Biomedical subjects

L Savas

Publications and source records attributed to L Savas.

At least 19 recordsLinked to original sources

PubMed2006

Nosocomial urinary tract infections: micro-organisms, antibiotic sensitivities and risk factors.

OBJECTIVE: Although urinary tract infections (UTIs) are the most common hospital-acquired infections, the epidemiology of these UTIs is not well defined in Turkey. The aim of this surveillance study was to determine micro-organisms responsible for UTI, their antibiotic sensitivities and to describe the incidence and risk factors of nosocomial urinary tract infections (NUTI). SUBJECTS AND METHODS: This was a prospective surveillance study including cases of NUTI in intensive care units and various inpatient clinics. This study was carried out between November 2000 and January 2002. The following information was recorded: patients' age, gender, type of infection (hospital-acquired), presence of urinary catheter, intensive care unit admission, duration of hospital stay, type of organisms isolated and their antimicrobial susceptibility. The diagnosis of NUTI was based on criteria established by the Centers for Disease Control, Atlanta. Mini Api and conventional culture methods were used to determine the causative agents. The agents were isolated on eosin methylene blue agar and 5% sheep blood agar Statistical analyses of data were by chi-square test and logistic regression. RESULTS: In this study, 618 (2.1%) nosocomial infections (NIs) were determined in 29,778 patients, and 178 of these infections were NUTI (28.8%, 178/618). The mean age of NUTI patients was 61.0 +/- 19.4 years (0-91 years) and 82 NUTI patients (46.1%) were male and 96 (53.9%) were female. The most frequently isolated micro-organism was Escherichia coli (31.4%) followed by Candida spp (21.3%), Klebsiella spp (10.6%) and Enterococcus spp (6.9%). Compared to the rate of other NIs, the rate of NUTI increased by 1.011 times per year of age, by 2.052 times in females and by 3.83 times in patients with urinary catheters (p < 0.05). The most effective antibiotics against Gram-negative bacteria were found to be imipenem and meropenem. CONCLUSIONS: Important factors to prevent NUTI are to avoid unnecessary urethral catheterization, to choose narrow spectrum antibiotics according to antibiotic sensitivities, to investigate regularly the causative micro-organisms and their resistance patterns and to update the treatment protocols.

Adolescent↗

PubMed2001

Expression of eukaryotic translation initiation factors 4E and 2alpha is increased frequently in bronchioloalveolar but not in squamous cell carcinomas of the lung.

BACKGROUND: When resting cells are stimulated by growth factors, an increase in protein synthesis follows that depends in part on two key eukaryotic translation initiation factors, 4E and 2alpha (eIF-4E and eIF-2alpha, respectively). In the normal cell, expression and activity of both factors are increased transiently, whereas they become elevated constitutively in oncogene-transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study, the authors investigated an association between the expression of these translation initiation factors and lung carcinogenesis. METHODS: The authors analyzed the expression of the protein synthesis initiation factors eIF-4E and eIF-2alpha by immunohistochemistry in bronchioloalveolar (BA) and squamous cell (SC) carcinomas of the lung. Western blot analysis was performed to validate the specificity of antibodies in detecting their cognate proteins. RESULTS: Both eIF-4E and eIF-2alpha were increased frequently in BA carcinomas, whereas only rarely did SC carcinomas demonstrate elevation of these translation initiation factors. An analysis of cyclin D1 expression did not show a strict correlation with the expression of eIF-4E and eIF-2alpha. CONCLUSIONS: Increased expression of either one or both translation initiation factors may facilitate accelerated growth and division of neoplastic cells in BA carcinoma of the lung. However, the current findings suggest a possibility that increased cell growth and proliferation in SC carcinoma may be achieved through a mechanism independent of increases in eIF-4E and eIF-2alpha expression.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2001

P504S: a new molecular marker for the detection of prostate carcinoma.

The ability to diagnose prostate carcinoma would be improved by the detection of a tumor-associated antigen. P504S, a cytoplasmic protein, was recently identified by cDNA library subtraction in conjunction with high throughput microarray screening from prostate carcinoma. The aim of this study was to establish the pattern of expression of P504S in prostate carcinoma and benign prostatic tissue. A total of 207 cases, including 137 cases of prostate carcinoma and 70 cases of benign prostate, from prostatectomies (n = 77), prostate needle biopsies (n = 112), and transurethral prostate resections (n = 18) were examined by immunocytochemistry for P504S. P504S showed strong cytoplasmic granular staining in 100% of prostate carcinomas regardless of Gleason scores and diffuse (>75% of tumor) staining in 92% of cases. In contrast, 171 of 194 (88%) of benign prostates, including 56 of 67 (84%) benign prostate cases and 115 of 127 (91%) cases of benign glands adjacent to cancers were negative for P504S. The remainders of benign prostates were focally and weakly positive for P504S. The staining pattern of these normal glands was different and easily distinguishable from that observed in prostate carcinoma. Expression of P504S was not found in basal cell hyperplasia, urothelial cells/metaplasia and small atrophic glands that may mimic prostate carcinoma. Our findings indicate that P504S is a highly sensitive and specific positive marker for prostate carcinoma.

Antibodies, Monoclonal↗

PubMed2001

An immunostaining panel for diagnosis of malignancy in mucinous tumors of the pancreas.

BACKGROUND: The diagnosis of malignancy in pancreatic mucinous cystic tumors depends on demonstrating invasion that may be focal and require extensive sectioning. OBJECTIVE: To explore markers that may indicate malignant potential in mucinous cystic tumors. DESIGN: Routinely processed sections from resected specimens of 12 normal pancreata, 14 pancreata with chronic pancreatitis, 9 mucinous cystic tumors, and 30 invasive adenocarcinomas were immunostained with antibodies to p53, HER-2/neu, epithelial growth factor receptor (EGFR), transforming growth factor alpha (TGF-alpha), and Ki-67. RESULTS: Expression of p53, HER-2/neu, and Ki-67 was significantly more frequent in mucinous tumors than in normal pancreatic tissue and chronic pancreatitis tissue (P =.0003 to.05). Strong expression (more than one third of cells positive) and strong intensity (2+ and 3+) of staining of p53 and EGFR were seen only in carcinomas. Coexpression of p53/HER-2/neu and EGFR/HER-2/neu and a frequency of Ki-67+ nuclei of greater than 5% of cells discriminated between mucinous tumors and normal pancreatic tissue and chronic pancreatitis tissue. p53 expression was significantly more frequent in carcinomas than in mucinous tumor (P =.0326). Coexpression of p53/EGFR discriminated between mucinous tumors and carcinomas; however, TGF-alpha was not discriminative. CONCLUSIONS: The immunostaining panel of p53, HER-2/neu, Ki-67, and EGFR can be helpful in indicating malignant potential in mucinous tumors of pancreas in routine pathology practice.

Adenocarcinoma↗

PubMed2000

Ubiquitin as a marker of cell injury in nonalcoholic steatohepatitis.

Ubiquitin (UB), an intracellular protein that binds to other proteins to target them for proteolysis, is associated with Mallory hyalin (MH), which supports a biopsy diagnosis of nonalcoholic steatohepatitis (NASH). We analyzed 54 liver biopsy specimens from 49 patients with a clinical diagnosis of NASH for immunoreactive UB and multiple features of necroinflammation, fibrosis, and Prussian blue-positive iron to determine whether the presence of immunoreactive UB increases detection of MH or correlates with other features of cell injury or mutations of the HFE gene. MH and UB were graded. Analysis for HFE gene mutations was performed in 48 patients. Biopsy diagnoses were distributed as follows: NASH, 42; steatosis, 10; and nonspecific changes, 2. UB was present in 20 specimens and MH in 23. Of 31 specimens with 0 MH, 6 had UB; of 14 with 1 + (questionable) MH, 7 had 1+ or 2+ UB. UB correlated positively and significantly with the diagnosis and grade of NASH, presence of MH, cell swelling, lobular inflammation, and fibrosis. Immunostaining for UB may enhance detection of MH in questionable cases, support the diagnosis of NASH, and indicate which patients may be at risk for progression of disease.

Adult↗

PubMed2000

Expression of cytokeratins 7 and 20 in carcinomas of the extrahepatic biliary tract, pancreas, and gallbladder.

BACKGROUND: Expression of cytokeratins 7 (CK7) and 20 (CK20) may help distinguish the site of origin for metastatic carcinomas. Little is known regarding their expression in biliary tract and pancreatic carcinomas. Our aim was to study the expression of CK7 and CK20 in these tumors. DESIGN: Fifty-three carcinomas of the extrahepatic bile ducts (n = 8), ampulla of Vater (n = 7), gallbladder (n = 11), and pancreas (n = 27), were retrieved from the surgical pathology files of the University of Massachusetts Medical Center. Formalin-fixed, paraffin-embedded sections were immunostained with mouse monoclonal antibodies to CK7 and CK20 using an avidin-biotin immunoperoxidase technique with microwave antigen retrieval. The percentage of cells positive for each antibody was assessed on a scale of 0 to 3 (0, <10%; 1+, 10% to 50%; 2+, 51% to 90%; 3+, >90%). RESULTS: The majority of carcinomas in all groups were positive for CK7 (CK7+) and negative for CK20 (CK20-). Of the CK7+ tumors, the majority of tumors in each group were 3+ positive. CONCLUSIONS: (1) Carcinomas of the extrahepatic biliary tract and pancreas are strongly positive for CK7 and negative for CK20 and can be included in the differential diagnosis of other carcinomas with this profile in metastatic sites. (2) The CK7/CK20 immunostaining profile will not identify the site of origin for tumors with extensive growth in the porta hepatis region.

Adult↗

PubMed1999

Upregulation of protein synthesis initiation factor eIF-4E is an early event during colon carcinogenesis.

A general increase in protein synthesis and a specific increase in the synthesis of growth-promoting proteins are necessary for mitogenesis. Regulation of protein synthesis, as well as preferential translation of some mRNAs coding for growth promoting proteins (e.g. cyclin D1), involves the essential protein synthesis initiation factor eIF-4E. This factor is induced by various oncoproteins, and, when overexpressed, it can transform cultured cells. In this report we explore the roles of eIF-4E in human neoplastic disorders of the colon and in the regulation of general and specific protein synthesis. We find that eIF-4E is increased in colon adenomas and carcinomas, and this increase is accompanied in most but not all cases by elevation of cyclin D1 levels. While general protein synthesis is increased by eIF-4E overexpression in cultured cells, only a small proportion of proteins is preferentially upregulated by eIF-4E, as revealed by two-dimensional gel electrophoresis. These results are consistent with the view that eIF-4E plays a role in carcinogenesis by increasing general protein synthesis and by preferentially upregulating a subset of putative growth promoting proteins. Our results, taken together with the recent findings that c-myc transcription is negatively regulated by APC and our earlier data on transcriptional activation of eIF-4E expression by c-Myc suggest that eIF-4E is a downstream target of the APC/beta-catenin/Tcf-4 pathway, and is strongly involved in colon tumorigenesis.

3T3 Cells↗

PubMed1999

Invariant chain expression in colon neoplasms.

Invariant chain (Ii) is a chaperone molecule that inhibits binding of endogenous antigens to class II molecules. High levels of Ii in cancer cells may prevent tumour antigen expression with class II and render the tumour less immunogenic. To correlate the expression of Ii and class II molecules in colon carcinomas with the density of tumour infiltrating lymphocytes (TILs), surgical specimens from a total of 48 patients with well-(WDAC), moderately (MDAC) and poorly differentiated adenocarcinomas (PDAC), adenoma with high-grade dysplasia (AdHGD) and adenomas were immunostained for Ii and class II antigen (HLA-DR). Aggregates of TILs were graded in H&E-stained sections. Normal colon epithelium was negative for Ii and HLA-DR. Invasive carcinomas showed a linear increase in the expression of Ii in the progression from low- to high-grade tumours, while there was no significant difference in HLA-DR expression across the groups. Invasive carcinomas showed a disproportionate increase in Ii over HLA-DR. Frequency of TILs showed inverse correlation with expression of Ii and tumour grade. This is the first demonstration that expression of Ii increases in the progression from low- to high-grade colon neoplasms and is most marked in the poorly differentiated carcinomas. Ii expression by carcinomas is inversely related to the frequency of TILs. The findings suggest that increased Ii renders the tumour less immunogenic and less likely to stimulate a host immune response.

Adenocarcinoma↗

PubMed1999

Expression of transforming growth factor-alpha and epidermal growth factor receptor in gastrointestinal stromal tumours.

Activation of epidermal growth factor receptor (EGFR) is associated with cell growth and transformation. Both transforming growth factor-alpha (TGF-alpha) and epidermal growth factor bind to and activate EGFR. We studied the expression of TGF-alpha and two EGFRs (HER-1 and HER-2) in gastrointestinal stromal tumours (GISTs) of the stomach (n = 9) and small intestine (n = 6) using standard immunostaining techniques in paraffin-embedded sections. Most GISTs expressed TGF-alpha, and a few expressed HER-1. All HER-1-positive tumours expressed TGF-alpha. These results suggest that a TGF-alpha/EGFR autocrine loop is present in GIST and that TGF-alpha promotes proliferation of GIST tumour cells through its interaction with HER-1 in at least some GISTs. This is the first description of an autocrine loop in GIST. In contrast, HER-2 is not expressed in any GIST.

Adult↗

PubMed1999

Expression of the eukaryotic translation initiation factors 4E and 2alpha in non-Hodgkin's lymphomas.

Transition of cells from quiescence to proliferation requires an increase in the rate of protein synthesis, which is regulated in part by two key translation initiation factors, 4E and 2alpha. The expression and activity of both factors are increased transiently when normal resting cells are stimulated to proliferate. They are constitutively elevated in oncogene transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study we investigate an association between the expression of translation initiation factors and lymphomagenesis. We have analyzed the expression of the protein synthesis initiation factors 4E and 2alpha by immunohistochemistry in reactive lymph nodes and several types of non-Hodgkin's lymphoma representing a wide range of clinical behaviors based on the Revised European-American Lymphoma behavioral classification. The study included 7 benign lymph nodes with follicular hyperplasia, 26 indolent lymphomas (6 marginal zone lymphomas, 7 small lymphocytic lymphomas, and 13 follicular lymphomas, grades 1 and 2), 16 moderately aggressive lymphomas (8 mantle cell lymphomas and 8 follicular lymphomas, grade 3), 24 aggressive lymphomas (14 large-B-cell lymphomas and 10 anaplastic large-cell lymphomas), and 15 highly aggressive lymphomas (7 lymphoblastic lymphomas and 8 Burkitt's lymphomas). Strong expression of initiation factors 4E and 2alpha was demonstrated in the germinal centers of reactive follicles. Minimal or no expression was seen in the mantle zones and surrounding paracortices, indicating that high expression of initiation factors 4E and 2alpha is associated with the active proliferation of lymphocytes. Most cases of aggressive and highly aggressive lymphomas showed strong expression of initiation factors 4E and 2alpha, in contrast to the cases of indolent and moderately aggressive lymphoma, in which their expression was intermediate between the germinal centers and the mantles of reactive follicles. A positive correlation was found between the expression of both initiation factors 4E and 2alpha and the Revised European-American Lymphoma behavior classification (P < 0.05). Thus, constitutively increased expression of initiation factors 4E and 2alpha may play an important role in the development of lymphomas and is correlated with their biological aggressiveness.

Blotting, Western↗

PubMed1998

The role of cell cycle regulatory proteins, cyclin D1, cyclin E, and p27 in thyroid carcinogenesis.

The cell cycle is controlled in part by cyclin-dependent kinases (CDKs), which are activated by forming complexes with cyclins. CDKs phosphorylate certain substrates to facilitate the proliferating cells through the cell cycle. CDK inhibitors (CDKIs) such as p27 inhibit cyclin-CDK complexes and function as a negative cell cycle regulator. The overexpression of the positive regulators (cyclins) or the underexpression of the negative regulators including p27 has been seen in a variety of neoplasms, but their role and interaction in thyroid carcinogenesis is yet to be established. We studied the expression of cyclins D1 and E, and the CDKI, p27 by immunohistochemistry in 116 cases, including 59 cases of follicular variant of papillary carcinoma (FVPC) and 57 cases of follicular adenoma (FA). The positive staining was divided into four grades: 1+ if less than 10%, 2+ if 11% to 25%, 3+ if 26% to 50%, and 4+ if greater than 50% of the nuclei of tumor cells stained positively. Cyclin D1 expression was seen in 37 (63%) FVPC and 34 (60%) FA. Cyclin E-positive cells were seen in 51 (86%) FVPC and 47 (82%) FA. No significant differences in the grade of cyclins D1 (P = .261) and E (P = .284) staining was seen between FVPC and FA. Of the 59 FVPC, 53 (89%) showed p27-positive cells; of these, 33 were 1+, nine were 2+, seven were 3+ and only four were 4+ positive. Conversely, all 57 FA were p27 positive, 53 were 4+, and four were 3+ positive. This difference in the grade of p27 staining between FVPC and FA was statistically significant (P < .001). This study shows a significant underexpression of p27 in FVPC compared with FA, suggesting that a decrease in p27 expression plays a more important role than overexpression of cyclins D1 and E alone in thyroid carcinogenesis and that p27 immunostaining may be helpful in the diagnosis of FVPC.

Adenocarcinoma, Follicular↗

PubMed1998

Expression of ICAM-1, VCAM-1, and LFA-1 in adenocarcinoma of the lung with observations on the expression of these adhesion molecules in non-neoplastic lung tissue.

Intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and the lymphocyte function-associated antigen (LFA-1) are cell adhesion molecules thought to play an important role in the complex process of airway inflammation and tumor cell growth. The aim of this study was to examine the distribution of ICAM-1, VCAM-1, and LFA-1 in adenocarcinoma of lung and in major cellular compartments of non-neoplastic lung tissue. We examined cellular compartments in tissue from five bronchoalveolar carcinomas, three acinar adenocarcinomas, and one colon cancer metastatic to the lung. The compartments in neoplasms included the tumor cells proper, endothelial cells within the tumor vasculature, tumor stromal cells, and tumor-infiltrating lymphocytes. The compartments in non-neoplastic lung tissue included lung endothelial cells, pulmonary lymphocytes, interstitial fibroblasts, Type II alveolar pneumocytes, and bronchial epithelial cells. ICAM-1 was expressed in tumor cells from all of the nine adenocarcinomas. In contrast, VCAM-1 expression was not identified in tumor cells from any of the nine adenocarcinomas. ICAM-1 was expressed in all cellular compartments of the non-neoplastic lung tissue, whereas VCAM-1 was expressed only in pulmonary lymphocytes and interstitial fibroblastic cells. LFA-1 was uniformly expressed in tumor-infiltrating lymphocytes from each of the nine tumors and all of the lymphocytes in non-neoplastic lung tissue. This study showed major differences in the expression of ICAM-1 and VCAM-1 in tumor cells from pulmonary adenocarcinoma and also provided evidence for a wider distribution of ICAM-1, compared with VCAM-1, in non-neoplastic cellular compartments of the lung. ICAM-1 expression was particularly noticeable in bronchial and alveolar epithelial cells. Upregulation of ICAM-1 in pulmonary adenocarcinoma might foster binding by LFA-1-bearing lymphocytes, with a possible impact on the vulnerability of tumor cells to host defense mechanisms.

Adenocarcinoma↗

PubMed1997

Inflammatory markers in chronic hepatitis C.

To test the hypothesis that inflammation in hepatitis C follows mechanisms common to immune-activated pathways, the distributions of T and B cells, adhesion molecules and transforming growth factor-beta (TGF-beta) were assessed in liver biopsies with chronic inflammation due to hepatitis C (HCV, n = 8) and other causes (non-HCV, n = 10). Frozen sections were immunostained using primary antibodies to CD2, CD20, CD4, CD8, intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM)-1, HLA-DR, lymphocyte function-associated antigen (LFA)-1, and TGF-beta. Inflammatory cells positive for each immunophenotypic marker were counted, and positive staining for adhesion molecules, HLA-DR and TGF beta was graded in triads and lobules and compared in HCV and non-HCV biopsies. In all biopsies, T cells were more frequent than B cells, both in triads and lobules. CD20+, CD4+, CD8+ and LFA-1+ cells were increased in HCV compared to non-HCV biopsies. Portal lymphoid aggregates were present in 6 of 8 HCV biopsies and 3 of 10 non-HCV biopsies. Aggregates consisted of CD20+, CD4+, CD8+ and LFA-1+ cells, and ICAM-1 and VCAM-1 were increased. Sinusoidal lining cells in HCV biopsies and non-HCV biopsies with inflammation expressed HLA-DR, ICAM-1, and CD4. TGF-beta was increased in foci of necrosis. Inflammation in chronic HCV involves common immune-mediated cellular effector pathways and the inflammation in the portal triads represents aggregation of both T and B cells, mediated in part by upregulation of adhesion molecules on portal stromal cells; this is possibly in response to antigens draining from necroinflammatory foci in the lobules. TGF-beta is increased in active necroinflammatory foci, but not in portal lymphoid aggregates.

Adult↗

PubMed1997

Frequency and distribution of DNA fragmentation as a marker of cell death in chronic liver diseases.

To study the early stages of cell death in various types of chronic liver injury, liver biopsies from a total of 26 patients, including 7 with chronic hepatitis C(CHC), 4 with chronic hepatitis B(CHB), 7 with alcoholic liver disease (ALD), 4 with autoimmune or drug hepatitis (AI/DH), and 4 with primary biliary cirrhosis(PBC), were examined by an in situ nucleotidyl transferase assay (ISNTA), which detects DNA fragmentation. Positive nuclei in hepatocytes and sinusoidal lining cells were counted in all parenchymal areas, excluding triads and areas of fibrosis, using a computer with Sigmascan software. The number of positive hepatocytes/mm2 was similar in the biopsies of patients with CHC, CHB, ALD and AI/DH, but significantly lower in PBC. The number of positive sinusoidal lining cells/mm2 was significantly greater in biopsies with CHC compared to CHB, ALD, AI/DH and PBC. Double staining revealed that the ISNTA-positive sinusoidal lining cells were also CD68 positive, indicating that they were Kupffer cells. The frequency of ISNTA positivity did not correlate with serum AST or ALT levels, steatosis, cell swelling or cirrhosis. ISNTA-positive hepatocytes were more frequent than acidophilic bodies in every disease category. We conclude that apoptosis may be a common pathway of cell death in different liver diseases, that the high frequency of DNA fragmentation in Kupffer cells in CHC suggests that during chronic hepatitis C infection activated Kupffer cells may be subject to regulatory control by apoptosis and that ISNTA is more sensitive than acidophilic bodies in assessing the degree of cell injury in the liver.

Adult↗

PubMed1997

Laminin and cathepsin B as prognostic factors in stage I non-small cell lung cancer: are they useful?

Laminin, a glycoprotein component of basement membrane, and cathepsin B, a lysosome-derived proteinase, are thought to play a role in the complex process of tumor invasion and metastasis. This study evaluates the possible prognostic significance of laminin degradation and cathepsin B expression in Stage I (T1NO, T2NO) human non-small cell lung cancer. Archival, formalin-fixed, paraffin-embedded lung tissue from patients with documented Stage I non-small cell cancer was studied in a series of 31 patients (14 men, 17 women; ages 40-82 yr; mean age, 67 yr) by using polyclonal antibodies against laminin and cathepsin B. The immunoexpression of laminin was assessed with respect to a continuous versus discontinuous pattern, whereas that of cathepsin B was semiquantitated according to a four-tiered grading scale: 0, 0% positive cells; 1, 1 to 9%; 2, 10 to 49%; and 3, more than 50% positive cells. Cox proportional hazards models and Kaplan-Meler survival analysis were used to evaluate the association of possible risk factors, including laminin and cathepsin B, with survival. Univariate analysis looking at possible associations of survival with age, sex, histologic type, degree of tumor differentiation, and tumoral stage (T1NO, T2NO) did not show significant association. Likewise, degradation of laminin and immunoexpression of cathepsin B did not show significant association with survival. Although previous studies suggested improved survival with increased laminin expression and decreased survival with high expression of cathepsin B, the results applying to intrastage (Stage I) non-small cell cancer suggest that the expression of laminin and cathepsin B has little prognostic significance.

Adult↗

PubMed1996

Effect of interferon therapy on bile duct inflammation in hepatitis C.

Inflammation of the bile ducts was studied in liver biopsies from patients with chronic hepatitis C to determine whether the frequency of inflamed bile ducts changes with therapy and correlates with other histological variables and expression of class I and II MHC antigens on ductal epithelium. Twenty patients treated at UMMC between 1991 and 1994 underwent needle biopsies of the liver before and after therapy with interferon alpha 2B (IFN). A complete response to therapy was defined as a return to normal serum alanine aminotransferase levels occurring and persisting during therapy. The number of inflamed bile ducts/total ducts (%IBDs), presence of piecemeal necrosis and lymphoid aggregates, and grade of inflammation were assessed in each high-power field in all areas with bile ducts. The frequencies of these variables were compared in cirrhotics and non-cirrhotics and in patients with complete or incomplete responses to IFN. Frozen sections of biopsies from 5 patients were immunostained using antibodies to HLA-DR and B-2 microglobulin, and positive staining was noted on bile ducts. Before therapy, the %IBD was slightly greater in patients with cirrhosis. After IFN, both %IBD and serum alkaline phosphatase levels decreased in non-cirrhotics who responded to IFN. The change in frequency of IBD with IFN paralleled the changes in the other histological features. No correlation was noted between bile duct inflammation and expression of class I and II antigens. The conclusion is that inflammation of the bile ducts occurs frequently in chronic hepatitis C, correlates with other features of inflammation in the triads, and decreases in response to IFN therapy.

Adult↗

PubMed1996

Leukemia with megakaryocytic differentiation following essential thrombocythemia and myelofibrosis. Case report and review of the literature.

Leukemias of megakaryocytic lineage are rare and heterogeneous clinical entities. The nomenclature published in the literature is confusing and perhaps inappropriate to designate these primary myeloproliferative disorders. We describe a patient with essential thrombocythemia who evolved through myelofibrosis and myeloid metaplasia to a final picture of leukemia with megakaryocytic differentiation in the peripheral blood. This case illustrates different aspects of a chronic myeloproliferative disorder where myelofibrosis and myeloid metaplasia are frequent but secondary events. We have reviewed the literature focusing on the role of clonal megakaryocytic proliferation in myelofibrosis and on the clinical characterization of leukemia with megakaryocytic phenotype. We also present our interpretation of the literature which indicates that a formal review of the nomenclature is urgently needed.

Female↗

PubMed1996

Immunohistochemical detection of bcl-2 protein in adenocarcinoma and non-neoplastic cellular compartments of the lung.

The expression of bcl-2 seems to influence the biologic activity of a variety of neoplasms. In this study, we examined bcl-2 protein expression in 47 surgically resected adenocarcinomas of the lung to determine its expression in the neoplastic and adjacent non-neoplastic cells. Seven squamous cell carcinomas, six small cell carcinomas, five non-neoplastic lung lesions, and five normal lungs were also studied. The bcl-2 protein was detected after antigen retrieval with bcl-2 monoclonal antibody using archival formalin-fixed, paraffin-embedded tissue material. Fifty-one of 52 cases had bronchioles that could be evaluated and all expressed bcl-2, and of these, 12 showed basal immunostaining, 17 showed luminal immunostaining, and 22 showed immunostaining in both cellular compartments. Thirty of the 47 adenocarcinomas expressed bcl-2, whereas four of seven squamous cell carcinomas and all six small cell carcinomas were bcl-2 positive. bcl-2 immunostaining was correlated with a survival using the Fisher exact test. There were no statistically significant differences in survival between patients with bcl-2-positive and bcl-2-negative adenocarcinomas (P = 0.332). Similar results were obtained using the Kaplan-Mier product limit survival analysis method (P = 0.356). Our study also showed that expression of bcl-2 is common in pulmonary adenocarcinomas and that bcl-2 expression may be found in the basal and the luminal surfaces of normal bronchioles.

Adenocarcinoma↗