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Biomedical subjects

E Becker

Publications and source records attributed to E Becker.

At least 19 recordsLinked to original sources
PubMed1997

Biosynthesis, processing, and intracellular transport of GM2 activator protein in human epidermal keratinocytes. The lysosomal targeting of the GM2 activator is independent of a mannose-6-phosphate signal.

The processing, intracellular transport, and endocytosis of the GM2 activator protein (GM2AP), an essential cofactor of beta-hexosaminidase A for the degradation of ganglioside GM2, was investigated in human epidermal keratinocytes. The GM2AP precursor is synthesized as an 18-kDa peptide, which is singly glycosylated, resulting in 22-kDa high mannose and 24-27-kDa complex glycoforms. A small portion of the 22-kDa form bears phosphomannosyl residues. About 30% of the GM2AP precursor is secreted during 12 h after synthesis, consisting almost exclusively of complex glycoforms. In a post-Golgi compartment, the intracellular remainder is converted to a 20-kDa mature form within 24 h, bearing a heavily trimmed N-glycan on a 17-kDa backbone. Interestingly, even nonglycosylated GM2AP is delivered to the lysosome, as shown by tunicamycin treatment and subcellular fractionation. Also, its endocytosis is independent of carbohydrate-linked signals and is even more effective for nonglycosylated GM2AP. We conclude that a mannose-6-phosphate-independent pathway for the lysosomal delivery of GM2AP exists in cultured human keratinocytes.

Biological Transport↗
PubMed1997

Characterization of the myosin heavy chains of avian adult fast muscles at the protein and mRNA levels.

High resolution anion-exchange chromatography of myosin subfragment-1 in avian fast muscles revealed five fast heavy chains (I-V) expressed in muscle-specific patterns. Sequence analysis of a unique peptide established that the proteins differed in primary structure and suggested correlation with heavy chain genes identified independently by Robbins and coworkers. The identities of the isoforms and their expression patterns were confirmed at the mRNA level by a reverse-transcription, 5'-anchored PCR procedure. The fast white pectoralis major muscle possessed heavy chain I, the posterior latissimus dorsi muscle, of similar fibre type, expressed heavy chains I, III and IV. The fast red adductor superficialis muscle expressed either, or both, of heavy chains II and IV. The lateral gastocnemius muscle, of mixed fibre type, expressed heavy chains II-V. In general, heavy chains I, III and V appeared to be favoured in fast white fibres, while heavy chains II and IV were characteristic of fast red fibres. These results imply a greater subtlety of fast muscle function than has previously been appreciated.

Amino Acid Sequence↗
PubMed1996

Involvement of microtubules in the control of adhesion-dependent signal transduction.

BACKGROUND: The adhesion of cells to the extracellular matrix (ECM) generates transmembrane signals that affect cell proliferation, differentiation and survival. These signals are triggered by interactions between integrin and the ECM and involve tyrosine phosphorylation of specific proteins, including focal adhesion kinase (FAK) and paxillin, and the assembly of focal adhesions and actin bundles. In matrix-adherent, serum-starved Swiss 3T3 cells, the system of focal adhesions and actin bundles is poorly developed, and the level of tyrosine phosphorylation of FAK and paxillin is low. A number of growth factors rapidly stimulate tyrosine phosphorylation of these proteins and the assembly of focal adhesions and actin bundles. Growth factors and adhesion to the ECM are both necessary for the subsequent transition of cells to the S-phase of the cell cycle. RESULTS: In serum-starved Swiss 3T3 cells, the disruption of microtubules by nocodazole or vinblastine, without the addition of external growth factors, induces the rapid assembly of focal adhesions and microfilament bundles, tyrosine phosphorylation of FAK and paxillin, and subsequent enhancement of DNA synthesis. All these effects require cell adhesion to the ECM and do not occur when cells are plated on substrates coated with poly-L-lysine or concanavalin A. Inhibitors of tyrosine phosphorylation and cell contractility also eliminate the effects of microtubule disruption on adhesion-dependent signal transduction. CONCLUSIONS: In ECM-attached cells, microtubule disruption activates the integrin-dependent signaling cascade, which leads to the assembly of matrix adhesions and the induction of DNA synthesis. The increase in cell contractility is an indispensable intermediate step in this signaling process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

TrkA receptor ectodomain cleavage generates a tyrosine-phosphorylated cell-associated fragment.

The extracellular domain of several membrane-anchored proteins can be released as a soluble fragment by the action of a cell surface endoproteolytic system. This cleavage results in the generation of a soluble and a cell-bound fragment. In the case of proteins with signaling capability, such as tyrosine kinase receptors, the cleavage process may have an effect on the kinase activity of the cell-bound receptor fragment. By using several cell lines that express the TrkA neurotrophin receptor, we show that this receptor tyrosine kinase is cleaved by a proteolytic system that mimics the one that acts at the cell surface. TrkA cleavage is regulated by protein kinase C and several receptor agonists (including the TrkA ligand NGF), occurs at the ectodomain in a membrane-proximal region, and is independent of lysosomal function. TrkA cleavage results in the generation of a cell-associated fragment that is phosphorylated on tyrosine residues. Tyrosine phosphorylation of this fragment is not detected in TrkA mutants devoid of kinase activity, suggesting that phosphorylation requires an intact TrkA kinase domain, and is not due to activation of an intermediate intracellular tyrosine kinase. The increased phosphotyrosine content of the cell-bound fragment may thus reflect higher catalytic activity of the truncated fragment. We postulate that cleavage of receptor tyrosine kinases by this naturally occurring cellular mechanism may represent an additional mean for the regulation of receptor activity.

Animals↗
PubMed1996

Radon mitigation at Birch Cliff Public School.

In 1991, Canadian Institute for Radiation Safety (CAIRS) conducted a radon screening program in all Metropolitan Toronto public schools. Birch Cliff Public School had a radon progeny level higher than the action level of 4.16 x 10(-7) Jm-3 (20 mWL). Follow-up radon testing was carried out at the school. Locations on the ground floor and in the basement were tested. All locations on the ground floor had radon progeny levels below the action level. Six locations in the basement had readings above the action level. All cracks and openings in the basement were sealed and a new heating/ventilating (HV) system for the basement was designed and installed. Then, the basement was tested again. Radon progeny levels are now well below the action level with an average of 7.43 x 10(-8) Jm-3 (3.57 mWL). This is about one fifth of the average radon progeny level found in the first stage of follow-up testing.

Air Pollutants, Radioactive↗
PubMed1996

Treatment of presumed fungal endophthalmitis with oral fluconazole.

Amphotericin B is the usual treatment for fungal endophthalmitis, but its toxicity and lack of oral bioavailability may limit its use in some patients. The authors report the successful management of two cases of presumed metastatic fungal endophthalmitis with oral fluconazole, a bis-triazole compound with a broad antifungal spectrum.

Administration, Oral↗
PubMed1995

A comparison of the costs of and quality of life after coronary angioplasty or coronary surgery for multivessel coronary artery disease. Results from the Emory Angioplasty Versus Surgery Trial (EAST).

BACKGROUND: The Emory Angioplasty Versus Surgery Trial (EAST) is a randomized trial that compares, by intention to treat, the clinical outcome and costs of percutaneous transluminal coronary angioplasty (PTCA) and coronary surgery for multivessel coronary artery disease. METHODS AND RESULTS: The primary end point was a composite of death, Q-wave myocardial infarction, and a large reversible thallium defect at 3 years. Multiple measures of quality of life also were made. Charges were assessed from the hospital UB-82 bills; professional charges were assessed from the Emory Clinic. Hospital charges were reduced to cost through step-down accounting methods. All costs and charges were deflated to 1987 dollars. Costs were assessed for the initial hospitalization and the cumulative costs of the initial hospitalization and additional revascularization procedures for up to 3 years. There was no difference in mortality or the primary end point. Mean initial hospital charges were $12,654 for the PTCA group and $20,214 for the surgery group (P < .0001). Professional charges were 4538 for PTCA and $9426 for surgery (P < .0001). Three-year hospital charges were $19,047 for PTCA and $21,174 for coronary surgery (P < .0001). Three-year professional charges were $6412 for PTCA and $9861 for surgery (P < .0001). Three-year total charges were $25,458 for PTCA and $31,033 for surgery (P < .0001). Total 3-year costs were $23,734 for PTCA and $25,310 for coronary surgery (P < .0001). There were more hospitalizations for angina and more antianginal medications used in the PTCA group, which would further narrow the differences in cost. CONCLUSIONS: There was no difference in the primary end point or its components at 3 years. Although the primary procedural costs of coronary surgery are more than for coronary angioplasty, this cost advantage is largely, although probably not completely, lost by 3 years because of more frequent additional procedures and other resource consumption after a first revascularization by PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1995

Risk of neoplastic and other diseases among people with heterozygosity for hereditary hemochromatosis.

BACKGROUND: Increased body iron stores have been associated with risk of heart attack in men and risk of cancer and colonic adenoma in both sexes. Because heterozygous carriers of hereditary hemochromatosis (HH) have on the average increased iron stores compared with noncarriers of the HH gene and comprise as much as 15% of the American population, disease risk in HH heterozygotes was investigated. METHODS: A community-based cohort was defined, in which the exposure variable was heterozygosity for HH. Heterozygotes were identified by mailing individuals homozygous for HH questionnaires concerning the health histories of their parents (predominantly heterozygotes or exposed). Spouses of the HH homozygotes were asked to complete accompanying questionnaires concerning their parents (unexposed). The frequencies for exposed and unexposed, age-adjusted relative risks (RR), and 95% confidence intervals (CI), of cancer, heart disease, and stroke as causes of death as well as the cumulative incidence of heart attack, diabetes, stroke, hypertension, colonic adenoma, and cancers of the lung, colorectum, breast, cervix, pancreas, stomach, and blood were estimated. RESULTS: Data were available for 1950 HH heterozygotes and 1656 unexposed subjects. Elevated RR were observed in HH heterozygotes in males for diabetes (RR, 1.16; 95% CI, 1.01-1.33), colorectal cancer (RR, 1.28; CI, 1.07-1.53), and hematologic malignancy (RR, 1.30; CI, 1.30-1.63), for colonic adenoma in females (RR, 1.29; CI, 1.08-1.53) and males (RR, 1.24; CI, 1.05-1.46), and for stomach cancer in females (RR, 1.37; CI, 1.04-1.79). CONCLUSIONS: Heterozygosity for HH is associated with increased risk for colorectal neoplasia, diabetes, hematologic malignancy, and gastric cancer. No increased risk of heart disease, cancer death, or cancers of the lung, breast, or cervix were demonstrated.

Adult↗
PubMed1995

Effects of NADPH oxidase inhibitors on hypoxic vasoconstriction in buffer-perfused rabbit lungs.

The involvement of NADPH oxidase in hypoxic pulmonary vasoconstriction (HPV) was investigated in buffer-perfused rabbit lungs, employing the inhibitors diphenyleneiodonium (DPI) and apocynin. Responses to the vasoconstrictors U-46619 and angiotensin II (ANG II) were used to test specificity. Lung nitric oxide (NO) generation was assessed by on-line monitoring of NO exhalation (chemiluminescence), and the efficacy of DPI and apocynin on the NADPH oxidase-dependent O2- generation was quantified in alveolar macrophages by fluorescent-activated cell sorter technique. In a concentration range between 1 and 5 mM, apocynin inhibited macrophage respiratory burst and HPV but similarly suppressed U-46619-induced vasoconstrictor responses. DPI inhibited macrophage O2- generation in concentrations > or = 0.5 microM. At doses between 0.5 and 1.5 microM, DPI blocked lung NO generation, thereby increasing HPV. At higher doses (4 microM), in contrast, DPI fully blocked the hypoxia-induced pressor responses, whereas the vasoconstrictor responses to U-46619 and [Asn1, Val5] ANG II were not diminished. In the presence of NG-monomethyl-L-arginine, used to block lung NO generation throughout, DPI exhibited only the monophasic selective inhibition of HPV. We conclude that apocynin lacks specificity for HPV, but DPI, in addition to inhibiting lung NO generation, causes selective blockade of the hypoxia-induced vasoconstriction. This finding supports the hypothesis that an NADPH oxidase is involved in hypoxia sensing or specific signal transduction events underlying HPV.

Acetophenones↗
PubMed1995

Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia.

Familial dysalbuminemic hyperthyroxinemia (FDH) is a form of euthyroid hyperthyroxinemia that is due to an increased affinity of serum albumin for T4. Unlike the many physiologically neutral alloalbumins that have been identified by serum electrophoresis, FDH variants have not been reproducibly resolved. In the present study, isoelectric focusing in the presence of the denaturants urea and Nonidet P-40, without reduction, produced two bands in the sera of unrelated FDH subjects in place of each of the major albumin bands in the sera of normal subjects. One band of each FDH pair migrated with the normal band; the second migrated at a slightly lower pI. The identity of the new bands as albumin was confirmed by N-terminal sequencing. The two bands of each pair were present in approximately equal amounts, consistent with the autosomal dominant nature of the condition, the expectation that FDH individuals would be heterozygous for normal albumin (Alb-A), and evidence that high and normal affinity T4-binding sites are equimolar or near equimolar. Similar findings in sera from Hispanic and non-Hispanic FDH subjects suggest that the same structural change may underlie the FDH phenotype from different populations. The slightly lower pI of the FDH-specific bands is consistent with the His for Arg substitution predicted by a G to A base transition recently reported in codon 218 of the gene for the variant albumin (Alb-FDH).

Detergents↗
PubMed1994

Memory bias in panic disorder.

We investigated selective memory effects in patients with panic disorder. Thirty patients with panic disorder and 20 normal controls learned panic-related, strongly pleasant, and strongly unpleasant words. During the incidental learning task, Ss imagined scenes combining the referent of a presented word with themselves. After a distractor task, Ss took a free-recall test. Panic Ss showed enhanced memory for panic-related words but not for positive or negative words.

Adult↗
PubMed1994

Personal exposure to nitrogen dioxide in the Los Angeles Basin.

A large scale study of human exposure to nitrogen dioxide (NO2) was conducted in the Los Angeles Basin, the only metropolitan area in the United States that exceeds the NO2 NAAQS. Data are available for a population representative sample of 482 households and 682 individuals. Personal exposures, as well as indoor and outdoor home levels, were monitored using passive time-integrating filter badges. Monitoring extended over a one-year period (May 1987 to May 1988), with each individual providing two consecutive days of data. Information was also collected on activity patterns, household and personal characteristics, and spatial and temporal variables. This paper describes the study design, summarizes the sample characteristics and representativeness, and presents the distribution of personal, indoor, and outdoor NO2 concentrations recorded by the monitors. Over the entire sample, median personal and outdoor levels were 35 ppb; median indoor levels were 24 ppb. Personal exposures for those in homes with gas ranges with pilot lights average 10 ppb greater than those with electric ranges, and 4 ppb greater than those with gas ranges without pilot lights. Forty percent of the variation in indoor concentrations is explained by outdoor levels; 59 percent of the variation in personal exposures is explained by indoor levels; and 48 percent of the variation in personal exposures is explained by outdoor levels.

Adolescent↗
PubMed1993

Olfactory event-related potentials in psychosis-prone subjects.

Previous studies in schizophrenic patients have suggested that there are changes in olfactory sensitivity. In order to externally validate a psychometrical assessment of the psychosis-risk indicated by schizotypic factors, this study was carried out to determine whether changes in olfactory perception could be determined even for persons merely at risk of developing schizophrenia. These 'psychosis-prone' subjects consistently scored high in either the scale for 'physical anhedonia' (PA) or the scale for 'perceptual aberration' (PAB). Thus, three groups were investigated (control, n = 11; PA, n = 12; PAB, n = 12). Each subject participated in one testing session where the two odorants, vanillin (pleasant) and hydrogen sulphide (unpleasant), were applied by means of a specially designed delivery apparatus. Subjects rated both the intensity and the hedonic quality of the stimuli. In addition, olfactory event-related potentials (OERP) were recorded after dichotomous stimulation. In general, there were only few significant differences between the three groups investigated. Contrary to expectations, ratings for pleasantness of vanillin were highest in PA subjects compared to PAB subjects and controls (p < 0.05). Correspondingly, OERP amplitudes in response to vanillin were largest within the PA group (p < 0.05). For hydrogen sulphide, PAB subjects showed the smallest OERP amplitudes (p < 0.05). In addition, it was observed that female subjects had significantly larger OERP amplitudes when compared to male subjects (p < 0.05), which possibly indicates gender differences in olfactory sensitivity.

Adult↗
PubMed1993

Multifocal osteoarticular tuberculosis: report of four cases and review of management.

We report the clinical, microbiological, and radiological features of four cases of multifocal osteoarticular tuberculosis, and we review the management of this condition. In each case the initial clinical diagnosis was one of malignant disease, and the possibility of tuberculous bone infection was overlooked. There was neither clinical nor radiological evidence of pulmonary involvement in any case. Antituberculous chemotherapy was initiated in two instances on the basis of histopathologic findings compatible with tuberculous osteomyelitis; such treatment was delayed in the other two cases until the diagnosis was confirmed by culture. Antituberculous chemotherapy alone was successful in three cases, while the fourth case required emergency anterior spinal decompression as well. Two patients developed additional skeletal lesions after the initiation of appropriate antituberculous chemotherapy. Multifocal osteoarticular tuberculosis must be considered in the differential diagnosis of multiple destructive skeletal lesions in all patients from areas where tuberculosis is endemic. This condition may mimic malignant disease both clinically and radiologically.

Adolescent↗