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Biomedical subjects

Z Meiner

Publications and source records attributed to Z Meiner.

At least 37 records · Page 2Linked to original sources
PubMed1995

Complete penetrance of Creutzfeldt-Jakob disease in Libyan Jews carrying the E200K mutation in the prion protein gene.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a prion disease which is manifest as a sporadic, inherited, and transmissible neurodegenerative disorder. The mean age at onset of CJD is approximately 60 years, and as such, many people destined to succumb undoubtedly die of other illnesses first. The delayed onset of CJD has complicated the analysis of inherited forms of the illness and led to the suggestion that mutations in the prion protein (PrP) gene are necessary but not sufficient for prion disease despite genetic linkage; indeed, an environmental factor such as a ubiquitous virus has been proposed as a second necessary factor. MATERIALS AND METHODS: To examine what appeared to be incomplete penetrance, we applied a life-table analysis to clinical and pedigree data from a cluster population of Libyan Jews in which the E200K mutation is prevalent. The study population included 42 affected and 44 unaffected members of 13 Libyan Jewish families, all of whom possessed the E200K mutation. RESULTS: The calculated value using life table analysis is 0.77 at age 70 which increases to 0.89 if a mutation carrier survives to age 80 and 0.96 if age 80 is surpassed. CONCLUSIONS: These data argue that the E200K mutation alone is sufficient to cause prion disease and does so in an age-dependent manner.

Adolescent↗
PubMed1994

Mutation in codon 200 and polymorphism in codon 129 of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease.

Various mutations in the prion protein (PrP) gene are associated with Creutzfeldt-Jakob disease (CJD), a transmissible fatal neurodegenerative disorder. Among Libyan Jews, CJD is a familial disease with an incidence about 100 times higher than the worldwide population. CJD in this community segregates with a point mutation at codon 200 of the PrP gene which causes the substitution of lysine for glutamate. This mutation was found in all definitely affected individuals and yields a maximum lod score of 4.85. Some healthy elderly mutation carries above 65 years of age were identified, suggesting partial penetrance. Homozygous patients have the same disease pattern and age of onset as heterozygous patients, which argues that CJD associated with the codon 200 lysine mutation is a true dominant disorder. In the caucasian population, Palmer et al. (1991) reported an association between homozygosity in a polymorphic site at codon 129 of the PrP gene, coding for either valine or methionine, with a tendency to acquire the sporadic or iatrogenic forms of CJD, as well as with disease age of appearance in the genetic type. The incidence of the polymorphism at codon 129 in the control Libyan population is similar to the one found in the caucasian population. In the Libyan CJD patients, the codon 200 mutation is within a Met129-encoding allele. The incidence of the Met allele is significantly higher in the affected pedigrees than in the control Libyan population; however, no difference was detected between CJD patients, codon 200 healthy carriers, and their normal family members.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Genetics and biochemistry of Creutzfeldt-Jakob disease in Libyan Jews.

A focus of Creutzfeldt-Jakob disease (CJD) among Jews from Libyan origin was identified in Israel 20 years ago. The incidence of the disease in this ethnic group is about 100 times more than in the worldwide population. The consumption of lightly cooked sheep brain has been invoked to explain the high incidence of CJD in this community. The discovery of mutations in the PrP gene which segregates with other familial prion diseases such as Gerstmann-Straussler syndrome (GSS) lead us to perform a molecular genetic study and compare it to an epidemiological survey among the Libyan community. The epidemiological data suggests a very high familial incidence of CJD in this population and a molecular genetic research elucidated that CJD segregates with a point mutation at codon 200 of the PrP gene resulting in the substitution of Lysine for Glutamate. This mutation was found in some 40 CJD patients of Libyan origin and was not found in one Moroccan Jew suffering from CJD. It was also absent in almost 100 healthy Libyan controls above the age of 60. This result strongly supports a genetic etiology for CJD pathogenesis in the Libyan Jewish community and disregards the previous culinary hypothesis. The disease is vertically transmitted in autosomal dominant inheritance with unknown penetrance. All our patients were heterozygote for the mutation except one homozygote patient. The course of the disease in this patient was identical to the heterozygote patients, strongly arguing that inherited CJD displays complete phenotypic dominance.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1994

Antibiotic induced meningitis.

Three patients with antibiotic induced meningitis, one following penicillin with seven episodes, are reported on--the first well documented description of penicillin induced meningitis. In this patient episodes of headache and nuchal rigidity appeared with and without CSF pleocytosis. Two patients had a total of five episodes of antibiotic induced meningitis after trimethoprim-sulphamethoxazole (co-trimoxazole) administration. The features common to all three patients were myalgia, confusion and low CSF glucose. CSF analysis was not a reliable method to differentiate antibiotic induced meningitis from partially treated bacterial meningitis.

Adolescent↗
PubMed1994

Cerebrotendinous xanthomatosis: molecular diagnosis enables presymptomatic detection of a treatable disease.

We report an early molecular diagnosis of cerebrotendinous xanthomatosis (CTX) in a Jewish Moroccan family with two affected siblings. The proband displayed characteristic manifestations of the disease, whereas a younger brother, homozygous for the mutant allele, was asymptomatic. Clinical studies in the younger patient disclosed mild cognitive impairment, peripheral neuropathy, and abnormal EEG. Elevated plasma cholestanol levels were evident in both affected patients, with documented normal levels in the molecularly diagnosed heterozygous family members. Molecular characterization of affected CTX families provides early diagnosis and treatment of homozygotes in the presymptomatic state as well as identification of heterozygotes, which is crucial for genetic counseling and for prenatal diagnosis.

Action Potentials↗
PubMed1993

Heparin-like molecules bind differentially to prion-proteins and change their intracellular metabolic fate.

PrPSc is the only known component of the scrapie prion. The difference between PrPSc and its normal isoform PrPc is probably conformational, since no difference has been found in the amino acid sequence or postranslational modifications between both proteins. Heparan sulfate (HS) has been shown to be a component of amyloid plaques in a number of diseases including the prion diseases. We now present evidence that PrP can specifically bind to heparin-like compounds and that this interaction might have a physiological significance. HS can increase the concentration of PrP in normal neuroblastoma cells, whereas low molecular weight heparin (LMWH) does not. In contrast, LMWH and other heparin-like molecules, excluding HS, can inhibit the synthesis of PrPSc in scrapie infected cells and reverse their phenotype back to normal as judged by measurement of PrPSc by immunoblotting and by infectivity experiments. Whether an interaction between PrP and glycosaminoglycans plays a direct role in the conversion of PrPc into PrPSc remains to be established.

Amino Acids↗
PubMed1993

Mutation and polymorphism of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease (CJD).

The inherited prion diseases are neurodegenerative disorders which are not only genetic but also transmissible. More than a dozen mutations in the prion protein gene that result in nonconservative amino acid substitutions segregate with the inherited prion diseases including familial Creutzfeldt-Jakob disease (CJD). In Israel, the incidence of CJD is about 1 case/10(4) Libyan Jews. A Lys200 substitution segregates with CJD and is reported here to be genetically linked to CJD with a lod score of > 4.8. Some healthy elderly Lys200 carriers > age 65 years were identified, suggesting the possibility of incomplete penetrance. In contrast, no linkage was found between the development of familial CJD and a polymorphism encoding either Met129 or Val129. All Libyan Jewish CJD patients with the Lys200 mutation encode a Met129 on the mutant allele. Homozygosity for Met129 did not correlate with age at disease onset or the duration of illness. The frequency of the Met129 allele was higher in the affected pedigrees than in a control population of Libyan Jews. The frequency of the Met129 and Val129 alleles in the control Libyan population was similar to that found in the general Caucasian population. The identification of three Libyan Jews homozygous for the Lys200 mutation suggests frequent intrafamilial marriages, a custom documented by genealogical investigations.

Age of Onset↗
PubMed1993

The effect of ventilatory muscle training on respiratory function and capacity in ambulatory and bed-ridden patients with neuromuscular disease.

Most patients with neuromuscular disease develop muscle weakness, including the ventilatory muscles leading to respiratory difficulty and, at times, respiratory insufficiency. We studied the effect of ventilatory muscle training on the ventilatory function and capacity of patients with various types of neuromuscular disease. The ambulatory patients were divided into three major groups. Group I (n = 6) patients with motor neuron disease (MND), such as amyotrophic latera sclerosis; Group II (n = 11) patients with myoneural junction disease (MNJ), such as myasthenia gravis and: Group III (n = 7) patients with muscle diseases such as progressive muscular disease. Patients were evaluated for their neuromuscular diagnosis and status of the disease. A complete physical examination and the various neuromuscular tests were performed. A complete respiratory evaluation was applied: pulmonary function tests (PFT), maximum inspiratory pressure (MIP). Patients then started ventilatory muscle training by resistive breathing, as a prophylactic treatment, for 10 min, three times daily, with a resistance which would induce fatigue. All tests were repeated every six weeks, and the results were as follow: forced vital capacity (FVC) changed from 38.8 +/- 12.3 to 53.2 +/- 9.6% (NS) of predicted value in group I, from 49.8 +/- 8.7 to 66.1 +/- 7.5% (p < 0.002) in group II, and from 47.0 +/- 7.5 to 53.3 +/- 7.6% (p < 0.04) in group III. Forced expiratory volume in one second (FEV1) was 34.8 +/- 11.0, 46.3 +/- 5, and 45.1 +/- 9% for the three groups, respectively, and did not change with training.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The locus coeruleus and dopaminergic function in rat brain: implications to parkinsonism.

Clinical and experimental evidence suggests that degeneration of the locus coeruleus (LC) may be responsible for certain symptoms of Parkinson's disease (PD). We have, therefore, studied the effects of LC lesion on dopamine (DA) metabolism in the rat striatum. Unilateral depletion of norepinephrine (NE) was obtained by stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the dorsal NE bundle (DNEB). Rats were sacrificed 1 or 3 weeks after lesioning. 6-OHDA induced approximately 50% depletion of NE in the ipsilateral hippocampus at 1 week postinjection, and over 75% depletion after 3 weeks. DNEB lesions had no effect on DA or DOPAC levels in the ipsi- or contralateral striatum at either time point. Lesions also failed to affect DA synthesis or utilization in either striatum. The metabolism of exogenous levodopa in the striatum was also unaffected. It is suggested that any possible effect of the LC on DA transmission in the striatum is not mediated by the DNEB.

Animals↗
PubMed1992

Presence of prion protein in peripheral tissues of Libyan Jews with Creutzfeldt-Jakob disease.

The prion protein (PrP) gene on chromosome 20 encodes a protein designated PrPC. An abnormal, protease-resistant isoform of PrPC, denoted PrPCJD or PrPSc, is present in the brains of patients with Creutzfeldt-Jakob disease (CJD). In Libyan Jews, CJD segregates with a point mutation at codon 200 of the PrP gene, resulting in the substitution of lysine for glutamate. In the present study, we examined the presence of PrP in fibroblasts and leukocytes derived from eight CJD patients with the codon 200 mutation. In cultured fibroblasts as well as in leukocytes, there was a significant increase in PrP as judged by immunocytochemistry in addition to immunoblotting. Most of the PrP in fibroblasts and leukocytes could be released from the external surface by phosphatidylinositol-specific phospholipase C, a property characteristic of PrPC. In leukocytes only, part of the protein was protease resistant, resembling PrPCJD. The concentration of PrP mRNA was similar in fibroblast lines derived from controls and CJD patients. These results suggest that in CJD patients carrying a mutation at codon 200 of the PrP gene, the metabolism of PrP, rather than PrP synthesis, is abnormal.

Animals↗
PubMed1991

Mutation of the prion protein in Libyan Jews with Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease is a transmissible neurodegenerative disorder that occurs more than 100 times more frequently among Libyan Jews than in the worldwide population. We examined 11 patients with the disease--10 Libyan Jews from Israel and 1 Libyan Jew from Italy--to determine whether abnormalities of the prion protein could be detected in them. Abnormal forms of this host-encoded protein are the predominant if not sole components of the transmissible agent that causes the disease. METHODS: The prion-protein open-reading frame in peripheral-leukocyte DNA from the Italian patient was amplified with the polymerase chain reaction and sequenced. Allele-specific oligonucleotide hybridization was used to assess a prion-protein codon 200 lysine mutation in the 10 Israeli patients and 37 control subjects. RESULTS: The prion-protein sequence in DNA from the Italian patient revealed a single nucleotide change (G----A) at the first position of codon 200 that resulted in a substitution of lysine for glutamate. This substitution was detected in all 10 Israeli patients, 8 of whom had a positive family history of Creutzfeldt-Jakob disease. One patient was homozygous for the lysine mutation, and her clinical course did not differ from that of the patients heterozygous for the mutation. The lysine mutation was not found in one Moroccan Jew from Israel with Creutzfeldt-Jakob disease. CONCLUSIONS: The codon 200 lysine mutation of the prion-protein gene is consistently present among Libyan Jews with Creutzfeldt-Jakob disease, strongly supporting a genetic pathogenesis of their illness. The similarity of the clinical courses of the patient homozygous for this mutation and the patients heterozygous for it argues that familial Creutzfeldt-Jakob disease is a true dominant disorder.

Adult↗
PubMed1991

Brain SPECT imaging in temporal lobe epilepsy.

Temporal lobe epilepsy is diagnosed by clinical symptoms and signs and by localization of an epileptogenic focus. A brain SPECT study of two patients with temporal lobe epilepsy, using 99mTc-HMPAO, was used to demonstrate a perfusion abnormality in the temporal lobe, while brain CT and MRI were non-contributory. The electroencephalogram, though abnormal, did not localize the diseased area. The potential role of the SPECT study in diagnosis and localization of temporal lobe epilepsy is discussed.

Adult↗
PubMed1991

Close association of HLA-B51 and B52 in Israeli patients with Behçet's syndrome.

Epidemiological data, family history, clinical data, and HLA typing were studied in three groups of patients with Behçet's syndrome: six Israeli Ashkenazi Jews, 29 non-Ashkenazi Jews, and three Israeli Arabs. HLA-B51 and B52 were present in 24/38 (63%) and 8/38 (21%), respectively, of the patients compared with 13/151 (9%) of the control group for both cases, a relative risk of 18.2 and 2.8 respectively. The syndrome was found in six of the 34 families. Ninety five per cent of the affected family members were either B51 or B52 positive. Eleven of the 14 families (79%) chosen for study contained a close relative of the proband who had recurrent oral ulcers. All the relatives with ulcers, except for one, were B51 or B52 carriers. Recurrent oral ulcers in the patients with Behçet's syndrome began a few years before other manifestations of the syndrome occurred. Our findings suggest that (a) HLA-B51 and HLA-B52 are primarily associated with Behçet's disease of Israeli patients; (b) the familial occurrence of this syndrome is high and occurs predominantly in the B5 positive group; (c) recurrent oral ulcers may be the first symptom of Behçet's syndrome, appearing early in life; HLA analysis can provide the clue for a correct diagnosis; (d) ulcer recurrence is common among members of a family containing a patient with Behçet's syndrome.

Behcet Syndrome↗