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Biomedical subjects

L Becker

Publications and source records attributed to L Becker.

At least 73 records · Page 4Linked to original sources
PubMed1997

Modulation of GABAA receptor function by tyrosine phosphorylation of beta subunits.

Protein tyrosine phosphorylation is a key event in diverse intracellular signaling pathways and has been implicated in modification of neuronal functioning. We investigated the role of tyrosine phosphorylation in regulating type A GABA (GABAA) receptors in cultured CNS neurons. Extracellular application of genistein (50 microM), a membrane-permeable inhibitor of protein tyrosine kinases (PTKs), produced a reversible reduction in the amplitude of GABAA receptor-mediated whole-cell currents, and this effect was not reproduced by daidzein (50 microM), an inactive analog of genistein. In contrast, intracellular application of the PTK pp60(c-src) (30 U/ml) resulted in a progressive increase in current amplitude, and this potentiation was prevented by pretreatment of the neurons with genistein. Immunoprecipitation and immunoblotting of cultured neuronal homogenates indicated that the beta2/beta3 subunit(s) of the GABAA receptor are tyrosine phosphorylated in situ. Moreover, genistein (50 microM) was found to be capable of decreasing GABAA currents in human embryonic kidney 293 cells transiently expressing functional GABAA receptors containing the beta2 subunit. Thus, the present work provides the first evidence that native GABAA receptors are phosphorylated and modulated in situ by endogenous PTKs in cultured CNS neurons and that phosphorylation of the beta subunits may be sufficient to support such a modulation. Given the prominent role of GABAA receptors in mediating many brain functions and dysfunctions, modulation of these receptors by PTKs may be important in a wide range of physiological and pathological processes in the CNS.

Animals↗
PubMed1997

Androgen support of lacrimal gland function.

The effects of dihydrotestosterone (DHT) (1 mg/kg) on biochemical parameters related to lacrimal secretion, basal tear flow rate, and pilocarpine-stimulated lacrimal gland fluid secretion, in mature ovariectomized rabbits were studied. The effects of the synthetic estrogen diethylstilbestrol (DES) (100 micrograms/kg), on lacrimal gland biochemical parameters in normal mature female rabbits was also studied. Ovariectomy decreased the total serum levels of testosterone (T) by 88.5% and androstenedione by 35.9%, without changing the levels of dehydroepiandrosterone (DHEA) of its sulfate. Ovariectomy caused a significant regression of the lacrimal glands, decreasing total DNA by 35%, and total protein by 22%. DHT treatment of ovariectomized animals prevented lacrimal gland regression, increasing total gland DNA (31%) and total protein (18%). DHT treatment also increases Na+, K(+)-ATPase activity (29%) and beta-adrenergic receptor binding sites (23%) compared to the ovariectomized group. DHT increased pilocarpine stimulated lacrimal gland fluid secretion (13.26 +/- 1.47 microL/min) compared to the ovariectomized group (7.72 +/- 0.41 microL/min), but DHT treatment paradoxically decreased basal tear flow rate (1.02 +/- 0.04 microL/min) as compared to the ovariectomized rabbits (1.96 +/- 0.12 microL/min). DES decreased the total serum T from 59.33 +/- 10.54 pg/mL to 21.5 +/- 6.06 pg/mL. DES decreased total Na+,K(+)-ATPase by 12% and increased beta-adrenergic receptor binding sites by 83.3%. These results suggest that androgens play a major role in supporting lacrimal gland secretory function. Additionally, they suggest that estrogens may influence certain aspects of lacrimal functions, although it is not clear to what extent those actions are elicited directly or indirectly.

Acid Phosphatase↗
PubMed1997

Polycyclic aromatic hydrocarbons (PAHs) in Antarctic Martian meteorites, carbonaceous chondrites, and polar ice.

Recent analyses of the carbonate globules present in the Martian meteorite ALH84001 have detected polycyclic aromatic hydrocarbons (PAHs) at the ppm level (McKay et al., 1996). The distribution of PAHs observed in ALH84001 was interpreted as being inconsistent with a terrestrial origin and were claimed to be indigenous to the meteorite, perhaps derived from an ancient martian biota. We have examined PAHs in the Antarctic shergottite EETA79001, which is also considered to be from Mars, as well as several Antarctic carbonaceous chondrites. We have found that many of the same PAHs detected in the ALH84001 carbonate globules are present in Antarctic carbonaceous chondrites and in both the matrix and carbonate (druse) component of EETA79001. We also investigated PAHs in polar ice and found that carbonate is an effective scavenger of PAHs in ice meltwater. Moreover, the distribution of PAHs in the carbonate extract of Antarctic Allan Hills ice is remarkably similar to that found in both EETA79001 and ALH84001. The reported presence of L-amino acids of apparent terrestrial origin in the EETA79001 druse material (McDonald and Bada, 1995) suggests that this meteorite is contaminated with terrestrial organics probably derived from Antarctic ice meltwater that had percolated through the meteorite. Our data suggests that the PAHs observed in both ALH84001 and EETA79001 are derived from either the exogenous delivery of organics to Mars or extraterrestrial and terrestrial PAHs present in the ice meltwater or, more likely, from a mixture of these sources. It would appear that PAHs are not useful biomarkers in the search for extinct or extant life on Mars.

Antarctic Regions↗
PubMed1997

The human GARS-AIRS-GART gene encodes two proteins which are differentially expressed during human brain development and temporally overexpressed in cerebellum of individuals with Down syndrome.

Purines are critical for energy metabolism, cell signalling and cell reproduction. Nevertheless, little is known about the regulation of this essential biochemical pathway during mammalian development. In humans, the second, third and fifth steps of de novo purine biosynthesis are catalyzed by a trifunctional protein with glycinamide ribonucleotide synthetase (GARS), aminoimidazole ribonucleotide synthetase (AIRS) and glycinamide ribonucleotide formyltransferase (GART) enzymatic activities. The gene encoding this trifunctional protein is located on chromosome 21. The enzyme catalyzing the intervening fourth step of de novo purine biosynthesis, phosphoribosylformylglycineamide amidotransferase (FGARAT), is encoded by a separate gene on chromosome 17. To investigate the regulation of these proteins, we have generated monoclonal and/or polyclonal antibodies specific to each of these enzymatic domains. Using these antibodies on western blots of Chinese hamster ovary (CHO) cells transfected with the human GARS-AIRS-GART gene, we show that this gene encodes not only the trifunctional protein of 110 kDa, but also a monofunctional GARS protein of 50 kDa. This carboxy-truncated human GARS protein is produced by alternative splicing resulting in the use of a polyadenylation site in the intron between the terminal GARS and the first AIRS exons. The expression of both the GARS and GARS-AIRS-GART proteins are regulated during development of the human cerebellum, while the expression of FGARAT appears to be constitutive. All three proteins are expressed at high levels during normal prenatal cerebellum development while the GARS and GARS-AIRS-GART proteins become undetectable in this tissue shortly after birth. In contrast, the GARS and GARS-AIRS-GART proteins continue to be expressed during the postnatal development of the cerebellum in individuals with Down syndrome.

Animals↗
PubMed1997

Fullerenes, fulleranes and polycyclic aromatic hydrocarbons in the Allende meteorite.

In this paper, we confirm our earlier observations of fullerenes (C60 and C70) in the Allende meteorite (Becker et al., 1994a, 1995). Fullerene C60 was also detected in two separate C-rich (approximately 0.5-1.0%) dark inclusions (Heymann et al., 1987) that were hand picked from the Allende sample. The amounts of C60 detected were approximately 5 and approximately 10 ppb, respectively, which is considerably less than what was detected in the Allende 15/21 sample (approximately 100 ppb; Becker et al., 1994a, 1995). This suggests that fullerenes are heterogeneously distributed in the meteorite. In addition, we present evidence for fulleranes, (C60Hx), detected in separate samples by laser desorption (reflectron) time-of-flight (TOF) mass spectrometry (LDMS). The LDMS spectra for the Allende extracts were remarkably similar to the spectra generated for the synthetic fullerane mixtures. Several fullerane products were synthesized using a Rh catalyst (Becker et al., 1993a) and separated using high-performance liquid chromatography (HPLC). Polycyclic aromatic hydrocarbons (PAHs) were also observed ppm levels) that included benzofluoranthene and corannulene, a cup-shaped molecule that has been proposed as a precursor molecule to the formation of fullerenes in the gas phase (Pope et al., 1993).

Carbon↗
PubMed1997

Long-term survival of an infant with 'anaplastic' astrocytoma.

Anaplastic astrocytomas are intermediate in differentiation between astrocytoma and glioblastoma multiforme. Survival with anaplastic astrocytoma is favorably affected by extensive anaplasia, maximal resection and presentation in early life. We report a 2-month-old infant who had a tumor of astrocytic lineage with anaplastic features of necrosis, nuclear atypia and mitotic activity. Following subtotal resection the child is alive but has a radiologically visible tumor.

Brain↗
PubMed1996

Extraterrestrial helium trapped in fullerenes in the Sudbury impact structure.

Fullerenes (C60 and C70) in the Sudbury impact structure contain trapped helium with a 3He/4He ratio of 5.5 x 10(-4) to 5.9 x 10(-4). The 3He/4He ratio exceeds the accepted solar wind value by 20 to 30 percent and is higher by an order of magnitude than the maximum reported mantle value. Terrestrial nuclear reactions or cosmic-ray bombardment are not sufficient to generate such a high ratio. The 3He/4He ratios in the Sudbury fullerenes are similar to those found in meteorites and in some interplanetary dust particles. The implication is that the helium within the C60 molecules at Sudbury is of extraterrestrial origin.

Carbon↗
PubMed1996

Incidence of cardiac arrest during self-transport for chest pain.

STUDY OBJECTIVE: To assess the incidence of cardiac arrest among patients who use self-transport to seek medical care for chest pain. METHODS: This was a retrospective cohort study of patients admitted to a CCU for suspected acute myocardial infarction (AMI) and patients experiencing out-of-hospital cardiac arrest preceded by symptoms in King County, Washington, between January 1, 1992, and July 31, 1994. Participants were identified through use of the databases compiled by the Myocardial infarction Triage and intervention Trial, which reviewed medical records in all area hospitals, and the Cardiac Arrest Surveillance System, which tracks all incidences in which CPR is performed by EMS personnel in King County. Patients whose sudden cardiac arrests were not preceded by symptoms were excluded. Hospital records were abstracted to find the means of transport for patients admitted to CCUs. For cardiac arrest patients, the medical history, presence of symptoms, means of transport, and prehospital death information were abstracted from paramedic field reports. Outcome (admission, discharge, or in-hospital death) was obtained from hospital records. An event cause (cardiac or other) was determined from death certificates, hospital records, or consultation with private physicians. RESULTS: During the 30-month study period, 13,187 patients sought help for cardiac symptoms and were either admitted to a CCU or died before admission after calling 911. A majority, 7,393 (59%), were transported by emergency medical services, and 5,182 (41%) used private transportation to obtain medical care; the means of transport could not be determined for 612 patients. Of the EMS group, 6,978 were admitted to the hospital without experiencing prehospital cardiac arrest, and 415 (5.6%) arrested before arriving at the hospital. Of the group using private transportation, 5,164 were admitted without arresting and 18 (.35%) arrested before arrival, after which 911 was called (P < .001). CONCLUSION: The incidence of cardiac arrest among patients who attempted to reach the hospital by private transportation was very low compared with the incidence among those who chose the EMS system for transport. This suggests that patient self-selection occurs, with the more seriously ill patients more commonly calling 911 for transport.

Aged↗
PubMed1996

Departmental role and scope in infection control: use of a template that meets Joint Commission requirements.

Since its inception in 1990, departmental role and scope in the infection control program have developed into the five important aspects currently defined by the Joint Commission. Each health care worker needs to understand his or her role in infection prevention and control, integrate it into daily activities, and articulate this role to others. This strategy for complying with Joint Commission standards meets customer needs and can easily be adapted for use in other medical centers. The process of defining departmental roles in the infection control program will continue to evolve with increased awareness of customer needs and emphasis on continuous quality improvement.

Hospital Departments↗
PubMed1996

Effects of transforming growth factor-beta 1 on nitric oxide synthesis by C2C12 skeletal myocytes.

The production of nitric oxide (NO) via the inducible form of NO synthase (iNOS) is regulated by a complex network of cytokines and endogenous hormones. Among these, transforming growth factor-beta (TGF-beta 1) is known to suppress iNOS expression and NO production by many cell types. To determine the effect of TGF-beta 1 on NO production by skeletal muscle cells, we stimulated C2C12 myocytes with interferon-gamma (IFN) and interleukin-1 (IL-1) in the presence or absence of TGF-beta 1. In contrast to findings in macrophages, TGF-beta 1 markedly enhanced NO production by skeletal muscle cells. Increases in NO production reflected significant increases in iNOS immunoreactive protein and iNOS mRNA. Elevated iNOS mRNA levels associated with TGF-beta 1 treatment were not due to an alteration in mRNA stability, but rather reflected a significantly increased transcriptional rate of the iNOS gene. These findings indicate that TGF-beta 1 enhances iNOS expression in skeletal muscle cells and suggest that the regulation of NO production by TGF-beta 1 may depend on the cell type studied.

Animals↗
PubMed1996

Expression of the inducible nitric oxide synthase gene in diaphragm and skeletal muscle.

Nitric oxide (NO) is a pluripotent molecule that can be secreted by skeletal muscle through the activity of the neuronal constitutive isoform of NO synthase. To determine whether skeletal muscle and diaphragm might also express the macrophage-inducible form of NO synthase (iNOS) during provocative states, we examined tissue from mice at serial times after intravenous administration of Escherichia coli endotoxin. In these studies, iNOS mRNA was strongly expressed in the diaphragm and skeletal muscle of mice 4 h after intravenous endotoxin and was significantly diminished by 8 h after challenge. Induction of iNOS mRNA was followed by expression of iNOS immunoreactive protein on Western immunoblots. Increased iNOS activity was demonstrated by conversion of arginine to citrulline. Immunochemical analysis of diaphragmatic explants exposed to endotoxin in vitro revealed specific iNOS staining in myocytes, in addition to macrophages and endothelium. These results may be important in understanding the pathogenesis of respiratory pump failure during septic shock, as well as skeletal muscle injury during inflammation or metabolic stress.

Animals↗
PubMed1996

Phototoxicity of non-steroidal anti-inflammatory drugs: in vitro studies with visible light.

Photosensitivity reactions due to non-steroidal anti-inflammatory drugs (NSAID) are well-known side-effects of these agents and are usually attributed to ultraviolet (UV) radiation. Eight NSAID (carprofen, diclofenac, ibuprofen, ketoprofen, naproxen, piroxicam, phenylbutazone, tiaprofenic acid) were assessed in a photohemolysis test for phototoxic effects in the visible light range. For the studies an experimental visible light lamp was used, emitting 5% UVA at most. To control for UVA-induced effects, additional samples were exposed to appropriate UVA doses from an UVA source and as well to the visible light lamp while being covered by a GG 400 or GG 420 filter. Photo-induced hemolysis was found after exposure to the visible light lamp with carprofen, ketoprofen, naproxen, piroxicam, phenylbutazone or tiaprofenic acid; diclofenac or ibuprofen did not cause photohemolysis. Control irradiation with UVA induced minor hemolysis only with carprofen, ketoprofen and tiaprofenic acid. When the samples were exposed to the filtered visible light lamp, using the GG 400 filter, photohemolysis was found with carprofen, naproxen and phenylbutazone and, using the GG 420 filter, with carprofen and phenylbutazone. Phototoxic effects induced by visible light may be of importance with regard to clinical photosensitization.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Effectiveness of physician-based interventions with problem drinkers: a review.

OBJECTIVE: To review the results of randomized controlled trials on the effectiveness of brief physician interventions with problem drinkers. DATA SOURCES: The MEDLINE and EMBASE databases were searched for articles published from 1966 and 1972 respectively, with the terms "problem/controlled/responsible/moderate/risk/drink"; "advice/drink"; "physician, nurse, general practitioner"; and "random." Forty-three articles were identified in the EMBASE search and 112 articles in the MEDLINE search. STUDY SELECTION: All trials examining the effectiveness of interventions by physicians in reducing alcohol consumption among problem drinkers attending a health-care facility were reviewed. Trials involving subjects attending an alcohol treatment clinic and those involving interventions delivered solely by nonphysicians were excluded. Eleven trials met the final selection criteria. DATA EXTRACTION: For each article, two of the authors independently assigned a score from 0 to 2 on a number of criteria for validity and generalizability. DATA SYNTHESIS: The four trials with the highest validity scores showed that men in the intervention groups reduced their weekly alcohol consumption by five to seven standard drinks more than the men in the control groups. Results for women were inconsistent. No convincing evidence of declines in alcohol-related morbidity among men or women was found. CONCLUSIONS: The trials support the use of brief interventions by physicians for patients with drinking problems. Although further studies are needed to determine their effect on morbidity and mortality, the public health impact of such interventions is potentially enormous. Further research is needed to determine which patients are best suited for brief interventions, the optimal intensity of treatment and which components of brief interventions are most effective. Research is also needed to establish which strategies are effective in inducing physicians to use brief interventions.

Alcohol Drinking↗