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Biomedical subjects

S L Perkins

Publications and source records attributed to S L Perkins.

At least 55 records · Page 3Linked to original sources

CD23 expression in transformed small lymphocytic lymphomas/chronic lymphocytic leukemias and blastic transformations of mantle cell lymphoma.

The immunophenotypic marker, CD23, has been shown to be a useful marker for the distinction of small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) from mantle cell lymphoma (MCL). The usefulness of this marker has not previously been analyzed in distinguishing various "large cell" transformations of SLL/CLL from blastic transformations of MCL (MCL-B). Thirteen cases of transformed SLL/CLL and six cases of MCL-B were analyzed for expression of CD23, either by flow cytometry of peripheral blood, bone marrow, or fresh tissue or by immunoperoxidase staining of paraffin-embedded archival tissue. All of the 13 cases of transformed SLL/ CLL expressed CD23 and all of the 6 cases of MCL-B were negative for CD23. Therefore, CD23 is retained in transformed SLL/CLL. It is a useful marker in distinguishing transformed SLL/CLL from MCL-B and thus might aid in distinguishing those cases that present de novo without a previous diagnosis of SLL/CLL or MCL.

Biomarkers, Tumor↗

Methotrexate-associated lymphoma in patients with rheumatoid arthritis: report of two cases.

This report describes 2 patients with longstanding seropositive rheumatoid arthritis (RA) treated with oral methotrexate (MTX) who developed large cell lymphoma of B cell phenotype. In situ hybridization studies showed nuclear staining for Epstein-Barr virus (EBV) within the malignant lymphoid cells. In both cases, the lymphoma was undetectable several weeks after diagnostic biopsy followed by discontinuation of MTX. These observations suggest that, in patients with RA who develop an EBV-associated lymphoproliferative disorder, a trial of discontinuation of immunosuppressive agents may be warranted before chemotherapy is considered. In addition, there is a need for a heightened awareness of the development of lymphoma in this patient population.

Aged↗

Dexamethasone inhibits trabecular cell retraction.

Glucocorticosteroids such as dexamethasone (Dex) are known to cause an increased resistance to aqueous outflow in the intact and cultured eye. We investigated whether Dex treatment of cultured endothelial or trabecular meshwork (TM) cells might interfere with the cell separations and retraction induced by the facility-enhancing agents ethacrynic acid (ECA), cytochalasin B and the calcium chelator EGTA. Our hypothesis was that Dex-induced changes in the response of our model cells in vitro might serve as a paradigm for those produced in the cells of the outflow pathway, perhaps through influencing the changing dimensions of the pathway for aqueous humor through the juxtacanalicular tissue and/or inner wall of Schlemm's canal. We treated calf pulmonary artery endothelial (CPAE) and human and porcine TM cells with Dex (1-100 microns, 1-9 days), and then assessed monolayer and cytoskeletal integrity by immunofluorescence microscopy for tubulin and direct fluorescence staining for F-actin after exposure to the agents named above. We found that Dex-pretreated CPAE and TM cells gradually (over 5-7 days) became refractory to the effects of both ECA and EGTA, but not to cytochalasin B. Despite the preservation of general cell shape and attachment after ECA in Dex-treated cells, microtubule disruption still took place as in controls. Dex-treated cells also demonstrated a reorganization of filamentous actin staining after ECA and EGTA. Combination experiments of ECA and EGTA in Dex-treated cells suggested that the Dex effects were due to a greater strength of cell-to-cell and cell-to-substrate attachment, possibly due to interference with the normal cellular signaling required for coordinated cellular retraction and junctional disruption.

Actins↗

bcl-2 is down-regulated in atypical endometrial hyperplasia and adenocarcinoma.

The bcl-2 protein, which protects cells from apoptosis, is normally expressed in a number of adult tissues. Dysregulated bcl-2 expression, secondary to (14;18) chromosomal translocation, seems to promote the development of follicular lymphomas, and recent findings of bcl-2 protein in several solid tumors suggest that it might contribute to the genesis of many other neoplasms. bcl-2 is also highly expressed in normal proliferative endometrium and markedly down-regulated in secretory endometrium, which suggests that its expression is estrogen regulated. Because the development of most endometrial carcinomas is associated with hyperestrogenic states, we began the investigation of the role of bcl-2 in endometrial carcinogenesis by immunohistochemically quantifying its expression in proliferative, hyperplastic, atypically hyperplastic, and carcinomatous endometrium. The results of this study show that bcl-2 is relatively highly expressed in proliferative (n = 11) and hyperplastic (n = 18) endometrium, with respective mean staining scores of 3.59 and 3.47 (scale, 0-4), but is significantly (P < 0.001) down-regulated in atypical hyperplasia (n = 11; score, 0.82), and adenocarcinoma (n = 34; score, 0.86). bcl-2 expression did not correlate with stage, grade, estrogen-receptor, or progesterone-receptor expression. Polymerase chain reaction analyses of DNA isolated from several endometrial carcinomas were negative for (14;18) translocation involving the bcl-2 gene. Thus, bcl-2 apparently plays no role in the progression of atypical hyperplasia to carcinoma or in the development of high-grade or advanced-stage endometrial carcinoma. These results, however, do not rule out the involvement of bcl-2 in very early, preatypical hyperplasia phases of endometrial carcinogenesis. Finally, the marked difference in bcl-2 expression in hyperplastic and atypically hyperplastic glands might prove to be diagnostically useful in the often difficult distinction of these entities.

Adenocarcinoma↗

Evaluation of the Du Pont Axial Separation system.

We evaluated the Du Pont Axial Separation Technology (AST) system, which permanently separates a blood specimen into serum or plasma and cells in 1 min. Blood was collected in axial processing containers by standard venipuncture techniques and processed in an Axial Separation Module. Paired patient samples (n = 48 serum pairs, n = 50 plasma pairs) revealed no clinically significant differences in results for common chemistry analytes from samples collected in Becton Dickinson Vacutainer Tubes and centrifuged conventionally vs those from samples collected and processed in the AST system, except for a bias in serum (but not plasma) lactate dehydrogenase activity. This bias was dependent on the extent of stretching of the clot during processing and could be minimized by clotting the blood sample horizontally (axially). We believe the rapid separation of blood by the AST system has the potential to substantially reduce preanalytical specimen handling time.

Blood Chemical Analysis↗

Association between creatinine-adjusted and unadjusted urine cotinine values in children and the mother's report of exposure to environmental tobacco smoke.

OBJECTIVE: To examine the association between parents' report of their child's secondhand smoke exposure and various adjustments of cotinine concentrations in random urine samples. METHODS: Urine cotinine and creatinine were measured in 109 six to 11-year-old children from predominantly upper middle-class families. Cotinine values were considered as: (a) unadjusted, (b) as a cotinine/creatinine ratio, (c) as adjusted based on a regression relationship between cotinine and creatinine, and (d) and (e) as a cotinine/creatinine ratio adjusted for age and sex. RESULTS: Little overlap in cotinine values occurred between exposed and nonexposed children, and a dose-response relationship was noted between the parental report and the urine cotinine values (r = 0.67). A modest improvement occurred in the correlation when the cotinine/creatinine ratio was considered. Considering exposure to cigarette smoke outside the home as well as in the household only improved the correlation when the former exposure was heavy. A high degree of concordance exists between the parents' report of exposure and the child's urine cotinine. CONCLUSIONS: The value of adjusting this biochemical parameter by various means may be a function of the particular sample being investigated, suggesting no one method is universally appropriate.

Child↗

Immunohistochemical staining for DNA topoisomerase II in non-Hodgkin's lymphomas.

DNA topoisomerase II (topo II) is the target of several clinically useful anticancer drugs. Several of these agents, such as doxorubicin and etoposide (VP-16), are used to treat non-Hodgkin's lymphomas (NHL). To understand the therapeutic selectivity of these drugs, a series of 33 cases of NHL for topo II were analyzed using an immunohistochemical technique that detects the enzyme in formalin-fixed, paraffin-embedded tissue. The average topo II index of high grade (Working Formulation) NHL was 48.6 with a range from 24.4 to 79.7. The average topo II index of low grade (Working Formulation) NHL was 4.4 with a range from 0.9 to 11.2. These two values are statistically different (P < .01). The intermediate grade (Working Formulation) NHL are a heterogeneous group based on topo II staining. The average topo II index value for the intermediate grade neoplasms was 26.7 with a range from 1.4 to 54.9. Because the proliferation marker Ki-67 has been shown to be of prognostic importance when used in the analysis of NHL, 27 cases for also were analyzed for MIB1 (Ki-67). The average MIB1 index of the high grade NHL was 59.8 with a range from 40.7 to 80.3. This average is statistically different (P < .01) than the average MIB1 index of 11.2 (range 1.7-28.3) found in the low grade NHL. Similar to results with topo II, the intermediate grade NHL was a heterogeneous group of tumors with respect to MIBI staining and had an average MIB1 index of 49.1 with a range from 8.9 to 86.7. These results show that high grade NHL have topo II and MIB1 indices that are significantly higher than low grade NHL. Intermediate NHL are more heterogeneous and have topo II and MIB1 indices that range from low to high.

Antibodies, Monoclonal↗

Immunohistochemical reference ranges for B lymphocytes in bone marrow biopsy paraffin sections.

The quantitation of B lymphocytes in paraffin-decalcified bone marrow sections is often used as supportive evidence of primary or residual B-cell lymphoproliferative disorders; however, well-defined normal ranges for B lymphocytes are not available. Thirty-four B5-fixed decalcified bone marrow sections were analyzed from a group of patients having an essentially normal bone marrow morphologic examination and lacking any evidence immunologic or hematopoietic disease. All samples were stained with CD20, CD45RA (4KB5), and DBA.44 for B cells, and CD45RO (UCHL-1) for T cells. Image analysis was performed on all cases. CD20-positive cells ranged from 0% to 5.97%. CD45RA positivity ranged from 0% to 5.48%. DBA.44 was positive in 0% to 2.07% of the cells. CD45RO positivity varied from 0% to 6.7%. These results provide useful immunohistochemical B-lymphocyte reference ranges in B5-fixed paraffin bone marrow sections.

Adult↗

Local concentrations of macrophage colony-stimulating factor mediate osteoclastic differentiation.

Macrophage colony-stimulating factor (M-CSF) is essential for differentiation of osteoclasts and macrophages from a common bone marrow precursor. Using ST-2 stromal cell/murine bone marrow coculture, we studied the effects of increasing amounts of M-CSF on differentiation of macrophages and osteoclasts. Addition of exogenous M-CSF caused a dose-dependent 98% decrease in tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, accompanied by a 2.5-fold increase in nonspecific esterase-staining macrophages. Similar decrease in osteoclastic functional activity, including 125I-labeled calcitonin binding and calcitonin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, were observed. Addition of exogenous M-CSF beyond 6 days in coculture had a decreasing ability to inhibit osteoclast formation, suggesting that M-CSF exerts its effects early in osteoclast differentiation, during the proposed proliferative phase of osteoclast formation. Similarly, early addition of neutralizing anti-M-CSF inhibited osteoclast formation, with diminishing effects beyond day 9. These results suggest that local high concentrations of M-CSF may influence the early determination of terminal differentiation into either macrophages or osteoclasts.

Acid Phosphatase↗

1,25 dihydroxyvitamin D3 stimulates differentiation of committed murine bone marrow-derived macrophage precursor cells.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] and macrophage colony-stimulating factor (M-CSF) both accelerate differentiation of marrow macrophages from which osteoclasts are derived. Previously, we showed that the steroid's effect on early macrophage precursors may be mediated through M-CSF, as the steroid enhances cytokine receptor expression. In contrast, 1,25-(OH)2D3 blunts M-CSF receptor expression on more mature, yet still pluripotential, hematopoietic precursors. Extending these observations to marrow cells committed to macrophage differentiation, we found that 1,25-(OH)2D3 causes a marked decrease in cellular proliferation despite a 2- to 3-fold increase in [125I]M-CSF binding in a similar dose-dependent metabolite-specific manner. Scatchard analysis demonstrated that increased binding reflects increased receptor capacity without an alteration in affinity. Steroid-induced M-CSF receptor enhancement reflects acceleration of protein appearance rather than overexpression, as treated and untreated cells ultimately exhibit equivalent binding. Increased M-CSF receptor expression is mirrored by increased c-fms messenger RNA levels, and actinomycin D or cycloheximide experiments indicate that new receptor synthesis, rather than mobilization of intracellular pools, is required. Thus, 1,25-(OH)2D3 differentially impacts on M-CSF receptor expression throughout the spectrum of bone marrow macrophage differentiation.

Animals↗

Simultaneous determination of alcohols and ethylene glycol in serum by packed- or capillary-column gas chromatography.

We developed a packed-column chromatographic procedure capable of simultaneous quantitation of methanol, ethanol, isopropanol, acetone, and ethylene glycol. This method was then updated to a rapid, sensitive, wide-bore capillary method. The packed-column system uses direct injection of 1 microL of Na2WO4/H2SO4-deproteinized serum onto a 1.8 m x 2 mm (i.d.) column packed with 80/100 HayeSep R. A linear temperature gradient from 90 to 205 degrees C allows complete elution of all components within 20 min; minimum detection limits are 2 mmol/L. The wide-bore capillary method uses 0.1 microL of sample deproteinized by ultrafiltration, injected onto a 30 m x 0.53 mm (i.d.) 3-microns Rtx-200 (Restek) column. Baseline resolution to a minimum detection limit of 0.1 mmol/L of all compounds is achieved in 5 min with a linear temperature gradient from 40 to 250 degrees C and dual internal standards of n-propanol and 1,2-butanediol.

1-Propanol↗

Work-up of lymphadenopathy in children.

Lymphadenopathy occurs frequently in childhood caused by both reactive and neoplastic origins. Correlation of clinical findings, historical information, and patient symptoms may provide important insights into the cause of lymphadenopathy. When malignancy is suspected or if a child does not respond to antibiotic therapy, nodal biopsy or cytological examination may be undertaken to establish a diagnosis. Proper handling of pathologic materials will enhance the pathologist's ability to make an accurate diagnosis and may allow for important ancillary testing to be performed.

Biopsy, Needle↗

Benign lymphadenopathies in children and adolescents.

This article provides and overview of the benign causes of lymphadenopathy (LA) in the pediatric population. Because of the topics' broad nature, this review is a selective one and primarily focuses on benign conditions of lymph nodes that may be confused with malignant disorders or have been described or better defined in recent years. Specifically, these will include infectious LA caused by Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), and cat scratch disease (CSD), LA associated with vaccination, drug-associated LA, progressive transformation of germinal centers (PTGC), LA associated with autoimmune disorders, histiocytic proliferations involving lymph nodes, and Kawasaki disease.

Adolescent↗

Classification of non-Hodgkin's lymphomas in children.

Pediatric non-Hodgkin's lymphomas (NHLs) comprise an important subset of childhood malignancies with characteristic clinical, histologic, cytogenetic, and immunologic findings. Lymphoblastic lymphoma, small noncleaved cell lymphoma, and large cell lymphomas comprise the vast majority of childhood NHLs. Proper distinction of these subsets of NHL has important therapeutic and prognostic implications for the patient.

Burkitt Lymphoma↗

Antigen expression and polymerase chain reaction amplification of mantle cell lymphomas.

Flow immunophenotyping, DNA content analysis, and polymerase chain reaction (PCR) amplification for t(11;14) and t(14;18) were performed on 11 cases of typical mantle cell lymphoma (MCL), 5 cases of apparent MCL with proliferation centers (MCL-PC), and 5 cases of small lymphocytic lymphoma (SLL). Immunophenotyping showed IgM (P < .001), Ig light (P < .001), and CD20 (P < .001) expression to be more intense in MCL than in SLL. In MCL-PC, the mean intensity of IgM, Ig light chain, and CD20 expression was intermediate to the intensities observed in MCL and SLL. Furthermore, in contrast to SLL, all MCL and 4 of 5 MCL-PC cases exhibited stronger CD20 than CD19 expression. CD10 expression was not observed in any case and CD5 expression was present in all SLL and MCL-PC cases and in 9 of 11 MCL cases. DNA content analysis showed an S-phase fraction of less than 3% in all cases studied and, except for 1 MCL case, all lymphomas were DNA diploid. The t(11;14) breakpoint junctions involving the bcl-1 major translocation cluster were amplified by PCR in 4 of 11 (36%) MCL cases and in none of the MCL-PC or SLL cases. The t(14;18) involving the bcl-2 major breakpoint region was not identified by PCR in any case. We conclude that the level of expression of surface antigens and the rapid detection of t(11;14) by PCR are potentially useful for distinguishing MCL and SLL in the clinical setting. Further investigations as to the biologic relationship between MCL, MCL-PC, and SLL, and the utility of t(11;14) PCR in these lymphomas are warranted.

Aged↗

Interleukin 4 enhances osteoblast macrophage colony-stimulating factor, but not interleukin 6, production.

To determine if interleukin 4's (IL-4) recently discovered skeletal effects could be explained by its effects on osteoblasts, we have examined IL-4's impact on macrophage colony stimulating factor (M-CSF) and interleukin 6 (IL-6) secretion by the murine osteoblastic cell line MC3T3-E1. Interleukin-4 increased colony-forming activity in MC3T3 supernatants two-threefold with colony cytomorphology, cytohistochemistry, and blockade of the effect by anti-M-CSF antibody, indicating that the IL-4-induced activity was M-CSF. MC3T3 M-CSF supernatant activity increased in a time-dependent manner with positive IL-4 effects seen after a 24-hour exposure. The maximal IL-4 effective dose was 100 U/ml where conditioned media from IL-4-treated cells contained twofold more M-CSF than control cells (400 U/ml versus 200 U/ml M-CSF) as detected by a sandwich M-CSF ELISA. Northern blots showed that IL-4 (200 U/ml) rapidly increased steady-state M-CSF mRNA levels with maximal induction observed by 2 hours followed by a decline to near basal levels by 24 hours. IL-4 also dose dependently increased M-CSF mRNA levels with maximal induction (fourfold) seen at 100 U/ml IL-4. In contrast to its impact on MC3T3 M-CSF production, IL-4 (200 U/ml) did not stimulate MC3T3 IL-6 secretion whereas IL-1 (1 pM) stimulated a 500-fold increase in MC3T3 IL-6 release.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗

CD30 antigen expression in florid immunoblastic proliferations. A clinicopathologic study of 14 cases.

Reactive immunoblastic proliferations may be confused with certain types of non-Hodgkin's lymphoma and Hodgkin's disease on morphologic grounds. In addition, a characteristic antigen, CD30 (Ki-1; BerH2) on these neoplastic entities may be observed in morphologically atypical yet reactive florid immunoblastic proliferations such as those associated with acute infectious mononucleosis. Although it has been documented, a large series determining the frequency and extent of CD30 antigen expression on a variety of nonneoplastic immunoblastic proliferations is lacking. The authors studied 14 florid immunoblastic proliferations (9 in lymph nodes and 5 in tonsils) for CD30 antigen expression and for B- and T-cell paraffin markers. In situ hybridization to determine the presence of Epstein-Barr virus (EBV) genomes also was performed. Cases were classified into monospot-positive acute infectious mononucleosis (4 cases), EBV-related lymphoproliferative disorder suggestive of acute infectious mononucleosis (5 cases), and other etiologies (5 cases). CD30 Antigen expression was found on the immunoblasts in cases from all three categories and overall in 9 (64%) of 14 specimens. CD30 reactivity in the positive cases varied from occasional to numerous positive cells; 4 samples (3 EBV-related lymphoid proliferations and 1 vaccine-related lymphadenopathy) had numerous CD30-reactive immunoblasts. Expression of CD30 antigen on B or T cells and prominence of B or T cells within a proliferation were variable. Significant "atypia" of immunoblasts was found only in EBV-related disorders and correlated with B-cell prominence of the infiltrate. Appropriate clinical correlation and ancillary laboratory data are necessary to assist in differentiating these CD30(+)-reactive disorders from similar-appearing malignant lymphomas. Most important, a fresh tissue sample should be procured and adequately processed to allow for comprehensive determination of clonality and cellular lineage.

Adolescent↗