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Biomedical subjects

B Clarke

Publications and source records attributed to B Clarke.

At least 37 records · Page 2Linked to original sources
PubMed2002

Plexiform spitz nevus.

In 1999, Spatz et al. reported the first 2 cases of a plexiform variant Spitz nevus. We describe another case of this variant on the upper thigh of a 10-year-old boy and discuss the differential diagnosis. Histologically, it comprised nodules of epithelioid cells with a plexiform arrangement distributed throughout the superficial and deep dermis. The cells had moderate eosinophilic cytoplasm with vesicular nuclei and prominent nucleoli. Intranuclear inclusions were present focally. The tumor nodules were embedded in a myxoid stroma with intratumoral and peritumoral inflammatory cells including both lymphocytes and eosinophils. There were occasional melanin-containing spindle-shaped cells. An intraepidermal component could not be assessed, since the lesion was ulcerated. The differential diagnosis includes both melanocytic and nonmelanocytic lesions exhibiting a plexiform pattern of growth as well as myxoid lesions.

Child↗
PubMed2001

Isolated amoebic appendicitis.

Amoebiasis, a disease of worldwide distribution, is endemic in tropical countries with suboptimal sanitation facilities. Isolated amoebic appendicitis (IAA) is regarded as a rare manifestation of the disease globally. Because there are no defined clinical features that distinguish IAA from bacterial appendicitis, diagnosis is usually dependent on histopathological examination. A 9-year retrospective study was undertaken to investigate the clinicopathological aspects of IAA. The main complaints were fever and abdominal pain. None of the patients had dysentery. The pre-operative clinical diagnosis was acute appendicitis and acute abdomen in 13 and 8 patients, respectively. In all cases the intra-operative diagnosis was acute appendicitis. Gross pathological appraisal revealed peritonitis and perforation in 19 and 17 cases, respectively. Histopathological examination of these appendices demonstrated appendiceal ulceration, transmural mixed inflammation, haematophagous amoebic trophozoites and necrosis in all cases. Vascular pathology comprised venous and capillary luminal plugging (11 cases), necrotising small vessel vasculitis (11 cases), thrombophlebitis of medium sized veins (9 cases) and arteritis with associated thrombosis (1 case). Organising fibrinopurulent peritonitis was present in 19 cases. Two appendices that appeared normal macroscopically demonstrated ulceration and inflammation that were confined to the mucosa and submucosa. All of 18 patients who were treated with metronidazole survived without further surgery, while three patients who were untreated succumbed to the disease. Appendicectomy, accurate histopathological appraisal thereof and optimal, timely management of IAA were critical to the favourable outcome in the present study.

Adult↗
PubMed2001

A phylogeny of the land snails (Gastropoda: Pulmonata).

We have undertaken the first large-scale molecular phylogenetic analysis of the Stylommatophora. Sequences of the ribosomal RNA gene-cluster were examined in 104 species of snails and slugs from 50 families, encompassing all the currently recognized major groups. It allows an independent test of the present classification based on morphology. At the level of families our molecular phylogeny closely supports the current taxonomy, but the deep branches within the tree do not. Surprisingly, a single assemblage including the families Achatinidae, Subulinidae and Streptaxidae lies near the base of the tree, forming a sister group to all remaining stylommatophorans. This primary division into 'achatinoid' and 'non-achatinoid' taxa is unexpected, and demands a radical reinterpretation of early stylommatophoran evolution. In particular, the Orthurethra appear to be relatively advanced within the 'non-achatinoid clade', and broadly equivalent to other super-familial clusters. This indicates that supposedly primitive features such as the orthurethran kidney are derived. The molecular tree also suggests that the origin of the Stylommatophora is much earlier than the main period of their diversification.

Animals↗
PubMed2001

Characterization of the glycosylation profiles of Alzheimer's beta -secretase protein Asp-2 expressed in a variety of cell lines.

Amyloid 39-42 beta -peptides are the main components of amyloid plaques found in the brain of Alzheimer's disease patients. Amyloid 39-42 beta-peptide is formed from amyloid precursor protein by the sequential action of beta- and gamma-secretases. Asp-2 is a transmembrane aspartic protease expressed in the brain, shown to have beta-secretase activity. Mature Asp-2 has four N-glycosylation sites. In this report we have characterized the carbohydrate structures in this glycoprotein expressed in three different cell lines, namely Chinese hamster ovary, CV-1 origin of SV40, and baculovirus-infected SF9 cells. Biantennary and triantennary oligosaccharides of the "complex" type were released from glycoprotein expressed in the mammalian cells, whereas mannose-rich glycans were identified from glycoprotein synthesized in the baculovirus-infected cells. Site-directed mutagenesis of the asparagine residues at amino acid positions 153, 172, 223, and 354 demonstrate that the protease activity of Asp-2 is dependent on its glycosylation.

Alzheimer Disease↗
PubMed2001

Cell cycle aberrations in the pathogenesis of squamous cell carcinoma of the uterine cervix.

Cancer cells are characterized by limitless proliferative autonomy and immunity to inhibitory and apoptotic signals, thus ensuring growth and metastasis [1]. Epidemiological studies have long implicated human papillomavirus (HPV) as a pathogenic agent in cervical cancer. Progress in cancer research now provides an understanding of how these characteristics are achieved by the interaction of HPV proteins with the cell cycle machinery. Expression of oncoproteins E7 and E6 induces immortalization of cells through their inhibitory effects on tumor suppressor proteins pRb and p53, respectively. Undermining of pRb's growth-inhibitory role with release of E2F transcription factors renders the cells independent of mitogenic stimuli. The abundance of growth transcription factors grants limitless proliferative potential by allowing expression of products such as cyclins A, E, and B, dihydrofolate reductase, and DNA polymerase which fuel the various stages of the cell cycle. There is subsequent disruption of both the G1-S and G2-M cell cycle checkpoints. Overexpression of cyclin E results in chromosomal instability and possible unmasking of genetic mutations, allowing disease progression. Cyclin A grants anchorage-independent growth, facilitating tissue invasion and tumor spread. Apoptotic and growth-inhibitory mechanisms are also evaded. p53 is degraded by E6 and its own downstream protein mdm2. Its other downstream protein, p21 is rendered ineffective against cyclin-cyclin-dependent kinase units by E7, as is p27. The understanding of the molecular pathology of disease will provide us with the ability to prognosticate and treat patients more effectively.

Animals↗
PubMed2001

A new method for assembling metabolic networks, with application to the Krebs citric acid cycle.

To understand why a molecular network has a particular connectivity one can generate an ensemble of alternative networks, all of which meet the same performance criteria as the real network. We have generated alternatives to the Krebs cycle, allowing group transfers and B(12)-mediated shifts that were excluded in previous work. Our algorithm does not use a reaction list, but determines the reactants and products in generic reactions. It generates networks in order of increasing number of reaction steps. We find that alternatives to the Krebs cycle are very likely to be cycles. Many of the alternatives produce toxic or unstable compounds and use group transfer reactions, which have unfavorable consequences. Although alternatives are better than the Krebs cycle in some respects, the Krebs cycle has the most favorable combination of traits.

Algorithms↗
PubMed2001

The influence of posture on perineal ultrasound imaging parameters.

A prospective clinical study was carried out to evaluate the influence of posture on perineal ultrasound imaging parameters. One hundred and thirty-two consecutive women presenting with symptoms of lower urinary tract dysfunction were examined by multichannel videourodynamics and perineal ultrasound, both supine and standing. Ultrasound included color Doppler imaging when available, i.e. in a subgroup of 99 patients. The position of the bladder neck at rest was higher in the supine position (P<0.001) and it descended further on Valsalva (P < 0.001), to reach an almost identical final position. There was a higher degree of urethral rotation on supine imaging (P = 0.001). Urethral funneling on Valsalva was more likely in the erect position (P < 0.001), as was urine leakage documented by color Doppler imaging (P < 0.001). The effect of a pelvic floor contraction was not significantly influenced by posture. Imaging of the urethrovesical junction should be undertaken in both supine and erect positions to document optimally both hypermobility and funneling or leakage.

Adult↗
PubMed2001

Translabial color Doppler urodynamics.

Color Doppler ultrasound is a new method for documenting fluid leakage in the setting of videourodynamic testing. In order to compare color Doppler ultrasound with traditional fluoroscopic imaging we performed a prospective blinded comparative clinical study. Fifty-two consecutive patients undergoing urodynamic investigations for symptoms of incontinence or prolapse were examined using fluoroscopy and translabial color Doppler ultrasound to document stress leakage. The investigators were blinded to each other's results. Both tests were performed at maximum bladder capacity and with an indwelling 5 Fr microtransducer catheter, in both the supine and the erect positions. Equivalent results for both methods were obtained in 48 out of 52 patients (Cohen's kappa = 0.82). It was therefore concluded that translabial color Doppler ultrasound imaging can reliably demonstrate leakage through the female urethra on Valsalva maneuver or coughing.

Adult↗
PubMed2001

Irritative symptoms after colposuspension: are they due to distortion or overelevation of the anterior vaginal wall and trigone?

Symptoms of bladder irritability are common after incontinence surgery but their cause is unknown. This study tests the hypothesis that irritative symptoms after colposuspension are due to distortion of the trigone. As part of longitudinal follow-up studies, 175 women were examined 6 months to 12 years after either an open or a laparoscopic Burch colposuspension. The main outcome measures were symptoms of bladder irritability (frequency, nocturia and urge incontinence) and ultrasound findings (bladder neck position at rest and on Valsalva, the presence of a colposuspension ridge, ridge depth and ridge distance, and trigonal angle). Two positive associations between ultrasound parameters and symptoms of bladder irritability were observed: urge incontinence was more likely in the presence of bladder neck funneling, and women with nocturia had a higher trigonal angle. Increased distortion of the trigone was associated with a reduced incidence of urge incontinence in the subgroup of patients after laparoscopic colposuspension. The data presented in this study do not support the hypothesis that symptoms of bladder irritability are due to trigonal distortion or overelevation.

Colposcopy↗
PubMed2001

The use of perineal ultrasound to quantify levator activity and teach pelvic floor muscle exercises.

Perineal ultrasound was used to detect and quantify levator activity by measuring the displacement of the internal urethral meatus against the inferoposterior margin of the symphysis pubis. Women who had previously been instructed in pelvic floor muscle exercises were more likely to contract the levator muscle when asked to do so than were those without previous instruction (P<0.0001). Of the 56 women who were unable to contract the pelvic floor on request, 32 (57%) eventually succeeded with visual ultrasound biofeedback. Pelvic floor muscle assessment and teaching can be used as an adjunct to the ultrasound assessment of urogynecologic patients, requiring at most 5 minutes. It allows quantification of lavator activity and can provide visual biofeedback, which is easily understood and readily accepted by women.

Adult↗
PubMed2001

The urethral pressure profile and ultrasound imaging of the lower urinary tract.

In a prospective study 105 patients with symptoms of stress incontinence underwent video-urodynamic testing, including resting urethral pressure profilometry and translabial ultrasound. The urethral pressure profile (UPP) included maximum urethral closure pressure (MUCP), functional length (FL) and area under the curve (AUC). Ultrasound parameters included urethral thickness, urethral rotation and bladder neck descent, as well as funneling/opening of the internal urethral meatus on Valsalva maneuver. Levator contraction strength was assessed measuring the cranioventral displacement of the internal meatus. Negative correlations between UPP data and age, parity and previous surgery were observed which were consistent with literature data. There was a positive correlation between the urethral AP diameter on ultrasound and the MUCP, which agrees with reports showing reduced sphincter thickness or volume in stress-incontinent women. Hypermobility on ultrasound did not correlate with UPP data. However, a lower MUCP correlated with extensive opening of the bladder neck. Finally, there was a trend towards poorer pelvic floor function with lower MUCP measurements.

Adult↗
PubMed2001

System, environmental, and policy changes: using the social-ecological model as a framework for evaluating nutrition education and social marketing programs with low-income audiences.

A variety of nutrition education interventions and social marketing initiatives are being used by the Food Stamp Program to improve food resource management, food safety, dietary quality, and food security for low-income households. The Social-Ecological Model is proposed as a theory-based framework to characterize the nature and results of interventions conducted through large public/private partnerships with the Food Stamp Program. In particular, this article suggests indicators and measures that lend themselves to the pooling of data across counties and states, with special emphasis on systems, environment, and public policy change within organizations at the community and state levels.

Food Services↗
PubMed2001

Phyllodes tumors of the breast: correlation of nucleolar organizer regions with histopathological malignancy grading, flow cytometric DNA analysis and clinical outcome.

To examine whether nucleolar organizer regions detected by argyrophilia (Ag-NOR counts) can be used as a prognostic indicator in phyllodes tumors of the breast, and to compare its usefulness with that of DNA flow cytometric analysis, 28 cases of breast phyllodes tumors (including 15 benign, two borderline and 11 malignant tumors) were subjected to Ag-NOR staining and counting as well as DNA flow cytometric analysis. S-phase fraction and DNA ploidy analysis showed useful trends for improving outcome predictions in malignant phyllodes tumors. However, high Ag-NOR counts were significant in predicting survival status (P = 0.013) and reached near statistical significance in predicting survival times (P = 0.07). In predicting survival status, results for Ag-NOR counts were significantly better than those for ploidy analysis (P = 0.02) and S-phase fraction (P < 0.01). Only S-phase fraction was significantly predictive of survival times (P = 0.025). It is concluded that Ag-NOR counts and DNA flow cytometric analysis, easily performed using paraffin sections, give information that can improve predictions made by histopathological classification. Ag-NOR counts are significant in predicting survival in the presence of histopathological features of malignancy.

Adolescent↗
PubMed2001

Myxoid invasive papillary urothelial carcinoma of the bladder and urethra.

An unusual case of myxoid transitional cell (urothelial) carcinoma occurring in a 75-year-old man is presented. The primary tumour in the bladder, which was treated by partial cystectomy, consisted of areas of conventional high grade invasive (into the lamina propria) papillary urothelial carcinoma with separate myxoid areas. The latter component accounted for 25% of the tumour. Nine months later, the patient presented with haematuria once again, and a tumour was detected in the urethra. This was excised and histological examination showed only myxoid tumour without any overlying dysplasia or obvious epithelial differentiation. The myxoid areas were positive for epithelial markers and negative for all mesenchymal markers. This case highlights an uncommon variety of papillary urothelial carcinoma that invokes a wide differential diagnosis. Immunohistochemistry is essential in making the correct diagnosis.

Aged↗
PubMed2001

Is the irritable bladder associated with anterior compartment relaxation? A critical look at the 'integral theory of pelvic floor dysfunction'.

The 'integral theory of pelvic floor dysfunction', first proposed by Petros and Ulmsten in 1990, claims that anterior vaginal wall relaxation is associated with symptoms of urgency, frequency, nocturia and urge incontinence. A retrospective study was designed to test this hypothesis. Imaging data and urodynamic reports from 272 women suffering from symptoms of lower urinary tract dysfunction were evaluated. Opening of the retrovesical angle, bladder neck descent, urethral rotation and descent of a cystocele during Valsalva were used to quantify anterior vaginal wall laxity. None of the tested parameters were associated with symptoms and signs of detrusor overactivity On the contrary, patients with higher grades of urethral and bladder descent were less likely to suffer from nocturia and urge incontinence and were less likely to have sensory urgency and detrusor instability diagnosed on urodynamic testing. The findings of this study therefore do not support this hypothesis of the 'integral theory'.

Adult↗
PubMed2000

History or current selection? A molecular analysis of 'area effects' in the land snail Cepaea nemoralis.

We have used molecular variation in microsatellite and mitochondrial DNA to throw light on the origins of enigmatic geographical patterns, known as 'area effects', in the shell polymorphisms of the land snail Cepaea nemoralis. Our aim was to assess the relative importance of recent selection and historical events in the formation of these patterns. On the Marlborough Downs in Wiltshire, England, the 'type locality' for area effects, the frequencies of microsatellites are significantly associated with the frequencies of alleles for shell banding. A less clear association is found between microsatellites and shell colour. Mitochondrial haplotypes show no significant relationships. Although the correlated geographical patterns could be the results of random genetic drift from an initially uniform array of populations, the magnitudes of the patterns, and of the correlations between them, seem too strong to have arisen by drift since the last glaciation. Our results suggest that invasions from refugia have been the most important factors in forming area effects.

Animals↗