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Y Yahav

Publications and source records attributed to Y Yahav.

At least 37 records · Page 2Linked to original sources
PubMed1994

Similar levels of mRNA from the W1282X and the delta F508 cystic fibrosis alleles, in nasal epithelial cells.

The effect of nonsense mutations on mRNA levels is variable. The levels of some mRNAs are not affected and truncated proteins are produced, while the levels of others are severely decreased and null phenotypes are observed. The effect on mRNA levels is important for the understanding of phenotype-genotype association. Cystic fibrosis (CF) is a lethal autosomal recessive disease with variable clinical presentation. Recently, two CF patients with mild pulmonary disease carrying nonsense mutations (R553X, W1316X) were found to have severe deficiency of mRNA. In the Jewish Ashkenazi CF patient population, 60% of the chromosomes carry a nonsense mutation, W1282X. Patients homozygous for this mutation have severe disease presentation with variable pulmonary disease. The presence of CF transcripts in a group of patients homozygous and heterozygous for this mutation was studied by reverse transcriptase PCR of various regions of the gene. Subsequent hybridization to specific CF PCR probes and densitometry analysis indicated that the CF mRNA levels in patients homozygous for the W1282X mutation are not significantly decreased by the mutation. mRNA levels were compared for patients heterozygous for the W1282X mutation. The relative levels of mRNA with the W1282X, and the delta F508 or the normal alleles, were similar in each patient. These results indicate that the severe clinical phenotype of patients carrying the W1282X mutation is not due to a severe deficiency of mRNA. In addition, the severity, progression, and variability of the pulmonary disease are affected by other, as yet unknown factors.

Alleles↗
PubMed1993

Mild cystic fibrosis and normal or borderline sweat test in patients with the 3849 + 10 kb C-->T mutation.

Different mutations in the cystic fibrosis (CF) gene appear to contribute to heterogeneity of the CF phenotype. We investigated 15 patients with CF who have the 3849 + 10 kb C-->T mutation. All were Ashkenazi Jews. Their clinical features were compared with those of CF patients with the delta F508/delta F508, W1282X/W1282X, W1282X/delta F508 mutations, which are known to be associated with a severe disease. Patients with the 3849 + 10 kb mutation were older, had been diagnosed as having CF at a more advanced age, and were in a better nutritional state. Sweat chloride values were normal (below 60 mmol/L) in 5 3849 + 10 kb patients (33%). 4 of these patients and 6 others (total 66%) had normal pancreatic function. However, age-adjusted pulmonary function did not differ between the two groups. None of the patients with 3849 + 10 kb C-->T had had meconium ileus or had liver disease or diabetes mellitus. We conclude that this mutation is associated with a mild type of CF.

Age Factors↗
PubMed1993

D-lactic acidosis: a treatable encephalopathy in pediatric patients.

A 20-month old infant, who had short bowel syndrome following extensive surgery for a mid gut volvulus, developed hyperchloremic acidosis, with a large anion gap after enteral feeding was instituted. The organic acidosis was at least partly due to an increased concentration of D-lactic acid. This patient, as did five other pediatric patients, presented with a typical encephalopathy syndrome. Early recognition of this syndrome and treatment with an intestinal antibiotic and discontinuation of enteral feeding enabled prompt correction of the hyperchloremic acidosis and a rapid clinical recovery.

Acidosis, Lactic↗
PubMed1992

Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease.

Only about 30% of the cystic fibrosis chromosomes in the Israeli cystic fibrosis patient populations carry the major CF mutation (delta F508). Since different Jewish ethnic groups tended to live as closed isolates until recent times, high frequencies of specific mutations are expected among the remainder cystic fibrosis chromosomes of these ethnic groups. Genetic factors appear to influence the severity of the disease. It is therefore expected that different mutations will be associated with either severe or mild phenotype. Direct genomic sequencing of exons included in the two nucleotide-binding folds of the putative CFTR protein was performed on 119 Israeli cystic fibrosis patients from 97 families. One sequence alteration which is expected to create a termination at residue 1282 (W1282X) was found in 63 chromosomes. Of 95 chromosomes, 57 (60%) are of Ashkenazi origin. Together with the delta F508 (23% in this group), G542X, N1303K, and 1717-1G----A mutations, the identification of 92% of cystic fibrosis chromosomes of Ashkenazi origin becomes possible. Patients homozygous for the W1282X mutation (n = 16) and patients heterozygous for the delta F508 and W1282X mutations (n = 22) had similarly severe disease, reflected by pancreatic insufficiency, high incidence of meconium ileus (37% and 27%, respectively), early age at diagnosis, poor nutritional status, and variable pulmonary function. In conclusion, the W1282X mutation is the most common cystic fibrosis mutation in the Ashkenazi Jewish patient population in Israel. This nonsense mutation is associated with presentation of severe disease.

Cystic Fibrosis↗
PubMed1989

Immediate effect of various treatments on lung function in infants with cystic fibrosis.

The immediate effect of four different modes of treatment was assessed by lung function tests on 19 infants with cystic fibrosis (CF) during the first year of life. The regimens were applied in a randomized fashion and consisted of aerosol inhalation of salbutamol (n = 8; SAL), aerosol inhalation of N-acetyl cysteine (n = 5; AC), chest physiotherapy (n = 6; CPT), and combined treatment with aerosol inhalation of SAL and AC followed by CPT (n = 6; COMB). Pulmonary function was measured before and shortly after therapy with each mode of treatment. Thoracic gas volume (Vtg) and specific airway conductance (SGaw) were measured by an infant whole body plethysmograph, and forced expiratory flow at resting lung volume (VmaxFRC) was determined with a thoraco-abdominal squeeze jacket. There was no correlation between baseline lung function and changes in any parameter due to treatment. Overall group comparison showed that the combined therapy resulted in a significant improvement in lung function when compared to any of the three treatments applied separately. There was no significant change in lung volumes in any individual group, but SGaw and VmaxFRC showed a small but significant improvement following the COMB treatment when compared with AC or CPT.

Acetylcysteine↗
PubMed1988

Variables affecting outcome from severe brain injury in children.

This study evaluates the outcome of 56 severely brain injured children (mean age 6.2 +/- 2.1 years) and relates the Initial Glasgow Coma Scale (IGCS), initial intracranial pressure (ICP int), maximal intracranial pressure (ICP max) and minimal cerebral perfusion pressure (CPP min) to quality of survival. Forty-one children sustained head trauma, five severe central nervous system infections and 10 were of miscellaneous etiology. Therapy consisted of mechanical hyperventilation, moderate fluid restriction, dexamethasone and diagnosis specific measures when indicated. Outcome was categorized according to the Glasgow outcome scale at discharge from the hospital. An IGCS of 3 was associated with 100% mortality, 7 and above resulted in 72% good recovery, 28% poor outcome and no mortality. ICP int of less than 20 torr was noted in (67%) of the patients, and did not correlate with ICP max or outcome. Conversely, ICP int in excess of 40 torr correlated well with ICP max and outcome. ICP max of less than 20 torr resulted in 57% good recovery, 36% poor outcome and 7% mortality. ICP max greater than 40 torr resulted in 7% poor outcome and 93% mortality (p less than 0.001). In head trauma, 32 patients (78%) were alive with mean ICP max 16.9 +/- 3.1 and CPP min 65.5 +/- 8.5 torr compared to 9 patients (22%) who died with mean ICP max 53.7 +/- 10.8 and CPP min 6 +/- 3.9 torr, (p less than 0.01). In children with infectious etiology 60% survived with mean ICP max 16 +/- 3 and CPP min 96 +/- 16 torr.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Injuries↗
PubMed1988

Sodium cromoglycate in asthma: correlation between response and serum concentrations.

The clinical response to sodium cromoglycate treatment was compared with its concentration in serum. Twenty five children with asthma entered a 10 week trial of two baseline weeks followed by eight weeks of treatment by the inhalation of 20 mg of sodium cromoglycate spincaps four times a day. Individual clinical response was determined by the differences between baseline and treatment periods of: (a) percentage of symptomless days (delta score 0); (b) diary derived daily score for four symptoms (delta DS); and (c) peak expiratory flow rate (delta PEFR). At the end of the treatment period, patients inhaled a 20 mg spincap of sodium cromoglycate and the technique of inhalation was graded. Concentrations of sodium cromoglycate in serum were measured by radioimmunoassay in samples withdrawn 5 to 120 minutes after inhalation. Delta Score 0, delta DS, and delta PEFR correlated significantly with the area under the concentration time curve. Both the area under the sodium cromoglycate concentration time curve and clinical response correlated significantly with inhalation technique score. We suggest that response of children with asthma to inhalation treatment with sodium cromoglycate is correlated to its serum concentrations.

Administration, Inhalation↗
PubMed1988

Lung function in infants with cystic fibrosis.

Lung function was measured in 28 infants with cystic fibrosis and repeated in 17 of the infants during the first year of life. Thoracic gas volume (TGV) and specific airway conductance (sGaw) were measured plethysmographically and maximum forced expiratory flow at functional residual capacity (VmaxFRC) was derived from the partial expiratory flow-volume curve. At the time of the initial evaluation respiratory function was correlated with the clinical condition of the infants but not with age. There was a good correlation between sGaw and VmaxFRC when both were expressed as percentages of the predicted normal values. On the basis of the normal range for sGaw the infants were divided into two groups. Group A (n = 9), who had normal sGaw, were younger and had a lower clinical score and normal VmaxFRC and TGV values. Group B (n = 19), who had low sGaw, had increased TGV and decreased VmaxFRC. There was no correlation with age for any measure of lung function for the population as a whole. Repeat testing was undertaken at intervals in 17 representative infants. In most of these infants the relation between sGaw and VmaxFRC was maintained; there was no evidence that VmaxFRC was affected before sGaw. There was no functional evidence that the earliest changes in cystic fibrosis occur in small airways, as reflected by changes in VmaxFRC in infancy.

Airway Resistance↗
PubMed1987

The gene encoding vasoactive intestinal peptide is located on human chromosome 6p21----6qter.

Vasoactive intestinal peptide (VIP) is a regulatory neuropeptide involved in a wide variety of functions, among them vasodilation, smooth muscle relaxation, sweat secretion, gastrointestinal peristalsis, and pancreatic function. A deficient VIP-innervation of sweat glands was recently described as a possible pathogenic factor in sweating of cystic fibrosis (CF) patients. To investigate a possible role for a defective VIP-gene in cystic fibrosis, we have used a panel of rodent-human hybrid cells, retaining defined complements of human chromosomes to localize the VIP-gene to the human chromosome region 6p21----6qter. As the CF gene was recently mapped to chromosome 7, we conclude that the VIP-gene is not the primary gene defect in this disease.

Animals↗
PubMed1982

Persistent cough a forme-fruste of asthma.

Fifteen children presented with persistent cough as the sole complaint. Physical examination was entirely within normal limits. Personal and family histories of atopy and blood eosinophilia suggested an allergic diathesis. Chest radiographs showed hyperinflation in many and spirometry showed bronchospasm in all the children studied. The added observation that theophylline and salbutamol were effective suggests that the condition is a manifestation of asthma.

Adolescent↗
PubMed1980

A new white forelock (poliosis) syndrome with multiple congenital malformations in two sibs.

Two Jewish Ashkenazi male sibs are reported as having a new syndrome consisting of a white forelock, distinct facial features associated with congenital malformations involving the eye, cardio-pulmonary and skeletal systems. It is postulated that the etiology of this disorder is genetic and transmitted either as an autosomal recessive or X-linked recessive conditions.

Abnormalities, Multiple↗