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Biomedical subjects

A Rashid

Publications and source records attributed to A Rashid.

At least 37 records · Page 2Linked to original sources
PubMed2001

Beta-catenin mutations in biliary tract cancers: a population-based study in China.

beta-Catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless/Wnt pathway. Activating mutations in exon 3 of the beta-catenin gene, at the phosphorylation sites for ubiquitination and degradation of beta-catenin, are present in a variety of cancers. Because alterations of the adenomatous polyposis coli (APC) gene are present in biliary tract cancers and the APC protein modulates levels of beta-catenin, we evaluated the role of beta-catenin in biliary tract cancer by sequencing the third exon of the beta-catenin gene among 107 biliary tract cancers and 7 gallbladder adenomas from a population-based study in CHINA: Point mutations of serine or threonine phosphorylation sites in exon 3 of beta-catenin were present in 8 of 107 (7.5%) biliary tract cancers and 4 of 7 (57.1%) gallbladder adenomas. Mutations of beta-catenin were more frequent in ampullary and gallbladder carcinomas than in bile duct carcinomas (P = 0.04) and in papillary adenocarcinomas than other histological types of carcinomas (P = 0.02). These results suggest that the molecular pathways of biliary tract neoplasms vary by anatomical subsite and histological subtype.

Adenoma↗
PubMed2001

Hypermethylation of the hMLH1 gene promoter is associated with microsatellite instability in early human gastric neoplasia.

A significant portion of gastric cancers exhibit defective DNA mismatch repair, manifested as microsatellite instability (MSI). High-frequency MSI (MSI-H) is associated with hypermethylation of the human mut-L homologue 1 (hMLH1) mismatch repair gene promoter and diminished hMLH1 expression in advanced gastric cancers. However, the relationship between MSI and hMLH1 hypermethylation has not been studied in early gastric neoplasms. We therefore investigated hMLH1 hypermethylation, hMLH1 expression and MSI in a group of early gastric cancers and gastric adenomas. Sixty-four early gastric neoplasms were evaluated, comprising 28 adenomas, 18 mucosal carcinomas, and 18 carcinomas with superficial submucosal invasion but clear margins. MSI was evaluated using multiplex fluorescent PCR to amplify loci D2S123, D5S346, D17S250, BAT 25 and BAT 26. Methylation-specific PCR was performed to determine the methylation status of hMLH1. In two hypermethylated MSI-H cancers, hMLH1 protein expression was also evaluated by immunohistochemistry. Six of sixty-four early gastric lesions were MSI-H, comprising 1 adenoma, 4 mucosal carcinomas, and 1 carcinoma with superficial submucosal invasion. Two lesions (one adenoma and one mucosal carcinoma) demonstrated low-frequency MSI (MSI-L). The remaining 56 neoplasms were MSI-stable (MSI-S). Six of six MSI-H, one of two MSI-L, and none of thirty MSI-S lesions showed hMLH1 hypermethylation (P<0.001). Diminished hMLH1 protein expression was demonstrated by immunohistochemistry in two of two MSI-H hypermethylated lesions. hMLH1 promoter hypermethylation is significantly associated with MSI and diminished hMLH1 expression in early gastric neoplasms. MSI and hypermethylation-associated inactivation of hMLH1 are more prevalent in early gastric cancers than in gastric adenomas. Thus, hypermethylation-associated inactivation of the hMLH1 gene can occur early in gastric carcinogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Differential expression of retinoic acid receptors and p53 protein in normal, premalignant, and malignant esophageal tissues.

PURPOSE: Esophageal cancer remains a significant health problem worldwide. The very low 5-year survival rates and rapid increase in the incidence of adenocarcinoma indicate the urgent need for early identification of and new approaches to the prevention and treatment of this cancer. METHODS: To find biomarkers for early identification of the disease, we analyzed nuclear retinoic retinoid receptor mRNAs, p53 protein, and the proliferation marker Ki 67 in surgical specimens of normal, mildly, and severely dysplastic and malignant esophageal tissues. RESULTS: Nuclear retinoid receptors (RAR-alpha, RAR-gamma, and RXR-alpha) were expressed in most (79%-100%) normal, dysplastic, and malignant esophageal mucosae, whereas expression of RAR-beta was progressively lost from normal esophagus to carcinoma (84%-54%). In contrast, expression of p53 protein and Ki 67 were dramatically increased in severely dysplastic and cancerous tissues of the esophagus (from 5% to 62%). CONCLUSIONS: Loss of RAR-beta expression and accumulation of p53 and Ki 67 proteins may serve as biomarkers for esophageal cancer.

Esophageal Neoplasms↗
PubMed2001

CpG island methylation in colorectal adenomas.

Methylation of cytosines in CpG islands silences gene expression. CpG island methylator phenotype (CIMP) in colorectal cancers is characterized by abnormal methylation of multiple CpG islands including those in several tumor suppressor genes such as p16, hMLH1, and THBS1. CpG island methylation has not been well characterized in adenomas. We evaluated methylation status at p16, MINT2, and MINT31 loci, which are frequently methylated in colorectal carcinomas, in 108 colorectal adenomas from a prospective study of 50 patients without cancer. Methylation at one or more loci was present in 48% (52 of 108) of adenomas with 25% (19 of 76) CIMP-high (two or more methylated loci) and 32% (24 of 76) CIMP-low (one methylated locus). The p16 gene was methylated in 27% (19 of 71) of adenomas. Methylation status of different adenomas from the same patient was not correlated (odds ratio, 0.93; P = 0.77). Adenomas with tubulovillous or villous histology were frequently methylated: 73% (17 of 26) versus 41% (35 of 85) of tubular adenomas (odds ratio, 3.46; P = 0.02). High levels of microsatellite instability were more frequent in adenomas without methylation (13% versus 2%; odds ratio, 8.48; P = 0.05). Our results indicate that methylation plays an important role early in colorectal tumorigenesis. CpG island methylation is more common in adenomas with tubulovillous/villous histology, a characteristic associated with more frequent predisposition to invasive carcinoma. Methylation is distinct from microsatellite instability and develops in individual adenomas rather than resulting from a field defect in an individual patient.

Adenoma↗
PubMed2001

Histopathological identification of colon cancer with microsatellite instability.

Cancer with high levels of microsatellite instability (MSI-H) is the hallmark of hereditary nonpolyposis colorectal cancer syndrome, and MSI-H occurs in approximately 15% of sporadic colorectal carcinomas that have improved prognosis. We examined the utility of histopathology for the identification of MSI-H cancers by evaluating the features of 323 sporadic carcinomas using specified criteria and comparing the results to MSI-H status. Coded hematoxylin and eosin sections were evaluated for tumor features (signet ring cells; mucinous histology; cribriforming, poor differentiation, and medullary-type pattern; sponge-like mucinous growth; pushing invasive margin) and features of host immune response (Crohn's-like lymphoid reaction, intratumoral lymphocytic infiltrate, and intraepithelial T cells by immunohistochemistry for CD3 with morphometry). Interobserver variation among five pathologists was determined. Subjective interpretation of histopathology as an indication for MSI testing was recorded. We found that medullary carcinoma, intraepithelial lymphocytosis, and poor differentiation were the best discriminators between MSI-H and microsatellite-stable cancers (odds ratio: 37.8, 9.8, and 4.0, respectively; P = 0.000003 to < 0.000001) with high specificity (99 to 87%). The sensitivities, however, were very low (14 to 38%), and interobserver agreement was good only for evaluation of poor differentiation (kappa, 0.69). Mucinous histopathological type and presence of signet ring cells had low odds ratios of 3.3 and 2.7 (P = 0.005 and P = 0.02) with specificities of 95% but sensitivities of only 15 and 13%. Subjective interpretation of the overall histopathology as suggesting MSI-H performed better than any individual feature; the odds ratio was 7.5 (P < 0.000001) with sensitivity of 49%, specificity of 89%, and moderate interobserver agreement (kappa, 0.52). Forty intraepithelial CD3-positive lymphocytes/0.94 mm2, as established by receiver operating characteristic curve analysis, resulted in an odds ratio of 6.0 (P < 0.000001) with sensitivity of 75% and specificity of 67%. Our findings indicate that histopathological evaluation can be used to prioritize sporadic colon cancers for MSI studies, but morphological prediction of MSI-H has low sensitivity, requiring molecular analysis for therapeutic decisions.

CD3 Complex↗
PubMed2001

Left circumflex coronary artery to left atrial fistula in a patient with mitral regurgitation after excision of a left atrial myxoma.

Acquired coronary artery to left atrial fistulas are rare and previously only described in mitral stenosis associated with left atrial thrombus or coronary arteriosclerosis. We present the case of a patient who developed a left circumflex coronary artery to left atrial fistula associated with mitral regurgitation 12 years after excision of a left atrial myxoma. This was successfully ligated at the time of mitral valve replacement.

Aged↗
PubMed2001

Revised estimates of mortality from burns in the last 20 years at the Birmingham Burns Centre.

The Birmingham Burns Centre has been regularly presenting its mortality estimates since its pioneering work in 1949 on the use of probit analysis. The last of these estimates that showed a significant improvement in survival was presented in 1971. This improvement was attributed to the introduction of topical 0.5% silver nitrate against Pseudomonas aeruginosa. In the last 20 years, several changes in management of burns have taken place following a better knowledge of its pathophysiology. This study shows our experience from the last 20 years by comparing mortality estimates between two successive 10-year periods i.e., 1979-1988 and 1989-1998. We used probit analysis for deriving lethal area 50 (LA 50) for various age groups. The comparison showed that the mortality curves between the two periods were identical suggesting no improvement in the chances of survival. Since the mortalities were so similar the data were combined. The LA 50s derived from this combined data when compared with our earlier series from 1965 to 1970 also did not show a significant change in mortality. We conclude that in our experience the chances of dying for a given severity of injury have not changed significantly for more than 20 years.

Adolescent↗
PubMed2001

Upper gastrointestinal tract injury in patients receiving kayexalate (sodium polystyrene sulfonate) in sorbitol: clinical, endoscopic, and histopathologic findings.

Kayexalate (sodium polystyrene sulfonate) in sorbitol has been demonstrated to cause colonic necrosis in a subset of uremic patients who are administered the cation exchange resin for treatment of hyperkalemia. Upper gastrointestinal damage associated with Kayexalate in sorbitol is reported far less frequently, and the clinicopathologic spectrum of disease in cases with upper gastrointestinal damage has not been investigated previously. The authors studied the clinical, endoscopic, and histologic features of 11 patients with Kayexalate crystals in biopsies from the esophagus (n = 7), stomach (n = 6), and duodenum (n = 2). The endoscopic appearance was markedly abnormal in all 11 patients. The effects of the medication closely mimicked other endoscopic and radiologic diagnoses in three cases, including esophageal carcinoma, Candidal esophagitis, and gastric bezoar. Histologic and/or endoscopic evidence of mucosal injury in the form of an ulcer or erosion was present in nine patients (82%). In four patients with mucosal injury, no other etiology apart from Kayexalate in sorbitol could be identified. In comparison with a cohort of patients with Kayexalate crystals in lower gastrointestinal specimens identified during the same period (11 patients) the frequency of associated mucosal damage was not significantly different (55%, p = 0.19), but no patient with upper gastrointestinal Kayexalate required surgical resection or died as a result of Kayexalate-induced mucosal injury. The results of this study provide evidence that Kayexalate in sorbitol can induce damage to the upper gastrointestinal tract. Recognition of Kayexalate crystals in histologic sections as a marker for sorbitol-induced mucosal damage may aid in establishing the correct diagnosis for clinically or endoscopically misleading lesions.

Aged↗
PubMed2001

Arthroconidia as vectors of dermatophytosis.

The characteristic macro- and microconidia produced by dermatophytes in cultures and those living as saprobes are not produced in any dermatophyte lesions observed to date. However, arthroconidia, defined as a genetically programmed disarticulation of septate hyphae to produce a chain of conidia, are produced by dermatophytes, both in culture and in lesions, under certain predisposing conditions. Arthroconidia are seen, for example, within nail-bed infections caused by Trichophyton rubrum; within nail-plate infections caused by Trichophyton mentagrophytes interdigitale; and in the infections of scalp hair by soil or geophilic dermatophytes, where chains of arthroconidia form near or on the surface of the infected hairs. Dr. Rashid discusses his electron microscope studies of the adherence and germination of arthroconidia and the penetration of the germ tubes and initial hyphae into the stratum corneum.

Candida albicans↗
PubMed2001

What happens in cidal and static action?

Using terbinafine and clotrimazole as examples, Dr. Rashid's electron microscopy images illustrate the differences between fungicidal and fungistatic drugs, respectively.

Antifungal Agents↗
PubMed2001

The skin we are in--knowledge and practices regarding skin cancer in pre-clinical medical students.

OBJECTIVE: To assess the level of knowledge about skin cancer in youth and to explore the influence of gender and system of education on their knowledge and practices. MATERIALS AND METHODS: A questionnaire-based study was conducted at The Aga Khan University Medical College (AKUMC), on Year 2 pre-clinical medical students. Descriptive analyses to examine the frequency distribution, chi-square test and factor analysis were applied using SPSS. RESULTS: Seventyone students participated in the study; 90% scored > 55% in the questions regarding knowledge of Malignant melanoma (MM), whereas in the questions assessing practice only 11% of the respondents scored > 52%. They were largely unaware that appearance of a new mole is a risk factor for MM (56% respondents incorrect) and that skin cancer is one of the most common cancers (54% respondents incorrect). 73% reported being sunburned at least once during childhood and 40% suffered sunburns at least once this summer, which points to the inadequacy of sun protection. The risk of MM may double if severe sunburns are experienced during childhood. Education system and gender did not affect the knowledge and practices. The popular sources of learning about skin cancer were magazines (52%) followed by television (42%). CONCLUSION: There is a need for epidemiological studies in Pakistani population regarding skin cancer. For preventing excessive solar exposure which leads to sunburns, we recommend interventions like a Pilot Program for photoprotection education and Sun Awareness Week to improve knowledge and sun protection behavior.

Adolescent↗
PubMed2000

Microsatellite instability in inflammatory bowel disease-associated neoplastic lesions is associated with hypermethylation and diminished expression of the DNA mismatch repair gene, hMLH1.

Twelve to 15% of sporadic colorectal cancers display defective DNA mismatch repair (MMR), manifested as microsatellite instability (MSI). In this group of cancers, promoter hypermethylation of the MMR gene hMLH1 is strongly associated with, and believed to be the cause of, MSI. A subset of colorectal neoplastic lesions arising in inflammatory bowel disease (IBD) is also characterized by MSI. We wished to determine whether hMLH1 hypermethylation was associated with diminished hMLH1 protein expression and MSI in IBD neoplasms. We studied 148 patients with IBD neoplasms, defined as carcinoma or dysplasia occurring in patients with ulcerative colitis or Crohn's disease. MSI was evaluated using multiplex fluorescent PCR to amplify loci D2S123, BAT-25, BAT-26, D5S346, and D17S250 in all cases. Lesions were characterized as high-frequency MSI (MSI-H) if they manifested instability at two or more loci, low-frequency MSI (MSI-L) if unstable at only one locus, or MS-stable (MSS) if showing no instability at any loci. Methylation-specific PCR was performed to determine the methylation status of the hMLH1 promoter region. hMLH1 protein expression was also evaluated by immunohistochemistry. Thirteen (9%) of 148 neoplasms arising in IBD were MSI-H, comprising 11 carcinomas and 2 dysplastic lesions. Sixteen additional lesions (11%) were MSI-L, comprising 11 carcinomas and 5 dysplastic lesions. The remaining 118 neoplasms (80%) were MSS. Six (46%) of 13 MSI-H, 1 (6%) of 16 MSI-L, and 4 (15%) of 27 MSS lesions showed hMLH1 hypermethylation (P = 0.013). Diminished hMLH1 protein expression in neoplastic cell nuclei relative to surrounding normal cell nuclei was demonstrated immunohistochemically in four of four (100%) hypermethylated lesions tested. In IBD neoplasia, hMLH1 promoter hypermethylation occurs frequently in the setting of MSI, particularly MSI-H. Furthermore, hMLH1 hypermethylation and MSI are strongly associated with diminished hMLH1 protein expression in IBD neoplasms. These findings suggest that hMLH1 hypermethylation causes defective DNA MMR in at least a subset of IBD neoplasms.

Adaptor Proteins, Signal Transducing↗
PubMed2000

p53 overexpression and K-ras gene mutations in primary sclerosing cholangitis-associated biliary tract cancer.

Cholangiocarcinoma occurs frequently in patients with primary sclerosing cholangitis (PSC). We evaluated the incidence and prognostic significance of p53 protein overexpression and K-ras gene mutations in patients with biliary tract cancer and PSC. p53 protein expression was determined in specimens from 12 patients with biliary tract cancer, using the antibody, D07. K-ras mutations were detected using DNA sequencing and a mutation ligation assay. Accumulation of p53 protein was detected in 6 of 12 tumors (50%). K-ras mutations were detected in 4 of 12 tumors (33%). Overall survival in patients with p53-negative tumors was significantly longer (P < 0.05) than that in patients with p53-positive (mutant) tumors. Similarly, overall survival was significantly longer (P < 0.05) in the absence of a K-ras mutation than in patients with a tumor containing a K-ras mutation. Mean interval from the time of diagnosis of PSC until the diagnosis of biliary tract cancer was significantly shorter (P < 0.05) in patients with p53 overexpression than in those patients without p53 overexpression (2 versus 47 months). p53 overexpression and K-ras mutations occur commonly in patients with PSC and biliary tract cancer and are associated with a shortened survival. Patients with longstanding PSC are less likely to have these genetic alterations and may have a better prognosis.

Adult↗
PubMed2000

Partner violence, social support, and distress among inner-city African American women.

This study examined the role of social support in the partner violence-psychological distress relation in a sample of African American women seeking medical care at a large, urban hospital (n = 138). Results from bivariate correlational analyses revealed that partner violence was related to lower perceived social support and greater psychological distress, and lower social support was related to more distress. Furthermore, findings based on path analysis indicated that low levels of social support helped account for battered women's increased distress. Findings point to the need for service providers to screen for partner violence in nontraditional sites, such as hospital emergency rooms, and to address the role of social support resources in preventive interventions with African American battered women.

Adult↗
PubMed2000

Phenotypic and molecular characteristics of hyperplastic polyposis.

BACKGROUND & AIMS: Patients with hyperplastic polyposis are reported to have multiple and/or large hyperplastic polyps (HPs) and an increased risk of colorectal cancer, but the phenotype and genetic alterations in hyperplastic polyposis have not been studied in detail. METHODS: We evaluated clinical-pathological and molecular characteristics of 129 HPs, 6 serrated adenomas, and 3 admixed hyperplastic-adenomatous polyps from 13 patients with hyperplastic polyposis (more than 20 HPs), 5 patients with a large HP (>/=1 cm in diameter), and 5 patients with multiple HPs (5-10 HPs). RESULTS: HPs in the right colon in contrast to the left colorectum had more frequent topographic dysregulation of p21(Waf-1/Cip1) expression (94% vs. 76%, P = 0.03) and of proliferation (92% vs. 53%, P = 0. 0001), but less frequent allelic loss of chromosome 1p (4% vs. 17%, P = 0.03). K-ras mutation was present in 8% of HPs, p53 gene product overexpression in none, and microsatellite instability in 3% without relationship to microsatellite instability in synchronous cancer. Patients with a large HP differed from those with multiple HPs in having a high frequency of right-sided HP (63% vs. 22%, P = 0.01) and of right-sided colon cancer (100% vs. 8%, P = 0.003). Hyperplastic polyposis was associated with a family history of colorectal cancer (P = 0.01) and with loss of chromosome 1p in HP (21% vs. 0%, P = 0.001). CONCLUSIONS: A hyperplastic polyp/dysplasia-to-adenocarcinoma sequence can be manifested in 3 distinct phenotypes consisting of patients with hyperplastic polyposis and chromosome 1p allelic loss in some HPs, in contrast to patients who have large, right-sided HPs or small numbers of HPs that lack 1p loss.

Adenoma↗