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Biomedical subjects

M Brown

Publications and source records attributed to M Brown.

At least 253 records · Page 14Linked to original sources
PubMed1997

Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4.

Cyclin D1 plays an important role in the development of breast cancer and is required for normal breast cell proliferation and differentiation associated with pregnancy. We show that ectopic expression of cyclin D1 can stimulate the transcriptional activity of the estrogen receptor in the absence of estradiol and that this activity can be inhibited by 4-hydroxytamoxifen and ICI 182,780. Cyclin D1 can form a specific complex with the estrogen receptor. Stimulation of the estrogen receptor by cyclin D1 is independent of cyclin-dependent kinase 4 activation. Cyclin D1 may manifest its oncogenic potential in breast cancer in part through binding to the estrogen receptor and activation of the transcriptional activity of the receptor.

Biomarkers, Tumor↗
PubMed1997

Human estrogen receptor (ER) gene promoter-P1: estradiol-independent activity and estradiol inducibility in ER+ and ER- cells.

Estrogen receptor (ER) is expressed at a low level in normal tissues such as breast and uterus but at a high level in breast and endometrial carcinomas. A proximal element (ERF-1) located between positions +133 and +204 relative to the promoter P1 major initiation site has been recently identified in ER+ cells and contributes to the differential promoter activity between ER+ and ER- cells. In this study, MCF7 and HeLa cells were transfected with chloramphenicol acetyltransferase constructs containing ER gene promoter P1 sequences. We show here that the sequences lying between nucleotides +13 to +212 are also essential for transcription at the ER gene promoter P1 in ER- cells, which do not express ERF-1. Interestingly, on gel shift experiments, a complex specific to ER- cells forms in the region spanning nucleotides +123 to +210. We also show that promoter P1 is responsive to estradiol in cells expressing endogenous (MCF7) or exogenous ER. We further demonstrate, using mutational analysis and gel retardation assays, that the three half-estrogen response elements located between nucleotides -420 and -892 are responsible for the estradiol inducibility of promoter P1. Because estradiol has a mitogenic effect on both breast and endometrial epithelial cells, our data would give an insight into the role of estrogens in the occurrence of breast and endometrial carcinomas.

Baculoviridae↗
PubMed1997

Comparison of current waveforms for the electrical stimulation of residual low frequency hearing.

Many cochlear prostheses employ charge-balanced biphasic current pulses. These pulses have little energy at low frequencies resulting in limited stimulation of low frequency hearing by mechanical responses to the electrical stimulus. However, if electro-mechanical transduction within the cochlea is nonlinear, electrical stimulation with asymmetric, charge-balanced current pulses may result in a mechanical response with significantly more low frequency energy. We estimated the mechanical response at low frequencies to pulsatile electrical stimulation of the cochlea. The auditory nerve compound action potential evoked by low frequency tones was forward-masked by a train of symmetric or asymmetric current pulses. Masking by asymmetric current pulses was not significantly different from masking by symmetric pulses matched for pulse duration and charge. In conclusion, there appears to be no advantage to using asymmetric current pulses for the mechanical stimulation of residual low frequency hearing by electrical stimulation of the cochlea.

Animals↗
PubMed1997

Variability of amplitude and area of the auditory nerve compound action potential.

The strength of neural response to sensory stimuli is often estimated by measurement of the amplitude of gross neural potentials. These gross potentials reflect the summed activity of a population of neurons. The amplitude of these potentials is dependent upon the synchrony of the contributing neural responses. We compared the variability of the peak-to-peak amplitude of the auditory nerve compound action potential (CAP) with that of the area under the peaks. The area under the peaks was significantly less variable than the amplitude for responses to low frequency stimuli. Responses to other stimuli showed differences in the same direction, but these were not significant. We conclude that the area under these peaks is a more precise measure of neural response than measurement of waveform amplitude at least for responses to low frequency stimuli.

Acoustic Stimulation↗
PubMed1997

A polymorphism of the 5 alpha-reductase gene and its association with prostate cancer: a case-control analysis.

Prostate cancer (CaP) is the most commonly diagnosed, nondermatological cancer in the United States. The development and progression of CaP is influenced by androgens. 5 alpha-Reductase, type II, converts testosterone to dihydrotestosterone and is critical to the development of the prostate. A TA dinucleotide repeat polymorphism exists in the 3' untranslated region of the 5 alpha-reductase type II gene. 5 alpha-Reductase alleles with longer TA repeats are more common in African-Americans, the group with the highest incidence of CaP. It has been hypothesized that the longer TA repeat alleles might be associated with increased risk of CaP. We studied this potential association within the Physician's Health Study, a predominantly Caucasian cohort study. Using PCR we identified the TA genotype in 590 men with CaP and 802 age-matched controls. The frequency of each allele in the controls was TA(0), 0.87, TA(9), 0.13, and TA(18), 0.01. Homozygotes for the longer TA alleles, TA(9) and TA(18), were underrepresented among cases with an odds ratio of 0.47 (confidence interval, 0.20-1.12), but this was not statistically significant (P = 0.08, two tailed). Our analysis does not support the prior hypothesis that longer TA alleles confer an increased risk of CaP in a predominantly Caucasian population; in fact, longer TA alleles are more prevalent in men without CaP.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1997

Necrotizing fasciitis: a case study.

Necrotizing fasciitis (NF) is a disease characterized by the destruction of the skin, subcutaneous fat, and fascia, with or without inflammation of the muscle tissue. NF carries a mortality rate in excess of 50 percent in neonates. Rapid diagnosis and initiation of antibiotics, along with meticulous nursing care, can provide an acceptable outcome for the neonate. This article reviews the pathophysiology, diagnosis, and treatment of NF; presents a case study; and provides a nursing care plan that supports treatment of this disease process.

Anti-Bacterial Agents↗
PubMed1997

Predisposing factors to spondyloarthropathies.

Predisposition to ankylosing spondylitis is largely genetic, and epidemiologic studies suggest that the environmental trigger is ubiquitous. HLA-B27 and -B60 predispose to ankylosing spondylitis, but in neither case is the mechanism of effect known. Other major histocompatibility complex and non-major histocompatibility complex genes are likely to influence susceptibility to spondyloarthritis as well as the disease pattern. Spondyloarthritis occurs in genetically predisposed individuals exposed to certain as yet undefined environmental triggers. A though genes within the major histocompatibility complex are clearly major determinants of susceptibility to spondyloarthritis, epidemiologic evidence suggests that their contribution accounts for less than 50% of the total. The mechanism of association of B27 with these diseases is unknown; we are currently unable to predict which B27 carriers will develop arthritis or which form of B27-associated spondyloarthritis they will develop. Lessons from transgenic animal experiments and technical and statistical advances in the field of genetics have greatly increased our ability to investigate these questions.

Humans↗
PubMed1997

Five years of work-related injuries and fatalities in Minnesota. Agriculture: a high-risk industry.

This report describes the Minnesota Fatality Assessment and Control Evaluation Study (MN FACE), a federally funded initiative to study fatal injuries in the workplace. The purpose of the program is to investigate various types of occupational fatalities and to identify risk factors that contribute to work-related fatalities. Initially, the MN FACE program only investigated fatalities related to falls, confined spaces, and electrocutions. In 1994, MN FACE also began investigating fatalities associated with agricultural work. Agriculture continues to be one of the nation's most hazardous industries, ranking fourth among industries in the United States at high risk for work-related fatalities. MN FACE investigated 46 agriculture-related fatalities during 1994-95. Forty-one percent of the fatalities involved tractors, and 66% of these accidents were tractor rollovers. Other leading causes of agricultural fatalities included grain bin and manure pit asphyxiations.

Accidents, Occupational↗
PubMed1996

p300 is a component of an estrogen receptor coactivator complex.

The estrogen receptor (ER) is a ligand-dependent transcription factor that regulates expression of target genes in response to estrogen in concert with other cellular signaling pathways. This suggests that the mechanism by which ER transmits an activating signal to the general transcription machinery may include factors that integrate these diverse signals. We have previously characterized the estrogen receptor-associated protein, ERAP160, as a factor that complexes with ER in an agonist-dependent manner. We have now found that the transcriptional coactivator p300 associates with agonist bound ER and augments ligand-dependent activation by ER. Our studies show that an ER coactivator complex involves a direct hormone-dependent interaction between ER and ERAP160, resulting in the recruitment of p300. In addition, antibodies directed against the cloned steroid receptor coactivator 1 (SRC1) recognize ERAP160. The known role of p300 in multiple signal transduction pathways, including those involving the second messenger cAMP, suggests p300 functions as a point of integration between ER and these other pathways.

Animals↗
PubMed1996

Reverse transcriptase mutations in HIV-1-infected children treated with zidovudine.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutations were detected in DNA from peripheral blood mononuclear cells from 11 of 12 HIV-1-infected children after 11-20 months of zidovudine monotherapy. The number of children with mutations detected at each codon were as follows: codon 41, 4; codon 67, 2; codon 70, 7; codon 215, 7; codon 219, 0. Codon 41 mutations were found only in the presence of a codon 215 mutation and in the absence of a codon 70 mutation. The codon 41/215 mutant combination was associated with decline in weight-for-age z score during therapy, weight < 10th percentile, CD4+ cell counts < 3rd percentile, and immune-complex dissociated HIV-1 p24 antigen (ICD p24 Ag) levels > 100 pg/ml. Patients developing the codon 70 mutation tended to have body weight > 30th percentile, CD4+ cell counts > 25th percentile, and ICD p24 Ag < 100 pg/ml. The codon 41 mutation was associated with clinical deterioration during a 6-month followup period.

Anti-HIV Agents↗
PubMed1996

Renal failure after two myocardial infarctions.

A 60-year-old man was admitted to the hospital for elective cardiac catheterization. He had had two myocardial infarctions (MI) one and two months earlier. After the second MI, he had been treated with tissue plasminogen activator and heparin. Since then, his blood urea nitrogen concentration had increased from 20 to 63 mg/dL and his blood creatinine concentration from 1.2 to 9.2 mg/dL.

Acute Kidney Injury↗