PubMed Health⌕ Search

Biomedical subjects

D Wexler

Publications and source records attributed to D Wexler.

33 records · Page 2Linked to original sources
PubMed1994

Mondini dysplasia and congenital cytomegalovirus infection.

We report a case of bilateral temporal bone anomalies in a child with symptomatic congenital cytomegalovirus infection and severe, bilateral sensorineural hearing loss identified at 3 months of age. High-resolution temporal bone computed tomography (HRCT) revealed bilateral findings of a short, malformed cochlea lacking an interscalar septum, a short and wide internal auditory canal, and an enlarged vestibular aqueduct, features diagnostic of bilateral Mondini dysplasia. To determine the importance of this observation, we completed HRCT in five additional children between 7 months and 9 years of age who had evidence of symptomatic congenital cytomegalovirus infection. One child with profound sensorineural hearing loss had severe bilateral temporal bone dysplasia with a small cochlea lacking an interscalar septum, an abnormal vestibule, and a large cochlear aqueduct. Of the remaining four children, hearing thresholds ranged from normal to profoundly decreased, but their HRCT scans were normal to visual inspection. When inner ear dimensions of these temporal bones were compared with norms established by Pappas and coworkers, however, seven of the eight ears had short cochleas and narrow lateral semicircular canals, and three ears had short or narrow vestibules. These results indicate that congenital cytomegalovirus infection may cause anomalies or growth disturbances of the temporal bone.

Child↗
PubMed1994

Total coronary artery occlusion late after successful coronary angioplasty of moderately severe lesions: incidence and clinical manifestations.

Coronary restenosis after balloon angioplasty is a slow process that develops over a few months. In some patients, with an initially successful angioplasty, an artery that originally had only moderate stenosis becomes totally occluded as a result of restenosis. This report describes 16 such patients out of 415 dilated lesions with late angiographic follow-up. Ten patients presented with stable angina pectoris, 5 had unstable angina and only one was admitted with a small myocardial infarction. Visible collaterals were present in 15 patients. Except for the patient who sustained myocardial infarction, none of the late angiograms showed the typical morphological features of acute lesion. We conclude that total coronary occlusion late after successful angioplasty of an artery that was moderately narrowed is rare. The 'restenotic' occlusion is a slow process that stimulates collateral formation and thus the risk of myocardial infarction is small.

Adult↗
PubMed1992

erbB-2 autophosphorylation is required for mitogenic action and high-affinity substrate coupling.

Autophosphorylation of gp185erbB-2 in vivo is confined to its carboxy terminus and is required for optimal erbB-2 transforming activity under conditions of receptor overexpression. It remains unresolved, however, to what extent autophosphorylation regulates erbB-2 mitogenic signaling in normal cells, nor is the biochemical basis for such a regulatory function known. To address these issues, we utilized a chimeric molecule encompassing the extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) fused to the transmembrane and intracellular domains of the erbB-2 product. In this EGFR/erbB-2 chimera, erbB-2 kinase activity is regulated by EGF binding. An EGFR/erbB-2 mutant bearing multiple Tyr----Phe substitutions at erbB-2 autophosphorylation sites (EGFR/erbB-2 5P) displayed markedly reduced phosphotyrosine content following EGF stimulation in comparison with the non-mutated chimera. When expressed in NR6 cells, the EGFR/erbB-2 5P mutant was unable to deliver a sizeable mitogenic signal when activated by EGF at physiological levels. In intact cells, the 5P mutant was still able to stimulate phosphorylation of the gamma isozyme of phospholipase C (PLC-gamma), a prototype erbB-2 substrate, although with a delayed time course, indicating that the 5P mutation decreased the affinity of the erbB-2 kinase for this substrate. This conclusion was further supported by the inability of the 5P mutant to associate with PLC-gamma in co-immunoprecipitation experiments. We infer that a major role of autophosphorylation is to increase the affinity of the erbB-2 kinase for its cellular substrates, so that, under physiological conditions, autophosphorylation is absolutely required for erbB-2 mitogenic signaling.

Amino Acid Sequence↗
PubMed1991

The juxtamembrane regions of the epidermal growth factor receptor and gp185erbB-2 determine the specificity of signal transduction.

The epidermal growth factor receptor (EGFR) and gp185erbB-2 are closely related tyrosine kinases. Despite extensive sequence and structural homology, these two receptors display quantitative and qualitative differences in their ability to couple with mitogenic signalling pathways. By using chimeric molecules between EGFR and erbB-2, we found that the determinants responsible for the specificity of mitogenic signal transduction are located in the amino-terminal half of the tyrosine kinase domain of either receptor. In the EGFR, mutational analysis within this subdomain revealed that deletion of residues 660 to 667 impaired receptor mitogenic activity without affecting its tyrosine kinase properties. This sequence is therefore likely to contribute to the specificity of substrate recognition by the EGFR kinase.

Amino Acid Sequence↗
PubMed1988

Neuroma of the common bile duct.

Two cases of neuroma of the common bile duct (CBD) associated with jaundice and cholangitis both 15 years after cholecystectomy are presented. The surgical treatment, excision of the diseased CBD, followed by Roux-en-Y biliary drainage in one case and excision of the tumor with T-tube drainage in the other, was curative. A review of the world literature revealed 20 prior cases of CBD neuromas, 19 associated with jaundice. None was diagnosed prior to operation or autopsy. Mortality of treatment was 15% and all deaths were associated with a failure to excise the neuroma.

Aged↗
PubMed1985

Physicians' and families' perspectives on the medical management of dementia.

The role of physicians in the long-term management of patients with the primary diagnosis of progressive dementia was investigated by surveying the opinions of 57 physicians and 47 family members. Respondents were asked to evaluate the difficulty and helpfulness of various activities physicians perform in the diagnosis, treatment, and management of patients with dementia. Both physicians and families rated the diagnostic services provided by physicians very highly. Although families found physicians' explanations of the diagnosis and prognosis extremely helpful, physicians reported this as an area of difficulty. Physicians and families expressed considerable frustration with the limited medical treatments and interventions for the relief of symptoms associated with dementia. Despite the acknowledged sensitivity of physicians to the social-psychological consequences of dementia, physicians were found to be least helpful in addressing these issues, either directly or through referral to allied health and social services. This study outlines areas of physician education that need improvement and calls for development of an interdisciplinary network of services for the biopsychosocial management of dementia.

Alzheimer Disease↗
PubMed1981

Plasma protein-binding parameters of prednisolone in immune disease patients receiving long-term prednisone therapy.

Prednisone and prednisolone bind in plasma to albumin and transcortin. In am attempt to determine whether prednisone side effects and/or type of disease correlated with prednisolone plasma protein binding, multiple plasma samples from 17 patients (three asthma, eight SLE, three RA, two PSS, one PAN) receiving long-term prednisone therapy were monitored during an interval between two prednisone doses. Prednisolone plasma protein binding was nonlinear and exhibited large intrapatient and interpatient variability. For the group, mean association constants of the prednisolone-albumin complex and the prednisolone-transcortin complex were 2.3 X 10(3) M-1 and 2.9 X 10(7) M-1, with coefficients of variation of 82% and 127%, respectively. SLE patients tended to have lower mean prednisolone association constants for albumin and transcortin than did other patients. The presence of corticosteroid side effects did not correlate with prednisolone plasma protein-binding parameters. The wide range of prednisolone free fraction noted in plasma from patients who achieved comparable total prednisolone plasma concentrations implies that administration of a uniform prednisone dose will not lead to a predictable clinical response.

Adolescent↗
PubMed1979

The binding of streptomycin to ribonucleotides.

Incubation of streptomycin (SM) with [32P]5'-ribonucleotides at pH 7.0 produces fractions that migrate towards the cathode in high voltage electrophoresis (HVE) separations at pH 3.5. SM appears to interact with pG, pA and pC but not with pU. The appearance of these [32P]-labeled fractions is dependent on incubation time and SM concentration. Incubation of nucleotides with dihydrostreptomycin (DSM) or SM reduced with sodium cyanoborohydride (NaBH3CN) at pH 5.0, does not produce detectable changes in [32P] nucleotide mobility on HVE; however, incubation with SM reduced with NaBH3CN at pH 7.0 does produce [32P]-labeled fractions migrating with a net positive charge. Elution of [32P]-labeled material migrating towards the cathode from SM-5'-nucleotide incubations and re-electrophoresis results in nucleotides migrating with pG, pA and pC markers. These data indicate a reversible interaction between the SM-streptose aldehyde and amino-group containing nucleotides. This type of interaction may form an additional binding site for SM to RNA, relative to DSM.

Chemical Phenomena↗
PubMed1977

Acquired zinc deficiency disease of skin.

Two patients, who were on long term parenteral hyperalimentation, developed skin lesions similar to those seen in acrodermatitis enteropathica. Both patients were treated with oral zinc sulphate and their skin lesions cleared completely. These patients are presented as an acquired zinc deficiency syndrome.

Female↗