Biomedical subjects

V Yahalom

Publications and source records attributed to V Yahalom.

5 recordsLinked to original sources

PubMed2001

Molecular defects underlying the Kell null phenotype.

Expression of the Kell blood group system is dependent on two proteins, Kell and XK, that are linked by a single disulfide bond. Kell, a type II membrane glycoprotein, is a zinc endopeptidase, while XK, which has 10 transmembrane domains, is a putative membrane transporter. A rare phenotype termed Kell null (Ko) is characterized by the absence of Kell protein and Kell antigens from the red cell membrane and diminished amounts of XK protein. We determined the molecular basis of eight unrelated persons with Ko phenotypes by sequencing the coding and the intron-exon splice regions of KEL and, in some cases, analysis of mRNA transcripts and expression of mutants on the cell surface of transfected cells. Six subjects were homozygous: four with premature stop codons, one with a 5' splice site mutation, G to A, in intron 3, and one with an amino acid substitution (S676N) in exon 18. Two Ko persons with premature stop codons had identical mutations in exon 4 (R128Stop), another had a different mutation in exon 4 (C83Stop), and the fourth had a stop codon in exon 9 (Q348Stop). Two Ko persons were heterozygous for two mutations. One had a 5' splice site mutation (G to A) in intron 3 of one allele that caused aberrant splicing and exon skipping, and the other allele had an amino acid substitution in exon 10 (S363N). The other heterozygote had the same amino acid substitution in exon 10 (S363N) in one allele and a premature stop codon in exon 6 (R192Stop) in the other allele. The S363N and S676N mutants, expressed in 293T cells, were retained in a pre-Golgi compartment and were not transported to the cell surface, indicating that these mutations inhibit trafficking. We conclude that several different molecular defects cause the Kell null phenotype.

Adult↗

PubMed2001

West Nile fever in Israel 1999-2000: from geese to humans.

West Nile virus (WNV) caused disease outbreaks in Israel in the 1950s and the late 1970s. In 1998 an outbreak of WNV in goose farms and evidence of infection in dead migratory birds were reported. Consequently, human diagnostic services for WNV were resumed, including virus isolation, serology, and RT-PCR. Risk factors for infection were assessed by a serological survey in 1999, which revealed a seroprevalence of (a) 86% in people who had close contact with sick geese, (b) 28% in people in areas along bird migration routes, and (c) 27% in the general population. Following two fatal cases in Tel Aviv in September 1999 and one encephalitis case in the southern Eilot region, a regional serological survey was initiated there. The survey revealed two more WNV-associated acute encephalitis cases, an IgG seroprevalence of 51%, and an IgM seroprevalence of 22%. In the summer of 2000, acute cases of WN disease were identified in the central and northern parts of Israel, involving 439 people. The outbreak started in mid-August, peaked in September, and declined in October, with 29 fatal cases, primarily in the elderly. During the outbreak, diagnosis was based on IgM detection. Four virus isolates were subsequently obtained from preseroconverted frozen sera. Sequence and phylogenetic analysis of 1662 bases covering the PreM, M, and part of the E genes revealed two lineages. One lineage was closely related to a 1999 Israeli bird (gull) isolate and to a 1999 New York bird (flamingo) isolate, and the other lineage was closely related to a 1997 Romanian mosquito isolate and to a 1999 Russian human brain isolate.

Adult↗

PubMed2000

Blood groups and their function.

The function(s) assigned to red blood cell membrane components is based on an observed effect in the red cells that lack the component, comparison of the protein sequence (predicted from the nucleotide sequence of the gene) to proteins of known function, and extrapolation of function of the component in other cells. The functions are varied and include membrane structure, transport, receptor, adhesion, enzyme activity, complement components, complement regulation and glycocalyx formation. Several components have more than one function.

Biological Transport↗

PubMed1997

Candida abscess of the thyroid in a patient with acute lymphocytic leukemia.

A case of Candida abscess of the thyroid in a patient with acute lymphoblastic leukemia is described. The patient developed this rare complication after treatment with steroids and combination chemotherapy, during therapy with broad spectrum antibiotics for febrile neutropenia. Prior to the thyroiditis the patient had pulmonary aspergillosis. The abscess developed during treatment with high dose Amphotericin B. Unlike previous cases, the Candida was isolated to the thyroid, with no evidence of Candidemia or Candida infection in other sites.

Abscess↗

PubMed1996

Microsatellite instability and p53 mutations in therapy-related leukemia suggest mutator phenotype.

During the last decade the frequency of therapy-related acute leukemia (t-leuk) and myelodysplastic syndrome (t-MDS) has been increasingly observed. Over the past 15 years, we treated 56 patients with t-leuk who had received prior chemotherapy (39%), radiotherapy (11%), or both (45%). The drugs received included alkylating agents and topoisomerase II inhibitors. The primary tumors included hematological malignancies (49%) and solid tumors such as breast or ovarian cancer. The median age at diagnosis of the primary tumor was relatively young (43 years +/- 18). Twelve patients had more than one primary tumor and 31 patients had a family history of malignancy. Karyotypic abnormalities were found in 91% of the patients. Prognosis was uniformly poor, with an overall median survival of 10 months. Twelve of the 18 patients examined (67%) had a multidrug resistance phenotype. P53 genes of the leukemic cells, as well as the original tumors, were analyzed in 21 patients using polymerase chain reaction (PCR) with single-stranded conformation polymorphism analysis followed by sequencing. P53 mutations were identified in 38% of these patients, a relatively high prevalence compared with other forms of MDS or de novo acute myeloid leukemia. Mutations were nongermline and restricted to the leukemic cells. We identified different p53 mutations in the various primary tumors of individual patients. The presence of a mutator phenotype was assessed by PCR analysis of microsatellites in eight loci (one trinucleotide repeat sequence, four dinucleotide, and three mononuclear repeat sequences). Microsatellite instability in two to seven loci were found in 15 of 16 (94%) of the patients. This instability is compatible with a mutator phenotype, which predisposes the patients to the development of malignancies including t-leuk.

Adult↗