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Biomedical subjects

M Samoszuk

Publications and source records attributed to M Samoszuk.

At least 19 recordsLinked to original sources
PubMed2001

Unique molecular markers in human endometriosis: implications for diagnosis and therapy.

Endometriosis originates in the uterine lining and affects ~20% of reproductive-age women. The disease often causes chronic pelvic pain, affects ovulatory function and influences fertility. Although laparoscopic diagnosis of uterine endometriosis is quite specific, direct visualisation can be difficult or inaccurate in some circumstances, and it is not useful for diagnosing extra-abdominal disease. Laparoscopy is an invasive procedure, has significant morbidity and cannot be carried out frequently to monitor efficacy of therapy and the possibility of recurrence. Thus, a specific, non-invasive diagnostic test is required. One intriguing area of research uses the technology of radioimmunotargeting, which has previously been used for cancer detection. This technique could have potential for the specific detection and eventual treatment of endometriosis. A marker, eosinophil peroxidase (EPO), has been identified that is expressed in ~90% of endometriosis specimens, and is not expressed or only weakly expressed in normal endometrium. The US Food and Drug Administration has approved a monoclonal antibody to EPO for investigation as an immunoimaging agent in cancers that exhibit eosinophilia. EPO targeting using this antibody could be useful for detecting and/or treating endometriosis.

Journal Article↗
PubMed2001

Uterine leiomyomas with Eosinophils: a clinicopathologic study of 3 cases.

Although leiomyomas (LMs) of the uterus are common, hematopoietic components within these tumors are not. Lymphoid and other hematopoietic elements have been previously recognized, but eosinophilic infiltrates in LMs have received little attention in the literature. The clinical and pathologic features of 3 cases of uterine LM with eosinophilic infiltration were studied. The patients ranged in age from 35 to 62 years and presented with abdominal and/or pelvic pain and abnormal uterine bleeding. None had peripheral blood eosinophilia or clinical evidence of allergy or parasitic infection. One patient had a benign LM, and the other 2 patients had smooth muscle tumors of uncertain malignant potential. The tumors contained variable numbers of eosinophils and Giemsa stains showed variable numbers of mast cells in addition to the eosinophils. We also performed immunohistochemical and in situ hybridization studies to assess for interleukin-5 (IL-5) and eotaxin in these LMs. There was no consistent association between the presence of eosinophils and either IL-5 or eotaxin in smooth muscle cells, suggesting that mechanisms other than IL-5 or eotaxin production may account for the eosinophilia. Because eosinophils are believed to be involved in wound healing, tissue remodeling, and fibrosis, their presence within LMs may reflect a response to tissue injury produced by the neoplasm rather than intrinsic recruitment by chemotactic factors produced by the smooth muscle cells. Their presence, however, does not appear to have any clinical significance.

Adult↗
PubMed2001

Detection of clonal T-cell receptor-gamma gene rearrangement by PCR/temporal temperature gradient gel electrophoresis.

Limited combinatorial and junctional diversity in TCR-gamma gene rearrangement can result in amplification products that are difficult to interpret when analyzed by conventional gel electrophoresis methods that separate DNA based on size (polymerase chain reaction [PCR]/polyacrylamide gel electrophoresis [PAGE]). We describe a simple approach to the detection of clonal TCR-gamma gene rearrangement using temporal temperature gradient gel electrophoresis (TTGE) that uses a gradual and uniform increase in the temperature of a constant denaturing gel to resolve different DNA molecules based on base pair composition. We tested 42 clinical specimens (30 blood specimens and 12 formalin-fixed paraffin-embedded tissues) for T-cell clonality by PCR/PAGE and PCR/TTGE. Concordant results were obtained in only 22 specimens (52%). Of the 20 discordant cases, 18 samples were positive by TTGE and negative by PAGE. For all of the discordant cases, the TTGE yielded results that correlated better with the clinical data than did the PAGE method. We conclude that PCR/TTGE is more accurate and easier to perform than current methods for detecting clonal populations of T cells.

Base Composition↗
PubMed2001

Hyperplasia of mantle/marginal zone B cells with clear cytoplasm in peripheral lymph nodes. A clinicopathologic study of 35 cases.

We describe 35 peripheral lymph nodes classified as mantle cell/marginal zone B-cell hyperplasia with clear cells using morphologic and immunologic findings. For the purpose of this study, we obtained clinical follow-up information and performed immunoglobulin gene rearrangement studies on paraffin sections by polymerase chain reaction. Architecturally, the nodes were suggestive of a benign process: no pericapsular infiltration, sinuses readily identified, scattered reactive follicles present, and paracortical nodular hyperplasia present. No monocytoid B cells were present. Focally, small lymphoid cells with round nuclei and clear cytoplasm (clear cells) formed monomorphic nodular, inverse follicular, and/or marginal zone patterns. Flow cytometry and immunohistochemical analysis revealed neither light chain restriction nor an aberrant B-cell phenotype. Immunoglobulin gene rearrangement studies showed a clonal band in 1 of 26 cases in which DNA was amplified. To ascertain the clinical relevance of this positive case, follow-up information was obtained 30 months after the initial biopsy; the 83-year-old woman was alive without treatment but had splenomegaly and bone marrow involvement by marginal zone B-cell lymphoma. The morphologic and immunologic criteria used for diagnosis of mantle cell/marginal zone B-cell hyperplasia with clear cytoplasm are valid; however, to rule out the possibility of occult lymphoma, immunoglobulin gene rearrangement studies and clinical follow-up are necessary.

Adult↗
PubMed2000

Degranulating eosinophils in human endometriosis.

Degranulating eosinophils have been described in most endometrial cancers. We hypothesized that endometriosis (ectopic, nonneoplastic endometrial tissue) would be an appropriate model system for determining whether eosinophil degranulation is part of a specific immune response to endometrial cancer or if it is related to the more general phenomenon of tissue remodeling (wound healing) that is common to both disorders. To test this hypothesis, we performed immunohistochemistry and Western blotting to evaluate the presence of eosinophil peroxidase (a marker of eosinophil degranulation) in normal endometrium (n = 20) and endometriosis samples (n = 24) and to define the coexpression of three eosinophil chemoattractants: interleukin-5 (IL-5), eotaxin, and regulated on activator-normal T cell expressed and secreted (RANTES). There was focally intense deposition of eosinophil peroxidase in the fibrotic connective tissue and blood vessels of 21 of 24 human endometriosis specimens; two samples showed weak staining, and only one tissue was negative for eosinophil degranulation. None of the 10 normal proliferative endometrial specimens had evidence of eosinophil degranulation, and four of 10 secretory tissues stained only weakly for eosinophil peroxidase. The presence of degranulating eosinophils was also associated with the presence of eotaxin and IL-5 in some samples and with RANTES in others. We conclude that the abundant presence of degranulating eosinophils in the fibrous regions of endometriosis supports the interpretation that eosinophils are involved in general tissue remodeling and wound healing rather than a tissue-directed immune response.

Blotting, Western↗
PubMed1997

Eosinophils and human cancer.

Eosinophils are rare granulocytes that are normally associated with allergic diseases or responses to various parasitic infections. Many types of human cancer, however, are also associated with extensive eosinophilia, either within the tumor itself, or in the peripheral blood, or in both locations. Special techniques such as autoflourescence or immunohistochemistry are sometimes needed to detect the presence of intact and degranulating eosinophils within the tumors. With the help of these techniques, extensive eosinophilia is most often seen in hematologic tumors such as Hodgkin's disease and certain lymphomas; however, many other types of cancer such as colon, cervix, lung, breast, and ovary also contain eosinophilia if diligently sought. Although the presence or absence of eosinophilia within these tumors does not appear to have a major influence on the prognosis of the patient, eosinophils may play an important role in the host interaction with the tumor, perhaps by promoting angiogenesis and connective tissue formation adjacent to the cancer. In addition, tumor-related eosinophilia provides some interesting clues into tumor biology, particularly with regard to production of cytokines by the tumor cells.

Carcinoma↗
PubMed1996

New marker for blood vessels in human ovarian and endometrial cancers.

Angiogenesis plays a critical role in tumor biology and may someday be a target for novel therapeutic interventions. To date, however, relatively few markers have been identified that can specifically distinguish between microvessels in benign versus malignant lesions. Here we report that the cationic heme-protein eosinophil peroxidase (EPO) was localized by in situ immunohistochemistry on the vascular endothelial cells and/or connective tissue stroma in 16 of 16 cases of human endometrial carcinoma and in 12 of 15 cases of ovarian carcinoma. Similar deposits of EPO were not detected in normal endometrial tissues or ovaries from five healthy subjects, in adjacent uninvolved tissues from four tumor-bearing subjects, or in any normal organs from five other subjects. These findings imply that eosinophil degranulation is a significant and previously unappreciated component of the interaction between ovarian and endometrial cancers and the host. Moreover, the abundant and highly specific nature of the EPO deposition near and within the microvessels of these cancers suggests that eosinophil degranulation is a new marker for tumor blood vessels that potentially could be exploited to treat these important types of cancers that currently lack highly effective therapies.

Adenocarcinoma↗
PubMed1995

Plasma cell myeloma associated with eosinophilia.

The association of plasma cell myeloma and eosinophilia is rare. The authors describe a 49-year-old man with plasma cell myeloma and marked absolute peripheral blood eosinophilia, 109.7 x 10(9)/L. Analysis of his bone marrow revealed cytologically atypical plasma cells that expressed monotypic IgG lambda and marked eosinophilia with normal maturation. A combination of steroids and chemotherapy resulted in a significant and sustained decrease in his absolute eosinophil count and bone marrow plasma cells. Analysis of the patient's pre-therapy serum revealed immunoreactive interleukin-3 (IL-3), but not IL-5 or granulocyte/macrophage colony stimulating factor (GM-CSF). The post-therapy serum sample was negative. Immunohistochemical analysis of the plasma cells for IL-3 and IL-5 was negative. This review of the literature has revealed five cases of plasma cell myeloma associated with eosinophilia described previously. In two patients, the eosinophilia was attributed to drug therapy. In the remaining cases, the pathogenesis of the eosinophilia was unexplained. In this case, IL-3 secreted either by the neoplastic cells at a level below detection by immunohistochemistry or by other cells in response to the presence of plasma cell myeloma may have played a role in causing the eosinophilia.

Bone Marrow↗
PubMed1994

Effects of interleukin 4 on production of IgE monoclonal antibodies directed against glucose oxidase.

Interleukin 4 is a cytokine that promotes the growth of B cells and the synthesis of IgE subclass antibody. Here we report the results of our study that was designed to determine if recombinant murine interleukin 4 (rmIL-4) can increase the yield of hybridomas secreting IgE subclass monoclonal antibodies directed against glucose oxidase. Three BALB/c mice (test group) were primed i.p. with 50 micrograms of glucose oxidase and then boosted i.v. 2 weeks later with 5 micrograms of glucose oxidase plus 200 ng of rmIL-4. A standard hybridoma fusion was performed 3 days later, and the fusion products were then cultured in the presence of 20 ng of rmIL-4 per milliliter. Another group of three mice underwent an identical immunization and fusion procedure, except that the rmIL-4 was omitted (control group). At 21 days after fusion, the test group had a significantly greater frequency of wells with hybridomas (average frequency = 191 per 1000 wells in test group versus 58 in control group; chi 2 = 1803; p = 0.0001) and wells containing IgG anti-glucose oxidase (mean of 23 per 1000 wells in test group versus 3 in control group; chi 2 = 506, p = 0.0001). Moreover, the IL-4-treated group had a significantly higher frequency of wells containing IgE antibodies (mean of 44 versus 11 in control group; chi 2 = 288, p = 0.0001) and IgE antibodies directed against glucose oxidase (mean of 5 per 1000 wells versus 2 in control group; chi 2 = 21, p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Malignant lymphomas of B-cell lineage with marked tissue eosinophilia. A report of five cases.

Tissue eosinophilia is commonly seen in Hodgkin's disease and non-Hodgkin's lymphomas of T-cell lineage. In contrast, eosinophilia is infrequent in non-Hodgkin's lymphomas of B-cell origin. We describe five-B-cell lymphomas with exuberant tissue eosinophils. According to the Working Formulation, three were classified as large-cell immunoblastic, one as small lymphocytic lymphoma/chronic lymphocytic leukemia, and one as low-grade, not further subclassified, with features of monocytoid B-cell lymphoma. Immunophenotypic studies in each case revealed B-cell lineage; neoplastic cells expressed monotypic immunoglobulin light chain (four of five cases) or pan-B-cell antigens (five of five cases) and were negative for T-cell antigens. Southern blot hybridization in one case revealed immunoglobulin gene rearrangements, further confirming B-cell lineage. Eosinophilopoiesis is stimulated by interleukin 5 (IL-5), and Epstein-Barr virus (EBV) has been shown to upregulate IL-5 production. Therefore, both EBV infection and IL-5 expression were investigated as possibly pathogenetic mechanisms for the eosinophilia. However, both in situ hybridization studies for EBV mRNA and IL-5 mRNA were negative in the neoplastic cells. In one tumor, IL-5 was abundant in the cytoplasm of the eosinophils, a pattern similar to that seen in five cases of Hodgkin's disease studied with the same technique. Although rare, marked tissue eosinophilia may be associated with B-cell non-Hodgkin's lymphomas. Immunophenotypic or molecular genetic analyses are needed to make the correct diagnosis.

Adult↗
PubMed1993

Interleukin-5 mRNA in three T-cell lymphomas with eosinophilia.

The objective of this controlled pilot study was to determine if mRNA coding for interleukin-5 (IL-5), a cytokine that promotes eosinophil differentiation, growth, and migration, could be detected in three T-cell lymphomas that were infiltrated extensively by eosinophils. To detect mRNA coding for IL-5, we performed an RNA polymerase chain reaction on mRNA extracted from three T-cell lymphomas with eosinophilia and from 29 positive and negative validation controls. Using this procedure, we detected a 293-base pair, IL-5-specific amplification product in the three cases of T-cell lymphoma with eosinophilia and in 11 of 12 positive validation controls, including 10 cases of Hodgkin's disease with eosinophilia. IL-5 mRNA was not detectable in the 17 negative validation controls. This preliminary study suggests that IL-5 mRNA is detectable by polymerase chain reaction in three cases of T-cell lymphoma with eosinophilia.

Actins↗
PubMed1993

IgE, Reed-Sternberg cells, and eosinophilia in Hodgkin's disease.

Tissues containing Hodgkin's disease tumors of the nodular sclerosis and mixed cellularity subtypes are frequently infiltrated by numerous degranulating eosinophils that release granule proteins such as eosinophil peroxidase and major basic protein. Until recently, the causes of the eosinophil infiltration and degranulation in Hodgkin's disease tumors were unknown. Analysis of Hodgkin's disease tissues by a sensitive and specific immunoperoxidase technique has now demonstrated the extensive presence of IgE in the Reed-Sternberg cells and adjacent cells of Hodgkin's disease tumors. Because eosinophils express a cell-surface receptor (CD23) for IgE and degranulate in the presence of IgE deposits, the extensive eosinophilia that is frequently present in Hodgkin's disease tumors is, at least in part, attributable to the IgE deposits within the tumor. In this review, we discuss the possible mechanisms and biological significance of IgE-related eosinophilia in Hodgkin's disease.

Animals↗
PubMed1993

Disseminated persistent lymphoid hyperplasia containing Epstein-Barr virus and clonal rearrangements of DNA.

We describe the pathologic, molecular, and clinical features of a 52-year-old man who had a 7-year history of widely disseminated, persistent lymphoid hyperplasia. Exuberant follicular and interfollicular lymphoid hyperplasia with some histologic features of Castleman's disease were present at various times in the submental and cervical lymph nodes, lacrimal and parotid glands, right and left orbits, mediastinum, and hard palate of this patient. Flow cytometric and immunoperoxidase studies of two of the specimens indicated a slight predominance of cells expressing lambda-immunoglobulin light chain. In one specimen, there were clonal rearrangement of DNA coding for immunoglobulin heavy chain and for the T-cell beta-receptor. When DNA from this specimen was also examined by the polymerase chain reaction technique, Epstein-Barr viral DNA was detected. This case suggests that Epstein-Barr virus may be associated with an unusual form of aggressive and persistent lymphoid hyperplasia that contains clonal rearrangements of DNA.

Castleman Disease↗
PubMed1993

Preclinical safety studies of glucose oxidase.

The purpose of this study was to develop preclinical safety data regarding the toxicologic and pharmacokinetic properties of glucose oxidase. Groups of adult BALB/c mice were injected with four doses of the enzyme ranging from 0.125 U of glucose oxidase/g b.wt. to 1 U/g b.wt., and the following responses were measured: survival, methemoglobin, glucose, blood urea nitrogen, creatine phosphokinase, erythrocyte count and body weight. We also compared the biodistribution of the enzyme in mice to the biodistribution of glucose oxidase conjugated to a monoclonal antibody. Finally, we assessed the histopathologic changes produced in mice by glucose oxidase and the binding of the enzyme to snap-frozen, human autopsy tissues. As expected, the acute toxicity of glucose oxidase was primarily due to methemoglobinemia (mean concentration 36% at the highest dose) and transient hypoglycemia (as low as 35 mg/dl). Furthermore, conjugated and unconjugated glucose oxidase had a blood half-life of less than 2 hr and concentrated in the liver and spleen. On the basis of our studies, we conclude that glucose oxidase has reasonably predictable toxicities and is, therefore, safe for human trials. The rapid uptake of conjugated and unconjugated glucose oxidase by the liver and spleen, however, may significantly limit the therapeutic targeting of glucose oxidase.

Animals↗
PubMed1993

Incidence of Epstein-Barr virus in AIDS-related lymphoma specimens.

We used the polymerase chain reaction, in situ hybridization, and immunohistochemical stains against latent membrane protein, CD23, and Epstein-Barr viral nuclear antigens 1 and 2 to identify Epstein-Barr virus (EBV) in fixed and unfixed (cryopreserved) AIDS-related lymphoma (ARL) specimens. The study included 17 cases of large-cell (immunoblastic) lymphoma, 11 cases of small non-cleaved cell lymphoma, and two cases of Hodgkin's disease. The EBV DNA was more frequently detected by polymerase chain reaction in cryopreserved specimens (94%) than in fixed specimens (17%). Significantly, the immunohistochemical and in situ hybridization studies detected evidence of EBV in only a small (< 10%) subset of the cells in 27 of 30 ARL specimens. We conclude that tissue fixation reduced the ability to detect EBV in ARL by polymerase chain reaction and that EBV was detectable in only a minority of cells in most ARL tissues.

Antigens, Viral↗
PubMed1992

IgE in Reed-Sternberg cells of Hodgkin's disease with eosinophilia.

Tissues containing Hodgkin's disease (HD) are frequently infiltrated by large numbers of eosinophils. Because eosinophils as well as Reed-Sternberg (RS) cells express membrane receptors (CD23) for IgE, this study was performed to determine if IgE is present in tissue sections of HD and to correlate the results, when possible, with serum IgE levels and the presence of interleukin-5 (IL-5) messenger RNA (mRNA) in RS cells. Paraffin-embedded, B-5-fixed slices of 13 cases of HD, one case of acquired immunodeficiency syndrome (AIDS)-related HD, seven cases of benign lymphoid hyperplasia (including two cases from HD patients), and five cases of B-cell lymphomas were analyzed by a sensitive immunoperoxidase staining technique that used a murine monoclonal antibody specific for human IgE. In the benign hyperplastic lymph nodes and non-Hodgkin's lymphomas, IgE was generally detectable only in rare plasma cells and in follicular dendritic cells. In 11 of the 14 cases of HD, including one case of AIDS-related HD, IgE was readily detectable within RS cells and variants and on the surrounding cells and connective tissue. These cases also had significant numbers of eosinophils, and IL-5 mRNA was detectable in three of the cases that were tested. Serum IgE was moderately elevated in the two serum specimens from HD patients that were available for analysis. The results of this study, therefore, indicate that some cases of HD contain abundant deposits of IgE, which may account for the extensive infiltration by eosinophils seen in this neoplasm.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1992

Epstein-Barr virus and interleukin-5 mRNA in acquired immunodeficiency syndrome-related lymphomas with eosinophilia.

Patients infected with the human immunodeficiency virus are at increased risk for developing intermediate-grade and high-grade B-cell lymphomas that in many instances contain Epstein-Barr viral (EBV) DNA. Because interleukin-5 (IL-5), a potent stimulator of eosinophil growth and differentiation, has been detected recently in EBV-infected B-cells, we hypothesized that some acquired immunodeficiency syndrome-related lymphomas with EBV DNA also might contain eosinophilia and IL-5. After reviewing files entered into our archives during the past 3 years, we identified four cases of human immunodeficiency virus-associated, high-grade, B-cell lymphomas that also contained extensive infiltration by eosinophils. Cryopreserved DNA from two of these four cases was available for amplification by the polymerase chain reaction, and both cases yielded an easily identifiable, EBV-specific amplification product. From one of these cases we also were able to extract mRNA and perform messenger amplification phenotyping (MAPPING) for the detection of mRNA coding for IL-5. After reverse transcription of mRNA from this case to cDNA and amplification by the polymerase chain reaction, we identified an amplification product that co-migrated with IL-5-positive controls in an agarose gel. We conclude that some AIDS-related lymphomas are associated with eosinophilia and that the eosinophilia may be related to EBV infection and transcriptional activation of the IL-5 gene.

Acquired Immunodeficiency Syndrome↗