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M Pras

Publications and source records attributed to M Pras.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pregnancy and amyloidosis: II. Suppression of amyloidogenesis during pregnancy.

The observation of a deleterious effect of pregnancy on kidney function in amyloidosis of familial Mediterranean fever suggests that pregnancy may enhance amyloidogenesis. To determine whether pregnancy may indeed affect amyloidogenesis, pregnant mice were made amyloidotic by administration of amyloid-enhancing factor (AEF) and AgNO3 at different points in time from conception, and amyloid- deposition was studied with the crush-and-smear technique. A possible effect of exogenous female sex hormones (beta-estradiol and progesterone) on amyloidogenesis was studied by administration of these hormones during amyloid induction in nonpregnant female mice. Amyloidogenesis was found to be significantly suppressed in mice during pregnancy. The reduction was possibly related to the effect of pregnancy on the inflammatory stimulus (AgNO3) and not on the administered AEF. Exogenous estrogen and progesterone failed to inhibit amyloidogenesis in nonpregnant mice. These findings suggest that pregnancy may suppress amyloidogenesis in mice. The suppression is caused by an anti-inflammatory effect of pregnancy. Estrogen and progesterone are probably unrelated to this finding.

Amyloidosis↗
PubMed2000

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Journal Article↗
PubMed2000

Protracted febrile myalgia of familial Mediterranean fever. Mutation analysis and clinical correlations.

Protracted febrile myalgia (PFM) is a rare form of vasculitic disease that affects patients with familial Mediterranean fever (FMF). Mutation analysis performed in 15 patients who suffered from this disorder showed that 9 of the 15 patients were homozygous for M694V. FMF in these 9 patients was associated with more severe symptoms compared to a group of 30 M694V homozygous FMF patients without PFM.

Adolescent↗
PubMed2000

Benefits and risks of minocycline in rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory disease affecting about 1% of the adult population. The pathophysiology of rheumatoid arthritis remains incompletely understood. An infectious aetiology of the disease has long been postulated, but not proved. Despite insufficient evidence for the infectious nature of this disorder, several antibacterials, such as sulfa compounds, tetracyclines and rifampicin, have been investigated in the treatment of rheumatoid arthritis. In the last few years, minocycline, a semi-synthetic derivative of tetracycline, has been extensively studied as a therapeutic agent for rheumatoid arthritis. The antirheumatic effect of minocycline can be related to its immunomodulatory and anti-inflammatory, rather than to its antibacterial properties. Its efficacy in rheumatoid arthritis has been reported in 2 open trials and in 3 double-blind controlled studies. The first 2 double-blind studies, 1 in The Netherlands and 1 in the US, were performed in patients with advanced disease. Both studies showed a modest, but statistically significant improvement in the clinical parameters of disease activity and in the erythrocyte sedimentation rate in the minocycline-treated patients. The US study also reported that patients in the minocycline group developed fewer erosions than those in the placebo group. This finding supports the role of minocycline as a disease modifying agent. The common adverse effects of minocycline reported in these 2 studies included gastrointestinal adverse effects, dizziness, rash and headaches. Less common adverse effects were intracranial hypertension, pneumonitis, persistent skin and mucosal hyperpigmentation, lupus-like syndrome and acute hepatic injury. The third double-blind study enrolled only seropositive rheumatoid arthritis patients with early disease (less than 1 year duration), and showed very encouraging results of significant improvement in the disease activity parameters in the minocycline treated group of patients. The same authors later reported that about half of these patients were in or near remission after 3 years of follow up. No adverse effects were reported in this study. Summarising the data of these 3 double-blind studies, we may conclude that minocycline may be beneficial in patients with rheumatoid arthritis, especially when given early in the disease course or in patients with a mild disease.

Animals↗
PubMed2000

Genotype-phenotype assessment of common genotypes among patients with familial Mediterranean fever.

OBJECTIVE: To study genotype-phenotype correlation for the 4 most common genotypes found among patients with familial Mediterranean fever (FMF). METHODS: Thirty patients with the M694V/M694V genotype, 32 with M694V/V726A genotype, 25 with M694V/E 148Q genotype, and 21 with V726A/V726A genotype were assessed for various clinical manifestations of FMF, and overall disease severity. RESULTS: Patients with the M694V/M694V genotype were found to have an earlier age of onset, higher frequency of joint involvement, higher frequency of erysipelas-like erythema, and required higher doses of colchicine to control the disease compared to the other 3 genotypes. CONCLUSION: The M694V/M694V genotype is associated with more severe disease compared to other common genotypes in patients with FMF.

Age of Onset↗
PubMed1999

Late-onset familial Mediterranean fever (FMF): a subset with distinct clinical, demographic, and molecular genetic characteristics.

To determine the prevalence and characterize demographic, clinical, and genetic features of familial Mediterranean fever (FMF) of late onset, all patients experiencing their first FMF attack at age 40 years or more were identified using the computerized registry of our FMF clinic, and then thoroughly interviewed and examined. The control group consisted of 40 consecutive FMF patients, who arrived at the FMF clinic for their regular follow-up visit and were 40 years of age or older at the time of the examination. The severity of the disease in patients and controls was determined using a modified score, developed previously. Mutational analysis in the FMF gene was performed using a commercial kit. Only 20 of 4000 (0.5%) patients had late-onset FMF. These patients were mostly men, of non-North African origin, P < 0.05 compared to controls. All had abdominal attacks and in most these were the only manifestation of their disease, P < 0.001. None had chronic or prolonged manifestations of FMF, for example, amyloidosis, chronic arthritis, or protracted myalgia, P < 0.001. The response to treatment was good despite using low colchicine dose, P < 0.05. The overall severity score indicated a mild disease, P < 0.001. Mutational analysis revealed absence of M694V homozygosity, P < 0.01, compared to our regular FMF population. We conclude that the onset of FMF in a late age defines a milder form of disease with typical clinical, demographic, and molecular genetic characteristics.

Adult↗
PubMed1999

Biochemical assay for amyloid beta deposits to distinguish Alzheimer's disease from other dementias.

Biochemical markers for Alzheimer's disease (AD) are of great value for precise diagnosis and in studies of the pathogenetic processes of this disease. A new biochemical assay allowing to differentiate AD from other forms of dementia is described. The assay is based on the extraction of amyloid beta (A beta) from milligram amounts of brain tissue by using 20% acetonitrile in 0.1% trifluoroacetic acid and its detection by Western blotting. The presence of the 4 kDa A beta was demonstrated in all cases of AD (n = 8) that were diagnosed by the independent histopathological examination of the postmortem tissues. No A beta was found in tissue extracts from seven out of eight cases of other forms of dementia. In contrast to other biochemical techniques of A beta detection in brain, the developed assay is simple; it does not require any special equipment and allows detection of A beta using milligram amounts of brain tissue.

Alzheimer Disease↗
PubMed1999

Pregnancy and amyloidogenesis: I. Offspring of amyloidotic mice are not predisposed to develop amyloidosis.

Amyloid enhancing factor (AEF) is a substance formed during amyloidogenesis that accelerates amyloid deposition in tissues. The administration of AEF followed by AgNO3 (inflammatory stimulus) to mice results in amyloidosis within 6 days. The purpose of the study was to determine whether the offspring of amyloidotic mice are exposed to maternal AEF during pregnancy and therefore become predisposed to the development of amyloidosis on inflammatory stimulus. To that end female mice were made amyloidotic by the administration of AEF and AgNO3, made pre-amyloidotic (a condition associated with self-generation of AEF) with a short course of casein, or treated with exogenous AEF without AgNO3; then mating and conception took place. The possible priming of offspring with maternal AEF was studied by the administration of AgNO3 alone (without AEF) to the offspring and the determination of the presence of amyloid deposits in their spleens. Despite the long-term effect of AEF and its high activity, amyloidosis did not develop in any of the studied offspring, implying that the newborn mice were not primed by maternal AEF. These findings suggest that amyloidotic mothers do not predispose their offspring to the risk of developing amyloidosis, probably because maternal AEF does not cross the placenta.

Amyloidosis↗
PubMed1999

Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: clinical characteristics and outcome.

We report 28 patients (20 male) with a syndrome characterized by abrupt onset of fever, malaise, aphthous stomatitis, tonsillitis, pharyngitis, and cervical adenopathy (PFAPA syndrome). Episodes of fever occurred at intervals of 5.1 +/- 1.3 weeks beginning at the age of 4.2 +/- 2.7 years. Fever, malaise, tonsillitis with negative throat cultures, and cervical adenopathy were reported in all 28 patients, aphthae in 19, headache in 5, abdominal pain in 5, and arthralgia in 3. Mild hepatosplenomegaly was observed in 6 patients. Mild leukocytosis, elevation of the erythrocyte sedimentation rate, and fibrinogen were found during attacks. These episodes of illness resolved spontaneously in 4.3 +/- 1.7 days. Serum IgD was found elevated (>100 U/mL) in 12 of the 18 patients tested (140.2 +/- 62.4 U/mL). Affected children grow normally, have no associated diseases, and have no long-term sequelae. Attacks were aborted by a single dose of oral prednisone (2 mg/kg) at the beginning of the attack in all 15 patients in whom this medication was prescribed. In 9 patients the syndrome has completely resolved (beginning at the age of 2.9 +/- 1.3 and lasting 8 +/- 2.5 years). In 3 other patients complete resolution of the attacks occurred after tonsillectomy was performed. PFAPA is sporadic, and no ethnic predilection was found. Increased awareness of the clinical syndrome has resulted in more frequent diagnosis and adequate treatment.

Age of Onset↗
PubMed1999

Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT.

Cystinuria (MIM 220100) is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids. Mutations in SLC3A1, encoding rBAT, cause cystinuria type I (ref. 1), but not other types of cystinuria (ref. 2). A gene whose mutation causes non-type I cystinuria has been mapped by linkage analysis to 19q12-13.1 (Refs 3,4). We have identified a new transcript, encoding a protein (bo, +AT, for bo,+ amino acid transporter) belonging to a family of light subunits of amino acid transporters, expressed in kidney, liver, small intestine and placenta, and localized its gene (SLC7A9) to the non-type I cystinuria 19q locus. Co-transfection of bo,+AT and rBAT brings the latter to the plasma membrane, and results in the uptake of L-arginine in COS cells. We have found SLC7A9 mutations in Libyan-Jews, North American, Italian and Spanish non-type I cystinuria patients. The Libyan Jewish patients are homozygous for a founder missense mutation (V170M) that abolishes b o,+AT amino-acid uptake activity when co-transfected with rBAT in COS cells. We identified four missense mutations (G105R, A182T, G195R and G295R) and two frameshift (520insT and 596delTG) mutations in other patients. Our data establish that mutations in SLC7A9 cause non-type I cystinuria, and suggest that bo,+AT is the light subunit of rBAT.

Amino Acid Sequence↗
PubMed1999

Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population.

Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever with serositis or synovitis. The FMF gene (MEFV) was cloned recently, and four missense mutations were identified. Here we present data from non-Ashkenazi Jewish and Arab patients in whom we had not originally found mutations and from a new, more ethnically diverse panel. Among 90 symptomatic mutation-positive individuals, 11 mutations accounted for 79% of carrier chromosomes. Of the two mutations that are novel, one alters the same residue (680) as a previously known mutation, and the other (P369S) is located in exon 3. Consistent with another recent report, the E148Q mutation was observed in patients of several ethnicities and on multiple microsatellite haplotypes, but haplotype data indicate an ancestral relationships between non-Jewish Italian and Ashkenazi Jewish patients with FMF and other affected populations. Among approximately 200 anonymous Ashkenazi Jewish DNA samples, the MEFV carrier frequency was 21%, with E148Q the most common mutation. Several lines of evidence indicate reduced penetrance among Ashkenazi Jews, especially for E148Q, P369S, and K695R. Nevertheless, E148Q helps account for recessive inheritance in an Ashkenazi family previously reported as an unusual case of dominantly inherited FMF. The presence of three frequent MEFV mutations in multiple Mediterranean populations strongly suggests a heterozygote advantage in this geographic region.

Amino Acid Substitution↗
PubMed1999

Pulmonary associations in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a hereditary periodic fever syndrome expressed by acute episodes of fever and painful manifestations. In this report, the pulmonary manifestations of FMF are reviewed, the most prominent of which are chest attacks due to pleuritis. Nephropathic amyloidosis of the AA type, which complicates FMF in most untreated patients, may progress to affect other organs, including the lungs, but this rarely produces noticeable symptoms. The common association between FMF and vasculitis makes pulmonary hemorrhage, infarction, or infiltrates highly possible. These complications, however, have been reported only rarely. Asthma was found to occur less often than expected in patients with FMF, but methodologic faults make this finding doubtful. Finally, the occurrence of mesothelioma in five patients with FMF who were not exposed to asbestos suggests a role for recurrent FMF serositis in the pathogenesis of this malignancy.

Amyloidosis↗
PubMed1999

MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a major cause of AA amyloidosis. Recently, the gene (MEFV) causing this disease was cloned and 16 disease associated mutations have been described. We have analyzed 178 FMF patients, 30 of whom also suffered from amyloidosis, for 4 mutations in MEFV. Mutations were identified in 29 of the FMF amyloidosis patients. 27 FMF amyloidosis patients were homozygous for M694V. One patient was found to be homozygous for both V726A and E148Q. In another patient E148Q and V726A were found on one allele, while V726A was found on the second allele. Amyloidosis was far more common among patients homozygous for M694V compared to patients with other mutations (P < 0.0001). In 3 patients homozygous for M694V, amyloidosis was the sole manifestation of the disease.

Amyloidosis↗
PubMed1999

Activation of the cytokine network in familial Mediterranean fever.

OBJECTIVE: To elucidate the role of cytokines in the pathogenesis of familial Mediterranean fever (FMF), an inherited disease characterized by attacks of serosal membrane inflammation. METHODS: Blood samples were obtained from patients with FMF during attacks and remission. The cytokine concentrations in plasma and in supernatants from whole blood stimulated by bacterial lipopolysaccharide (LPS) were determined. RESULTS: There were 27 patients with FMF, of whom 8 were studied during attacks, 9 during remission and 10 during both attack and remission. FMF attacks did not affect levels of plasma tumor necrosis factor-alpha (TNF-alpha) or interleukin 1beta (IL-1beta). In contrast, compared to remission, FMF attacks were associated with significantly higher mean levels of plasma IL-6 [8.4 pg/ml, 95% confidence interval (CI) 7.8-8.9 in remission vs 59 pg/ml, CI 21.4-96.7 during attacks; p=0.0005], sTNFr p55 (1.3 ng/ml, CI 1.2-1.4, vs 1.98 ng/ml, CI 1.6-2.3; p=0.005), and sTNFr p75 (2.9 ng/ml, CI 2.5-3.3, vs 4.09 ng/ml, CI 3.2-4.9; p=0.0249). The TNF-alpha, IL-1beta, and IL-6 content in supernatants derived from LPS stimulated blood cells was not modified by the attacks of FMF. Significant lower TNF-alpha release in LPS stimulated whole blood was detected in patients who were sampled in a later stage of the attacks (r=-0.54, p=0.047). CONCLUSION: Our results suggest that the cytokine network is activated during attacks of FMF. IL-6 appears to play an important role in the evolution of FMF attacks. Whether TNF-alpha or IL-1beta has a function in initiating the attacks remains to be established.

Acute Disease↗
PubMed1998

Biochemical and clinical studies in Libyan Jewish cystinuria patients and their relatives.

Cystinuria is a hereditary disorder manifested by the development of kidney stones. Three subtypes of the disease have been described, based on urinary excretion of cystine and the dibasic amino acids in heterozygotes, and oral loading tests in homozygotes. Cystinuria is very common among Libyan Jews living in Israel. Recently, we mapped the disease-causing gene in Libyan Jews to 19q, and have shown a very strong founder effect. In this report we present the results of biochemical and clinical studies performed on Libyan Jewish cystinuria patients and members of their families. High levels of cystine and the dibasic amino acids in heterozygotes support previous data that cystinuria in Libyan Jews is a non-type I disease. Oral loading tests performed with lysine showed some degree of intestinal absorption, but less than in normal controls. Previous criteria for determining the disease type, based solely on urinary amino acid levels, proved useless due to a very wide range of cystine and the dibasic amino acids excreted by the heterozygotes. Urinary cystine levels were useful in distinguishing between unaffected relatives and heterozygotes, but were unhelpful in differentiating between heterozygotes and homozygotes. Urinary levels of ornithine or arginine, and the sum of urinary cystine and the dibasic amino acids, could distinguish between the last two groups. Among stone formers, 90% were homozygotes and 10% were heterozygotes; 15% of the homozygotes were asymptomatic.

Chromosome Mapping↗
PubMed1998

Clinical differences between North African and Iraqi Jews with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disease causing attacks of fever and serositis. The gene causing this disease, designated MEFV, was mapped to the short arm of chromosome 16, but has not yet been cloned. North African and Iraqi Jews constitute the two largest population groups suffering from the disease in Israel. In this report we compared the severity of the disease between these two populations. North African Jews were found to have a more severe disease manifested by an earlier age of onset, an increase in frequency and severity of joint involvement, a higher incidence of erysipelas-like erythema, and a higher dose of colchicine required to control symptoms. The involvement of additional genes, environmental factors, and different mutations in MEFV, may explain the clinical variation in disease severity between these two population groups.

Adult↗