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Biomedical subjects

D Zamir

Publications and source records attributed to D Zamir.

At least 19 recordsLinked to original sources

Arterial compliance: is it reduced in antiphospholipid syndrome?

To assess vascular compliance in patients with antiphospholipid syndrome (APS), or antiphospholipid antibodies (aPLs) positivity in comparison to healthy people and diabetes mellitus patients. Twenty-five patients with APS or aPLs, 33 healthy people (HP), 28 patients with diabetes mellitus (DM) underwent pulse wave analysis. Data calculated included the small artery elasticity (SAE), large artery elasticity (LAE) and systemic vascular resistance (SVR). Statistical analysis was performed as appropriate. The patient group was divided into two subgroups: APS-1 with warfarin treatment, and APS-2 without warfarin treatment. All patients and healthy subjects were matched by gender, body mass index and lipid profiles. Patients in APS-1 group were significantly younger in comparison to three other groups. After the adjustment for age, we found that SAE in APS-1 group did not differ from SAE in the HP group (6.4+/-1.8 ml/mmHg x 100 and 5.54+/-3.4 ml/mmHg x 100, respectively, P>0.05). In contrast, SAE in the group APS-2 was significantly lower (3.41+/-1.2 ml/mmHg x 100) than in the APS-1 and was almost equal to SAE in the DM group (4.2+/-2.37 ml/mmHg x 100). The SAE in the APS-2, DM and HP groups was inversely correlated with age, whereas in the APS-1 group we did not find such correlation. This pilot study showed abnormal small vascular elasticity in the patients with positive aPL, relative to the healthy subjects. The APS patients, treated with warfarin had the normal vascular function. This data support the hypothesis that APS may be associated with diffuse changes in the arterial wall, and may be a risk factor for atherosclerotic disease.

Adult↗

A genetic map of candidate genes and QTLs involved in tomato fruit size and composition.

In order to screen for putative candidate genes linked to tomato fruit weight and to sugar or acid content, genes and QTLs involved in fruit size and composition were mapped. Genes were selected among EST clones in the TIGR tomato EST database (http://www.tigr.org/tdb/tgi/lgi/) or corresponded to genes preferentially expressed in the early stages of fruit development. These clones were located on the tomato map using a population of introgression lines (ILs) having one segment of Lycopersicon pennellii (LA716) in a L. esculentum (M82) background. The 75 ILs allowed the genome to be segmented into 107 bins. Sixty-three genes involved in carbon metabolism revealed 79 loci. They represented enzymes involved in the Calvin cycle, glycolysis, the TCA cycle, sugar and starch metabolism, transport, and a few other functions. In addition, seven cell-cycle-specific genes mapped into nine loci. Fourteen genes, primarily expressed during the cell division stage, and 23 genes primarily expressed during the cell expansion stage, revealed 24 and 26 loci, respectively. The fruit weight, sugars, and organic acids content of each IL was measured and several QTLs controlling these traits were mapped. Comparison between map location of QTLs and candidate gene loci indicated a few candidate genes that may influence the variation of sugar or acid contents. Furthermore, the gene/QTL locations could be compared with the loci mapped in other tomato populations.

Chromosome Mapping↗

Advanced backcross QTL analysis of a Lycopersicon esculentum x L. pennellii cross and identification of possible orthologs in the Solanaceae.

In this study, the advanced backcross QTL (AB-QTL) mapping strategy was used to identify loci for yield, processing and fruit quality traits in a population derived from the interspecific cross Lycopersicon esculentum E6203 x Lycopersicon pennellii accession LA1657. A total of 175 BC(2) plants were genotyped with 150 molecular markers and BC(2)F(1) plots were grown and phenotyped for 25 traits in three locations in Israel and California, U.S.A. A total of 84 different QTLs were identified, 45% of which have been possibly identified in other wild-species-derived populations of tomato. Moreover, three fruit-weight/size and shape QTLs ( fsz2b.1, fw3.1/ fsz3.1 and fs8.1) appear to have putative orthologs in the related solanaceous species, pepper and eggplant. For the 23 traits for which allelic effects could be deemed as favorable or unfavorable, 26% of the identified loci had L. pennellii alleles that enhanced the performance of the elite parent. Alleles that could be targeted for further introgression into cultivated tomato were also identified.

Alleles↗

The different patterns of blood pressure elevation by rofecoxib and nabumetone.

Hypertension and knee osteoarthritis (OA) are frequent comorbidities. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to relieve pain in such patients. In the last decade selective NSAIDs are used more commonly since they lead to less gastrointestinal complications. As has been shown, the treatment with NSAIDs may cause a mild rise of arterial blood pressure (BP). The influence of selective NSAIDs on BP, particularly in hypertensive patients has still to be investigated. The aim of this study was to determine arterial BP changes in patients suffering from stable arterial hypertension and knee OA and treated with rofecoxib or nabumetone. Two groups of patients with knee OA and stable arterial hypertension received either 25 mg rofecoxib once daily or namebutone 2000 mg once daily during the first week of treatment and 1000 mg for the following 3 weeks. Twenty-four hour arterial BP monitoring was performed prior to initiation of treatment and at the end of a 4-week period. The results were that no changes were found in the mean systolic and diastolic characteristics of BP in the rofecoxib treatment group during day time (delta systolic BP -0.4 mm Hg and delta diastolic BP -0.4 mm Hg), while nocturnal BP increased significantly: delta systolic BP +15.7 mm Hg and delta diastolic BP +8.5 mm Hg. The mean systolic arterial pressure in the nabumeton group raised delta systolic BP 2.9 mm Hg in the daytime and 5 mm Hg during the night-time after the treatment. The mean diastolic arterial pressure also rose delta diastolic 3.2 mm Hg and 4.9 mm Hg at day and night hours respectively. In conclusion rofecoxib treatment did not change arterial BP during day time hours, however, there was a distinct increase in night-time systolic and diastolic BP leading to a disappearance of the physiological diurnal variation. Nabumetone caused a moderate increase of day and night BP, without changes in biological diurnal variation.

Anti-Inflammatory Agents, Non-Steroidal↗

[An unusual coincidence of thrombotic thrombocytopenic purpura and pernicious anemia].

A 52 year old man was admitted for hospitalization due to dizziness and weakness that appeared in the previous 2 weeks. Anemia and thrombocytopenia, as well as elevated levels of lactic dehydrogenase, reticulocytosis and schistocytes on blood smear, all suggested thrombotic thrombocytopenic purpura. However, B12 deficiency was also diagnosed. The diagnosis of pernicious anemia was reassured by both fundic biopsy and the existence of antiparietal cells antibodies and anti-intrinsic cells antibodies. A few courses of plasmapheresis along with parenteral B12 stabilized his physical condition and he was released with no need for further treatment, and only required ambulatory follow-up.

Anemia, Pernicious↗

Two tightly linked QTLs modify tomato sugar content via different physiological pathways.

Congenic lines that differ in a single defined chromosome segment are useful for the study of complex phenotypes, as they allow isolation of the effect of a particular quantitative trait locus (QTL) from those of the entire genome. We conducted high-resolution QTL mapping of a 9-cM introgression, originating from the wild tomato species Lycopersicon pennellii, in two extremely different genetic and physiological backgrounds. In the "indeterminate" glasshouse background we identified only a single QTL ( Brix9-2-5) that affects the total soluble solids of the fruit [mainly sugars, measured in Brix units (B)]. This QTL was previously delimited within the gene for an apoplastic invertase, Lin5, that modulates sugar partitioning to the fruit. Analysis of the effects of the same chromosome segment in "determinate", open-field tomatoes, revealed two QTLs, 0.3 cM apart: the fruit-specific Brix9-2-5 that affects B only, and the shoot-specific PW9-2-5, which accounts for an altered growth habit resulting in increases in plant weight, yield, and B. This study highlights the power of the congenic approach for dissecting developmental pathways leading to complex phenotypes.

Base Sequence↗

Genome-wide dissection of Fusarium resistance in tomato reveals multiple complex loci.

Resistance to different pathogenic races of Fusarium oxysporum f. sp. lycopersici (F. o. lycopersici) was explored at two genomic levels in tomato. Six independent Fusarium resistance loci were identified by comparing the responses of a complete set of 53 lines carrying different introgressed regions of the Lycopersicon pennellii genome in a L. esculentum background. The loci confer varying degrees of resistance to different races of the pathogen. Corresponding map positions from different tomato species were aligned and in some cases revealed parallel resistance to F. o. lycopersici with qualitative changes in race specificities. One of the loci identified corresponds to the previously characterized complex resistance locus I2, which is involved in resistance to F. o. lycopersici race 2. A novel member of this locus, I2C-5, which belongs to the NBS-LRR family of resistance genes, was cloned and shown to confer partial resistance in transgenic plants. Thus, at a particular complex locus gene members can confer full or partial resistance to F. o. lycopersici race 2. The results of our whole-genome mapping analysis underline the robust independent origin of resistance to a particular disease and demonstrate the conservation of resistance features at syntenic loci, together with the rapid diversification of genes for innate resistance within loci.

Base Sequence↗

Control of a community-wide outbreak of hepatitis A by mass vaccination with inactivated hepatitis A vaccine.

The epidemiology and control of hepatitis A virus was investigated during an outbreak of hepatitis A in a village in Israel. Postexposure administration of immune globulin to contacts was ineffective in controlling the outbreak. However, within 2 weeks of starting a mass immunization campaign with hepatitis A vaccine, the incidence of hepatitis A declined dramatically; the last case occurred 6 weeks after the immunization program began. The study demonstrated that while postexposure administration of immune globulin may diminish but not entirely arrest transmission of hepatitis A virus, active hepatitis A vaccination is a safe and effective intervention that can be used safely in hepatitis A virus antibody-positive children.

Child↗

Improving plant breeding with exotic genetic libraries.

Naturally occurring variation among wild relatives of cultivated crops is an under-exploited resource in plant breeding. Here, I argue that exotic libraries, which consist of marker-defined genomic regions taken from wild species and introgressed onto the background of elite crop lines, provide plant breeders with an important opportunity to improve the agricultural performance of modern crop varieties. These libraries can also act as reagents for the discovery and characterization of genes that underlie traits of agricultural value.

Breeding↗

Epidemiology of hepatitis B virus infection among family members of chronic carriers in Israel.

BACKGROUND: Hepatitis B is a major problem worldwide. Israel has intermediate endemicity for hepatitis B virus, and an annual carrier rate of 1-3%. OBJECTIVE: To evaluate both the prevalence of HBV infection among family members of HBV carriers and the competence of family practitioners in performing a comprehensive assessment. METHODS: A total of 152 HB surface antigen-positive blood donors were discovered in our subdistrict during the years 1993-97. Their family physicians were questioned regarding the patients' family members. Specific information on 85 spouses and 200 children was also obtained. RESULTS: Among the 85 married carriers, 5 of the spouses (5.9%) were found to be HBsAg positive. None of the 200 children was HBsAg positive. We found that in a third (n = 52) of the patients, the sexual partner had never been tested by a primary care physician. Patients were not routinely tested for HB e antigen or anti-HBe antibodies. Neither the parents nor the siblings had undergone any serological evaluation. However, most family members of the carriers had received an HBV vaccine from their family physicians. CONCLUSIONS: Our findings show that horizontal transmission of HBV among spouses of HBV carriers still exists. We did not find any vertical transmission, probably due to male predominance and previous vaccination. Family physicians should be trained to perform an extensive serological evaluation of family members of patients with chronic HBV infection, including parents and siblings, and should vaccinate seronegative family members.

Adult↗

[Myocardial infarction due to cocaine].

Cocaine is a common drug. Myocardial infarcts and brain infarcts related to the use of cocaine were previously reported in the medical literature. We report a 34 year old patient admitted for severe chest pain, a few minutes after cocaine use. He was found to have an acute myocardial infarction with significant left ventricle dysfunction. Coronarography conducted a few days later was found to be normal. Cocaine use may cause acute myocardial infarction in young and healthy people with no other risk factors.

Adult↗

An alternative pathway to beta -carotene formation in plant chromoplasts discovered by map-based cloning of beta and old-gold color mutations in tomato.

Carotenoid pigments in plants fulfill indispensable functions in photosynthesis. Carotenoids that accumulate as secondary metabolites in chromoplasts provide distinct coloration to flowers and fruits. In this work we investigated the genetic mechanisms that regulate accumulation of carotenoids as secondary metabolites during ripening of tomato fruits. We analyzed two mutations that affect fruit pigmentation in tomato (Lycopersicon esculentum): Beta (B), a single dominant gene that increases beta-carotene in the fruit, and old-gold (og), a recessive mutation that abolishes beta-carotene and increases lycopene. Using a map-based cloning approach we cloned the genes B and og. Molecular analysis revealed that B encodes a novel type of lycopene beta-cyclase, an enzyme that converts lycopene to beta-carotene. The amino acid sequence of B is similar to capsanthin-capsorubin synthase, an enzyme that produces red xanthophylls in fruits of pepper (Capsicum annum). Our results prove that beta-carotene is synthesized de novo during tomato fruit development by the B lycopene cyclase. In wild-type tomatoes B is expressed at low levels during the breaker stage of ripening, whereas in the Beta mutant its transcription is dramatically increased. Null mutations in the gene B are responsible for the phenotype in og, indicating that og is an allele of B. These results confirm that developmentally regulated transcription is the major mechanism that governs lycopene accumulation in ripening fruits. The cloned B genes can be used in various genetic manipulations toward altering pigmentation and enhancing nutritional value of plant foods.

Chloroplasts↗

A recombination hotspot delimits a wild-species quantitative trait locus for tomato sugar content to 484 bp within an invertase gene.

In nature, genetic variation usually takes the form of a continuous phenotypic range rather than discrete classes. The genetic variation underlying quantitative traits results from the segregation of numerous interacting quantitative trait loci (QTLs), whose expression is modified by the environment. To uncover the molecular basis of this variation, we characterized a QTL (Brix9-2-5) derived from the green-fruited tomato species Lycopersicon pennellii. The wild-species allele increased glucose and fructose contents in cultivated tomato fruits in various genetic backgrounds and environments. Using nearly isogenic lines for the QTL, high-resolution mapping analysis delimited Brix9-2-5 to a single nucleotide polymorphism-defined recombination hotspot of 484 bp spanning an exon and intron of a fruit-specific apoplastic invertase. We suggest that the differences between the Brix9-2-5 alleles of the two species are associated with a polymorphic intronic element that modulates sink strength of tomato fruits. Our results demonstrate a link between naturally occurring DNA variation and a Mendelian determinant of a complex phenotype for a yield-associated trait.

Alleles↗

Comparative genetics of nucleotide binding site-leucine rich repeat resistance gene homologues in the genomes of two dicotyledons: tomato and arabidopsis.

The presence of a single resistance (R) gene allele can determine plant disease resistance. The protein products of such genes may act as receptors that specifically interact with pathogen-derived factors. Most functionally defined R-genes are of the nucleotide binding site-leucine rich repeat (NBS-LRR) supergene family and are present as large multigene families. The specificity of R-gene interactions together with the robustness of plant-pathogen interactions raises the question of their gene number and diversity in the genome. Genomic sequences from tomato showing significant homology to genes conferring race-specific resistance to pathogens were identified by systematically "scanning" the genome using a variety of primer pairs based on ubiquitous NBS motifs. Over 70 sequences were isolated and 10% are putative pseudogenes. Mapping of the amplified sequences on the tomato genetic map revealed their organization as mixed clusters of R-gene homologues that showed in many cases linkage to genetically characterized tomato resistance loci. Interspecific examination within Lycopersicon showed the existence of a null allele. Consideration of the tomato and potato comparative genetic maps unveiled conserved syntenic positions of R-gene homologues. Phylogenetic clustering of R-gene homologues within tomato and other Solanaceae family members was observed but not with R-gene homologues from Arabidopsis thaliana. Our data indicate remarkably rapid evolution of R-gene homologues during diversification of plant families.

Alleles↗

Smoking and first acute myocardial infarction: age, mortality and smoking cessation rate.

BACKGROUND: Cigarette smoking is a major contributor to the risk of acute myocardial infarction and the subsequent morbidity and mortality. Physicians can play an important role in smoking cessation among patients with AMI because of their frequent contact with the patient during the event. OBJECTIVES: To study the prevalence of smoking, age, localization of coronary occlusion, mortality and rate of smoking cessation in consecutive patients who were diagnosed with a first AMI in our center in 1989-93. METHODS: The study included 1,510 consecutive patients with first AMI: 973 men (512 smokers, 52.6%) and 537 women (215 smokers, 40%), whose mean age was 64.1 +/- 6.7 and 68.6 +/- 5.2 years respectively. RESULTS: The median age at the first AMI in non-smoking and smoking men differed significantly (70.4 +/- 6.8 vs. 56.6 +/- 6.1 years, P < 0.001) while the difference in the women was smaller (70.4 +/- 6.9 vs. 66.8 +/- 7.2). The proportion of smokers/non-smokers among men was greater at a younger age and decreased proportionally with age. The overall mortality was 11.3% with a significant difference in mortality rate in the younger age groups between smokers and non-smokers (1% vs. 0% in the age group 31-40 years, P < 0.05, and 6.1% vs. 0.8% in the 41-50 year age group, P < 0.001). Only 62% of the smokers who survived the AMI declared that they had received anti-smoking advice from a physician during hospitalization. The cessation rate in this group was significantly higher than in smokers who had not been cautioned against smoking (56% vs. 18%). CONCLUSIONS: Current smokers sustained their first AMI more than one decade earlier than non-smokers, and the younger smokers had a higher mortality rate. The majority of the smokers who received anti-smoking advice during their hospitalization for AMI quit smoking in the year following the acute event.

Adult↗