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Biomedical subjects

S Ehrlich

Publications and source records attributed to S Ehrlich.

At least 19 recordsLinked to original sources
PubMed2000

Increased transmission of intermediate alleles of the FMR1 gene compared with normal alleles among female heterozygotes.

Fragile X syndrome (Fra X) is the most common heritable disease accounting for mental retardation and is caused by an expanded CGG repeat in the first exon of the FMR1gene. Previous studies have shown an increased fertility rate among fragile X carrier mothers and a preponderance of mentally retarded boys among the male offspring. In this study, we examined the transmission of the intermediate allele in the lower range of CGG repeats in carrier mothers found randomly in a screening program of the normal population. We tested 10,587 healthy women with no family history of mental retardation and identified 138 (1.3%) who were carriers of the intermediate allele (51-200 CGG repeats). Of these, 107 underwent prenatal testing during 108 pregnancies for Fra X in the fetus. Of the 108 pregnancies, the abnormal allele was transmitted in 67 (segregation ratio = 0.62, P < 0.012). We found a significant increase in the transmission of the abnormal allele by mothers who had between 51 and 60 repeats (segregation ratio = 0.69 [P < 0.007] for the group with 51-55 repeats, and 0.74 [P < 0.04] for the group with 56-60 repeats), but no increase by mothers who had more than 61 repeats. This suggests a genetic advantage for the abnormal allele in the 51- to 60-repeat range.

Alleles↗
PubMed2000

Molecular analysis of CD26-mediated signal transduction in T cells.

CD26 or dipeptidylpeptidase IV (DPP IV) is a cell surface protease involved in T cell activation. It is a type II transmembrane glycoprotein consisting of a large extracellular part, a single transmembrane region and a short cytoplasmic tail without any common signalling motifs. To eluciate the mechanisms involved in CD26-mediated signalling we have constructed C-terminal deletion mutants of the human CD26 molecule and transfected them into murine T cell hybridomas. Stimulation experiments show that most of the extracellular part of CD26 can be deleted without affecting its costimulatory activity. The membrane proximal glycosylation rich region of CD26 is sufficient to transduce costimulatory signals. Activation of T cells via CD26, however, is not mediated by the important T cell receptor associated adaptor proteins LAT and TRIM as shown in colocalization assays.

Animals↗
PubMed2000

Measuring and modeling facial affect.

In recent years, researchers in computer science and human-computer interaction have become increasingly interested in characterizing perception of facial affect. Ironically, this applied interest comes at a time when the classic findings on perception of human facial affect are being challenged in the psychological research literature, largely on methodological grounds. This paper first describes two experiments that empirically address Russell's methodological criticisms of the classic work on measuring "basic emotions," as well as his alternative approach toward modeling "facial affect space." Finally, a user study on affect in a prototype model of a robot face is reported; these results are compared with the human findings from Experiment 1. This work provides new data on measuring facial affect, while also demonstrating how basic and more applied research can mutually inform one another.

Adolescent↗
PubMed1998

The transmembrane region of CD2-associated signal-transducing proteins is crucial for the outcome of CD2-mediated T-cell activation.

Signalling through the CD2 molecule was shown previously to employ similar signalling molecules as the T-cell receptor (TCR). Here, we show that CD2-mediated signalling is strongly influenced by the expressed transmembrane region of the employed signal-transducing molecule. We used TCR-negative cells expressing chimeric fusion proteins that consist of human interleukin-2 (IL-2) receptor alpha-chain-derived sequences (hCD25) fused to mouse-specific zeta-chain segments (hCD25-zeta). One set of TCR-negative cell lines expressed the hCD25-derived extracellular part fused to mouse-specific transmembrane and cytoplasmic zeta-protein sequences ('TZZ'). The second type of cell lines expressed the hCD25-derived extracellular and transmembrane portions fused to the mouse-specific zeta-chain cytoplasmic segment ('TTZ'). After cross-linking the hCD25-zeta molecules with specific monoclonal antibodies (mAb), all TCR-negative cell lines produced similar amounts of IL-2. Cross-linking with stimulating pairs of CD2-specific mAb, however, led to IL-2 production only in cell lines expressing the zeta-chain-specific transmembrane segment. Co-cross-linking of CD25 and CD2 molecules resulted in an effective stimulation of both TZZ- and TTZ-expressing cell lines. Moreover, TTZ- and TZZ-expressing cell lines differed in their pattern of tyrosine-phosphorylated proteins after stimulation with hCD25-specific mAb. Thus, although CD2 and TCR molecules share signalling components and pathways, the fine tuning of CD2 co-receptor function appears to be regulated in part by transmembrane regions of signal-transducing molecules like the TCR-associated zeta-chain.

Antibodies, Monoclonal↗
PubMed1997

Clinical evidence for a neuromodulator action of endothelin in the hypothalamic-pituitary-adrenal axis in man.

In order to investigate whether the ubiquitous signalling peptide endothelin might also act as a neuromodulator in the stimulation of the hypothalamic-pituitary-adrenal axis, 15 patients (4 female, 11 male, aged 35-67 years) with hypopituitarism were investigated and the results were compared to those of 8 healthy male volunteers (aged 24-31 years). Patients and controls received double-blind in random order either 0.1 IE per kg body weight regular insulin (insulin induced hypoglycemia) or 1 ml 0.9% sodium chloride (placebo) on 2 separate days. Control subjects only received on an additional day 0.1 IE per kg body weight regular insulin plus glucose 10% (euglycemic hyperinsulinemic glucose clamp). In control subjects hypoglycemia resulted in a significant increase in adrenocorticotropin (ACTH) and cortisol which was preceded by an increase in circulating endothelin levels (p < 0.01 vs placebo and euglycemic clamp) while endothelin, ACTH and cortisol remained unchanged both after placebo and in the euglycemic hyperinsulinemic clamp. In contrast, patients with hypopituitarism showed neither changes in circulating endothelin levels nor a stimulation of the hypothalamic-pituitary-adrenal axis during insulin-induced hypoglycemia. These data demonstrate that 1) endothelin levels are enhanced by metabolic stress 2) the responsiveness of endothelin levels to metabolic stress is linked to the presence of an intact pituitary gland and 3) endothelin might be involved in the stimulation of the hypothalamic-pituitary-adrenal axis.

Adrenocorticotropic Hormone↗
PubMed1996

A biological function for the XP motif within the N terminus of major histocompatibility complex class II-associated peptides.

A high proportion (up to 30%) of major histocompatibility complex (MHC) class II-bound peptides in the mouse and humans contains a proline residue at the N-terminal penultimate position (XP motif). We used a set of ovalbumin (OVA)-specific and hen egg lysozyme (HEL)-specific T cell hybridomas and asked whether the XP motif in MHC class II-associated peptides might influence the stimulation of T cells. We created N-terminally substituted variants of OVA323-339, an H2-Ad restricted OVA epitope and of HEL50-63, a dominant epitope in the context of H2-Ak. Our results show that the N-terminal sequence of MHC class II-bound peptides has a strong impact for the overall stimulation of specific T cells. Proline at the N terminus of antigenic peptides, in contrast to other amino acids, is tolerated or even enhances the recognition of MHC class II-bound peptides significantly.

Amino Acid Sequence↗
PubMed1995

Major histocompatibility complex class II-associated peptides determine the binding of the superantigen toxic shock syndrome toxin-1.

Superantigens bind to major histocompatibility complex (MHC) class II proteins and interact with variable parts of the T cell antigen receptor (TCR) beta-chain. Cross-linking the TCR with MHC class II molecules on the antigen-presenting cell by the superantigen leads to T cell activation that plays an essential role in pathogenesis. Recent crystallographic data have resolved the structure of the complexes between HLA-DR1 and staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin-1 (TSST-1), respectively. For TSST-1, these studies have revealed possible contact sites between the superantigen and the HLA-DR1-bound peptide. Here, we show that TSST-1 binding is dependent on the MHC-II-associated peptides by employing variants of T2 mutant cells deficient in loading of peptides to MHC class II molecules as superantigen-presenting cells. On HLA-DR3-transfected T2 cells, presentation of TSST-1, but not SEB, was dependent on HLA-DR3-associated peptides. Thus, although these superantigens can be recognized in the context of multiple MHC class II alleles and isotypes, they clearly bind to specific subsets of MHC molecules displaying appropriate peptides.

Amino Acid Sequence↗
PubMed1995

Effusion criteria and clinical importance of glenohumeral joint fluid: MR imaging evaluation.

PURPOSE: To investigate the clinical importance of glenohumeral joint (GHJ) fluid. MATERIALS AND METHODS: The amount of GHJ fluid in 17 volunteers and 208 consecutive patients was graded at magnetic resonance imaging with T2-weighted fat-suppressed coronal oblique images by two blinded observers. Thorough historical data and physical examination results were available for 108 patients. Presence and grade of GHJ fluid were correlated with age, sex, presence of osteophytes activity scale, supraspinatus tenderness, clinical impingement, prior subacromial injections, rotator cuff tears (RCTs), joint tenderness, joint pain, and history of trauma. RESULTS: GHJ fluid was seen in 40% (n = 83) of patients and in only 6% (n = 1) of volunteers. The volume of fluid correlated with osteophytes (P = .04), increasing age (P = .0001), and RCTs (P = .005). No correlation was found with activity rating, focal tenderness, joint pain, diagnosis of impingement, impingement grade, supraspinatus insertional tenderness, subacromial injection, prior trauma, or sex. CONCLUSION: The presence of GHJ fluid appears to be abnormal and in most cases is related to RCTs and osteoarthritis. It seems to be unrelated to activity, tenderness, or impingement.

Adult↗
PubMed1994

Linkage localization of the thoraco-abdominal syndrome (TAS) gene to Xq25-26.

The thoraco-abdominal syndrome (TAS) presents a closure defect confined to the ventral midline, manifested as ventral hernia of various degrees in all affected individuals and antero-lateral diaphragmatic defect manifested almost exclusively in affected males. The syndrome is inherited as an X-linked dominant trait affecting blastogenesis (XLB mutation). We studied 27 members of the TAS family for linkage on the X chromosome. The best lod score of 5.5 at theta 0.04 was found for the HPRT locus on Xq26.1. A multilocus lod score of 12.4 was observed when the linkage analysis utilized additional markers in Xq25-26.

Abdomen↗
PubMed1994

Acromioclavicular joint fluid: determination of clinical significance with MR imaging.

PURPOSE: To determine the clinical significance of fluid in the acromioclavicular (AC) joint. MATERIALS AND METHODS: A total of 108 patients with clinical shoulder problems and 16 volunteers underwent MR imaging with a 1.5-T unit. Coronal T1- and T2-weighted images were evaluated for the presence of AC joint fluid, glenohumeral joint fluid, and AC joint osteophytes. Medical records were reviewed for the presence of clinical signs and symptoms. RESULTS: AC joint fluid was commonly seen in the patients (67%) but was rare in the volunteers (12%). The presence of AC joint fluid was associated with advancing patient age, presence of osteophytes, and fluid in the glenohumeral joint. AC joint fluid was not associated with focal tenderness, prior corticosteroid injections, history of trauma, findings of impingement, evidence of rotator cuff tear on MR images, or gender. CONCLUSION: AC joint fluid appears to be an asymptomatic manifestation of osteoarthritis.

Acromioclavicular Joint↗
PubMed1993

Electrophysiological evaluation of moricizine in patients with sustained ventricular tachyarrhythmias: low efficacy and high incidence of proarrhythmia.

In patients with history of sustained ventricular tachycarrhythmias, the efficacy and safety of moricizine have not been systematically evaluated by electrophysiological studies. We performed electrophysiological testing in these patients in the drug-free state and then after moricizine loading, and evaluated the safety profile of moricizine during in-hospital loading and follow-up. The study population comprised of 31 patients with clinically sustained ventricular tachyarrhythmia. The underlying heart disease was coronary in 25 patients, cardiomyopathy in 5 patients, and none in 1 patient. The left ventricular (LV) ejection fraction ranged from 15%-69% (mean 39 +/- 15%). During the baseline drug-free electrophysiological testing, sustained ventricular tachycardia was inducible in 27 patients, ventricular fibrillation in 1 patient, and reproducible, nonsustained ventricular tachycardia (15-25 sec) in 3 patients. All 31 patients received moricizine to the maximum tolerated dose (851 +/- 185 mg) over a period of 2-7 days. Six patients developed ventricular proarrhythmia within the first 4 days. Proarrhythmia required multiple cardioversions in three patients, was not associated with QT prolongation, and spontaneously resolved 6-24 hours after withdrawal of moricizine. Of the remaining 25 patients, 24 underwent electrophysiological testing on moricizine and 4 patients (16%) were rendered noninducible. The VT cycle length in the other 20 patients slowed from 243 +/- 30 msec to 299 +/- 60 msec (P < 0.09). Four noninducible patients, two patients with inducible but slowed VT and one patient who had refused further testing were discharged on moricizine.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1993

Efficacy of pacemaker tachycardia termination algorithms: is electrophysiological testing alone adequate?

UNLABELLED: Selection of an optimal pacemaker tachycardia reversion algorithm is generally performed utilizing programmed electrical stimulation (PES). Multiple tachycardias are induced and various tachycardia termination protocols are tested for reversion success. However, PES may induce nonclinical tachycardia and result in an inaccurate assessment of subsequent reversion effectiveness for spontaneous tachycardia. To investigate this question, we compared tachycardia reversion protocol success for PES-induced tachycardia versus spontaneously occurring tachycardia in 16 patients with atrially placed Intermedics 262-12 antitachycardia pacemakers. The pacemaker has tachycardia response counters, and the reversion success was calculated from these counters. This was performed by comparing the percent of time 1 degree versus 2 degrees modality use occurred; crossover to the 2 degrees modality implied failure of the 1 degree modality to convert the tachycardia. PES was used to induce multiple episodes of tachycardia and spontaneous episodes of tachycardia were recorded over time by pacemaker counters. The pacemaker 1 degree modality success was then compared for spontaneous and induced arrhythmias. RESULTS: A total of 53 discrete data comparisons of PES versus spontaneous tachycardia counters were performed in the 16 patients. PES reversion success occurred 85% +/- 22% of the time versus a spontaneous reversion success of 88% +/- 22%. However, the Spearman rank correlation coefficient test demonstrated nonsignficant overall correlation (P < 0.01), and Pearson correlation on an individual patient basis varied widely (r value from < 0.1 to 1.0). CONCLUSIONS: When utilizing the same termination algorithm, the percentage conversion of tachycardias occurring spontaneously and induced by PES is similar but does not correlate well overall. This suggests that PES may not be a good linear predictor of the long-term success of antitachycardia pacing algorithms.

Adolescent↗
PubMed1992

Optimal daytime feeding regimen to prevent postprandial hypoglycemia in type 1 glycogen storage disease.

To determine the optimal daytime dietary regimen for type 1 glycogen storage disease (GSD), we used uncooked cornstarch (UCS) at a basal glucose production rate (GPR) in single and divided doses, with mixed meals at 0700 and 1700 h. This regimen was compared with a 1.5 times larger single dose of UCS at 0700 h, and with dextrose at GPR at 1200 h. Two-hour UCS loads (amount equal to GPR in 2 h) given with a mixed meal at 0700 h and 180 min later maintained mean blood glucose (BG) concentrations at greater than or equal to 4.2 mmol/L for 300 min. BG was significantly greater from 240 to 300 min compared with a single 4-h UCS load, and at 300 min compared with a single 6-h UCS load. Similar effects were noted when the divided UCS regimen was given with a mixed meal at 1700 h, but not when isoenergetic amounts of dextrose were given on the same schedules with a mixed meal at 1200 h. A daytime schedule of six UCS feedings (with the three main meals and 180 min later) at GPR maintains BG at concentrations that should minimize biochemical abnormalities and optimize clinical outcome in patients with GSD.

Adolescent↗
PubMed1991

Unrecognized stenosis by angiography documented by intravascular ultrasound imaging.

This report documents how intravascular ultrasound imaging was used to diagnose a short "napkin-ring" stenosis that was missed by coronary angiography. Intravascular ultrasound revealed a lumen of 2.6 x 2.5 mm in diameter and 5.0 mm2 in cross-sectional area, with a residual atheroma that occluded 63% of available cross-sectional area at the stenosis.

Angiography↗