PubMed Health⌕ Search

Biomedical subjects

J C Chambers

Publications and source records attributed to J C Chambers.

36 records · Page 2Linked to original sources
PubMed1997

Pulmonary autograft procedure for aortic valve disease: long-term results of the pioneer series.

BACKGROUND: Pulmonary autograft replacement of the diseased aortic valve has not been widely practiced due to concerns regarding late autograft competence and the consequences of creating pulmonary valve disease. To investigate this, the fate of the pioneering series of patients has been determined. METHODS AND RESULTS: The 131 hospital survivors of the pulmonary autograft operation at the National Heart Hospital from 1967 to 1984 were identified and their outcomes determined to 1994. Age at operation was 11 to 52 years, and 109 patients were male. Autograft implantation was orthotopic subcoronary (107), free-standing root (20), or Dacron mounted (2). In 113 patients, homografts replaced the native pulmonary valve. Ten and 20 years after operation, survival was 85% and 61%, freedom from autograft replacement was 88% and 75%, and freedom from replacement of pulmonary position homografts was 89% and 80%, respectively. Causes of deaths (53) included chronic heart failure (13), complications of reoperation (12), and endocarditis (7). Autograft regurgitation, the most common indication for reoperation, appeared primarily technical in nature, usually due to cusp prolapse. Degeneration was found in only 3 of 30 explanted autografts, and the young patients showed no increase in late valve failure. Homografts outperformed other valve replacements in the pulmonary position, but patients with orthotopic subcoronary and root autografts survived similarly. CONCLUSIONS: The pulmonary autograft offers low rates of degeneration, endocarditis, and thromboembolism for a period lasting >20 years, particularly in the young, with reoperation mainly required for malpositioning of the autograft cusps. The capacity of the autograft to maintain viability with minimal degeneration is not matched by any other biological valve replacement.

Adolescent↗
PubMed1991

Determinants of genital human papillomavirus infection in young women.

Carcinoma of the cervix has several well-established epidemiologic risk factors, including multiple sexual partners and early age at first intercourse. Human papillomavirus (HPV) infection appears to have an etiologic role in the development of cervical neoplasia, but evidence linking HPV infection to known risk factors for cervical cancer has been inconsistent. The lack of expected correlations may be due to the inaccuracy of HPV assays previously used. A polymerase chain reaction DNA amplification method for the detection of HPV was used to investigate the determinants of genital HPV infection in a cross-sectional sample of 467 women attending a university health service. In contrast to studies using less accurate detection methods, the risk factors for HPV infection found here were consistent with those for cervical neoplasia. The risk of HPV infection was strongly and independently associated with increasing numbers of sexual partners in a lifetime, use of oral contraceptives, younger age, and black race. Age at first intercourse, smoking, and history of a prior sexually transmitted disease were correlated with, but not independently predictive of, HPV infection. These results demonstrate that the key risk factors for cervical carcinoma are strongly associated with genital HPV infection. This correlation suggests that HPV has an etiologic role in cervical neoplasia and reaffirms the sexual route of HPV transmission.

Adolescent↗
PubMed1988

Genomic structure and amino acid sequence domains of the human La autoantigen.

La is an autoimmune RNA-binding protein of 47 kDa that plays a role in the transcription of RNA polymerase III. Both genomic and complementary DNAs were isolated that encompass the coding sequence of the human La molecule. The genomic clones encompass 11 exons and a putative G/C-rich promoter upstream of the mRNA start site. The cDNA sequence encodes a protein of 408 amino acids and can be divided into two structural domains based upon amino acid content and protease sensitivity. An unusually long stretch of 130 amino acids, much of which was predicted to form a stable alpha-helix, was found near the middle of the protein between the two domains. A ribonucleoprotein (RNP) consensus sequence was found just NH2-terminal to the long alpha-helix. The RNP consensus sequence is split into two exons by the fifth intron. Expression of three separate fragments of the La protein in Escherichia coli showed that a strongly autoimmune-reactive portion resides in the fragment containing the RNP consensus sequence and most of the long alpha-helical core. Autoantibodies from La patients also reacted with the terminal regions of the protein, but the extent of reactivity varied among patients. Differences in reactivity of autoantibodies to each portion of La protein may reflect an evolution of recognition of different epitopes during the development of the autoimmune response. These findings support an antigen-driven mechanism for autoimmune reactivity.

Amino Acid Sequence↗
PubMed1988

Quantitative immunoassay of anti-La antibodies using purified recombinant La antigen.

A purified recombinant La fusion protein was tested in an enzyme-linked immunosorbent assay to quantitate anti-La responses. This protein contained the immunodominant region of the La molecule fused to beta-galactosidase. In solid-phase assays, recombinant La protein was solubilized in urea and bound to polystyrene wells without loss of immunoreactivity. The recombinant-based enzyme-linked immunosorbent assay proved to be a sensitive method for the detection of anti-La binding, and it accurately distinguished anti-La precipitin positive sera from normal sera.

Antibodies↗
PubMed1986

The effect of human calcitonin on the cytoplasmic spreading of rat osteoclasts.

We previously found that calcitonin (CT), which inhibits osteoclastic bone resorption, abolished the cytoplasmic motility of isolated osteoclasts. The transition from motility to immotility was accompanied by a characteristic change in cell shape which coincided with the loss of pseudopodial ruffling activity and gradual cytoplasmic retraction. In this report we used computer-assisted morphometry to quantify the reduction in cytoplasmic spreading induced by human CT (hCT). Osteoclasts, isolated from neonatal rat long bones, were allowed to spread on a plastic surface for 120 min. The outlines of six osteoclasts were recorded on a time-lapse video recorder. hCT, other hormones, or plasma samples were then added. The outlines of the same six osteoclasts were recorded after incubation, and the area covered by the cells after incubation was calculated as a percentage of the area covered by the same cells before hormone addition. Osteoclastic spreading was reduced by hCT in a dose-dependent manner and was significantly decreased by concentrations of 2 pg/ml and above. High concentrations of PTH and 1,25-dihydroxyvitamin D3 had no effect on osteoclasts. This technique is a sensitive and quantitative assay of hCT concentration which is unaffected by the presence of other calcium-regulating hormones likely to be present in plasma.

Aged↗
PubMed1985

Isolation and analysis of cDNA clones expressing human lupus La antigen.

Several cDNA clones of the La antigen recognized by certain lupus autoantibodies were isolated from lambda gt11 expression libraries made from human liver. Recombinant clones were used to hybrid-select HeLa cell mRNA that was subsequently translated in vitro into a single protein species that comigrated with HeLa cell La protein. The in vitro translated protein was reactive with anti-La patient sera and was identical to the authentic La protein by peptide mapping. By analyzing overlapping cDNA clones, we mapped an antigenic site of La protein at the terminal 12% of the carboxyl end of the molecule. Within this region we identified a unique decapeptide of high hydrophilicity that may constitute a La antigenic determinant. We further demonstrated that the La antigen expressed from the recombinant clones can be used in a definitive enzyme-linked assay (ELISA) for the classification of sera from patients with systemic lupus erythematosus.

Antigens↗
PubMed1984

Characterization and idiotypic analysis of an anti-RNP monoclonal antibody.

To investigate mechanisms of anti-RNP antibody expression in autoimmune disease, idiotypes of a monoclonal anti-RNP of murine origin were analysed. This antibody, designated 4L1, was obtained from a MRL-lpr/lpr mouse and shown to have anti-RNP specificity by gel analysis of radiolabelled cellular RNA. An anti-idiotypic antiserum was prepared in a rabbit to 4L1 and rendered specific for idiotype by absorption with IgG from B6 mice and two BALB/c myelomas of the same chain composition as 4L1 (IgM kappa). In competition ELISA assays, this antiserum detected idiotypes commonly expressed in sera of MRL-lpr/lpr mice irrespective of the presence of anti-RNP. These idiotypes were not exclusive to this autoimmune strain, however, and could also be identified in normal mice. To identify other antibodies with this idiotype, a panel of MRL hybridomas was tested. This analysis demonstrated idiotypic cross-reactivity between 4L1 and two anti-Sm monoclonal antibodies derived from another animal. These results suggest that 4L1 belongs to a larger idiotype bearing family only some of whose members may have aberrant expression.

Animals↗
PubMed1983

Association between the 7 S RNA and the lupus La protein varies among cell types.

The La antigen recognized by certain lupus erythematosus autoantibodies was found to be predominantly associated with 7 S RNA in baby hamster kidney cells and human Raji cells, but not in HeLa cells where mainly the 7-2 RNA was associated with the La protein. In mouse myeloma cells (MPC-11) and mouse lymphoma cells (WEHI) that secrete immunoglobulins, equal amounts of 7 S and 7-2 RNAs were present in anti-La immunoprecipitates. The highly conserved 7 S RNA is a component of the signal recognition particle involved in protein secretion (Walter, P., and Blobel, G. (1982) Nature (Lond.) 299, 691-698), and its association with the La antigen appeared to be cell-type specific. Thus, it is possible that the La-7 S RNA association correlates with the abundance of 7 S RNA or with the secretory activity of the cell type.

Animals↗
PubMed1982

Induction of sister chromatid exchanges by 5-fluorodeoxycytidine: correlation with DNA methylation.

Chinese hamster ovary cells grown in medium containing 10 microM 5-fluorodeoxycytidine for forty-eight hours were found to have up to 5% of the deoxycytidine residues of the DNA substituted by this analog. Cytological studies of these cells showed that the incorporated 5-FdC caused a two-fold increase of sister chromatid exchanges (SCE) over the control level. However, 5-FdC was capable of inducing SCE only after it had been present in the cell for at least two cycles of DNA synthesis. This is in contrast to several other chemicals that we have tested which induced SCE immediately after the first DNA synthesis. We consider the possibility that the delayed effect may be related to hypomethylation of cytosine in the newly replicated DNA.

Animals↗
PubMed1982

Dissection of a replication origin of Xenopus DNA.

A previously cloned 503-base pair (bp) EcoRI segment of genomic DNA from Xenopus laevis selected for enhancement of replication of its vector plasmid was moved to the EcoRI site of pBR322. This plasmid designated pJCC31 and five other clones, which were made by cleaving the 503-bp segment in relation to a dispersed repeated sequence and subcloning, were compared with pBR322 for replication by microinjection into Xenopus eggs. The replication measured by incorporation of a 32P-labeled nucleotide as well as semiconservative segregation and dilution of N6-methyladenine at the EcoRI sites showed pJCC31 to be about 15 times as efficient as pBR322. The next most efficient subclone, pJCC31-2, contains an insert with a complete 320-bp dispersed repeated sequence bracketed by an 8-bp direct repeat. This observation, along with our previous report that repeated sequences of the Alu family in the human genome enhanced replication of the vector plasmid nearly as much as that of the presumptive Xenopus origin, leads to the hypothesis that members of a subset of the short dispersed repeated sequences in vertebrates function as origins for chromosomal replication. Preliminary studies also show that the presumptive Xenopus origin contains a RNA polymerase promoter that increases the transcription of the plasmid when it is microinjected into Xenopus oocytes.

Animals↗
PubMedDate not supplied

Genital human papillomavirus infection in female university students as determined by a PCR-based method.

The presence of genital human papillomavirus (HPV) was determined at cervical and vulvar sites using two methods, the Food and Drug Administration-approved ViraPap test and polymerase chain reaction (PCR) DNA amplification technology, in 467 women presenting to a university health service for a routine annual gynecologic examination. The PCR system afforded the sensitive detection of a broad spectrum of genital HPV types. Using PCR, we found that 46% of the study population was infected with HPV; the ViraPap test showed a prevalence of 11% infected. PCR analyses demonstrated that 69% of the HPV-positive women were infected at both genital sites. Subsequent HPV-type determination showed that 33% of the study population had HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, or other previously isolated types, and 13% had yet unidentified types. Almost all (92%) of the women diagnosed by Papanicolaou smear with condylomatous atypia or dysplasia (n = 12) were HPV positive. The PCR method proved to be an informative and rapid way to detect HPV in large numbers of clinical samples. Our results demonstrate that genital HPV infection is common among sexually active young women.

Adult↗
PubMedDate not supplied

Human papillomaviruses and cervical neoplasia in South Carolina.

Human papillomaviruses (HPVs), particularly types 16, 18, and 33, have recently been suggested as etiological agents for cervical neoplasia. However, few studies have explored this relationship among low-income minority women. This case-control study of cervical intraepithelial neoplasia (CIN), detected by Pap smear screening among South Carolina women, investigates the association between HPV positivity and the cytological continuum of CIN. Cervical spatulas and cytobrushes used to collect Pap smears from all women attending health department family planning clinics in three coastal South Carolina counties were saved for subsequent HPV detection and typing. Among this cohort of approximately 6000 cervical samples collected from March through December 1991, those with CIN, atypia, and other cervical abnormalities and women with normal cervical cytology were identified. Women with CIN II or III (n = 28) were 21.9 times more likely to be HPV 16, 18, or 33 positive, while women with CIN I (n = 114) were 11.7 times more likely to be HPV 16/18/33 positive when compared with women having normal cervical cytology (n = 223) and adjusting for potential confounders. Women with atypia (n = 115) were 3.0 times more likely to be HPV 16/18/33 positive. A chi 2 test for trend in increasing HPV 16/18/33 prevalence with increasing severity of cervical lesions was highly significant (P = 0.0001). HPV 6 and 11 were not associated with CIN, nor was there a significant trend of increasing prevalence with increasing severity of cervical lesions. Worthy of further research is our finding that the overall prevalence of HPV positivity was low in this relatively high-risk population of low-income, primarily black women.

Adolescent↗