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Biomedical subjects

L Baron

Publications and source records attributed to L Baron.

At least 19 recordsLinked to original sources
PubMed2006

Predictive value of magnification chromoendoscopy for diagnosing invasive neoplasia in nonpolypoid colorectal lesions and stratifying patients for endoscopic resection or surgery.

BACKGROUND AND STUDY AIMS: In nonpolypoid colorectal lesions, the presence of irregular, distorted glands in the colon (a disrupted crypt pattern) on magnification chromoendoscopy (MCE) is strongly associated with submucosal invasive cancer. The aim of the present study was to evaluate the ability of MCE to differentiate between an invasive crypt pattern and a noninvasive crypt pattern, including nonneoplastic lesions, and to assess the ability of this MCE classification to predict invasiveness and allow patients to be selected for endoscopic resection or surgical resection. PATIENTS AND METHODS: In a prospective study including 1560 colonoscopies, 153 flat or depressed colorectal lesions were evaluated with MCE among 534 colorectal lesions; the remainder had a polypoid appearance. The pit pattern was classified as nonneoplastic (type II) or neoplastic (types III - V), and the latter was subdivided into noninvasive (types III or IV) or submucosally invasive (type V). Lesions with a nonneoplastic and noninvasive neoplastic appearance were resected endoscopically if technically feasible, whereas those with a type V pattern were resected surgically. The resection specimens were analyzed histologically in relation to the Vienna classification. RESULTS: Using this management strategy based on the pit pattern, 86 % (n = 70) of the type II lesions were hyperplastic; the remaining 11 had low-grade intraepithelial neoplasia. Type III and IV lesions (n = 58) represented either low-grade or high-grade intraepithelial neoplasia in 95 % of the cases. Three patients had sm1 (n = 2) or sm2/3 invasive cancers. Among the patients with type V lesions (n = 14), 11 had invasive cancers (four sm1 and seven sm2/3). Endoscopic differentiation based on the pit pattern thus had a positive predictive value (PPV) of 86 % and a negative predictive value of 96 % for distinguishing between nonneoplastic and neoplastic lesions. The pit pattern criteria for distinguishing between invasive and noninvasive neoplasia (including nonneoplastic lesions), and hence the choice between endoscopic and surgical resection, had a PPV of 79 % and a NPV of 98 %. Excluding nonneoplastic lesions, the NPV would be 95 %. CONCLUSIONS: The endoscopic pit pattern on MCE has only a moderate predictive value for nonneoplastic lesions, so that leaving these flat hyperplastic lesions in place on the basis of the endoscopic magnification appearance alone cannot be generally recommended. However, MCE has a good predictive value for guiding management toward either endoscopic resection (if technically feasible) or surgical resection.

Adult↗
PubMed2002

Fighting colorectal cancer: molecular epidemiology differences among Ashkenazi and Sephardic Jews and Palestinians.

BACKGROUND: To evaluate and compare differences in the molecular genetics among high-risk (Ashkenazi Jews), intermediate-risk (Sephardic Jews) and low-risk (Palestinians) groups for colorectal cancer who live in the same geographical region. PATIENTS AND METHODS: The 1995-1996 records from the Tel Aviv Medical Center and Muqased hospital (East Jerusalem) randomly identified patients with colorectal cancer. There were 25 patients from each ethnic group. Epidemiological data were obtained from interviews with the patients and from their hospital charts. The levels of cyclin D1, beta-catenine, p27, p53, Ki-67 and Her-2/neu proteins were determined by immunohistochemistry. The main outcome measures were the association between gene expression and colorectal incidence in the different ethnic groups. RESULTS: Ashkenazi Jews have the highest rate of colorectal cancer, and are diagnosed at an early stage compared with Palestinians (72% and 33% of the cases are in Dukes' A and B, respectively), and, hence, this may explain the better 5-year survival rate among this group. Sephardic Jews are diagnosed at a more advanced stage, the tumors are poorly differentiated and they lack p27. Palestinians have significantly higher cyclin D1 levels. There was a statistically significant inverse correlation between the expression of beta-catenine and cyclin D1, as well as p53 and p27 (P <0.05). CONCLUSIONS: Increased expression of cyclin D1, p53, Ki-67, beta-catenine and Her-2/neu, and decreased expression of p27 may be important events in the three ethnic groups with colorectal cancer. The lower mortality rate among Ashkenazi Jews may be partially explained by their better molecular biology profile.

Aged↗
PubMed2002

Breast dose variability in a bi-racial population undergoing screening mammography.

This study evaluated individual and population dose variability during screening mammography, among 570 white and black women in South Carolina, USA. Aspects of dosimetry that were considered include compressed breast thickness (CBT), number of films per screening session, and dose in previous or subsequent sessions. Breast dose was log-normally distributed in the population, with a geometric mean of 6.6 mGy per session. Doses were significantly higher for black women, for women with high CBT or who receive more than two views per breast, and for the mediolateral oblique, compared to the craniocaudal, view. No relationship was observed between age and dose. Total dose per breast varied by a factor of 20 across the study population, but the individual's dose varied little among repeat screening sessions, especially after adjusting for the number of films received per session. These results may inform assessments of the projected risks of inducing breast cancer from screening mammography.

Adult↗
PubMed2002

Mammography dose in relation to body mass index, race, and menopausal status.

Mammography dose increases with compressed breast thickness (CBT), but few studies have examined other correlates of dose. The purpose of this study was to evaluate the relation between factors such as race, age, body mass index (BMI), CBT, and menopausal status and mammography screening dose, measured for 509 women in a US population. A multiple linear regression model was developed for dose, based on consideration of these factors as well as examination characteristics. BMI and number of films during examination were positively related to dose. After adjusting for these factors, high CBT also leads to higher dose. Whites receive lower doses than black women but differences are slight after controlling for the effects of CBT and BMI, which were significantly higher among black women. Pre-menopausal women receive higher doses, after adjusting for all other factors, than post-menopausal women. Jointly, these factors account for approximately 75% to 80% of the variability in dose among this study population. Because rates of overweight are increasing in the US, average doses from mammography may be increasing as well.

Adult↗
PubMed2001

Factors influencing choice between mastectomy and lumpectomy for women in the Carolinas.

BACKGROUND AND OBJECTIVES: The Carolinas have been documented to have a low rate of breast-conserving surgery. The purpose of this study was to determine factors that influence women's choice between mastectomy and lumpectomy. METHODS: An anonymous questionnaire was designed for the study and was mailed to women on the mailing lists of cancer organizations in North and South Carolina. Women who had initially been treated in 1995-1998 were included. RESULTS: The rate of breast-conserving surgery (BCS) was 18% and actually declined from a high of 23% in 1995. The highest rate of BCS was in private hospitals rather than academic health science centers. Fifty-four of the 212 respondents believed they were given a choice between mastectomy and BSC and, of these, only 15% (n = 80) chose BSC. Women in the two treatment groups differed in education and income. Sources of treatment-related information included cancer organizations, popular media, friends, family, and the Internet. The most important factor to both groups was perceived probability of cure. Avoidance of radiation treatments was a factor among the mastectomy group. CONCLUSIONS: The low rate of BCS for the region was confirmed. Many women are still unconvinced that BSC offers as great a likelihood of cure as mastectomy.

Adult↗
PubMed2001

Three-dimensional optical tomographic imaging of breast in a human subject.

We present for the first time a full three-dimensional (3-D) reconstruction of absorption images of breast from continuous-wave (cw) measurements performed on a premenopausal woman. Our 3-D optical images clearly reveal a large primary tumor as well as a small secondary tumor in a separate location of the breast. The multiple tumors identified by our 3-D optical imaging have been confirmed by the subsequent biopsy examination of the breast. Quantitative information of the optical images obtained is provided in terms of the location, size, and absorption coefficient of the tumors.

Biopsy↗
PubMed1999

High performance DNA sequencing, and the detection of mutations and polymorphisms, on the Clipper sequencer.

The Visible Genetics Clipper sequencer is a new platform for automated DNA sequencing which employs disposable MicroCel cassettes and 50 microm thick polyacrylamide gels. Two DNA ladders can be analyzed simultaneously in each of 16 lanes on a gel, after labeling with far-red absorbing dyes such as Cy5 and Cy5.5. This allows a simultaneous bidirectional sequencing of four templates. We have evaluated the Clipper sequencer, by cycle-sequencing of an M13 single-stranded DNA standard, and by coupled amplification and sequencing (CLIP) of reverse-transcribed human immunodeficiency virus (HIV-1) RNA standards and clinical patient samples. (i) Limitations of instrument. We have examined basic instrument parameters such as detector stability, background, digital sampling rate, and gain. With proper usage, the optical and electronic subsystems of the Clipper sequencer do not limit the data collection or sequence-determination processes. (ii) Limitations of gel performance. We have also examined the physics of DNA band separation on 50 microm thick MicroCel gels. We routinely obtain well-resolved sequence which can be base-called with 98.5% accuracy to position approximately 450 on an 11 cm gel, and to position approximately 900 on a 25 cm gel. Resolution on 5 and 11 cm gels ultimately is limited by a sharp decrease in spacing between adjacent bands, in the biased reptation separation regime. Fick's (thermal) diffusion appears to be of minor importance on 6 cm or 11 cm gels, but becomes an additional resolution-limiting factor on 25 cm gels. (iii) Limitations of enzymology. Template quality, primer nesting, choice of DNA polymerase, and choice between dye primers and dye terminators are key determinants of the ability to detect mutations and polymorphisms on the Clipper sequencer, as on other DNA sequencers. When CLIP is used with dye-labeled primers and a DNA polymerase of the F667Y, delta(5'--> 3' exo) class, we can routinely detect single-nucleotide mutations and polymorphisms over the 0.35-0.65 heterozygosity range. We present an example of detecting therapeutically relevant mutations in a clinical HIV-1 RNA isolate.

Bacteriophage M13↗
PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome IV has been determined. Apart from chromosome XII, which contains the 1-2 Mb rDNA cluster, chromosome IV is the longest S. cerevisiae chromosome. It was split into three parts, which were sequenced by a consortium from the European Community, the Sanger Centre, and groups from St Louis and Stanford in the United States. The sequence of 1,531,974 base pairs contains 796 predicted or known genes, 318 (39.9%) of which have been previously identified. Of the 478 new genes, 225 (28.3%) are homologous to previously identified genes and 253 (32%) have unknown functions or correspond to spurious open reading frames (ORFs). On average there is one gene approximately every two kilobases. Superimposed on alternating regional variations in G+C composition, there is a large central domain with a lower G+C content that contains all the yeast transposon (Ty) elements and most of the tRNA genes. Chromosome IV shares with chromosomes II, V, XII, XIII and XV some long clustered duplications which partly explain its origin.

Base Sequence↗
PubMed1997

Induction of cyclins E and A in response to mitogen removal: a basic alteration associated with the arrest of differentiation of C2 myoblasts transformed by simian virus 40 large T antigen.

We previously showed that C2 myoblasts transformed by simian virus 40 large T antigen (SVLT) stop the myogenic process after the induction of myogenin and of high Rb levels; the induced Rb, however, becomes notably phosphorylated. We have analyzed the protein levels and activities of cyclin-dependent kinases (cdks) in untransformed C2 cells and in transformants of either SVLT or the cytoplasmic mutant NKT1 (which permits differentiation) upon a shift from growth medium (GM) to mitogen-poor differentiation medium (DM). After the shift, cdk4 levels remained constant and cdk6 levels decreased in all cell types; cdk2 minimally increased only in SVLT cells. Cyclin D1 was downregulated in DM in all cell types, and cyclin D3 was upregulated (albeit less strongly in SVLT cells than in the others). In contrast, a dramatic difference between SVLT cells and the other cells was observed for cyclins E and A, which essentially disappeared (as protein and RNA) in normal C2 and NKT1 cells upon the shift from GM to DM, whereas they increased in SVLT cells. Concurrently, cdk2 activity ceased in C2 and NKT1 cells in DM, whereas it persisted at 20% of the GM level in SVLT cells. cdk4 activity was detectable in all cells only in GM. Cyclin E and A induction thus appeared to sustain enough Rb phosphorylation to interfere with tissue-specific expression, with cdk activity not high enough to activate cyclin self-regulation. In DM, cdk2 complexed to D3 was underphosphorylated in all cells, and SVLT allowed strong inductions of p21 and p27 without affecting their complexes with cdks.

Amino Acid Sequence↗
PubMed1997

From long range mapping to sequence-ready contigs on human chromosome 6.

Our aim is to construct physical clone maps covering those regions of chromosome 6 that are not currently extensively mapped, and use these to determine the DNA sequence of the whole chromosome. The strategy we are following involves establishing a high density framework map of the order of 15 markers per Megabase using radiation hybrid (RH) mapping. The markers are then used to identify large-insert genomic bacterial clones covering the chromosome, which are assembled into sequence-ready contigs by restriction enzyme fingerprinting and sequence tagged site (STS) content analysis. Contig gap closure is performed by walking experiments using STSs developed from the end sequences of the clone inserts.

Chromosomes, Human, Pair 6↗
PubMed1996

Stress resilience, locus of control, and religion in children of Holocaust victims.

Two hundred eight children of Holocaust survivors who were born after their parents' Holocaust experience (children of survivors; COS) and 70 children of parents who left Europe after Hitler's rise to power in 1933 but managed to escape or avoid the Holocaust (children of escapees; COE) were recruited from various Jewish organizations. Research was conducted using questionnaires that were returned by mail. Measures of stress resilience (Kobasa, 1982; Kobasa & Puccetti, 1983), locus of control (Nowicki-Strickland, 1973), and religion (Jewish identity) were administered to all participants. The COS were found to have less resistance to stress and to identify less with feelings of being Jewish. The appropriateness of using COE as a control group and the difficulty of incorporating the unique experiences of the parents into a research study about the intergenerational transmission of coping style is discussed.

Adult↗
PubMed1993

Narcissism, interpersonal adjustment, and coping in children of Holocaust survivors.

We tested the theory of intergenerational transmission, which suggests that the Holocaust trauma, combined with circumstances in the survivors' lives (early loss of a parent, was a child survivor, had a hiding experience) and circumstances in their children's lives (having a father who survived, being the first-born or only child, and not participating in a children of survivors group) would result in poorer interpersonal adjustment and coping and greater narcissism than in children of survivors without these circumstances and children of parents who imigrated from Europe before World War II. Three hundred fifty children (241 children of Holocaust survivors and 109 children o escaped European-born partners) completed four scales of the California Psychological Inventory (Gough, 1988), the O'Brien Multiphasic Narcissism Inventory (O'Brien, 1987), and the Hardiness scale (Kobasa & Puccetti, 1983). The results failed to support the attribution of adjustment and personality differences in children of survivors to survivor status.

Adaptation, Psychological↗
PubMed1992

A high endrin concentration in a fatal case.

Gas chromatography coupled to mass spectrometry was employed to quantify endrin in biological fluids in a death attributed to endrin overdose. The blood concentration of endrin was 544.9 mg/l. Results are discussed in the light of the existing literature.

Adult↗
PubMed1992

Biomolecular regulation of the IgE immune response. I. Cell-associated IgE and in vitro IgE synthesis.

Several cell types, including mast cells, basophils, macrophages/monocytes, lymphocytes, platelets and eosinophils, may bind or contain IgE. To investigate the source of cell-associated IgE and its relation to spontaneous IgE synthesis, peripheral blood mononuclear cells from allergic and non-allergic donors were examined. Using a combination of different cell fractionation techniques and varying methods for extraction of cell-associated IgE, data were obtained indicating that monocytes constitute a major source of cell-associated IgE in human blood. The amount of cell-associated IgE in peripheral blood mononuclear cells from allergic and non-allergic donors varied more than 100-fold but correlated closely to the level of serum IgE (r = 0.84, p < 0.001, n = 38). Spontaneous and mitogen-induced in vitro syntheses of IgA, IgE and IgG were compared for allergic and non-allergic donors. Only one donor with very high serum IgE demonstrated spontaneous or mitogen-induced in vitro IgE synthesis despite synthesis of IgA and IgG.

Asthma↗
PubMed1991

Tn5 mutagenesis of the Salmonella typhimurium 100 kb plasmid: definition of new virulence regions.

In this study, the 100 kb plasmid of Salmonella typhimurium, which is known to contribute to the pathogenicity of the organism, was tagged with the transposon Tn5 to define regions of the plasmid contributing to overall virulence. Eleven randomly selected vir::Tn5 plasmids carried by the plasmid-free S. typhimurium strain WS1321 were physically mapped and then examined in mice for subcutaneous LD50 value, ability to induce splenomegaly, and ability to grow to high numbers in the spleens of infected mice. Nine strains were found to be virulence-attenuated and showed varied levels of growth in the spleens of subcutaneously infected BALB/c mice. Eight of these nine strains carried Tn5 insertions which lie outside the previously defined virulence region. These studies corroborate the findings of other investigators as well as defining novel regions of the 100 kb virulence plasmid involved in the pathogenicity of this organism.

Animals↗
PubMed1990

Inhibitory effects of quinolones on pro- and eucaryotic DNA topoisomerases I and II.

As a means of gaining information on the selectivity of quinolone antibacterial agents, we examined their effect on four topoisomerases, topoisomerases I and II purified from Escherichia coli and calf thymus. The inhibition of supercoiling and relaxation activities was monitored by using the classical gel electrophoresis assay. Eight quinolones were assayed by using the four enzymes. Gyrase was much more sensitive to quinolones than the other topoisomerases which can therefore be inhibited by moderate concentrations of certain quinolones. No good correlation was observed between the activity on gyrase and on the other enzymes, since the ratio varied from 15 to more than 8,500. On the contrary, there was a good correlation between early inhibition of DNA synthesis, inhibition of gyrase, and MICs.

Animals↗