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Biomedical subjects

E Pras

Publications and source records attributed to E Pras.

At least 73 records · Page 4Linked to original sources
PubMed1996

Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2.

Carney complex is an autosomal dominant syndrome characterized by multiple neoplasias, including myxomas at various sites and endocrine tumors, and lentiginosis. The genetic defect(s) responsible for the complex remain(s) unknown. We studied 101 subjects, including 51 affected members, from 11 North American kindreds with Carney complex. Blood samples were collected from patients and their family members. Hospital records, photographs, and tissue specimens of deceased individuals were reviewed. DNA was extracted from blood samples, patient-derived cell lines, and/or paraffin-embedded tissues. Linkage analysis was performed with highly polymorphic microsatellite markers, distributed over areas of the human genome harboring the most likely candidate genes. The most prevalent clinical manifestation in patients with Carney complex was spotty skin pigmentation, similar to that observed in Peutz-Jeghers and other lentiginosis syndromes. Skin and cardiac myxomas, Cushing syndrome, and acromegaly were present in 62, 30, 31 and 8 percent of the patients, respectively. Linkage was obtained for three markers on the short arm of chromosome 2 (2p16), with a maximum two-point lod score of 5.97 at theta = 0.03 for the marker CA-2 (odds in favor of linkage 10(6):1. The flanking markers CA7 and D2S378 defined a region of approximately 6.4 cM that is likely to contain the gene(s) associated with Carney complex. Candidate genes in the proximity, including the propiomelanocortin and the DNA-mismatch repair hMSH2 genes, were excluded. We conclude that the genetic defect(s) responsible for Carney complex map(s) to the short arm of chromosome 2 (2p16). This region has exhibited cytogenetic aberrations in atrial myxomas associated with the complex, and has been characterized by microsatellite instability in human neoplasias.

Canada↗
PubMed1996

Isolated limb perfusion of an irradiated foot with tumor necrosis factor, interferon, and melphalan.

A 57-year-old woman presented with the second recurrence of a high-grade malignant fibrous histiocytoma of the right foot, following previous local resection plus curative adjuvant radiotherapy. The first recurrence of the lesion was treated by isolated limb perfusion with cisplatin; the second recurrence was treated by isolated limb perfusion with tumor necrosis factor, interferon, and melphalan. The tumor and the area that had been irradiated showed a bluish color a few hours after tumor necrosis factor perfusion. Amputation of the right foot and leg below the knee had to be performed because of severe necrosis.

Amputation, Surgical↗
PubMed1996

Concurrent chemo- and radiotherapy in patients with locally advanced carcinoma of the cervix.

BACKGROUND: The feasibility of concurrent chemotherapy and radiotherapy for advanced primary carcinoma of the cervix was evaluated and the results were compared to historical controls. PATIENTS AND METHODS: In a single institution study, patients (n = 74) with primary cervical carcinoma received 3 cycles carboplatin/5-fluorouracil concurrent with radiotherapy followed by salvage hysterectomy (group I). Treatment results were compared with those of a historical control group (n = 39) (group II), treated similarly but without chemotherapy. RESULTS: In group I median follow-up is 28 months (12-68+) and in group II 23 months (14-90+ months). The 5-year overall survival, progression-free survival and local recurrence free survival for group I and II are, respectively, 69% versus 38% (P < 0.003), 67% versus 38% (P < 0.005) and 84% versus 43% (P < 0.0001). Two patients in each group developed posttreatment enteritis. CONCLUSIONS: Radiotherapy with concurrent carboplatin and 5-fluorouracil resulted in a better overall survival, disease free survival and local disease free survival compared to historical controls. The toxicity of this schedule did not exceed that of radiation alone in historical controls.

Adult↗
PubMed1996

Cytogenetic and microsatellite alterations in tumors from patients with the syndrome of myxomas, spotty skin pigmentation, and endocrine overactivity (Carney complex).

Carney complex (CC) is a familial multiple neoplasia and lentiginosis syndrome, transmitted in an autosomal dominant manner. It is the only familial form of cardiac and skin myxomas known and includes endocrine neoplasms causing Cushing's syndrome [primary pigmented nodular adrenocortical disease (PPNAD)] and acromegaly (GH-producing adenoma). The molecular defect leading to CC remains unknown, but was recently mapped to chromosome 2p16 by linkage analysis. This region has exhibited cytogenetic aberrations in atrial myxomas from patients with CC and harbors the hMSH2 and hMSH6 genes, which are involved in the preservation of microsatellite length stability of replicating human cells. In the present study, we examined 15 tumor and normal tissue specimens from 13 patients with CC [GH-producing adenoma (n = 1), adrenal tumors (PPNAD, n = 8), thyroid cancer (n = 1), normal adrenal gland (n = 1)] and 4 cultured cell lines [heart myxoma (n = 3) and eyelid myxoma (n = 1)]. Chromosome analysis was obtained by standard cytogenetic techniques. One of the myxoma cell lines and 3 PPNAD specimens contained multiple telomeric associations (tas). The normal adrenocortical tissue from a patient with PPNAD contained no apparent chromosomal anomalies, whereas the neighboring PPNAD tissue demonstrated tas. DNA was extracted from peripheral blood, tumor cell lines, and frozen or paraffin-embedded tissues and subjected to PCR amplification with primers from 64 microsatellite locations covering chromosomes 1 and 3-22 and 14 loci covering chromosome 2. The alterations detected were loss and gain of heterozygosity (LOH and GOH; 49% and 26%, respectively), deletions of both alleles (DEL; 10%), and microsatellite length instability (15%). GOH and LOH were the most frequent changes, with telomeric markers significantly over-represented (P < 0.05). Chromosomes 6, 11, 22, 10, and 19 demonstrated mostly LOH, GOH, or DEL in over 40% of the informative loci tested (73%, 59%, 47%, 46%, and 44%, respectively), whereas markers on chromosome 2 showed only microsatellite length instability (10%). The degree of genomic instability and its type were independent of tumor type (P > 0.1). We conclude that tumors and tumor cell lines from patients with CC demonstrate significant genomic, but not microsatellite length, instability. Thus, the CC gene(s) on chromosome 2p16 is different from the hMSH2 and hMSH6 genes and has dominant, rather than recessive, tumorigenic function. This gene(s) appears to be involved in the regulation of genomic stability of dividing cells, in particular the structure of telomeres in replicating chromosomes and/or the function of the mitotic apparatus.

Acromegaly↗
PubMed1996

Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246.

This report presents refined genetic mapping data for the gene causing familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation. We sampled 65 Jewish, Armenian, and Arab families and typed them for eight markers from chromosome 16p. Using a new algorithm that permits multipoint calculations for a dense map of markers in consanguineous families, we obtained a maximal LOD score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype at D16S283-D16S94-D16S246 was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Moreover, the 2.5-kb allele at D16S246 was significantly associated with FMF in Moroccan and non-Moroccan Jews but not in Armenians or Arabs. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, we analyzed the Moroccan linkage-disequilibrium data by using Luria-Delbrück formulas and simulations based on a Poisson branching process. These methods place the FMF susceptibility gene within 0.305 cM of D16S246 (2-LOD-unit range 0.02-0.64 cM).

Algorithms↗
PubMed1995

The importance of the groin node status for the survival of T1 and T2 vulval carcinoma patients.

The purpose of this study was to analyze (1) the prognostic factors for survival of T1 and T2 carcinoma patients and (2) the impact of the initial groin node status for the time to recurrence and site of recurrence. We performed a follow-up study on 190 women with a T1 or T2 squamous cell carcinoma of the vulva. Data were obtained on age and general medical condition, the clinical and histological characteristics of the primary tumor and the inguinofemoral lymph nodes, treatment, recurrences, and survival. The standard treatment was radical vulvectomy with bilateral inguinofemoral lymphadenectomy supplemented with postoperative radiotherapy to the primary site, groin, and pelvic side walls if groin metastases were present. Compared to patients without lymph node metastases in the groin, the relative risk of dying within a given time period was estimated to be 2.47 (limits of the 95% confidence interval: 1.24, 4.93) and 9.69 (3.90, 24.03) for patients with unilateral and bilateral node metastases, respectively. The number of metastatic lymph nodes or their intra- or extranodal growth was not associated with survival. The relative risk of dying within a given time period was 2.71 (1.36, 5.40) for patients with a T2 tumor compared to those with a T1 tumor and 2.37 (1.31, 4.31) for patients with vasoinvasive growth compared to those without capillary-lymphatic tumor infiltration. Tumor thickness, differentiation grade, and multifocal growth did not determine survival. In the multivariate Cox regression analysis, the presence of inguinofemoral lymph node metastases proved to be the most important prognostic factor for patients' survival. Of the 119 patients who underwent lymphadenectomy but in whom no groin node metastases were found, 6 (5%) patients manifested an early recurrence (i.e., residual cancer or a recurrence within 2 years after the diagnosis). In contrast, of the 51 patients with histologically documented groin node metastases, 15 (29.4%) manifested an early recurrence and these recurrences appeared equally distributed over the primary site and other sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Mutations in the SLC3A1 transporter gene in cystinuria.

Cystinuria is an autosomal recessive disease characterized by the development of kidney stones. Guided by the identification of the SLC3A1 amino acid-transport gene on chromosome 2, we recently established genetic linkage of cystinuria to chromosome 2p in 17 families, without evidence for locus heterogeneity. Other authors have independently identified missense mutations in SLC3A1 in cystinuria patients. In this report we describe four additional cystinuria-associated mutations in this gene: a frameshift, a deletion, a transversion inducing a critical amino acid change, and a nonsense mutation. The latter stop codon was found in all of eight Ashkenazi Jewish carrier chromosomes examined. This report brings the number of disease-associated mutations in this gene to 10. We also assess the frequency of these mutations in our 17 cystinuria families.

Americas↗
PubMed1995

[Cystinuria and urolithiasis].

Cystinuria is a hereditary metabolic disorder which causes urinary lithiasis. Patients with cystinuria present at an earlier age (17 years), and with larger stones than patients with other types of urinary stones. As a result of frequent formation of new stones and multiple operations, many patients suffer from obstructive nephropathy and deterioration of kidney function. During the past decade we treated and followed 51 patients with cystine urolithiasis from 39 families. Screening disclosed another family member with cystinuria in 56% of the cases. The diagnosis of cystinuria was only made an average of 2 years after a patient first presented. In the group 12 kidneys had been removed due to various complications and in 7 kidneys there was significant deterioration of function. Each patient underwent a mean of 5.8 surgical interventions, including open operations, extra-corporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotripsy (PCNL) and urethroscopy, but most still had residual stone fragments. To prevent complications from cystine urolithiasis every effort should be made to detect the disease early, including screening of families of patients with cystinuria and close follow-up of all family members. Early detection of stones, before they become large makes noninvasive treatment with ESWL possible, whereas large stones require PCNL. Patients should be urged to maintain high urine outputs and to continue uninterrupted treatment with penicillamine or tiopronin, and urinary alkalinization.

Cystinuria↗
PubMed1994

T-cell subsets in acute psychotic schizophrenic patients.

Two-color flow cytometric analysis was performed on peripheral blood lymphocytes of 16 untreated schizophrenic patients during an acute psychotic attack and 16 healthy control subjects to evaluate differences in T-cell subpopulations. In schizophrenic patients, we observed decrease in CD4+ 2H4+ (suppressor-inducer) and CD8+ 2H4+ (suppressor-effector) T-cell subsets. The selective loss of 2H4+ cell markers both on helper and suppressor T cells was not correlated to the severity of the acute psychosis. Our results may indicate a mechanism of an immune disequilibrium in schizophrenic patients during an acute psychotic attack.

Acute Disease↗
PubMed1994

Localization of a gene causing cystinuria to chromosome 2p.

Cystinuria is an autosomal recessive disorder of amino acid transport. It is a common hereditary cause of kidney stones worldwide, and is associated with significant morbidity. In 17 affected families, we found linkage between cystinuria and three chromosome 2p markers. Maximal two-point lod scores between cystinuria and D2S119, D2S391 and D2S288 were 8.23 (theta = 0.07), 3.73 (theta = 0.15) and 3.03 (theta = 0.12), respectively. Analysis of recombinants and multipoint linkage data indicated that the most likely order is cen-D2S391-D2S119-cystinuria-D2S177-tel. We also observed high rates of homozygosity for markers in this chromosomal region among 11 affected offspring of consanguineous marriages. Based on its map position and function, the recently cloned SLC3A1 amino acid transporter gene is a primary candidate gene for this disease.

Amino Acid Transport Systems, Basic↗
PubMed1994

Pacemaker endocarditis. Report of 44 cases and review of the literature.

We conducted a retrospective study to characterize the clinical course, microbiologic spectrum, and risk factors for endocarditis and for associated mortality in a large series of patients with documented pacemaker endocarditis. Using a computerized search through the medical records of 10 major hospitals in Israel from 1982 to 1992, and carefully reviewing the charts, we identified 44 patients with pacemaker endocarditis. The cases were categorized as definite (n = 25), probable (n = 12), or possible (n = 7) infective endocarditis based on strict case definition. Fever and chills were the most common symptoms. Increased ESR, leukocytosis, microscopic hematuria, and anemia were the most common laboratory findings. A relatively high proportion of the patients were diabetic. The most common source of endocarditis was infection acquired by the placement procedure or infection of the pacemaker pouch. Demographic, clinical, and laboratory features were similar to those of endocarditis patients of a similar age range without pacemakers, although the frequency of fever and chills was higher in our patients than in those patients and splenomegaly, vascular embolic phenomena, and new or changing murmurs were rare in our patients. The major pathogens were Staphylococcus aureus and Staphylococcus epidermidis, similar to other series of pacemaker-associated bacteremia and similar to the microbiologic findings of early prosthetic-valve endocarditis. However, this microbiologic profile is different from that of native-valve endocarditis. Although the present series did not show a statistically significant advantage to electrode removal over conservative treatment, when analyzed together with pooled data from other studies, it suggests that the surgical approach is preferable.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Evidence for linkage of the gene causing familial Mediterranean fever to chromosome 17q in non-Ashkenazi Jewish families: second locus or type I error?

Familial Mediterranean fever (FMF) is an autosomal recessive disorder of unknown pathogenesis, characterized by recurrent, self-limited attacks of fever with synovitis, peritonitis, or pleurisy. Using DNAs from affected Israeli families, we have recently mapped the gene causing FMF (designated MEF) to the short arm of chromosome 16, with two-point lod scores in excess of 20. In this report we consider the possibility of a second FMF susceptibility locus. Before discovering linkage to markers on chromosome 16, we had found suggestive evidence for linkage to chromosome 17q, with the following maximal two-point lod scores: D17S74 (pCMM86), Z = 2.47, (theta = 0.20); D17S40 (pLEW101), Z = 2.15 (theta = 0.15); D17S35 (CRI-pP3-1), Z = 1.78 (theta = 0.15); D17S46 (pLEW108), Z = 1.69 (theta = 0.18), D17S254, Z = 2.30 (theta = 0.20). Moreover, multipoint linkage analysis using D17S74 and D17S40 as fixed loci gave Z = 3.27 approximately 10 centimorgans (cM) telomeric to D17S40. Data with the chromosome 17 markers alone in our families suggested locus heterogeneity. Nevertheless, our families were not separable into complementary subsets showing linkage either to chromosome 16 or to chromosome 17. We also examined the possibility that the positive lod scores for chromosome 17 might reflect a secondary, modifying locus. By several measures of disease severity, families with positive lod scores for chromosome 17 loci had no worse disease than those with negative lod scores for these loci. We conclude that chromosome 17 does not encode a major FMF susceptibility gene for some of the families, nor does it encode a disease-modifying gene. Rather, it would appear that linkage to chromosome 17 is a "false positive" (type I) error. These results reemphasize the fact that a lod score of 3.0 corresponds to a posterior probability of linkage of 95%, with an attendant 1 in 20 chance of observing a false positive.

Blotting, Southern↗
PubMed1993

Familial Mediterranean fever (FMF) in Moroccan Jews: demonstration of a founder effect by extended haplotype analysis.

Familial Mediterranean fever (FMF) is an autosomal recessive disease causing attacks of fever and serositis. The FMF gene (designated "MEF") is on 16p, with the gene order 16cen-D16S80-MEF-D16S94-D16S283-D16S291-++ +16pter. Here we report the association of FMF susceptibility with alleles as D16S94, D16S283, and D16S291 among 31 non-Ashkenazi Jewish families (14 Moroccan, 17 non-Moroccan). We observed highly significant associations at D16S283 and D16S291 among the Moroccan families. For the non-Moroccans, only the allelic association at D16S94 approached statistical significance. Haplotype analysis showed that 18/25 Moroccan FMF chromosomes, versus 0/21 noncarrier chromosomes, bore a specific haplotype for D16S94-D16S283-D16S291. Among non-Moroccans this haplotype was present in 6/26 FMF chromosomes versus 1/28 controls. Both groups of families are largely descended from Jews who fled the Spanish Inquisition. The strong haplotype association seen among the Moroccans is most likely a founder effect, given the recent origin and genetic isolation of the Moroccan Jewish community. The lower haplotype frequency among non-Moroccan carriers may reflect differences both in history and in population genetics.

Alleles↗
PubMed1993

Refined mapping of the gene causing familial Mediterranean fever, by linkage and homozygosity studies.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. We recently reported linkage of the gene causing FMF (designated "MEF") to two markers on chromosome 16p. To map MEF more precisely, we have now tested nine 16p markers. Two-point and multipoint linkage analysis, as well as a study of recombinant haplotypes, placed MEF between D16S94 and D16S80, a genetic interval of about 9 cM. We also examined rates of homozygosity for markers in this region, among offspring of consanguineous marriages. For eight of nine markers, the rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEF more precisely on the basis of homozygosity rates alone would be difficult, for two reasons: First, the high FMF carrier frequency increases the chance that inbred offspring could have the disease without being homozygous by descent at MEF. Second, several of the markers in this region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location.

Base Sequence↗