Models that predict the risk of developing breast cancer.
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Biomedical subjects
Publications and source records attributed to B Breuer.
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The influence of transforming growth factor-beta (TGF-beta) on the expression of different forms of small proteoglycans was investigated in human skin fibroblasts and in a human osteosarcoma cell line. TGF-beta was not found to act as a general stimulator of small proteoglycan biosynthesis. In both cell types, an increased expression of the core protein of proteoglycan I was found. However, there was a profound decrease in the expression of a 106 kDa core protein, and either no alteration or a small decrease in the biosynthesis of the collagen-binding small proteoglycan II core protein. These results show that the production of individual members of the small proteoglycan family is differentially regulated.
The fluorescent dye Hoechst 33342 is able to differentiate F9 EC cells at low concentrations. This differentiation is accompanied by synthesis of large amounts of laminin, production of a well-developed cytoskeleton, disappearance of the SSEA-1 antigen, and synthesis of large amounts of fibronectin, all characteristics of the primitive endoderm. The dye immediately blocks the cells at the S/G2 phase of the cell cycle and produces a complete arrest in proliferation. This effect is not specific for the nullipotent F9 cell line, as multipotent EC cell lines like PCC3, P19, and PCC4 can also be easily differentiated into the same pathway by treatment with the Hoechst dye. In contrast, the dye has no remarkable effects on terminal differentiated, immortalized cells like NIH 3T3 or the parietal endoderm-like cell PYS-2.
STUDY OBJECTIVE: Buffered lidocaine was compared with plain lidocaine as a local anesthetic for simple lacerations. DESIGN: Randomized, double-blind, prospective clinical trial. SETTING: Urban emergency department. TYPE OF PARTICIPANTS: Ninety-one adult patients with simple linear lacerations were enrolled. Patients with allergy to lidocaine and patients with an abnormal mental status were excluded. INTERVENTIONS: Each wound edge was anesthetized with either plain or buffered lidocaine using a randomized, double-blind protocol. The pain of infiltration was measured with a previously validated visual analog pain scale. MEASUREMENTS AND MAIN RESULTS: Analysis of pooled data and paired data (using patients as their own controls) revealed that infiltrating buffered lidocaine was significantly less painful than plain lidocaine (P = .03 and P = .02, respectively). There was no significant difference in the anesthetic effectiveness of the two agents during suturing. CONCLUSION: Buffered lidocaine is preferable to plain lidocaine as a local anesthetic agent for the repair of simple lacerations.
From a mouse genomic DNA library we have isolated sequences containing the entire coding region for histone H1(0) mRNA, flanked by several kb at both the 3' and 5' ends. Deletions of the 5' upstream region ligated to the chloramphenicol acetyltransferase (CAT)-encoding gene as a reporter, have shown that a region from bp -400 to -600 is necessary and sufficient for efficient transcription. We have also shown that treatment of F9 teratocarcinoma cells with retinoic acid and cyclic AMP (which differentiates F9 cells to parietal endoderm) clearly increases CAT activity several times over the level found in untreated F9 cells. This increase was observed in transient, as well as in stably transfected cells. Analysis of the deletions in differentiating cells indicates that the element responsible for the observed increase in CAT activity, is contained within the first 700 bp upstream from the H1(0) mRNA cap site.
We have isolated and characterized cDNA clones coding for the H1 histone subtype H1(0) in mouse teratocarcinoma cells. The mRNA is 2100 nt long and contains a coding sequence which is highly related to that of the human H1(0) gene. Using this cDNA as a probe, we have shown that, in comparison to undifferentiated F9 cells, differentiated F9 teratocarcinoma cells contain large amounts of H1(0) mRNA. This increase takes place very early during differentiation and does not correlate with changes in the rate of cell division. This indicates that the accumulation of H1(0) mRNA is not the result of reduced proliferation. Most likely on the contrary, the increase in the amount of H1(0) and the resulting effects on the formation of high order chromatin structures are parts of the differentiation program induced in F9 cells.
To study the assembly of intermediate filaments in vivo we have transfected fibroblast cell lines with the cDNAs coding for keratins 8 and 18 under the control of the promoter of the SV40 early region and followed keratin expression by RNA hybridization, two-dimensional gel electrophoresis, and immunofluorescence analysis. When expressed individually, keratins 8 and 18 failed to polymerize into intermediate filaments but formed granular aggregates of variable size distributed throughout the cytoplasm as seen by staining with specific antibodies. The expression of one of these two keratins did not induce the synthesis of its partner or of any other keratin. Coexpression of the two keratins produced filamentous structures, frequently perinuclear, indicating that the two types of polypeptides were able to assemble into intermediate filaments but could not form the cytoskeleton characteristic of epithelial cells. These results demonstrate that assembly in heterocomplexes stabilizes keratins against cellular degradation, helping to explain why excess pools of simple keratins have never been detected.
A prospective study to determine if regular leisure-time physical activity (including recreational walking) is associated with fracture risk was conducted in a large cohort (N = 3110) of free-living elderly men and women in the retirement community of Dunedin, Florida. Sixty-three percent of the cohort was female, all were white, and the average age was 73.0 years +/- 5.3 (SD). Participants in regular physical activity at baseline had a reduced risk of fracture; the risk ratio (RR) of fracture for men and women, respectively, was RR = 0.41, 95% CI = 0.17 to 1.01 and RR = 0.76, 95% CI = 0.50 to 1.15. Walking at least one mile 3 times/week appeared to offer a protective effect for both sexes. After controlling for potentially confounding variables including body mass and selected health conditions, the RR for regular physical activity on fracture incidence in men and women remained essentially unchanged. We conclude that regular physical activity such as walking may protect against fracture in older persons.
This paper describes novel and rapid thin-layer chromatography procedures for the analysis of fatty acids and methyl esters using silver-impregnated alumina sheets. These techniques are known in most laboratories, and the equipment is readily available. The fatty acid method allows a separation of petroselinic (C18:1 delta 6c), oleic (C18:1 delta 9c), elaidic (C18:1 delta 9t), erucic (C22:1 delta 13c), and brassidic acids (C22:1 delta 13t), and the methyl ester method gives an excellent resolution with respect to the number, configuration, and position of the unsaturated centers. Sufficient separation for the subsequent ozonolysis and chromatographic quantification of isomeric C18 and C22 fatty acid methyl esters is obtained with both methods.
The risk of the spread of hepatitis B virus infection from deinstitutionalized, mentally retarded carriers to pupil and staff school contacts in the New York City public school system was measured serologically in a three-phase study from 1978 to 1982. In the third phase, undertaken in 1982, blood samples were drawn and questionnaires were completed on students and staff tested in either of the first two phases and on comparison groups with intermediate and no known school exposure to deinstitutionalized carriers. Univariate and logistic regression analyses revealed that staff and pupils with a history of classroom exposure to a hepatitis B virus carrier had significantly increased prevalences of hepatitis B virus infection (13.4%, odds ratio = 1.9; 9.3%, odds ratio = 2.5, respectively). Similarly, yearly seroconversion rates of 1.3% and 0.67% indicate that staff and, to a lesser extent, pupils are at increased risk of infection.
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The relationships of serum lipids with Alzheimer's disease (AD) and other dementias in very old patients are not clear. All residents of an academic nursing home were studied clinically for dementia and for serum lipids. All those autopsied over a 7.7-year period had apolipoprotein E (apoE) genotyping and detailed neuropathological examination. Those with pathologically defined criteria for AD (n = 84) were compared to all others who also had clinical dementia but did not show AD changes (n = 22). In contrast to most other reports of serum lipids in very old patients with AD, total cholesterol (TC) and low density lipoprotein cholesterol levels were each significantly higher for those with AD. The lipid-AD associations were progressively stronger with increasing pathological certainty of AD diagnosis. These relationships remained significant after adjustment for apoE genotype and for other known risk factors. The lipid-AD associations in a very old cohort, and prior evidence that elevated TC in middle life is a risk factor for later dementia, prompt consideration of factors associated with lipid metabolism in the development of Alzheimer's dementia.
OBJECTIVE: To examine the prevalence of bedrails and observe whether use of bedrails can be decreased during a bedrails-reduction initiative. DESIGN: A serial, cross-sectional, observational study of bedrail use. PATIENTS AND SETTING: An 816-bed not-for-profit nursing facility with academic affiliation and closed medical staff. Median age of residents was 88.1 (range 62-108); 74% were women and 26% were men. MEASUREMENTS: Observed use of bedrails with classification of bedrail configurations into Enclosure Levels based on percentage of bedsides enclosed; serial census of bedrail use during a restraint-reduction effort. RESULTS: Bedrail configurations fell into five Enclosure Levels based on percentage of the bed enclosed. Over 9 months, total bedrail prevalence increased from 50 to 56%; however, the highest Enclosure Levels decreased from 7.7 to 3.9%. CONCLUSIONS: Bedrail configurations can be placed on a continuum of enclosure, and highest Enclosure Levels can be decreased during a bedrails-reduction program.
This study compares the prevalence of elevated serological levels of erbB-2 and myc proteins in 36 breast cancer patients and 25 healthy, ambulatory female controls. The controls were frequency matched to the cases by age and ethnicity. Oncoprotein levels were determined blind to the "case-control status" of the individual from whom the specimen was derived. Corresponding tissue levels were examined in tumors of the 13 cases from whom sufficient tissue was available. Serum oncoproteins were elevated as follows: erbB-2 in one control (4%) compared with nine cases (25%; PFisher's exact = 0.03); myc in no control (0%) compared with seven cases (19%; PFisher's exact = 0.02). Elevated serum levels of erbB-2 or myc oncoproteins were detected in four of the seven cases (57.1%) of in situ cancer without evidence of infiltration. In all cases with elevated serum oncoproteins where tumor tissue was available, the corresponding protein was elevated in the tumor. The three cases who had elevated preoperative serum oncoprotein levels and from whom it was possible to procure postoperative specimens had normal postoperative serum oncoprotein levels. We conclude that (a) erbB-2 and myc oncoproteins are elevated in a proportion of breast cancer patients, (b) the tumor seems to be the source of the serum elevation, and (c) these proteins may be useful as part of a panel of biomarkers of early malignant disease.