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Biomedical subjects

A Brian West

Publications and source records attributed to A Brian West.

30 records · Page 2Linked to original sources
PubMed2003

Regeneration of hepatocyte 'buds' in cirrhosis from intrabiliary stem cells.

BACKGROUND/AIMS: In massive hepatic necrosis, hepatic stem cells constitute a canal of Hering derived, cytokeratin 19 (CK19) positive 'ductular reaction' (DR). Whether DRs in cirrhosis are activated stem cells (so called 'buds') or biliary metaplasia of cholestatic, injured hepatocytes is still debated. We investigate derivation of intraseptal hepatocytes (ISHs) from DRs and from the biliary tree in cirrhosis. METHODS: Explants of hepatitis B and C, alcohol, primary biliary cirrhosis and primary sclerosing cholangitis-related cirrhosis were examined. ISHs were quantified and their associations with DRs and cholestasis recorded. 3D-reconstruction of ISHs and nearby bile ducts was performed in blocks from hepatitis C and primary sclerosing cholangitis cirrhosis. RESULTS: Seven hundred seventy five/830 (94%) ISHs were associated with CK19 positive DRs. ISHs without ductular reactions were more likely to show cholestatic features (P<0.0001). In 3D, ISHs were seen to bud directly from the biliary tree. In summary: ISHs: (1) are usually associated with stem cell-like DRs; (2) are rarely cholestatic, leaving the associated DRs unexplained; and (3) are linked to the biliary tree in 3D. Dynamic proliferation rates in hepatitis C over time suggest that hepatocyte replication diminishes in late stages, with an associated activation of the biliary stem cell compartment. CONCLUSIONS: We therefore suggest that the biliary tree, from at least its smaller branches up to the canals of Hering, are composed of or at least harbor facultative hepatic stem cells, and that ISH largely represent 'buds' of newly formed hepatocytes.

Biliary Tract↗
PubMed2003

Stellate-cell lipidosis in liver biopsy specimens. Recognition and significance.

Hepatic stellate-cell lipidosis due to hypervitaminosis A can lead to cirrhosis, which can be averted by restricting vitamin A intake. Other causes, including the use of synthetic retinoids, have been postulated. We studied the frequency and etiology of stellate-cell lipidosis in patients undergoing liver biopsy for reasons other than vitamin A abuse. Fourteen cases (1.1%) were identified retrospectively among 1,235 nontransplant liver biopsy specimens examined from January 1995 through December 1999. Diagnostic criteria included the following: lipid-laden cells in the space of Disse; small, dark, crescent-shaped nuclei with inconspicuous nucleoli; and wispy cytoplasmic strands separating fat droplets. Patient details, reason for biopsy, and medication use were studied. Reasons for biopsy included hepatitis C (10 cases), abnormal liver enzyme levels (2 cases), methotrexate use (1 case), and alcohol abuse (1 case). Hypervitaminosis A was not suspected clinically in the 5 patients who used oral vitamin A or 3 who used topical tretinoin (Retin-A). In 6 patients, no cause of stellate-cell lipidosis was discerned. Stellate-cell lipidosis should be reported to alert clinicians to a potentially preventable form of liver injury.

Adipocytes↗
PubMed2003

Multiplex DNA short tandem repeat analysis. A useful method for determining the provenance of minute fragments of formalin-fixed, paraffin-embedded tissue.

A tiny fragment of high-grade carcinoma was found in histologic sections and in the paraffin block of a benign cervical polyp from a patient with no clinical evidence of malignancy. Thus, it raised the suspicion of block contamination. No malignant tumor was processed the same day as the polyp; however, a similar tumor had been processed 6 days earlier. Multiplex DNA short tandem repeat analysis was applied to paraffin-extracted tissue samples obtained from the polyp, the suspected contaminant, the patient's additional cervical biopsy specimen, and the putative source of contamination. The results demonstrated that the suspected contaminant and the patient's cervical tissue could not have come from the same patient and that the suspected contaminant derived from the tumor processed earlier, without reasonable doubt. We hypothesize that this friable tumor escaped from cassettes into the processor and contaminated the polyp specimen. Multiplex DNA short tandem repeat analysis can be applied to determine the provenance of minute tissue samples in surgical pathology.

Adult↗
PubMed2002

Epithelioid gastrointestinal stromal tumor of the stomach with liver metastases in a 12-year-old girl: aspiration cytology and molecular study.

Gastrointestinal stromal tumor (GIST), a stromal tumor of the gastrointestinal tract defined as CD117 (c-kit)-positive neoplasm, occurs primarily in adults. GIST with CD117 (c-kit) mutation and certain cytogenetic abnormalities is associated with malignancy, though a definite relationship between prognosis and molecular alterations remains to be elucidated. We report the cytologic features of an epithelioid GIST arising in the stomach of a child and metastatic to the liver, and the molecular mutational analysis of both the primary gastric tumor and the liver metastasis. Literature of pediatric GISTs was also reviewed. Fine needle aspiration of the liver metastasis, processed by Ultrafast Papanicolaou stain, showed fragments of cohesive small epithelioid cells with bland oval nuclei and unipolar cytoplasm transected by capillaries. Immunohistochemically, all nodules in the stomach and liver expressed CD117 (c-kit). Interestingly, some of the gastric tumor clusters were uniformly CD34 positive, whereas others were uniformly CD34 negative, suggesting heterogeneity of tumor clones. The presence of neurosecretory granules further subtyped the tumor into gastric autonomic nerve tumor (GANT). Molecular mutational analysis, performed in both the gastric tumor and the liver metastasis, showed no sequence abnormality in exons 9, 11, and 13 of CD117 (c-kit). Cytogenetic study revealed normal karyotype. These features might suggest a different molecular mechanism leading to malignancy in certain GISTs arising in children.

Biomarkers, Tumor↗
PubMed2002

Occupation and risk of esophageal and gastric cardia adenocarcinoma.

BACKGROUND: Adenocarcinomas of the esophagus and gastric cardia have risen dramatically in incidence over the past few decades, however, little research has been conducted on the occupational risk factors for these cancers. METHODS: In this population-based case-control study, lifetime job histories were compared between cases of esophageal adenocarcinoma (n = 283), gastric cardia adenocarcinoma (n = 259), and population controls (n = 689). Odds ratios (OR) and 95% confidence intervals (CI) for ever employment and by duration in various occupational and industrial categories were calculated using unconditional logistic regression. RESULTS: The risk of esophageal adenocarcinoma was elevated for persons ever employed in administrative support (OR = 1.5; 95%CI = 1.0-2.1); financial, insurance, and real estate (OR = 1.6; 95%CI = 1.0-2.4); and health services (OR = 2.2; 95%CI = 1.2-3.9). The risk of gastric cardia adenocarcinoma was increased among transportation workers (OR = 1.7; 95%CI = 1.1-2.6), as well as among carpenters (OR = 1.8; 95%CI = 0.9-3.9) and workers in the furniture manufacturing industry (OR = 2.4; 95%CI = 0.9-6.3). However, we observed few duration-response relations between length of employment in any category and cancer risk. CONCLUSIONS: This study revealed associations of esophageal adenocarcinoma with employment in administrative support, health services, and a category of financial, insurance, and real estate industries, and of gastric cardia adenocarcinoma with transportation and certain woodworking occupations. Some of these findings may be due to the play of chance associated with the multiple comparisons made in this study. Our results suggest that, overall, workplace exposures play a minor role in the etiology and upward trend of esophageal and gastric cardia adenocarcinomas.

Adenocarcinoma↗
PubMed2002

Clear cell carcinoma of the breast with immunohistochemical evidence of divergent differentiation.

Primary clear cell carcinoma of the breast is a rare tumor. The clear cell morphology of the neoplastic population in these tumors has been ascribed to the presence of intracellular lipid, mucin or glycogen, or to myoepithelial, apocrine, or neuroendocrine differentiation. However, a clear cell neoplasm exhibiting evidence of a range of differentiation has not been previously reported. We describe a case of a glycogen-rich primary clear cell breast carcinoma occurring in a 59-year-old woman that showed positivity for apocrine and neuroendocrine markers, as well as possible myoepithelial differentiation. The tumor was a 4-cm mass composed predominantly of periodic acid-Schiff-positive clear cells arranged in a solid, infiltrative pattern. Immunohistochemical staining of the tumor cells was variably positive for cytokeratin, progesterone receptors, gross cystic disease fluid protein-15, neuron specific enolase, chromogranin, and S-100 protein and negative for estrogen receptors, smooth muscle actin, CD31, and CD34. The patient refused any form of further investigation or treatment, but shows no evidence of recurrence or metastatic disease after 18 months of follow-up.

Adenocarcinoma, Clear Cell↗
PubMed2002

Distribution of Peyer's patches in the distal ileum.

BACKGROUND AND AIMS: Peyer's patches play a major role in intestinal immunity, are portals of entry for significant pathogens, and may be important in Crohn's disease. Whereas their microscopic anatomy and immune function are well described, surprisingly little is known of their macroscopic anatomy and distribution. Our aim was to assess their number, area, and distribution in the normal distal ileum, with particular reference to patient age. METHODS: Distal ilea (200 cm) obtained at autopsy from 55 adults without intestinal disease were opened along the mesenteric border, fixed in acetic acid, and transilluminated. Peyer's patches were counted, and the length, breadth, and distance from the ileocecal valve were recorded. RESULTS: Patches were most numerous in the terminal 10-15 cm where they formed a lymphoid ring. More proximal patches were oval, antimesenteric, and irregularly spaced. By area, 46% of patch tissue occurred in the terminal 25 cm. The mean number of patches ranged from 29.4 +/- 5.4 in the youngest group studied, to 19.0 +/- 3.0 in the oldest. Total patch area was greatest in the group aged 21-30 (47.4 +/- 1.0 cm2). CONCLUSION: Peyer's patches are concentrated in the distal 25 cm of ileum but extend proximally for 200 cm. The variation in their size, shape, and distribution in different individuals is greater than often appreciated and may influence the presentation of diseases centered on these structures.

Adolescent↗
PubMed2002

Altered cellular distribution of tuberin and glucocorticoid receptor in sporadic fundic gland polyps.

Gastric fundic gland polyps (FGPs) are considered hamartomas, and various gastrointestinal hamartomas are associated with tuberous sclerosis complex (TSC). The aim of this study was to investigate a possible link between TSC proteins (hamartin and tuberin) and sporadic FGPs. We examined 33 sporadic FGPs and 26 biopsies of normal fundic mucosa by immunohistochemistry. Nuclear immunoreactivity for tuberin was dramatically reduced or lost in most sporadic FGPs, and tuberin unexpectedly accumulated in the cytoplasm in oxyntic glands. About 18% (6/33) of FGPs were immunopositive in an average of 1.7% of oxyntic cell nuclei, compared with 77% (20/26) of controls in an average of 24.4% of oxyntic cell nuclei (P <.01). No change in hamartin was noted. We further examined the tuberin-associated proteins glucocorticoid receptor (GCR) and p27. Nuclear immunoreactivity for GCR was lost in most sporadic FGPs, but p27 distribution was normal. Sporadic FGPs had a low frequency of staining for Ki-67 except for some cells from cystic components, which is consistent with their slow growth. Our results are consistent with the hypothesis that tuberin may play an important role in pathogenesis of sporadic FGPs. First, an altered cellular localization of tuberin may lead to the deregulation of cell proliferation by interrupting its interaction with hamartin. Second, altered cellular localization of tuberin may preclude its negative regulation of gene transcription mediated by GCR.

Adult↗
PubMedDate not supplied

The pathology of diverticulosis coli.

Left-sided diverticulosis coli is a common condition in western communities, with 30% to 50% of adults over the age of 60 being affected. It predominantly involves the sigmoid colon. The diverticula (pseudodiverticula) are pockets of mucosa bounded by muscularis mucosae and invested with a thin layer of submucosa, that are forced out through weak points in the muscularis propria, the tips ending in the colonic subserosa. The weak points in the muscle coat are the sites of entry of the nutrient vessels of the colonic mucosa. Diverticulosis is attributed to increased colonic intraluminal pressure while straining at stool in individuals who eat low-fiber diets. Muscular hypertrophy, shortening of the bowel, and thickened mucosal folds due to mucosal redundancy are characteristic of this condition. Complications of diverticulosis include bleeding, diverticulitis, peridiverticular abscess, perforation, stricture, and fistula formation. However, most individuals with diverticulosis are asymptomatic, without evidence of complications. Mucosal changes in the diverticula in uncomplicated diverticulosis include an increased lymphoid infiltrate, development of lymphoglandular complexes, mucin depletion, mild cryptitis, architectural distortion, Paneth cell metaplasia, and ulceration. The mucosa of the remainder of the sigmoid colon (ie, the nondiverticular mucosa) is usually normal, but in about 1% of cases it has features that are indistinguishable from ulcerative colitis or from Crohn's disease (segmental colitis associated with diverticular disease, SCAD). Such cases pose a difficult diagnostic challenge as patients with SCAD respond to medical or surgical therapy for diverticular disease, whereas those with ulcerative colitis or Crohn's disease will develop other manifestations of their disease in time and require different treatment. In SCAD, the mucosal changes are confined to the area of diverticulosis; therefore, histologic evaluation of the rectum (which is unaffected by diverticulosis) and more proximal bowel can be helpful in the differential diagnosis.

Colon↗