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Biomedical subjects

E Adam

Publications and source records attributed to E Adam.

At least 37 records · Page 2Linked to original sources
PubMed2000

Photocontrol of subcellular partitioning of phytochrome-B:GFP fusion protein in tobacco seedlings.

Photomorphogenesis of higher plants is regulated by photoreceptors including the red/far-red light-absorbing phytochromes, blue-UV/A sensing cryptochromes and as yet uncharacterized UV/B receptors. Specific phototransduction pathways that are controlled by either individual or interacting photoreceptors mediate regulation. Phytochrome B (phyB) is the major red light-sensing photoreceptor. Phototransduction mediated by this light sensor has been shown to include light-dependent nuclear import and interaction of phyB with transcription factor-like proteins in the nucleus. Here we report that nuclear import of phyB and physiological responses regulated by this photoreceptor exhibit very similar wavelength- and fluence rate-dependence. Nuclear import of phyB is insensitive to single red, blue and far-red light pulses. It is induced by continuous red light and to a lesser extent by continuous blue light, whereas far-red light is completely ineffective. The data presented indicate that light-dependent partitioning of phyB exhibits features characteristic of blue light responsiveness amplification, a phenomenon that is thought to be mediated by interaction of phyB with CRY1.

Cell Compartmentation↗
PubMed2000

Endocervical curettage in evaluating abnormal cervical cytology.

OBJECTIVE: To determine the role of endocervical curettage (ECC) in the evaluation of women with abnormal cervical cytology and following treatment for cervical intraepithelial neoplasia. STUDY DESIGN: A retrospective chart review using the records of 2,126 patients who were seen at the Colposcopy Clinic, Baylor College of Medicine, between 1980 and 1995. All patients were referred because of an abnormal cervical smear and underwent repeat Pap smear, colposcopic examination in each case with biopsies as indicated, endocervical curettage and treatment, consisting of either cryotherapy, laser vaporization or a LOOP electrosurgical excision procedure. Following treatment, Pap smears were performed on a scheduled basis, and ECC was performed annually. RESULTS: The ECC was negative in 1,849 (87%) of the women. It was abnormal in 33% of women with unsatisfactory colposcopy and 10% of women with satisfactory colposcopy. ECC was abnormal in 21% of patients with a negative biopsy result and 42% of patients who did not have a biopsy performed. There was a significant increase in abnormal ECC results with increasing age. ECC had a high positive predictive value for ectocervical disease (86%) and a high negative predictive value for endocervical disease (90%). One year following treatment, < 4% of patients with a negative cervical smear had a high grade lesion detected on ECC. CONCLUSION: The use of ECC is helpful in detecting disease missed by routine colposcopy and biopsy and is most likely to detect ectocervical disease rather than true endocervical disease. Following treatment, ECC does not appear to be significantly more reliable than the Pap smear in detecting the presence of significant residual disease.

Adolescent↗
PubMed2000

Frequency of coexistence of cytomegalovirus and Chlamydia pneumoniae in atherosclerotic plaques.

BACKGROUND: Cytomegalovirus (CMV) and Chlamydia pneumoniae (C. pneumoniae) antigens and DNA sequences have been demonstrated in atherosclerotic plaques by several investigators. Most significantly, CMV DNA was found both in atherosclerotic lesions as well as in uninvolved areas of aortas and carotid artery, whereas C. pneumoniae was mostly detected in advanced carotid atherosclerotic lesions. METHODS AND RESULTS: Atherosclerotic plaques removed from seventeen patients during carotid endarterectomy were analysed for the simultaneous presence of CMV and C. pneumoniae DNA sequences using polymerase chain reaction (PCR). Of the seventeen samples, nine (53%) were positive for CMV DNA sequences and seven (41%) contained C. pneumoniae DNA sequences. Four samples (24%) were positive for both CMV and C. pneumoniae DNA. CMV DNA or C. pneumoniae DNA was detected in 12 (71%) of 17 carotid plaques and 2 additional patients had high titers of antibodies to CMV. CMV DNA and C. pneumoniae DNA were found in the same tissue specimens in 4 (24%) patients. CONCLUSIONS: These results present evidence that CMV DNA and/or C. pneumoniae DNA can be detected in 71% of carotid atherosclerotic plaques and in some instances DNA of both agents in the same tissue. The possible pathogenetic role of these agents in the initiation or promotion of the development of atherosclerotic plaques deserves increased attention.

Adult↗
PubMed1999

HIV-1 tat transcriptional activity is regulated by acetylation.

The human immunodeficiency virus (HIV) trans- activator protein, Tat, stimulates transcription from the viral long-terminal repeats (LTR) through an RNA hairpin element, trans-activation responsive region (TAR). We and others have shown that trans-activator protein (Tat)-associated histone acetyltransferases (TAHs), p300 and p300/CBP-associating factor (PCAF), assist functionally in the activation of chromosomally integrated HIV-1 LTR. Here, we show that p300 and PCAF also directly acetylate Tat. We defined two sites of acetylation located in different functional domains of Tat. p300 acetylated Lys50 in the TAR RNA binding domain, while PCAF acetylated Lys28 in the activation domain of Tat. In support of a functional role for acetylation in vivo, histone deacetylase inhibitor (trichostatin A) synergized with Tat in transcriptional activation of the HIV-1 LTR. Synergism was TAR-dependent and required the intact presence of both Lys28 and Lys50. Mechanistically, acetylation at Lys28 by PCAF enhanced Tat binding to the Tat-associated kinase, CDK9/P-TEFb, while acetylation by p300 at Lys50 of Tat promoted the dissociation of Tat from TAR RNA that occurs during early transcription elongation. These data suggest that acetylation of Tat regulates two discrete and functionally critical steps in transcription, binding to an RNAP II CTD-kinase and release of Tat from TAR RNA.

3T3 Cells↗
PubMed1999

Is human papillomavirus testing of value in clinical practice?

The objective of this review was to evaluate the current status of human papillomavirus testing in predicting the presence of high-grade or invasive disease in the cervix in women with Papanicolaou smears reported as atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion. This is a review of many of the studies already published evaluating the utility of human papillomavirus testing as part of the triage for patients whose Papanicolaou smears were reported as ASCUS or low-grade squamous intraepithelial lesion. Two triage approaches for follow-up of such patients are presented, and recommendations are made as to which is most cost-effective and safe. Data related to human papillomavirus testing were obtained with both currently available commercial kits for detection of high-risk human papillomavirus and the polymerase chain reaction. There was variation in results reported, possibly related to populations studied. The approach to management by cytologic screening and colposcopy, when indicated, appeared over the long term to be equal to human papillomavirus testing. In our opinion current human papillomavirus testing is of little clinical use to the practitioner. Its use should be limited to appropriately designed and implemented research studies.

Cervix Uteri↗
PubMed1999

Evidence of SV40 infections in hospitalized children.

Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.

Adolescent↗
PubMed1999

Light quality-dependent nuclear import of the plant photoreceptors phytochrome A and B

The phytochrome (phy) family of plant photoreceptors controls various aspects of photomorphogenesis. Overexpression of rice phyA-green fluorescent protein (GFP) and tobacco phyB-GFP fusion proteins in tobacco results in functional photoreceptors. phyA-GFP and phyB-GFP are localized in the cytosol of dark-adapted plants. In our experiments, red light treatment led to nuclear translocation of phyA-GFP and phyB-GFP, albeit with different kinetics. Red light-induced nuclear import of phyB-GFP, but not that of phyA-GFP, was inhibited by far-red light. Far-red light alone only induced nuclear translocation of phyA-GFP. These observations indicate that nuclear import of phyA-GFP is controlled by a very low fluence response, whereas translocation of phyB-GFP is regulated by a low fluence response of phytochrome. Thus, light-regulated nucleocytoplasmic partitioning of phyA and phyB is a major step in phytochrome signaling.

Journal Article↗
PubMed1998

Cancer risk in women exposed to diethylstilbestrol in utero.

CONTEXT: The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero. OBJECTIVE: To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up. DESIGN: A cohort study with mailed questionnaires and medical record review of reported cancer outcomes. PARTICIPANTS: A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s. MAIN OUTCOME MEASURES: Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters. RESULTS: To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result. CONCLUSIONS: Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years.

Adenocarcinoma, Clear Cell↗
PubMed1998

Phosphorylation of bovine leukemia virus Tax protein is required for in vitro transformation but not for transactivation.

The Tax proteins of the oncovirinae viruses are phosphorylated transcriptional activators that exhibit oncogenic potential. The role of phosphorylation in their functional activities remains unknown. As a model for the Human T-cell leukemia virus type I (HTLV-I), Bovine Leukemia Virus (BLV) permits the characterization of viral replication and leukemogenesis in vivo. Here, we show that the BLV Tax protein is phosphorylated on serine residues 106 and 293 both in insect and in mammalian cells. These sites can also be efficiently phosphorylated by the cdc2 and MAP kinases in vitro. Mutation of these residues does not affect the capacity of the Tax protein to function as a transactivator. Indeed, the Tax proteins mutated at one or both serines increase LTR-directed viral transcription at levels similar to those obtained with wild-type Tax in cell culture. Moreover, inhibition of Tax phosphorylation by W7, a calmodulin antagonist, does not alter its transactivation activity. Thus, phosphorylation on serines 106 and 293 is not required for transactivation by Tax. However, simultaneous substitution of both serines into alanine residues destroys the capacity of Tax to cooperate with the Ha-ras oncogene to transform primary rat embryo fibroblasts and induce tumors in nude mice. When the serines were replaced with aspartic acid residues, the oncogenic potential of Tax was maintained indicating that the negative charge rather than the phosphate group itself was required for Tax oncogenicity. Finally, to assess the role of the serine residues in vivo, recombinant viruses which express the Tax mutants were constructed and injected into sheep. It appeared that the mutated proviruses replicate at levels similar to the wild-type virus in vivo. We conclude that Tax phosphorylation is dispensable for transactivation and viral replication in vivo but is required for its oncogenic potential in vitro.

Animals↗
PubMed1998

Control of protein splicing by intein fragment reassembly.

Inteins are protein splicing elements that mediate their excision from precursor proteins and the joining of the flanking protein sequences (exteins). In this study, protein splicing was controlled by splitting precursor proteins within the Psp Pol-1 intein and expressing the resultant fragments in separate hosts. Reconstitution of an active intein was achieved by in vitro assembly of precursor fragments. Both splicing and intein endonuclease activity were restored. Complementary fragments from two of the three fragmentation positions tested were able to splice in vitro. Fragments resulting in redundant overlaps of intein sequences or containing affinity tags at the fragmentation sites were able to splice. Fragment pairs resulting in a gap in the intein sequence failed to splice or cleave. However, similar deletions in unfragmented precursors also failed to splice or cleave. Single splice junction cleavage was not observed with single fragments. In vitro splicing of intein fragments under native conditions was achieved using mini exteins. Trans-splicing allows differential modification of defined regions of a protein prior to extein ligation, generating partially labeled proteins for NMR analysis or enabling the study of the effects of any type of protein modification on a limited region of a protein.

Bacterial Proteins↗
PubMed1998

Is human papillomavirus testing an effective triage method for detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia?

OBJECTIVE: Our purpose was to assess the usefulness of the polymerase chain reaction assay for detection of human papillomavirus infection for prognostic value in the triage strategies for high-grade (grade 2 or 3) cervical intraepithelial neoplasia in women referred for colposcopy after abnormal Papanicolaou smears. STUDY DESIGN: A total of 1007 women referred to a colposcopic clinic providing care for an indigent population were studied. Four hundred fifty-four women were referred after two Papanicolaou smears reported as atypical squamous cells of undetermined significance or low grade-squamous cervical intraepithelial lesion, and 553 were referred after a single smear reported as high-grade squamous intraepithelial lesion. All women had a cervical smear, colposcopy-directed biopsy, and endocervical curettage performed. A sample for human papillomavirus deoxyribonucleic acid detection by polymerase chain reaction was obtained. RESULTS: High-risk human papillomavirus types were detected in 463 (46%) of 1007 women studied. There was a significant increase of the frequency of high-risk human papillomavirus by the increasing severity of biopsy findings ranging from 32.7% in women without cervical intraepithelial neoplasia on biopsy to 60% in women having grade 2 or 3 on the biopsy specimen. Women having a negative Papanicolaou smear found to have high-risk human papillomavirus deoxyribonucleic acid at the time of colposcopy had a significantly higher rate of grade 2 or 3 cervical intraepithelial neoplasia on the biopsy specimen than did women without high-risk human papillomavirus. There was no such difference observed in women with a cytologic finding of low- or high-grade squamous intraepithelial lesions at the time of colposcopy. The polymerase chain reaction assay appears to be more sensitive than the commercial human papillomavirus profile test. The positive predictive value for grade 2 or 3 cervical intraepithelial neoplasia of both tests was similar (21.7% and 22.8%, respectively). CONCLUSION: The human papillomavirus is associated with high-grade cervical intraepithelial neoplasia, but the screening for human papillomavirus deoxyribonucleic acid does not have prognostic value in women reported as having atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions on two precolposcopy Papanicolaou smears.

Biopsy↗
PubMed1998

Epithelial glycoprotein-2 expression is subject to regulatory processes in epithelial-mesenchymal transitions during metastases: an investigation of human cancers transplanted into severe combined immunodeficient mice.

The human cell-surface antigen epithelial glycoprotein-2 recognized by the monoclonal antibody MOC-31 is an epithelial tumour-associated glycoprotein expressed in non-squamous carcinomas. MOC-31 immunoreactivity was investigated in human breast, colon, ovarian and lung cancer cell lines, grown either in vitro or in severe combined immunodeficient (SCID) mice as solid tumours and/or metastases. Three of four small-cell lung cancer cell lines (NCI-H69, OH3 and SW2) and three of four ovarian cancer cell lines (SoTu 1, 3 and 4) expressed epithelial glycoprotein-2. In contrast, all three breast (MCF-7, BT20, T47D) and all three colon (HT29, CACO2, SW480) cancer cell lines strongly reacted with monoclonal antibody MOC-31. A notable difference in MOC-31 immunoreactivity was observed in spontaneously formed lung metastases of HT29 colon cancer cells. Whereas larger metastases (> 30 cells) reacted with a similar staining pattern to the primary tumour, smaller metastases did not. These findings indicate that differentiation processes during the epithelial-mesenchymal transition occur in metastases, which lead to a transient loss of epithelial glycoprotein-2 expression during the migratory and early post-migratory period. This loss of antigen expression indicates that the process of metastases formation is a regulatory event, and this transient loss of antigen expression might represent a potential obstacle to antibody-based therapy in the setting of minimal residual disease.

Animals↗
PubMed1998

Cytochrome c biogenesis is involved in the transposon Tn5-mediated bleomycin resistance and the associated fitness effect in Escherichia coli.

The transposon Tn5 ble gene and the Escherichia coli alkylation-inducible aidC locus are co-operatively involved in the resistance to the anti-cancer drug and DNA-cleaving agent bleomycin and enhance fitness of bacteria in the absence of the drug. In this report, we demonstrate that the aidC locus is identical to nrfG, the last gene of the nrf operon involved in the periplasmic formate-dependent nitrite reduction. In the presence of Ble, NrfG expression is specifically induced and restores both bleomycin resistance and its associated beneficial growth effect in an aidC- strain. In vitro DNA protection assays reveal that purified Ble prevents bleomycin-mediated DNA breakage, as do bleomycin-binding proteins. Similarities between haems of the cytochrome c biogenesis nrf pathway and iron bleomycin suggest a DNA repair-independent molecular mechanism for both bleomycin resistance and increased viability. The Ble protein binds bleomycin and prevents DNA breakage. It also induces the nrf locus that may assimilate bleomycin into haem for extracellular transport or inactivate bleomycin. Inactivation of potent DNA oxidants confers a better fitness to the bacterium carrying the transposon, suggesting a symbiotic relationship between host and transposon.

Anti-Bacterial Agents↗
PubMed1998

Rest and exercise hemodynamics after the Ross procedure: an echocardiographic study.

BACKGROUND: Aortic prosthetic valves with superior hemodynamic performance are associated with more complete regression of left ventricular hypertrophy and better left ventricular function postoperatively. The near normal function of the pulmonary autografts at rest is well documented, however, exercise data has been seldom reported. The purpose of this study is to evaluate the hemodynamic performance of pulmonary autografts in the aortic position and the homografts used to reconstruct the right ventricular outflow tract during conditions of high cardiac output by means of dobutamine stress echocardiography. METHODS: Between May 1995 and February 1998, 67 patients were submitted to a Ross operation at our institution. Twenty of these patients had a mean age of 28.6+/-8.3 years and a mean follow-up time of 15.7+/-5.9 months. They were studied by dobutamine stress echocardiography to evaluate rest and exercise hemodynamics of the pulmonary autografts as well as of the aortic and pulmonary homografts used to reconstruct the right ventricular outflow tract. Dobutamine infusion was started at 5 microg/kg with incremental doses up to 40 microg/kg in every case. RESULTS: With dobutamine infusion, heart rate increased from 71+/-10 to 142+/-11 beats/min, left ventricular systolic volume from 86.8+/-33.9 mL to 115.9+/-52.6 mL, and cardiac output from 6.3+/-2.9 L/min to 16.8+/-7.4 L/min. Left ventricular function was considered satisfactory at rest and during exercise in all patients. The mean gradient across the autograft increased from 1.03+/-0.95 mmHg to 4.03+/-2.05 mmHg and maximal instantaneous gradient from 2.45+/-2.21 mmHg to 9.54+/-4.85 mmHg. The mean effective orifice area for the autografts were 3.5+/-1.3 cm2 at rest and 3.3+/-1.4 cm2 during exercise. The patients with mild aortic insufficiency at rest had no increase in the degree of regurgitation with exercise. In the right ventricular outflow tract, the mean gradient across the homograft increased from 9.06+/-5.29 mmHg to 17.55+/-9.76 mmHg and maximal instantaneous gradient from 21.4+/-12.5 mmHg to 41.5+/-23.1 mmHg. CONCLUSIONS: Pulmonary autografts exhibit normal hemodynamic performance at rest and during exercise after the Ross operation. However, mild-to-moderate gradients are common at the right ventricular outflow tract and should be carefully monitored.

Adolescent↗
PubMed1998

Immunohistochemical detection of the MUC1 gene product in human cancers grown in scid mice.

Alterations in mucin expression have been detected in many clinically relevant cancers and, in particular, the polymorphic epithelial mucin, encoded by the MUC1 gene, has attracted considerable attention. We investigated its expression in human breast, colon, ovarian, lung, and skin cancer cells and their metastases grown in severe combined immunodeficient (scid) mice using three different monoclonal antibodies (HMFG-1, HMFG-2, and SM3). Four of five breast cancer cell lines, three of five colon cancer cell lines, two of three small-cell carcinoma of the lung cell lines, and A 431 cells all expressed the MUC1 gene product. Neuraminidase predigestion often enhanced HMFG-1 immunoreactivity, which was more widespread and stronger than SM3 immunoreactivity. A considerable heterogeneity of MUC1 gene product expression was observed in the same tumors grown in different mice. The binding pattern between single-cell/small-cell clusters (up to 10 cells) and larger cell number aggregates varied. The results indicate that the MUC1 gene expression both in primary tumors and metastases is not tightly controlled within a particular tumor cell line. Because of this heterogeneous antigen expression in vivo, it appears impossible to target all metastatic deposits by a single monoclonal antibody directed against the MUC1 gene product. (J Histochem Cytochem 46:127-134, 1998)

Animals↗