included preparation of high-density lipoproteins (HDLs) and their separation by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). The SAA proteins (Mr 12,000) were electroeluted and afterwards purified from SDS by gel permeation chromatography on a Fractogel TSK-40F column in aqueous 50% acetonitrile-0.1% TFA. Finally, the SAA proteins free from SDS were fractionated by high-performance liquid chromatography on a Vydac 214TP54 column (250 x 4.6 mm I.D., particle size 5 microm), yielding two major fractions with k=5.2 and k=5.5. The N- and C-terminal sequence analyses and mass spectrometry demonstrated the purity of these two major fractions and their identity with apo SAA1 (k=5.2) and apo SAA2 (k=5.5). The developed procedure is applicable to small amounts of pooled murine plasma (6-7 ml) and could be readily modified from small to large scale preparations.

Acute-Phase Reaction↗
PubMed1997

A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups.

Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) on chromosome 16p13.3. We have recently constructed a 1-Mb cosmid contig that includes the FMF critical region. Here we show genotype data for 12 markers from our physical map, including 5 newly identified microsatellites, in FMF families. Intrafamilial recombinations placed MEFV in the approximately 285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (approximately 200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among the Armenians. A sizable minority of Iraqi Jewish and Armenian carrier chromosomes appeared to be derived from the North African Jewish ancestral haplotype. We observed a unique FMF haplotype common to Iraqi Jews, Arabs, and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that some of these mutations arose before the affected Middle Eastern populations diverged from one another.

Alleles↗
PubMed1997

Construction of a 1-Mb restriction-mapped cosmid contig containing the candidate region for the familial Mediterranean fever locus (MEFV) on chromosome 16p 13.3.

In this paper we describe the assembly and restriction map of a 1.05-Mb cosmid contig spanning the candidate region for familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation localized to 16p13.3. Using a combination of cosmid walking and screening for P1, PAC, BAC, and YAC clones, we have generated a contig of genomic clones spanning approximately 1050 kb that contains the FMF critical region. The map consists of 179 cosmid, 15 P1, 10 PAC, 3 BAC, and 17 YAC clones, anchored by 27 STS markers. Eight additional STSs have been developed from the approximately 700 kb immediately centromeric to this genomic region. Five of the 35 STSs are microsatellites that have not been previously reported. NotI and EcoRI mapping of the overlapping cosmids, hybridization of restriction fragments from cosmids to one another, and STS analyses have been used to validate the assembly of the contig. Our contig totally subsumes the 250-kb interval recently reported, by founder haplotype analysis, to contain the FMF gene. Thus, our high-resolution clone map provides an ideal resource for transcriptional mapping toward the eventual identification of this disease gene.

Base Sequence↗
PubMed1997

Criteria for the diagnosis of familial Mediterranean fever.

OBJECTIVE: To establish a new set of criteria for the diagnosis of familial Mediterranean fever (FMF). METHODS: Twenty-seven features and manifestations typical of FMF were studied to determine their prevalence in 105 patients with FMF and 106 controls. Diagnosis of FMF in the study group was based on clinical judgment. Controls were patients with a variety of other diseases who presented to the emergency room or outpatient clinics with recurrent episodes of pain in body sites usually involved in FMF attacks. Manifestations observed to be significantly more common in FMF patients than in controls were incorporated into the rule proposed for diagnosis of FMF, based on a model of major, minor, and supportive criteria. RESULTS: Two sets of diagnostic criteria were established. A conservative criteria set for diagnosis of FMF was based on the presence of 1 major or 2 minor criteria, or 1 minor plus 5 supportive criteria, and a simple criteria set for diagnosis of FMF required 1 major or 2 minor criteria. The sensitivity and specificity of these 2 criteria sets were >95% and >97%, respectively. CONCLUSION: The proposed new sets of criteria were highly sensitive and specific, and could be used to readily diagnose FMF and to distinguish FMF from other periodic febrile diseases.

Adolescent↗
PubMed1997

Chronic colchicine treatment does not impair glucose tolerance in familial Mediterranean fever patients.

OBJECTIVE: To investigate a long-term colchicine treatment in inhibiting normal release of insulin, in response to a glucose load. SETTING: The Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer. PATIENTS: Thirty-one familial Mediterranean fever (FMF) patients, treated continuously with colchicine (1.0-2.0 mg.day-1) for 2-13 years. METHODS: A standard oral glucose tolerance test (OGTT) was performed to study the effect of long-term colchicine treatment on glucose-induced insulin response. An intravenous glucose tolerance test (IVGTT) was then performed on randomly chosen FMF patients (n = 9) and age-matched controls (n = 5). Glucose was administered 30 min after intravenous colchicine (2 mg) infusion. The sum of 1st- and 3rd-min insulin levels served as an index of early-phase insulin release. RESULTS: Based on the Office Guide to Diagnosis of Glucose Intolerance [13], one subject exhibited impaired glucose tolerance and two others had abnormal dynamics of glucose during the test but normal values at 120 min. Insulin values were normal in all participants. No significant differences were found in maximal glucose and insulin concentration, nor in the insulin release index between FMF colchicine-treated and healthy controls. CONCLUSIONS: Based on these findings, no impairment in glucose dynamics could be demonstrated in chronically colchicine treated patients, compared to untreated controls.

Administration, Oral↗
PubMed1997

Seronegative spondyloarthropathy in familial Mediterranean fever.

To define a possible association between familial Mediterranean fever (FMF) and seronegative spondyloarthropathy (SNSA) and to study features of SNSA in FMF patients, we screened for the presence and manifestations of SNSA in 3,000 FMF patients attending the National Center for FMF in our institution. This population included 160 patients with chronic arthritis, most who suffered from SNSA. Patients were considered to suffer from SNSA if they had chronic arthritis, inflammatory back/neck pain, and sacroiliitis. Patients who had other diseases associated with SNSA were excluded. Eleven patients, nine men and two women, with chronic monoarthritis or oligoarthritis, grade 2 (four patients) or grades 3 to 4 (seven patients), sacroiliitis, and inflammatory back pain met the criteria for diagnosis of SNSA of FMF. These patients were rheumatoid factor (RF) and HLA-B27 negative. In seven patients, spondyloarthropathy developed while they received colchicine, and in four before colchicine. Most patients responded to treatment with nonsteroidal antiinflammatory drugs, but three required second-line agents. These findings suggest that SNSA is one of the musculoskeletal manifestations of FMF that may occur despite colchicine therapy and requires specific treatment.

Achilles Tendon↗
PubMed1997

Detection of serum amyloid A-derived proteins in formalin-fixed paraffin-embedded tissues: reliability of the method and expansion of its spectrum.

To further assess the reliability of the Shtrasburg method for detection of amyloid A in formalin-fixed, paraffin-embedded tissues and to expand the spectrum of the amyloid proteins analyzed by this method, we studied formalin-fixed, paraffin-embedded amyloid-containing tissues obtained from patients with the following types of amyloidosis: amyloid A, light chain, transthyretin, calcitonin, beta2 microglobulin, and senile seminal vesicle. The tissue samples were deparaffinized, processed, and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the Western blot technique. Only specimens from patients with amyloid A amyloidosis gave protein bands: a single 8.5-kd band in lanes of all tissues studied, except thyroid tissue, which displayed two bands of about 5 and 10 kd. Other types of amyloid failed to show any protein band. These findings suggest that the Shtrasburg method is sensitive, specific, and reliable and may have an important role in the diagnosis of amyloidosis.

Amyloidosis↗
PubMed1997

Attacks of pericarditis as a manifestation of familial Mediterranean fever (FMF).

Familial Mediterranean fever (FMF) is characterized by recurrent attacks of febrile serositis. While arthritis, pleuritis and peritonitis are common in FMF, no association of pericarditis with FMF has been described in detail. We retrospectively studied about 4000 FMF patients, using a computer chart review. Pericarditis was diagnosed when patients sustained attacks of pleuritic retrosternal chest pain and had typical findings in the electrocardiogram, echocardiogram or chest radiogram. The incidence and features of pericarditis in FMF were compared to published data. Over a period of 20 years, one or more episodes of pericarditis were recorded in 27 patients, a significantly higher incidence than in the general population (68 vs. 6 per 10(5) per year, p < 0.001). Each patient experienced 1-3 pericarditis attacks, lasting a mean of 4.2 days, accompanied by high temperature and symptoms of FMF attack at another site. The pericarditis attack resolved spontaneously and left no sequelae. FMF patients with pericarditis were comparable to other FMF patients in most demographic and clinical parameters. Pericarditis may be considered another rare manifestation of FMF.

Adolescent↗
PubMed1997

Molecular analysis of cystinuria in Libyan Jews: exclusion of the SLC3A1 gene and mapping of a new locus on 19q.

Cystinuria is a hereditary disorder of amino acid transport and is manifested by the development of kidney stones. In some patients the disease is caused by mutations in the SLC3A1 gene, which is located on the short arm of chromosome 2 and encodes a renal/intestinal transporter for cystine and the dibasic amino acids. In Israel cystinuria is especially common among Jews of Libyan origin. After excluding SLC3A1 as the disease-causing gene in Libyan Jewish patients, we performed a genomewide search that shows that the Libyan Jewish cystinuria gene maps to the long arm of chromosome 19. Significant linkage was obtained for seven chromosome 19 markers. A maximal LOD score of 9.22 was obtained with the marker D19S882. Multipoint data and recombination analysis placed the gene in an 8-cM interval between the markers D19S409 and D19S208. Significant linkage disequilibrium was observed for alleles of four markers, and a specific haplotype comprising the markers D19S225, D19S208, D19S220, and D19S422 was found in 11 of 17 carrier chromosomes, versus 1 of 58 Libyan Jewish noncarrier chromosomes.

Amino Acid Transport Systems, Basic↗
PubMed1997

Familial Mediterranean fever and hyperimmunoglobulinemia D syndrome: two diseases with distinct clinical, serologic, and genetic features.

OBJECTIVE: To determine whether the 2 periodic febrile syndromes familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS) are distinct diseases. METHODS: Clinical manifestations of the diseases were analyzed by physicians experienced with FMF and HIDS. Serum immunoglobulin (Ig) levels were studied in 70 patients with FMF using nephelometry or ELISA and compared with Ig levels in 50 patients with HIDS. Genetic linkage of HIDS with the chromosome 16 polymorphic locus RT70, currently used for refined localization of the FMF susceptibility gene (MEFV), was studied in 9 HIDS families (18 patients) using polymerase chain reaction amplification and gel electrophoresis. RESULTS: The main clinical features distinguishing FMF from HIDS were lymphadenectomy, skin eruption, and symmetrical oligoarthritis in HIDS, and monoarthritis, peritonitis, and pleuritis in FMF. Increased IgG levels were found in 12 patients with FMF (17%), IgA in 16 (23%), IgM in 9 (13%), and IgD in 9 (13%), significantly lower than the prevalence reported for HIDS. We found no evidence for genetic linkage between HIDS and the chromosome 16 marker RT70. CONCLUSION: HIDS and FMF are different entities, clinically, immunologically, and genetically.

Chromosomes, Human, Pair 16↗
PubMed1996

Low-molecular-weight heparin during pregnancy and delivery: preliminary experience with 41 pregnancies.

OBJECTIVE: To describe experience with 41 pregnancies treated with the low-molecular-weight heparin enoxaparin. METHODS: The medical charts of 34 women (a total of 41 pregnancies) treated between January 1992 and March 1995 with the low-molecular-weight heparin enoxaparin were reviewed. Most patients (87.5%) received one daily 40-mg injection. In all cases, treatment was continued throughout labor, delivery, and the immediate postpartum period. RESULTS: Therapy was administered for 5-280 days (median 91). One case of a thromboembolic event was recorded during treatment. No systemic or local side effects were reported. During pregnancy, only one patient had mild vaginal bleeding, which resolved spontaneously while therapy was continued. There was no excessive intrapartum bleeding in any of these patients, whether delivered vaginally or abdominally. During treatment, 19 of the 34 patients underwent 24 surgical procedures, including 13 cesarean deliveries, without excessive bleeding. Epidural anesthesia was used during labor in nine of the patients, with no specific complications. The corrected perinatal mortality rate, (ie, the rate of fetal death after 24 weeks' gestation plus neonatal death, excluding a neonate with multiple anomalies) for those neonates delivered after 24 weeks' gestation was 2.7%. There were no cases of intraventricular hemorrhage in any of the neonates. CONCLUSION: This preliminary series, the largest reported to date, demonstrates the relative safety and efficacy of low-molecular-weight heparin therapy in pregnancy and delivery.

Adult↗
PubMed1996

The changing face of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a genetic disease characterized by painful febrile "attacks" of serositis and the development of amyloidosis. Although FMF has been extensively studied and described, new data have accumulated during the last decade. This report gives an update, focusing specifically on (1) newly characterized manifestations, such as acute scrotal "attacks," protracted febrile myalgia, and spondyloarthropathy; (2) progress made in the diagnosis and treatment of FMF-amyloidosis; (3) experience acquired with colchicine, establishing its safety in common practice, childhood, conception, and pregnancy; (4) colchicine's role in the prevention and treatment of FMF-amyloidosis; (5) new laboratory findings; and (6) new considerations in the differential diagnosis. The most important achievement in recent years, however, is the mapping of the FMF susceptibility gene to chromosome 16p, a finding that raises hopes for prompt cloning of the gene and elucidation of the mechanisms involved in FMF expression.

Cohort Studies↗
PubMed1996

Binding of human serum amyloid A (hSAA) and its high-density lipoprotein3 complex (hSAA-HDL3) to human neutrophils. Possible implication to the function of a protein of an unknown physiological role.

Serum amyloid A (SAA) is an acute-phase serum protein which exists in the body in a complex with high-density lipoprotein (HDL3). It is involved in chronic inflammation and neoplastic diseases in an as yet unknown manner. Toward an understanding of the possible physiological role of SAA we initiated a study of its association with blood proinflammatory cells with which it may interact functionally in vivo. In the following we describe the binding characteristics of recombinant human SAA to human neutrophils (polymorphonuclear leukocytes; PMNLs) and their plasma membranes. Scatchard analysis of rSAA binding and displacement curves revealed Kd in the nanomolar range. The C-terminal domain of the protein, i.e. amino acid residues 77-104, which might reside in serum following SAA degradation and amyloid A formation, was found to inhibit efficiently the binding of the whole protein to neutrophils. The interaction of SAA, and of its related peptides while complexed in HDL3, with human PMNs was also studied. The results suggest that SAA may be involved, in an as yet unknown manner, in the neutrophil-associated inflammatory mechanism.

Amino Acid Sequence↗