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Biomedical subjects

J Willis

Publications and source records attributed to J Willis.

At least 19 recordsLinked to original sources
PubMed2006

Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer.

Clusterin (CLU) has been implicated in various cell functions involved in carcinogenesis and tumour progression. There are two known CLU protein isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is proapoptotic, and a secretory form (sCLU) is prosurvival. CLU expression has been associated with tumorigenesis of various malignancies, including tumours of prostate, colon, and breast. Furthermore, CLU expression is modulated by many factors that are believed to regulate tumour growth and/or apoptosis, including 1,25-dihydroxyvitamin D3, transforming growth factor beta-1, ultraviolet radiation, and IR. sCLU upregulation appears to be a general molecular stress response. Presently, preliminary results indicate that therapeutic modalities targeting CLU may be effective in cancer treatment. However, such strategies should make sure that nCLU is not eliminated or reduced. This review summarizes our present understanding of the importance of CLU in various physiological functions including tumour growth, and discusses its relevance to future cancer therapy.

Apoptosis↗
PubMed2005

A comparison of esomeprazole and lansoprazole for control of intragastric pH in patients with symptoms of gastro-oesophageal reflux disease.

BACKGROUND: Intragastric acid suppression is the most direct measure of the pharmacodynamic efficacy of proton pump inhibitors, which are the most effective drugs for acid-related diseases. AIM: To compare the effectiveness of once and twice daily dosing of lansoprazole and esomeprazole in controlling intragastric acidity (target gastric pH > 4.0) over a 24-hour period. METHODS: In an open-label, two-way crossover study, 45 Helicobacter pylori-negative patients with gastro-oesophageal reflux disease were randomized to receive one of two regimens: 30 mg lansoprazole or esomeprazole 40 mg once daily. Intragastric pH was assessed by 24-hour pH monitoring on day 5 of each regimen. Dosing was increased to twice daily and pH was reassessed on day 10. Following a 14-day washout, patients were crossed over to the other medication and the dosage regimens and pH assessments were repeated. RESULTS: Data were analysed from 35 patients who completed all scheduled assessments and had 24-hour monitoring for each end-point. Mean time pH > 4.0 and mean 24-hour pH were highest for esomeprazole 40 mg twice daily, followed by lansoprazole 30 mg twice daily, esomeprazole 40 mg once daily and lansoprazole 30 mg once daily. Esomeprazole 40 mg twice daily provided superior control of intragastric pH compared with either once or twice daily dosing of lansoprazole and once daily dosing of esomeprazole (P < 0.01). Esomeprazole 40 mg once daily was comparable with lansoprazole 30 mg twice daily and both were superior to lansoprazole 30 mg once daily (P < 0.01). CONCLUSIONS: Response to acid suppression treatment depends on the treatment selected. Esomeprazole 40 mg twice daily provided better control of intragastric pH than all other regimens evaluated. Esomeprazole 40 mg daily, however, was comparable with lansoprazole 30 mg twice daily and superior to lansoprazole 30 mg once daily.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

The accuracy of meningioma grading: a 10-year retrospective audit.

Although descriptive classifications of meningioma subtypes are well established, there has been inconsistency in the categorization of meningiomas into benign, atypical and anaplastic groups. The aim of this study was to reassess the incidence of atypical (grade II) meningiomas over a 10-year period by applying the World Health Organization (WHO) 2000 classification system. A secondary aim was to determine if grade II and III tumours were becoming more common. Sections of 314 meningiomas resected between 1994 and 2003 were retrieved from the archives of the Western General Hospital's neuropathology unit in Edinburgh. They were reassessed and graded by using the WHO 2000 classification system. The reviewers were blind to the original classification and grading. There was a gradual increase in the numbers of meningiomas being resected annually over the 10-year period. On reclassification, 78% of the meningiomas were classified as grade I, 20.4% as grade II and 1.6% as grade III. With regard to grade II meningiomas classified by using the WHO 2000 classification system, 38.1% had originally been classified as grade I prior to 2000, whereas 13.6% had originally been classified as grade I after 2000. In most cases, reclassification was due to formal counts of mitotic figures. Atypical meningiomas are diagnosed more frequently under the current WHO classification system than they were under the previous classification systems. Although the current WHO (2000) classification is more prescriptive than its predecessors, interobserver variability is likely to remain because of the subjective nature of some of the criteria.

Adolescent↗
PubMed2004

Beneficial effect of microsurgical varicocelectomy on human sperm DNA integrity.

BACKGROUND: Human sperm DNA damage may adversely affect reproductive outcomes, and the spermatozoa of infertile men possess substantially more DNA damage than that of fertile men. To date, there is no available treatment for men with high levels of sperm DNA damage. The objective of this study was to examine the effect of varicocelectomy on sperm DNA denaturation (DD, an index of sperm DNA damage) in infertile men with a clinical varicocele. METHODS: We reviewed the reports of 37 men who underwent microsurgical varicocelectomy at our institution from September 2001 to July 2002. Standard semen parameters and the percentage of spermatozoa with DD (monitored by flow cytometry analysis of acridine orange-treated spermatozoa) were assessed before and 6 months after varicocelectomy. RESULTS: The percentage of spermatozoa with DD decreased following varicocelectomy compared with pre-operatively (27.7 versus 24.6%, respectively, P < 0.05). Sperm concentration and the percentages of motile sperm and normal forms (WHO criteria) increased following varicocelectomy, but the difference did not reach statistical significance. CONCLUSIONS: Our data suggest that varicocelectomy can improve human sperm DNA integrity in infertile men with varicocele. These data represent the first report of improved sperm DNA integrity after therapy and further support the beneficial effect of varicocelectomy on human spermatogenesis.

Adult↗
PubMed2003

Risk factors leading to Cryptosporidium infection in men who have sex with men.

OBJECTIVES: Cryptosporidiosis is a devastating illness in people with HIV/AIDS yet there have been no analytical epidemiological studies measuring risk factors leading to cryptosporidiosis in men who have sex with men (MSM). The objective of this study was to measure the risk factors for exposure to Cryptosporidium among MSM. METHODS: The study was a case-control design. It recruited MSM who had laboratory confirmed Cryptosporidium infection between 1997 and 2000. Participants answered a questionnaire about potential risk factors leading to exposure to Cryptosporidium. RESULTS: 10 cases and 24 controls were recruited. Men having more than one sexual partner in the past month were more likely to have had Cryptosporidium diarrhoea p=0.034 (OR 6.67, CI (1.15 to 38.60). Insertive anal sex (p=0.059) and attending a sex venue one or more times (p=0.059) also increased the odds of having cryptosporidiosis. CONCLUSION: The study results suggest that sexual behaviour is a significant risk factor for cryptosporidial diarrhoea in MSM. The results will be used to inform risk groups about behaviours that may put them at increased risk of cryptosporidial diarrhoea.

Case-Control Studies↗
PubMed2002

Case-control studies of sporadic cryptosporidiosis in Melbourne and Adelaide, Australia.

Few studies have assessed risk factors for sporadic cryptosporidiosis in industrialized countries, even though it may be numerically more common than outbreaks of disease. We carried out case-control studies assessing risk factors for sporadic disease in Melbourne and Adelaide, which have water supplies from different ends of the raw water spectrum. In addition to examining drinking water, we assessed several other exposures. 201 cases and 795 controls were recruited for Melbourne and 134 cases and 536 controls were recruited for Adelaide. Risk factors were similar for the two cities, with swimming in public pools and contact with a person with diarrhoea being most important. The consumption of plain tap water was not found to be associated with disease. This study emphasizes the need for regular public health messages to the public and swimming pool managers in an attempt to prevent sporadic cryptosporidiosis, as well as outbreaks of disease.

Adolescent↗
PubMed2002

CCR5 genotyping in an Australian and New Zealand type 1 diabetes cohort.

Infiltration of pancreatic tissue by autoreactive T-cells involves secretion of multiple cytokines and chemokine receptor expression. Genetically determined variation in cell surface expression of the chemokine receptor CCR5 may result in differences in inflammatory cell migration in response to relevant chemokines. Adolescents with type 1 diabetes (T1D) from Australia and New Zealand were genotyped for CCR5-delta32 (n = 626). The allele frequency was compared with that of 253 non-diabetic Australian adolescents and with that of 92 adults with systemic lupus erythematosus. A reduced allele frequency was seen in T1D compared with controls (0.092 vs. 0.123, p = 0.05). This difference was not seen for the cohort of patients with SLE (freq = 0.114). A reduction in the number of CCR5-delta32/delta32 homozygotes, who lack CCR5, in the T1D cohort was also seen and while not statistically significant (2 observed compared to 5.25 expected; p = 0.12) is interesting. These results suggest a partial protection from T1D for CCR5-delta32 homozygous individuals is possible and that CCR5 has a potential role in the pathogenesis of T1D.

Adolescent↗
PubMed2002

Familial aggregation of Barrett's oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults.

BACKGROUND: Although familial clusters of Barrett's oesophagus and oesophageal adenocarcinoma have been reported, a familial predisposition to these diseases has not been systematically investigated. AIMS: To determine whether Barrett's oesophagus and oesophageal (or oesophagogastric junctional) adenocarcinoma aggregate in families. PATIENTS AND METHODS: A structured questionnaire eliciting details on reflux symptoms, exposure history, and family history was given to Caucasian case (n=58) subjects with Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma, and to Caucasian control (n=106) subjects with symptomatic gastro-oesophageal reflux disease without Barrett's oesophagus. Reported diagnoses of family members were confirmed by review of medical records. RESULTS: The presence of a positive family history (that is, first or second degree relative with Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma) was significantly higher among case subjects compared with controls (24% v 5%; p<0.005). Case subjects were more likely to be older (p<0.001) and male (74% v 43% male; p<0.0005) compared with control subjects. In a multivariate logistic regression analysis, family history was independently associated with the presence of Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma (odds ratio 12.23, 95% confidence interval 3.34-44.76) after adjusting for age, sex, and the presence of obesity 10 or more years prior to study enrollment. CONCLUSIONS: Individuals with Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma are more likely to have a positive family history of Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma than individuals without Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma. A positive family history should be considered when making decisions about screening endoscopy in patients with symptoms of gastro-oesophageal reflux.

Adenocarcinoma↗
PubMed2001

22q13 deletion syndrome.

We have recently collected clinical information on 37 individuals with deletion of 22q13 and compared the features of these individuals with 24 previously reported cases. The features most frequently associated with this deletion are global developmental delay, generalized hypotonia, absent or severely delayed speech, and normal to advanced growth. Minor anomalies include dolicocephaly, abnormal ears, ptosis, dysplastic toenails, and relatively large hands. As with many terminal deletions involving pale G-band regions, the deletion can be extremely subtle and can go undetected on routine cytogenetic analysis. In fact, 32% of the individuals in our study had previous chromosome analyses that failed to detect the deletion. Eight of 37 individuals had deletion of 22q13 secondary to an unbalanced chromosome translocation. In the newborn, this deletion should be considered in cases of hypotonia for which other common causes have been excluded. In the older child, this syndrome should be suspected in individuals with normal growth, profound developmental delay, absent or delayed speech, and minor dysmorphic features. We recommend high-resolution chromosome analysis and fluorescence in situ hybridization studies, or molecular analysis to exclude this diagnosis.

Abnormalities, Multiple↗
PubMed2001

Testing for colon neoplasia susceptibility variants at the human COX2 locus.

BACKGROUND: Siblings and other first-degree relatives of patients with "sporadic" (i.e., apparently nonfamilial) colorectal cancer or precursor adenomatous colon polyps have an increased risk of developing colon neoplasia. This observation suggests the presence of inherited genetic determinants for sporadic colon neoplasia. Mice homozygous for a null cyclooxygenase 2 (COX2) (also called PTGS2) allele have a dramatically reduced susceptibility to the development of intestinal adenomas. In humans, use of pharmacologic inhibitors of COX2 enzyme activity are associated with reduced risk of colon neoplasia. This study examined whether the human COX2 locus may be linked to colon neoplasia in humans. METHODS: We used the affected sibling-pair method to test for linkage of the human COX2 locus to colon neoplasia. RESULTS: We examined 74 concordantly affected sibling pairs from 46 sibships with colon neoplasia. One hundred five siblings from these sibships were diagnosed with either colorectal cancer or colon adenomatous polyps before age 65 years. No linkage between COX2 and colon neoplasia was found by use of a multipoint model-free linkage analysis (estimate of allele sharing was 0.44; standard error = +/-0.04; 95% confidence interval = 0.36 to 0.52). Moreover, even allowing for heterogeneity, the potential that a COX2 colon neoplasia susceptibility variant was present within a substantial subset of these sibships was strongly excluded under either a recessive or a dominant inheritance model (95% confidence to exclude a model in which 2.7% or more of the sibling pairs harbor a dominant susceptibility allele). CONCLUSIONS: This study of concordantly affected sibling pairs thus demonstrates that variations in the COX2 gene are unlikely to be a source of individual susceptibility to colon neoplasia in humans.

Adenomatous Polyposis Coli↗
PubMed2001

Biologic variability of sperm DNA denaturation in infertile men.

OBJECTIVES: To examine sperm DNA denaturation (DD) in fertile and infertile men and assess the variability of conventional semen parameters and sperm DD in repeated semen samples from infertile men. METHODS: Twenty-one consecutive nonazoospermic, infertile men each submitted two semen samples, 2 to 6 weeks apart. We examined semen samples from consecutive fertile men (n = 10) presenting for vasectomy as controls. Standard semen parameters (World Health Organization criteria) and sperm chromatin structure (evaluated by flow cytometry analysis of acridine orange-treated spermatozoa and expressed as the percentage of spermatozoa with denatured DNA) were monitored. RESULTS: Fertile men had a significantly higher sperm concentration and percentage of sperm motility and a significantly lower percentage of sperm with DD than did infertile men (36 +/- 5.2 x 10(6)/mL versus 12.5 +/- 2.2 x 10(6)/mL, 60.0% +/- 5.2% versus 30.1% +/- 4.1%, and 8.9% +/- 1.9% versus 20.3% +/- 2.5%, respectively, P <0.05). The sperm concentration, sperm motility, and percentage of spermatozoa with DD were not significantly different between the first and second semen samples from the infertile men. Sperm DD showed the lowest average within-subject coefficient of variation (SD/mean), followed by motility and concentration (coefficient of variation 21%, 24%, and 35%, respectively). CONCLUSIONS: Our data demonstrate that infertile men have significantly higher sperm DD compared with fertile men and that sperm DD exhibits a low coefficient of variation ( approximately 20%) on repeated assessment. These data suggest that sperm DD has a relatively low degree of biologic variability.

DNA↗
PubMed2001

High-resolution endoscopic imaging of the GI tract: a comparative study of optical coherence tomography versus high-frequency catheter probe EUS.

BACKGROUND: Both optical coherence tomography (OCT) and catheter probe EUS (CPEUS) are candidates for high-resolution imaging of the GI wall, but their potential roles in this clinical context have not been investigated. METHODS: OCT and CPEUS were used to image normal-appearing portions of the GI tract at the same sites. CPEUS was performed with a 20-MHz or a new 30-MHz catheter probe. RESULTS: Forty-four histologically confirmed normal sites in 27 patients were evaluated. With OCT, mucosa and muscularis mucosa were clearly seen at all sites. Except for stomach, OCT demonstrated the submucosa in all sites. OCT penetration ranged from 0.7 to 0.9 mm. Microscopic structures such as esophageal glands, intestinal villi, colonic crypts, and blood vessels were easily identified. CPEUS penetration ranged from 10 mm to 20 mm, and 5 to 7 distinct layers were discernible. However, both mucosa and submucosa were seen as thin layers without microscopic detail. CONCLUSION: OCT resolution is superior to high-frequency CPEUS, but depth of penetration is limited to mucosa and submucosa. OCT images the major structural components of the mucosa and submucosa whereas CPEUS does not. Potentially, OCT and high-frequency CPEUS may be complementary for clinical imaging.

Endoscopy, Gastrointestinal↗
PubMed2001

Perceptions of body hair on white women: effects of labeling.

This study examined 118 college students' perceptions of a White woman with body hair as a function of two different possible attributions. Participants reacted to a video of a young woman described as being either a feminist or as having a medical condition that hindered shaving. Students rated the woman on a variety of interpersonal traits. Analysis showed a main effect for body hair and for description but no interaction. The woman with body hair, whether for feminist or alternative reasons, was rated as significantly less friendly, moral, and relaxed, as well as more aggressive, unsociable, strong, nonconformist, dominant, assertive, independent, and in better physical condition than the same woman without body hair. Implications and directions for research are suggested.

Adult↗
PubMed2000

Endosonographic assessment of multimodality therapy predicts survival of esophageal carcinoma patients.

BACKGROUND: Standard endosonographic (EUS) staging criteria are unreliable for staging esophageal carcinoma after neoadjuvant therapy; however, measurement of tumor size reduction can identify patients who have achieved a pathologic response. In the current study the authors prospectively compared survival between patients classified as responders and those classified as nonresponders by EUS. METHODS: The maximal transverse cross-sectional area of the tumor was measured before and after neoadjuvant therapy in patients who were candidates for multimodality treatment. Response was defined as a > or = 50% reduction in tumor area. RESULTS: A total of 59 patients at 2 centers were followed for a median of 19 months. EUS assessed response in 34 patients (58%). Overall, responders had a median survival of 17.6 months compared with 14.5 months for nonresponders (P < 0.005). Survival was significantly longer in responders compared with nonresponders in the patient subgroup who underwent surgical resection (19.7 months vs. 14.6 months; P < 0. 005), the patient subgroup with adenocarcinoma (21.4 months vs. 10.8 months; P < 0.005), and the patient subgroup initially classified as having T3N1 disease (17.6 months vs. 14.1 months; P < 0.05). Survival was not found to differ significantly between responders and nonresponders in the subgroup of patients with squamous cell carcinoma. EUS response was the only clinical variable that was associated with survival time in a multivariate analysis (relative hazard = 0.27; P < 0.005). CONCLUSIONS: Patients with esophageal carcinoma who respond to neoadjuvant treatment as identified by EUS measurement of reduction in tumor size have a significantly better prognosis than nonresponders.

Adenocarcinoma↗
PubMed2000

Methylene blue-directed biopsies improve detection of intestinal metaplasia and dysplasia in Barrett's esophagus.

BACKGROUND: Endoscopically applied methylene blue selectively stains specialized columnar epithelium in Barrett's esophagus. METHODS: The diagnostic yield and cost of cancer surveillance in patients with Barrett's esophagus using methylene blue-directed biopsies (MBDB) were compared with surveillance using a "jumbo" random biopsy technique in a prospective, sequential, controlled trial. Esophagogastroduodenoscopy was performed with either MBDB or random biopsy in a randomized sequence. The proportions of various types of epithelia in each biopsy were estimated and dysplasia was graded in a blinded fashion. RESULTS: Forty-three patients with short- (n = 8), limited- (n = 10), and long-segment (n = 25) Barrett's esophagus were studied. Using MBDB technique, the average number of biopsies obtained per patient was significantly lower and the proportion of specialized columnar epithelium in each specimen was significantly higher compared with random biopsy. Dysplasia or cancer was diagnosed in significantly more MBDB specimens (12% vs. 6%, p = 0.004). Despite fewer biopsies per patient using MBDB, dysplasia or cancer was diagnosed in significantly more patients (44% vs. 28%, p = 0.03) than by random biopsy technique. MBDB cost less and detected more cancers than random biopsy. CONCLUSIONS: MBDB is a more accurate and cost-effective technique than random biopsy for diagnosing specialized columnar epithelium and dysplasia/cancer, particularly in long-segment Barrett's esophagus.

Adult↗
PubMed2000

High-resolution endoscopic imaging of the GI tract using optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) has demonstrated the microscopic structure of the gastrointestinal (GI) tract mucosa and submucosa in vitro. We evaluated a prototype OCT system and assessed the feasibility of OCT in the human GI tract. METHODS: The 2.4 mm diameter prototype OCT probe, inserted through an endoscope, provides a 360-degree radial scan. Images (6.7 frames/sec) are displayed on a television monitor. Tissue contact is not required. In patients undergoing elective endoscopy, OCT images were obtained of normal mucosa (confirmed by biopsy). RESULTS: Seventy-two sites were imaged (38 patients): esophagus (21), stomach (12), duodenum (11), terminal ileum (4), colon (15), and rectum (9). Varying the distance between the probe and the mucosal surface produced images of the GI wall of varying depth. When held about 1 mm above the mucosal surface, the images consisted of mucosal structures such as colonic crypts, gastric pits, and duodenal villi. With the probe held against the wall, the OCT image comprised several layers interpreted as mucosa, muscularis mucosae, and submucosa. Structures including blood vessels were evident within the submucosa. A probe with a 0.5 mm working distance to the focal point provided the best images. Reducing the frame rate to 4.0 per second facilitated image interpretation. CONCLUSIONS: OCT is feasible in the human GI tract and provides interpretable high-resolution images of mucosa and submucosa.

Adult↗
PubMed2000

Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer.

Aberrant promoter methylation and the associated loss of gene expression is a common accompaniment of human cancers. Nonetheless, it has been challenging to demonstrate in any given tumour that methylation of a specific gene was causal and not consequent to malignant transformation. In this regard, our attention was drawn to the genesis of gastric cancers in individuals with hereditary diffuse gastric cancer (HDGC). These individuals harbour germline mutations in the gene encoding E-cadherin, CDH1, but their cancers have consistently demonstrated absence of loss of heterozygosity at the CDH1 locus. These findings suggested the hypothesis that CDH1 promoter methylation might function as the 'second genetic hit' in the genesis of these cancers.

Alleles↗