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Biomedical subjects

C Cowan

Publications and source records attributed to C Cowan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Use of touch preps for intraoperative diagnosis of sentinel lymph node metastases in breast cancer.

BACKGROUND: Intraoperative touch prep (TP) is highly accurate for determining positive breast cancer margins and thereby reducing the need for second surgeries. It also may be useful in determining the status of the sentinel lymph node (SLN) during the initial surgical resection. The objective of this study was to test the ability of intraoperative TP to predict metastatic disease and, thus, the necessity for axillary lymph node dissection (ALND) at the time of SLN biopsy. METHODS: Fifty-five patients with invasive breast cancer were entered in the SLN biopsy protocol. The SLN was identified by gamma probe, dissected, and sent to pathology for TP and permanent sections. Level I and II ALND was then performed. Any radiolabeled LN in the lymphadenectomy specimen also was sent for TP and permanent sections. RESULTS: A total of 124 radiolabeled lymph nodes (LNs) were submitted for TP; of these, 93 (75%) were SLNs. Pathologic diagnosis by TP was correct compared with permanent sections for 99.2% of the nodes. There were no false positives. There was one (0.8%) false negative. The positive predictive value was 100% and the negative predictive value was 99%. Sensitivity was 95.7% and specificity was 100%. CONCLUSIONS: TP is a simple, quick, and accurate method for detecting metastatic disease in the SLN and, when used intraoperatively, enables the surgeon to determine whether or not an ALND is necessary at the time of the initial surgery.

Adult↗
PubMed1998

Sentinel lymph node biopsy for staging breast cancer.

BACKGROUND: Determination of axillary nodal status is essential for the staging of breast cancer since nodal status is one of the most important predictors of survival. The objective of this study was to test the hypothesis that the histology of the first draining lymph node (LN) accurately predicts the histology of the rest of the axillary LNs. METHODS: Fifty-five patients with operable invasive breast carcinoma and clinically negative axillary lymph nodes were studied. Patients were injected with Technetium-99 (99Tc) sulfur colloid around the primary tumor. A hand-held gamma detector probe was used to identify the sentinel LN (SLN). After the SLN was identified and removed, a level I and II lymphadenectomy was performed. RESULTS: The SLN was identified in 53 (96.3%) of the 55 patients entered into the trial. The sensitivity was 88.2% and the specificity was 100%. The positive predictive value was 100% and the negative predictive value was 94.6%. The accuracy of the study was 96.2%. CONCLUSIONS: The SLN biopsy for breast cancer staging is highly accurate in our hands and has the potential to decrease the morbidity and cost of managing patients with breast cancer without compromise of staging.

Adult↗
PubMed1998

Targeting of the Yersinia pestis YopM protein into HeLa cells and intracellular trafficking to the nucleus.

The YopM virulence protein of Yersinia pestis has been described as binding human alpha-thrombin and inhibiting thrombin-induced platelet aggregation in vitro. However, recent studies have shown that a YopM-CyaA fusion protein could be targeted vectorially into eukaryotic cells through the Yersinia type III secretion system. In this study, our objective was to characterize YopM's fate in more detail. We followed YopM in the culture medium and inside infected HeLa cells. We confirmed that the native YopM is targeted into HeLa cells, where it is insensitive to exogenous trypsin. The bacteria must be surface located to target YopM, and YopB and YopD are necessary, whereas the LcrE protein (called also YopN) makes this process more efficient. Immunofluorescence localization revealed that YopM, in contrast to YopE, is not only targeted to the cytoplasm but also trafficks to the cell's nucleus by means of a vesicle-associated pathway that is strongly inhibited by brefeldin A, perturbed by monensin or bafilomycin A1 and dependent upon microtubules (decreased by colchicine and nocodazole). These findings revealed a novel interaction of Yersinia pestis with its eukaryotic host.

Bacterial Outer Membrane Proteins↗
PubMed1997

Feasibility and applicability of coronary stent implantation with the direct brachial approach: results of a single-center study.

Implantation of stents in selected patients improves outcome after coronary angioplasty. Newer antiplatelet regimes limit access site complications associated with stenting by the percutaneous femoral approach, but a substantial proportion of patients will require anticoagulant therapy for concomitant disease or will have peripheral vascular disease that prevents access from the leg. We investigated procedural success rates and outcome in consecutive patients undergoing elective stent implantation in our institution. In 73 patients who were receiving anticoagulation therapy and were stented by a direct approach to the left brachial artery, 98.6% of stents were successfully deployed, with a major vascular access site complication rate of 1.4%. Equipment consumption, procedural success rate, and fluoroscopy time were similar in patients stented by the direct brachial or percutaneous femoral approach. Where the percutaneous femoral approach is precluded or patients are anticoagulated, stent procedures can be successfully performed by the direct brachial approach with a low rate of access site complications, even when large-caliber guiding catheters are required.

Adult↗
PubMed1997

Personality disorders in people with learning disabilities: a community survey.

The prevalence of personality disorders has been determined by studies of both the general population and mental handicap hospitals. The present study attempts to determine the prevalence of personality disorders in a community sample and to check the implications for treatment. A community sample of learning disability service users was surveyed by obtaining a rating from a good informant to establish demographic data, level of functioning and the nature of personality disorders, if any, using the ICD-10 version of the Standardized Assessment of Personality (SAP). Fifty per cent of the sample had personality abnormalities, and 31% had sufficient impairment of the social and occupational domains and personal distress to warrant a diagnosis of personality disorder. These findings are compared with previous studies. Paranoid, schizoid, impulsive and dissocial personality abnormalities were seen to be associated with a high referral rate to psychiatric services and needed considerable therapeutic input. The prevalence of personality abnormalities in community populations with a learning disability is high. The SAP is a useful instrument for screening. This subpopulation makes significant demands on community psychiatric services.

Adult↗
PubMed1995

Degenerative changes in myometrium simulating diffuse leiomyomatosis after treatment with gonadotrophin releasing hormone analogue.

Degenerative changes are encountered relatively frequently in uterine leiomyomas. Morphologic changes within leiomyomas, particularly necrosis and alterations in cellularity, have been described following treatment with gonadotrophin releasing hormone analogue, but the effects of this form of treatment on the morphology of the normal myometrium are less well documented. A case is reported of a 42 year old woman with a history of menorrhagia in whom a combination of degenerative and iatrogenic changes resulted in a histological appearance resembling diffuse leiomyomatosis.

Adult↗
PubMed1994

Exon size affects competition between splicing and cleavage-polyadenylation in the immunoglobulin mu gene.

The alternative RNA processing of microseconds and microns mRNAs from a single primary transcript depends on competition between a cleavage-polyadenylation reaction to produce microseconds mRNA and a splicing reaction to produce microns mRNA. The ratio of microseconds to microns mRNA is regulated during B-cell maturation; relatively more spliced microns mRNA is made in B cells than in plasma cells. The balance between the efficiencies of splicing and cleavage-polyadenylation is critical to the regulation. The mu gene can be modified to either reduce or improve the efficiency of each reaction and thus alter the ratio of the two RNAs produced. However, as long as neither reaction is so strong that it totally dominates, expression of the modified mu genes is regulated in B cells and plasma cells. The current experiments reveal a relationship between the C mu 4 exon size and the microseconds/microns expression ratio. The shorter the distance between the C mu 4 5' splice site and the nearest upstream 3' splice site, the more spliced microns mRNA was produced. Conversely, when this exon was expanded, more microseconds mRNA was produced. Expression from these mu genes with altered exon sizes were regulated between B cells and plasma cells. Since RNA processing in the mu gene can be considered a competition between defining the C mu 4 exon as an internal exon (in microns mRNA) versus a terminal exon (in microseconds mRNA), exon size may affect the competition among factors interacting with this exon.

Animals↗
PubMed1993

Thyrotoxicosis increases right to left shunt in congenital cyanotic heart disease.

We wish to report two cases of congenital cyanotic heart disease in whom coexisting thyrotoxicosis increased the right to left shunt. We review the literature on the cardiac and respiratory effects of thyroid hormone to try to explain this phenomenon. Two patients, one with Fallot's tetralogy (diagnosed at 68 years of age), the other with a ventricular septal defect, developed thyrotoxicosis which resulted in a dramatic but reversible deterioration in their cardiac condition. We conclude that thyrotoxicosis increases right to left shunt in congenital cyanotic heart disease. This effect is profound but reversible. We suggest that when an unexplained rapid deterioration occurs in patients with congenital cyanotic heart disease, thyrotoxicosis should be excluded.

Adult↗
PubMed1991

The Yersinia pestis V antigen is a regulatory protein necessary for Ca2(+)-dependent growth and maximal expression of low-Ca2+ response virulence genes.

The low-Ca2+ response is a multicomponent virulence regulon of the human-pathogenic yersiniae in which 12 known virulence genes are coordinately regulated in response to environmental cues of temperature, Ca2+, and nucleotides such as ATP. Yersinial growth also is regulated, with full growth yield being permitted at 37 degrees C only if Ca2+ or a nucleotide is present. In this study, we constructed and characterized a mutant Yersinia pestis specifically defective in the gene encoding the V antigen, one of the virulence genes of the low-Ca2+ response. An in-frame internal deletion-insertion mutation was made by removing bases 51 through 645 of lcrV and inserting 61 new bases. The altered lcrV was introduced into the low-Ca2+ response plasmid in Y. pestis by allelic exchange, and the resulting mutant was characterized for its two-dimensional protein profiles, growth, expression of an operon fusion to another low-Ca2+ response virulence operon, and virulence in mice. The mutant had lost its Ca2+ and nucleotide requirement for growth, showed diminished expression of Ca2(+)-and nucleotide-regulated virulence genes, and was avirulent in mice. The mutation could be complemented with respect to the growth property by supplying native V antigen operon sequences in trans in high copy number (on pBR322). Partial complementation of the growth defect and almost complete complementation of the virulence defect were seen with a lower-copy-number complementing replicon (a pACYC184 derivative). The data are consistent with the interpretation that V antigen is bifunctional, with a role in regulating growth and expression of low-Ca2+ response virulence genes in addition to its putative role as a secreted virulence protein.

Antigens, Bacterial↗
PubMed1990

Duplicative activation mechanisms of two trypanosome telomeric VSG genes with structurally simple 5' flanks.

In the mammalian bloodstream, African trypanosomes express variant surface glycoprotein (VSG) genes from a family of long and complex telomeric expression sites. VSG switching generally occurs by the duplication of different VSG genes into these sites by gene conversion involving a series of 70 base pair (70bp) repeats in the 5' flank. In contrast, when VSG is first synthesised by trypanosomes in the tsetse fly at the metacyclic stage, a separate set of telomeric expression sites is activated. These latter telomeres appear not to act as recipients in gene conversion. We have found that the structure of two such expression sites is simple, with very short 70bp repeat regions and very little other sequence in common with bloodstream expression sites. However, the two telomeres readily act as donors in VSG gene conversion in the bloodstream and we show for one a consistent association of the conversion 5' end point with the short 70bp repeat region. These findings help explain why a very predictable set of VSGs is expressed in the tsetse fly and have implications for VSG gene conversion mechanisms.

Animals↗