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Biomedical subjects

P Ehrlich

Publications and source records attributed to P Ehrlich.

At least 19 recordsLinked to original sources
PubMed1995

A common keratin 5 gene mutation in epidermolysis bullosa simplex--Weber-Cockayne.

The Weber-Cockayne subtype of epidermolysis bullosa simplex is an inherited skin-fragility disorder characterized by basal keratinocyte lysis and epidermal blistering confined primarily to the hands and feet. The disorder results from a mutation in either the keratin 5 or keratin 14 gene, which encode the peptide components of the obligate heterodimeric keratin intermediate filaments of the basal cell. We have determined that a T-->G substitution mutation in keratin 5, which results in a Ile-->Ser change at codon 161, is common among patients with the Weber-Cockayne disease variant, accounting for six of 13 cases tested. The observed high frequency of this mutation may result from either a mutational hot spot or a founder effect. The potential utility of this common mutation in confirming disease status in some at-risk individual is discussed.

Base Sequence↗
PubMed1995

Epidermolysis bullosa simplex: a keratin 5 mutation is a fully dominant allele in epidermal cytoskeleton function.

To explore the relationship between abnormal keratin molecules, 10-nm intermediate filament (IF) organization, and epidermal fragility and blistering, we sought to determine the functional consequences of homozygosity for a dominant keratin defect. We describe a family with an autosomal dominant skin-blistering disorder, epidermolysis bullosa simplex, Koebner subtype (EBS-K), that has a novel point mutation, occurring in the keratin 5 gene (KRT5), that predicts the substitution of an evolutionarily conserved lysine by an asparagine residue (K173N). Unlike previous heterozygous mutations located within the initial segment of domain 1A of keratin molecules, K173N heterozygosity did not result in severe disease or clumping of keratin filaments. One family member was found to be homozygous for the K173N allele, having inherited it from each of her affected first-cousin parents. Despite a lack of normal keratin 5 molecules, and an effective doubling of abnormal molecules, available for heterodimerization with keratin 14 during IF formation, there were no significant differences in the clinical severity or the ultrastructural organization of the keratin IF cytoskeleton of the homozygous individual. These data demonstrate that the K173N mutation behaves as a fully dominant allele and indicate that a limited number of abnormal keratin molecules are sufficient to impair cytoskeletal function and elicit epidermal fragility and blistering.

Alleles↗
PubMed1993

A keratin 14 mutational hot spot for epidermolysis bullosa simplex, Dowling-Meara: implications for diagnosis.

Recently, two patients with the Dowling-Meara subtype of epidermolysis bullosa simplex (EBS-DM) were reported with different mutations in codon 125 of the keratin 14 gene. To determine whether these are common mutations, we screened ten EBS-DM patients and their families using single nucleotide primer extension. Four of ten unrelated EBS-DM patients had a G-->A substitution at base pair 434 of codon 125, whereas one case out of ten had a C-->T substitution at position 433 of the same codon. The G434A alteration cosegregated with the disorder in two multigenerational families; no recombination events were detected. In these two families, linkage analysis provided significant evidence in favor of linkage between G434A and the EBS-DM phenotype, with a LOD score of 3.29 at a recombination rate of 0%. Codon 125 substitutions identified in three unrelated sporadic EBS-DM patients were not found in their clinically unaffected parents. Together, these data provide compelling genetic evidence that the codon 125 substitutions are causal for EBS-DM. The high frequency of mutation at this site in individuals with EBS-DM now makes DNA-based diagnosis of this disorder feasible.

Amino Acid Sequence↗
PubMed1992

Predicting the volume of health and social services: integrating cognitive impairment into the modified Andersen framework.

This investigation examined cognitive impairment as a predictor of the volume of community services used by older adults. Predictors of service volume were selected according to the modified Andersen framework and tested with 97 health care and 246 social service clients of a large multiservice agency. Results for health care clients showed that the effects of four predictors differ depending on clients' level of cognitive impairment; living arrangement, presence of secondary caregivers, client depression and task burden of the primary caregiver. No differences in predictor of social service use were observed for cognitively impaired and lucid clients.

Aged↗
PubMed1991

TOPS: a consumer approach to Alzheimer's respite programs.

Time Off Promotes Strength (TOPS), a program for caregivers of Alzheimer's victims, provides in-home and day program services. Through application of a service/training model adapted from the Global Deterioration Scale (Reisberg, 1983), the TOPS program maintains a high quality of services with a limited but highly trained professional staff. Caregiver independence and autonomy are emphasized, as is a flexible system that accommodates the ever-changing needs of both caregivers and care recipients.

Allied Health Personnel↗
PubMed1991

Phase I study of safety and pharmacokinetics of a human anticytomegalovirus monoclonal antibody in allogeneic bone marrow transplant recipients.

This study examined the safety and pharmacokinetic profile of a potentially therapeutic and fully human anti-CMV monoclonal antibody (SDZ MSL-109) in a phase I dose escalation trial in patients receiving allogeneic bone marrow transplants. Fifteen adult marrow transplant patients, twelve with chronic myelogenous leukemia and three with acute nonlymphocytic leukemia, in cohorts of five patients each, were administered monoclonal antibody intravenously at doses of 50, 250, and 500 micrograms/kg at approximately three-week intervals for six months. Administration of the monoclonal antibody was associated with minimal side effects and no dose-related toxicity. Antibody elimination curves in all dose groups were consistent with a two-compartment model with an alpha half-life at the low, middle, and high dose groups of 1.03, 0.82, and 0.79 days, and a beta half life of 13.9, 14.0, and 16.5 days, respectively. The volume of distribution decreased with repetitive dosing to approximate the plasma volume in each patient and the pharmacokinetic profile was comparable to that of human IgG. There was no host antiidiotypic or antiallotypic antibody formation, indicating that MSL-109 was not immunogenic. Further studies are warranted to assess the potential efficacy of human monoclonal anti-CMV disease in marrow transplant recipients and other patients with immunodeficiency disorders.

Adult↗
PubMed1990

Nonparasitic splenic cysts: a case report and review.

Cysts of the spleen are rare but usually benign. The authors describe the case of a young woman with a splenic cyst who underwent splenectomy. Ultrasonography and computed tomography have helped improve the preoperative diagnosis of nonparasitic splenic cysts, and as the use of ultrasonography increases, so will the finding of incidental splenic cysts. Whether all splenic cysts enlarge is unknown, and it is uncertain whether all small asymptomatic cysts need treatment. The cysts may enlarge, become infected or rupture. Total splenectomy has been the most common treatment in the past, but, because of the risk of postsplenectomy sepsis, partial splenectomy may be preferred when technically possible.

Adult↗
PubMed1989

Umbilical artery Doppler blood velocity waveforms in normal and abnormal gestations.

Blood velocity patterns in peripheral arteries reflect hemodynamic characteristics, particularly systemic vascular resistance. Doppler blood velocity waveforms in umbilical arteries (UA) indirectly assess placental vascular resistance (P1VR) and therefore an abnormal waveform value may serve as an index of placental insufficiency associated with elevated P1VR. We prospectively studied the ratio of peak-systolic to end-diastolic velocities (A/B ratio) in the UA of 113 normal fetuses on 121 occasions over a period of 4 years. A range-gated, pulsed Doppler, duplex, two-dimensional, real-time echocardiogram (ECHO) allowed placement of the sample volume in the UA by direct vision; hard copy of the tracing was later analyzed. Hand calipers allowed measurement of the fetal cardiac cycle length (RR) and A/B ratio, which were compared with gestational age (EGA), echo-derived total cardiac dimension (TCD), and aortic root size (AO). Normative data were analyzed by least squares linear regression and compared to data in several high-risk groups. In the normal fetus, there was an orderly pattern with advancing gestational age of linearly decreasing A/B ratio and increasing TCD, AO, and RR. The A/B ratio varied inversely with TCD and AO, but was independent of RR. In a group of 20 hypertensive patients, 6 had elevated A/B ratios; of 18 diabetic pregnancies, 4 had elevated A/B ratios. In other high-risk groups, 4 of 21 patients were abnormal: sickle-cell disease (1 case), systemic lupus erythematosus (1 case), and intrauterine growth retardation (2 cases). In conclusion, Doppler A/B ratios in the UA of normal patients, like cardiac size, show an orderly pattern of change with EGA independent of RR.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗
PubMed1987

Detection of conformational changes in human chorionic gonadotropin upon binding to rat gonadal receptors.

After binding to rat testicular or ovarian luteinizing hormone (LH) receptors, human chorionic gonadotropin (hCG) and mammalian LH can be detected with monoclonal antibodies directed against a conserved epitope on the beta subunit of the hormones. Two such anti-hCG/anti-LH monoclonal antibodies, known as B105 and B110, compete with one another for binding to this epitope region on free and receptor-bound hormone. By comparing the affinities of B105 and B110 for these two forms of hCG, we have detected apparent changes in the structure of the hormone which develop subsequent to receptor binding. Whereas the affinity of B105 for receptor-bound hCG is approximately 10-fold lower than that for free hCG, the affinity of B110 for receptor-bound hCG is nearly 20-fold greater than that for free hCG. Both B105.hCG and B110.hCG complexes bind to the receptor; however, they have approximately 25 and 50% lower affinity than hCG. Thus, although B110 binds better to the form of hCG which is bound to receptors, binding of B110 to hCG does not appear to induce a conformational change in the hormone which facilitates hormone-receptor binding. Consequently, both B105 and B110 partially inhibit binding of hCG to its receptors. Fab fragments of B105 and B110 are as effective as intact B105 and B110 in inhibiting the binding of labeled B105 and B110 to hCG-receptor complexes, suggesting that circular complexes which might be formed by the interaction of divalent antibody, two molecules of hCG, and two membrane-bound receptors or one divalent receptor are not contributing to the affinity of the antibodies for receptor-bound hCG. Alternatively, formation of circular complexes can explain an increase in apparent affinity of B105 for ovine or bovine LH-receptor complexes. Data obtained with B105 suggest either that the structure of the epitope is altered following binding or that a portion of the epitope is partially obscured when hCG binds to the receptor. In contrast, the data obtained using B110 are not explained by models in which steric factors reduce the affinity of the antibody for the hormone-receptor complex. Therefore, as a minimal explanation for these observations, we postulate that the conformation of the B105/B110 epitope region is altered following binding of the hormone to receptors. The nature of the conformational change and its relationship to LH/hCG action is unknown.

Animals↗
PubMed1985

Late results after operations for hiatus hernia.

Thirty-two children with gastroesophageal reflux were operated by different techniques which included Nissen's fundoplication in 14 patients. Twenty-one patients could be reexamined, eighteen of whom were without complaints. Being familiar with different operative techniques provides the opportunity to decide from case to case which one to choose.

Adolescent↗
PubMed1985

Size isomers of testosterone-estradiol-binding globulin exist in the plasma of individual men and women.

We isolated testosterone-estradiol-binding globulin TeBG rapidly and in high yield from pooled pregnancy plasma. It showed two bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). Both bands stained with three different monoclonal antibodies to TeBG, thus demonstrating their immunological similarity. Freshly drawn, individual sera, from men, women, and pregnant patients were submitted to microaffinity chromatography, a procedure which partially purifies TeBG in approximately 4 hr. The partially purified plasma was submitted to SDS PAGE, followed by immunoblotting. The blotted TeBG exhibited the same two bands seen in the isolated, purified protein. The size heterogeneity observed in TeBG purified to: proteolysis occurring during isolation; a peculiarity of pregnancy plasma; or heterogeneity attendant upon the use of pooled plasma for isolation.

Chromatography, Affinity↗
PubMed1982

Increased specificity in human cardiac-myosin radioimmunoassay utilizing two monoclonal antibodies in a double sandwich assay.

In some instances, even the increased resolution that may be afforded in immunoassays by the use of monoclonal antibodies fails to effect resolution among molecules that share many epitopes. An immunoradiometric assay that simultaneously measured two different epitopes on the same molecule was devised to overcome this difficulty in the differentiation between cardiac- and skeletal-myosin light chains. Three monoclonal antibodies were examined that were 100% (1C5), 25% (2B9) and 17% (4F10) cross reactive, respectively, between the two antigens. One antibody of the pair to be studied was immobilized to cyanogen bromide-activated Sepharose 4B while the other was iodinated with 125I using the lactoperoxidase method. The antigen was mixed with the immobilized antibody, the labeled antibody was added and the precipitate then washed and counted in a gamma counter. When both antibodies of the pair to be studied (immobilized and labeled) were the same (2B9), no radioactivity above background was bound to the precipitate, indicating that the second antibody could not bind to an already occupied epitope. When two different antibodies were employed, the specificity of the assay increased over that of a single antibody. The cross reactivity of a pair approximated the product of the cross reactivities of the individual antibodies. Thus, 1C5 and 2B9 were 25% cross reactive together, 1C5 and 4F10 17% cross reactive, and 2B9 and 4F10 4.3% cross reactive.

Antibodies, Monoclonal↗