Search PubMed⌕ Search

Biomedical subjects

L M Weiss

Publications and source records attributed to L M Weiss.

At least 91 records · Page 5Linked to original sources
PubMed1998

Paraffin section detection of the c-kit gene product (CD117) in human tissues: value in the diagnosis of mast cell disorders.

The c-kit gene product (CD117) is known to be expressed by a variety of normal human tissue cell types, including breast epithelium, germ cells, melanocytes, immature myeloid cells, and mast cells. To further characterize the expression of this antigen, 117 normal human tissues and 576 human tumors were studied by paraffin section immunohistochemistry. Varying degrees of CD117 expression were identified in various normal cells and in 53% of all tumors studied. In most cases (42% of total), CD117 expression was weak. Expression was most common in mast cell disease (100%), testicular germ cell tumors (100%), endometrial carcinomas (100%), papillary and follicular thyroid carcinomas (100%), small cell carcinomas (91%), malignant melanomas (90%), and ovarian epithelial carcinomas (87%). Strong immunoreactivity was only identified in cases of mast cell disease (11 of 11 cases), serous ovarian carcinoma (3 of 16), malignant melanoma (2 of 40), small cell lung carcinoma (one of seven), and adenoid cystic carcinoma (one of one). Although the pattern of reactivity was primarily cytoplasmic, a membrane staining pattern was seen in a subset of cases, and strong membrane staining was identified in normal mast cells and all cases of mast cell disease. The lack of tumor specificity of weak expression of this antigen limits its diagnostic utility in most cases. However, the strong membrane reactivity for CD117 identified in mast cells may be useful in the diagnosis of mast cell disorders.

Antibody Specificity↗
PubMed1998

Microsporidiosis: molecular and diagnostic aspects.

The term 'microsporidia' is a nontaxonomic designation which is used to refer to a group of intracellular parasites belonging to the phylum Microspora. These eukaryotic obligate intracellular protozoans have been described infecting every major animal group, especially insects, fish and mammals. They are important agricultural parasites in commercially important insects, fish, laboratory rodents, rabbits, fur-bearing animals, and primates. There is now an increasing recognition of microsporidia as important opportunistic pathogens in persons infected with the human immunodeficiency virus (HIV). Microsporidia possess ribosomes with features resembling prokaryotes. Phylogenetic analysis of the rRNA sequence from several of the microsporidia suggests that these organisms were early branches in the eukaryotic evolutionary line. The data on these molecular phylogenetic relationships are reviewed in this paper. Inroads have recently been made into the molecular biology of these organisms and these data are also presented. Diagnosis of microsporidia infection from stool examination is possible and has replaced biopsy as the initial diagnostic procedure in many laboratories. These staining techniques can be difficult, however, due to the small size of the spores. The specific identification of microsporidian species has classically depended on ultrastructural examination. With the cloning of the rRNA genes from the human pathogenic microsporidia it has been possible to apply polymerase chain reaction (PCR) techniques for the diagnosis of microsporidial infection at the species level. Both staining and PCR techniques for the diagnosis of microsporidia are reviewed.

Animals↗
PubMed1998

Detection of Enterocytozoon bieneusi in fecal specimens by polymerase chain reaction analysis with primers to the small-subunit rRNA.

Microsporidia are the suspected etiology of diarrhea in up to 30% of immunocompromised patients with AIDS. Epidemiological investigation of these organisms has been hampered by the lack of easy methods of detection. Currently, definitive identification requires small bowel biopsy and transmission electron microscopy (TEM) to confirm the species of microsporidia involved. We describe a method for the detection of microsporidia in stool specimens that utilizes polymerase chain reaction (PCR) analysis with use of primers V1 and EB450 based on the small-subunit rRNA gene of Enterocytozoon bieneusi. A guanidium thiocyanate (GuSCN) method was utilized to extract microsporidian DNA from feces. Consistent amplification was detected in stool samples from three patients with TEM-confirmed microsporidiosis due to E. bieneusi by means of these techniques. Optimization of this PCR reaction revealed that the sensitivity of the reaction was increased by the addition of dimethyl sulfoxide. This PCR method allows for detection of E. bieneusi in stool specimens and will be applied to epidemiological investigations of this organism in the future.

Animals↗
PubMed1998

TNP-470 is an effective antimicrosporidial agent.

Therapy for microsporidia, which cause diarrhea and a wasting syndrome in persons with AIDS, has had limited success. Fumagillin, a naturally secreted water-insoluble antibiotic, has in vitro activity against microsporidia and has been used successfully in the treatment of superficial keratitis in patients with AIDS, but systemic therapy has been limited by toxicity of the currently available fumagillin salt. TNP-470, a semisynthetic analogue of fumagillin, was studied in vitro and in the athymic nude mouse model of microsporidiosis. RK13 cells were infected with microsporidia of the family Encephalitozoonidae and treated at day 3 with TNP-470. This agent was highly effective, with an ID50 (50% inhibitory dose compared with control) of 0.001 microg/mL. TNP-470 also demonstrated in vivo activity against Encephalitozoon cuniculi, with prolonged survival and the prevention of the development of ascites in infected athymic mice. These data suggest that the fumagillin derivative TNP-470 is a promising agent for the treatment of microsporidiosis.

Animals↗
PubMed1998

Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature.

Oncocytic neoplasms of the adrenal gland are rare. We describe the clinicopathologic and immunohistochemical findings of seven oncocytic adrenocortical neoplasms, five oncocytomas, and two oncocytic neoplasms of uncertain malignant potential. Three tumors were studied using electron microscopy. These neoplasms occurred in five women and two men (median age, 55 years) with no clinical evidence that the neoplasms were functional. The size of the neoplasms varied from 5.0 cm to 13.5 cm. Histologically, each neoplasm was composed exclusively of oncocytes. The oncocytomas had very low or absent mitotic activity and no evidence of necrosis. The two oncocytic neoplasms of uncertain malignant potential had increased mitotic activity and necrosis but no evidence of invasion or metastases. Nuclear atypia, either focal or generalized, was found in all neoplasms. Immunohistochemical studies performed using fixed, paraffin-embedded sections showed strong reactivity with the mitochondrial antibody mES-13 in all neoplasms. Four of five oncocytomas and one oncocytic neoplasm of uncertain malignant potential expressed keratin, predominantly keratin 18, as shown using the CAM 5.2 and AE3 antibodies. Two neuroendocrine-associated markers, neuron specific enolase and synaptophysin, were positive in seven and five neoplasms, respectively. However, all neoplasms were negative for the other neuroendocrine markers tested, including chromogranin A, tyrosine hydroxylase, and dopamine beta-hydroxylase, as well as for epithelial membrane antigen, S100, and p53. Using the MIB-1 (Ki-67) antibody, proliferative activity was increased in both oncocytic neoplasms of uncertain malignant potential. All six patients with available clinical follow-up data are alive without evidence disease, although the follow-up interval is relatively short (< 2 years) for the two patients with oncocytic neoplasms of uncertain malignant potential. We conclude that oncocytic adrenocortical neoplasms are nonfunctional tumors that can become large before they are detected by radiologic studies. The majority of neoplasms are benign and should not be misdiagnosed as carcinoma.

Adenoma, Oxyphilic↗
PubMed1998

Effect of cytokines on growth of Toxoplasma gondii in murine astrocytes.

Cytokines play a significant role in the regulation of Toxoplasma gondii in the central nervous system. Cytokine-activated microglia are important host defense cells in central nervous system infections. Recent evidence indicates that astrocytes can also be activated by cytokines to inhibit intracellular pathogens. In this study, we examined the effect of gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 on the growth of T. gondii in a primary murine astrocyte culture. Pretreatment of astrocytes with IFN-gamma resulted in 65% inhibition of T. gondii growth. Neither TNF-alpha, IL-1, nor IL-6 alone had any effect on T. gondii growth. IFN-gamma in combination with either TNF-alpha, IL-1, or IL-6 caused a 75 to 80% inhibition of growth. While nitric oxide was produced by astrocytes treated with these cytokines, inhibition of T. gondii growth was not reversed by the addition of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine. Furthermore, IFN-gamma in combination with IL-1, IL-6, or TNF-alpha also induced inhibition in astrocytes derived from syngeneic mice deficient in the enzyme inducible nitric oxide synthase. This finding suggests that the mechanism of cytokine inhibition is not nitric oxide mediated. Similarly, the addition of tryptophan had no effect on inhibition, indicating that the mechanism was not mediated via induction of the enzyme indoleamine 2, 3-dioxygenase. The mechanism of inhibition remains to be elucidated. Results from this study demonstrate that cytokine-activated astrocytes are capable of significantly inhibiting the growth of T. gondii. These data indicate that astrocytes may be important host defense cells in controlling toxoplasmosis in the brain.

Animals↗
PubMed1998

Bradyzoite development in Toxoplasma gondii and the hsp70 stress response.

Toxoplasma gondii is a well-described ubiquitous Apicomplexan protozoan parasite that is an important opportunistic pathogen. The factors affecting the transition of tachyzoites to the latent bradyzoite stage remain to be defined. The induction of bradyzoite development in vitro has been linked to temperature, pH, mitochondrial inhibitors, sodium arsenite, and many of the other stressors associated with heat shock protein (hsp) induction. There is evidence for other organisms that hsps are developmentally regulated. Therefore, we examined whether hsp induction is an early event in bradyzoite differentiation. Extracellular and intracellular T. gondii cells, after exposure to pH 8.1 or 7.1, were analyzed for the expression of inducible hsp70 by using monoclonal antibody C92F3A-5 (specific to hsp70). Western blotting demonstrated that a 72-kDa protein reactive with C92F3A-5 (hsp70), which we believe is part of the hsp70 family, is induced during bradyzoite development. By immunofluorescence and immunoelectron microscopy, we were able to demonstrate that hsp70 staining colocalized to T. gondii expressing bradyzoite-specific antigens and the presence of hsp70 in bradyzoites isolated from mouse brain. Quercetin, a bioflavonoid which inhibits the synthesis of hsp90, hsp70, and hsp27, suppresses the induction of bradyzoite development in vitro. Reverse transcription-PCR with conserved hsp70 primers demonstrated an increase in hsp70 in T. gondii on exposure to conditions which induce bradyzoite formation. A T. gondii hsp70 was subsequently cloned and sequenced by using this amplified fragment. We believe our evidence suggests that hsps are important in the process of bradyzoite differentiation.

Amino Acid Sequence↗
PubMed1998

Deletion of Epstein-Barr virus latent membrane protein 1 gene in Japanese and Brazilian gastric carcinomas, metastatic lesions, and reactive lymphocytes.

A 30-bp deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene has been reported in nasopharyngeal carcinoma and EBV-associated malignant lymphomas. Information on this deletion in EBV-associated gastric carcinoma (EBVaGC) is limited. The association of gastric carcinoma (GC) with EBV was examined by EBV-encoded RNA (EBER) in situ hybridization in 510 patients from Japan and 80 patients from Brazil. We studied the prevalence of 30-bp LMP1 gene deletion in EBVaGC in Japan (29 cases) and Brazil (four cases) in comparison with the corresponding EBER1-positive metastatic lesions in lymph nodes (10 cases) and EBV-infected reactive lymphocytes from dissected nonmetastatic lymph nodes (22 cases), microdissected non-neoplastic gastric mucosa of EBVaGC (five cases), and EBV-nonassociated GC (25 cases). We studied the status of the LMP1 gene by Southern blot hybridization of polymerase chain reaction products obtained after amplification with primers flanking the site of the deletion. We also performed EBV typing and LMP1 protein immunohistochemistry. EBV DNA was amplified by polymerase chain reaction in 30 of 33 EBVaGC cases, 8 of 10 metastatic carcinomas, 14 non-neoplastic tissues from 27 EBVaGC cases, and 12 of 25 non-EBV-associated GC cases with EBER1-positive lymphocytes. The 30-bp LMP1 gene deletion was observed in 23 of 26 (88.5%) cases of EBVaGC from Japan and two of four (50%) cases of Brazilian EBVaGC as compared with EBER1-positive reactive lymphocytes from 11 of 14 (78.6%) EBVaGC cases and 9 of 12 (75%) cases of non-EBV-associated GC. The variant type (the 30-bp deletion variant or nondeleted wild type) of LMP1 gene was the same among reactive lymphocytes, primary and secondary lesions of EBVaGC in all cases for which all three tissue types were studied (six of six). There was no correlation between the presence of the 30-bp deletion with depth of cancer invasion or presence of metastasis. Type A was detected in all available EBV-positive cases. The similar high incidence of 30-bp deletion in LMP1 gene in both carcinoma cells and reactive lymphocytes in EBVaGC cases suggests that this deletion may not be relevant to the pathogenesis of EBVaGC.

Adult↗
PubMed1998

Detection of Epstein-Barr Virus in inflammatory pseudotumor.

Inflammatory pseudotumors appear to represent a heterogeneous group of diseases that share common histopathologic features. A subset of these tumors, particularly those in the spleen and liver, harbor the Epstein-Barr virus (EBV) in spindled cells. Methods for detecting EBV in these tumors and the reliability of the different detection methods are discussed. Some EBV-positive inflammatory pseudotumors contain an increase in EBV-positive follicular dendritic cells and demonstrate monoclonal EBV genomes. At least one such case has recurred locally as an unusual EBV-positive follicular dendritic cell tumor. These rare reports support the concept of a distinct EBV-positive, follicular dendritic cell type of inflammatory pseudotumor that may be at increased risk for local recurrence. Many more cases of this rare type of inflammatory pseudotumor must be studied and reported before the clinical validity of such a distinction can be proven. Although EBV detection in spindled cells is unusual, it has been demonstrated in rare smooth muscle tumors arising in immunosuppressed children and young adults.

Granuloma, Plasma Cell↗
PubMed1998

Characterization and function of the microsporidian polar tube: a review.

Microsporidia are eukaryotic, obligate intracellular organisms defined by their small spores containing a single polar tube that coils around the interior of the spore. After appropriate stimuli the germination of spores occurs. Conditions that promote germination vary widely among species, presumably reflecting the organism's adaptation to their host and external environment as well as preventing accidental discharge in the environment. It appears that calcium may be a key ion in this process. Regardless of the stimuli required for activation, all microsporidia exhibit the same response to the stimuli, that is, increasing the intrasporal osmotic pressure. This results in an influx of water into the spore accompanied by swelling of the polaroplasts and posterior vacuole. The polar tube then discharges from the anterior pole of the spore in an explosive reaction and is thought to form a hollow tube by a process of eversion. If the polar tube is discharged next to a cell, it can pierce the cell and transfer the sporoplasm into this cell. Polar tubes resist dissociation in detergents and acids but dissociate in dithiothreitol. We have developed a method for the purification of polar tube proteins (PTPs) using differential extraction followed by reverse phase high performance liquid chromatography (HPLC). This method was used to purify for subsequent characterization PTPs from Glugea americanus, Encephalitozoon cuniculi, E. hellem and E. intestinalis. These proteins appear to be members of a protein family that demonstrate conserved characteristics in solubility, hydrophobicity, mass, proline content and immunologic epitopes. These characteristics are probably important in the function of this protein in its self assembly during the eversion of the polar tube and in providing elasticity and resiliency for sporoplasm passage.

Animals↗
PubMed1998

Epstein-Barr virus-associated nuclear antigen-1 carboxy-terminal gene sequences in Japanese and American patients with gastric carcinoma.

We examined Epstein-Barr virus (EBV)-associated nuclear antigen-1 (EBNA-1) gene carboxy (C)-terminal deletions occurring in gastric carcinoma and noncarcinoma tissues from two different ethnic populations. Previously reported EBNA-1 C-terminal region amino acid sequence variations include five subtypes based on the amino acid at codon 487: Prototype (P)-ala, which is found in the B95.8-derived prototype virus; P-thr; Variant (V)-pro; V-leu; and V-val. Using polymerase chain reaction to amplify fragments of the EBNA-1 gene, followed by gene sequencing, we identified a single EBNA-1 gene sequence variant (V-val') in all 25 cases of known EBV-positive gastric carcinoma and all 8 cases of known EBV-positive reactive follicular hyperplasia from Japan. All 17 cases of known EBV-positive American gastric carcinomas had a single EBNA-1 gene sequence, including 3 P-ala or P-ala variants, 9 P-thr, 4 V-leu or V-leu variants, and 1 V-val'. All 11 cases of American reactive lymphoid tissue also had a single EBNA-1 gene sequence, including 2 P-ala variants, 5 P-thr or P-thr variants, and 4 V-leu. Variant EBNA-1 sequences were more common in both carcinoma and non-neoplastic tissues than the prototype sequence, whether from Japan or America. The EBNA-1 gene sequences found in the two ethnic populations differed, suggesting that variation in EBNA-1 gene sequence is due to polymorphisms present within pre-existing viral strains prevalent within various ethnic populations. The EBNA-1 gene sequences in reactive tissues were similar to those in malignant tissues from the same ethnic population, suggesting that the differences in EBNA-1 gene sequences do not result from mutation occurring during neoplastic transformation and that there may not be a selective cell tropism for different EBNA-1 proteins, as previously suggested.

Amino Acid Substitution↗
PubMed1998

Frequency of bcl-2 expression in non-Hodgkin's lymphoma: a study of 778 cases with comparison of marginal zone lymphoma and monocytoid B-cell hyperplasia.

The oncoprotein, bcl-2, is expressed in various types of non-Hodgkin's lymphoma (NHL). Immunodetection of this protein is a useful method for distinguishing follicular hyperplasia from follicular lymphoma. Although bcl-2 might also be a useful marker for distinguishing reactive monocytoid B-cell hyperplasia from its putative malignant counterpart, marginal zone lymphoma, there were no extensive studies to date that tested this. Therefore, we performed a survey of bcl-2 expression in 778 cases of NHL using immunohistochemical techniques applied to routinely processed and paraffin-embedded tissues. Of 20 reactive monocytoid B-cell hyperplasias, none were bcl-2 positive, compared with 118 (79%) of 150 marginal zone lymphomas (P = .001). With respect to the follicular lymphomas in our study, of the 110 Grade I lymphomas, 107 (97%) were bcl-2 positive, 119 (83%) of the 143 Grade II lymphomas were positive, and 71 (74%) of the 96 Grade III lymphomas were positive. The bcl-2 positivity of Burkitt-like high-grade B-cell lymphoma was significantly different from that of Burkitt's lymphoma (4 [67%] of 6 vs. 0 of 5; P = .02). T-cell NHL had a significantly lower bcl-2 positivity than did B-cell NHL (10 [45%] of 22 vs. 627 [83%] of 756; P = .0001). Therefore, bcl-2 is a highly sensitive marker for follicular lymphoma and a useful marker for distinguishing reactive monocytoid B-cell hyperplasia from marginal zone lymphoma The significant difference in bcl-2 positivity between Burkitt-like high-grade B-cell lymphoma and Burkitt's lymphoma suggests an additional diagnostic use for this protein.

B-Lymphocytes↗
PubMed1997

Appraisal of intratumoral microvessel density, MIB-1 score, DNA content, and p53 protein expression as prognostic indicators in patients with locally confined renal cell carcinoma.

BACKGROUND: The prognostic values of intratumoral microvessel density (iMVD), tumor cell proliferation rate, DNA content (ploidy), and p53 protein expression are controversial or have not been well studied in patients with renal cell carcinoma (RCC) confined to the kidney. METHODS: A uniform group of 52 clear cell (conventional) RCCs confined to the kidney (classified as T1N0M0 or T2N0M0) were analyzed for iMVD, MIB-1 score, DNA content, S-phase fraction, and p53 protein expression by immunohistochemical methods or flow cytometry. iMVD was evaluated in a single area (X200, 1.15 mm2) representative of the highest MVD (neovascular "hot spot") after independently highlighting endothelial cells with antibodies specific for factor VIII-related antigen (F8/86) and CD31 (JC/70A). The MIB-1 antibody (Ki-67 antigen) score was used as a marker for the tumor cell proliferation rate. DNA content and S-phase fraction were determined by flow cytometry using paraffin embedded tissue. p53 expression was assessed using the D07 antibody. RESULTS: The median time of clinical follow-up was > 9 years. Eleven patients died of disease; the median time to death was 26 months. iMVD counts using antifactor VIII and anti-CD31 were tightly correlated (correlation coefficient = 0.89). S-phase fraction was higher in aneuploid tumors than in diploid tumors (mean, 12.4% vs. 4.3%; P = 0.01). Using univariate survival analyses, tumor size (stage classification pT1 vs. PT2; P = 0.01) and nuclear grade (P = 0.04) were associated with shortened survival. No statistically significant differences in survival were found for iMVD, MIB-1 score, DNA content, S-phase fraction, or p53 expression. Only two cases strongly expressed p53 protein; both tumors were of high nuclear grade. Using multivariate survival analyses, nuclear grade and tumor size were the only independent prognostic factors (best model P = 0.002). CONCLUSIONS: In this study, nuclear grade and tumor size were found to be independent predictors of survival in locally confined clear cell (conventional) RCC, as has been shown previously for locally confined RCC in general. MIB-1 score, iMVD counts, DNA content, S-phase fraction, and p53 expression did not contribute additional prognostic information.

Adult↗
PubMed1997

Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society.

Pathologists and pediatric hematologist/ oncologists of the World Health Organization's Committee on Histiocytic/Reticulum Cell Proliferations and the Reclassification Working Group of the Histiocyte Society present a classification of the histiocytic disorders that primarily affect children. Nosology, based on the lineage of lesional cells and biological behavior, is related to the ontogeny of histiocytes (macrophages and dendritic cells of the immune system). Dendritic cell-related disorders of varied biological behavior are dominated by Langerhans cell histiocytosis, but separate secondary proliferations of dendritic cells must be differentiated. Juvenile xanthogranuloma represents a disorder of dermal dendrocytes, another dendritic cell of skin. The hemophagocytic syndromes are the most common of the macrophage-related disorders of varied biological behavior. Guidelines for distinguishing the exceedingly rare malignant diseases of histiocytes from large cell lymphomas through the use of a battery of special studies are provided.

Cell Lineage↗
PubMed1997

Primary plasmacytoma of lymph nodes.

Primary plasmacytoma of the lymph nodes is very rare, and there are fewer than 20 reported cases. These cases appeared to have a better prognosis than other extramedullary plasmacytomas, with rare recurrence and no progression to myeloma after treatment. To better characterize the clinicopathological features and the pathogenesis of primary plasmacytoma of the lymph nodes, we reviewed our consultation files and retrieved seven such cases. The age of presentation ranged from 39 to 76 years (median age, 59 years), with three women and four men. The clinical follow-up varied from 1 to 14 years. All patients presented with enlarged lymph nodes and had an indolent clinical course, except for one patient with slow progression and increasing numbers of bone marrow plasma cells. Five patients were treated with excision only and two with excision and chemotherapy. None of the patients had recurrence or developed multiple myeloma. All cases showed immunoglobulin light chain restriction, four with monotypic lambda and three with monotypic kappa. One patient had extensive nodal amyloid deposition. Four cases had monoclonal heavy chain expression, three with monoclonal immunoglobulin (Ig) G and one with monoclonal IgM. All cases were negative for CD20 and CD43, and six cases expressed CD79a. Overexpression of p53 and bcl-2 was not detected by immunostaining in any of the cases. Epstein-Barr viral (EBV) RNA was not detected in all seven cases by in situ hybridization, and no Kaposi's sarcoma-associated herpesvirus (KSHV) DNA sequences were detected by polymerase chain reaction in five cases. Our results confirm a more favorable outcome and rare progression to multiple myeloma in primary nodal plasmacytomas after excision or chemotherapy. The results of oncoprotein and viral studies suggest that the pathogenesis of primary nodal plasmacytoma may not be due to bcl-2- and p53-associated changes or viral-induced changes by EBV and KSHV.

Adult↗
PubMed1997

Posttransplant lymphoproliferative disorder in liver allograft biopsies: a comparison of three methods for the demonstration of Epstein-Barr virus.

Posttransplant lymphoproliferative disorder (PTLD) is associated with Epstein-Barr virus (EBV), and may clinically resemble acute allograft rejection. Three methods to show EBV in tissue were evaluated in 15 liver allograft biopsies from 12 patients including four with PTLD: (1) semiquantitative polymerase chain reaction (PCR) for EBV DNA; (2) in situ hybridization for EBV RNA (EBER); and (3) immunoperoxidase for EBV latent membrane protein (LMP). Index cases had a PCR dot blot result of "positive" or "weak positive." Findings were correlated with histology, clinical data, therapy, and outcome. All four PTLD patients had a clinical diagnosis of acute rejection. All four showed EBV: PCR 4, EBER 4, LMP 3, Liver function tests were elevated in three, but EBV viral capsid antigen (VCA) IgM was not increased in three, but EBV viral capsid antigen (VCA) IgM was not increased in three. Immunosuppression was withdrawn and all four patients underwent a second transplantation. One died 4 days posttransplant with disseminated PTLD, two died of sepsis at 1.5 and 14 months, and one is well at 3 years without PTLD. Eleven biopsies without PTLD showed: acute rejection 7, acute rejection and hepatitis 1, hepatitis B 1, and non-inflammatory changes 2. In this group, EBV results included: PCR weak positive in 10 and 1+ in one, EBER negative in ten and rare positive cells in one, LMP negative in 11. Liver function tests were elevated in 10, whereas VCA IgM was not increased in three and increased in one. Patients with acute rejection were treated with increased immunosuppression: none developed PTLD, with follow-up of at least 6 months in nine cases. Two patients died within 4 months of biopsy. One patient with PTLD in tonsils had a liver biopsy showing both acute rejection and EBV (PCR 1+, rare EBER + small cells). Histological studies combined with special EBV detection methods, can be useful to evaluate atypical lymphoid infiltrates in liver allograft biopsies and confirmation of a diagnosis of PTLD. All three methods are useful; EBER and PCR are the most sensitive. EBER and LMP can use paraffin sections.

Antigens, Viral↗
PubMed1997

Deletion of Epstein-Barr virus latent membrane protein 1 gene in United States and Brazilian Hodgkin's disease and reactive lymphoid tissue: high frequency of a 30-bp deletion.

A 30-basepair (bp) deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene has been reported in nasopharyngeal carcinoma and EBV-associated malignant lymphomas. Prior studies have found the deletion in about 10% to 28% of cases of Hodgkin's disease (HD), particularly in cases with aggressive histology. We studied the prevalence of 30-bp LMP1 gene deletion in EBV-positive HD in the United States (US) (12 cases) and Brazil (26 cases) with comparison to reactive lymphoid tissues (21 cases) and HD without EBV-positive Reed-Sternberg cells (15 cases). We studied the status of the LMP1 gene by Southern blot hybridization of polymerase chain reaction (PCR) products obtained after amplification with primers spanning the site of the deletion. We also performed EBV typing, EBER1 in situ hybridization, and LMP1 protein immunohistochemistry. EBV was detected in 12/26 (46%) cases of HD from the US and 26/27 (96%) cases of Brazilian HD. The 30-bp LMP1 gene deletion was observed in 4/12 (33%) cases of EBV-positive HD from US, and 12/26 (46%) cases of Brazilian EBV-positive HD, including 3 cases of type B EBV, as compared with 12/21 (57%) reactive lymphoid tissues and 9/15 (60%) cases of EBV-negative HD. US and Brazilian HD showed a higher prevalence of the 30-bp LMP1 gene deletion, compared with studies of others. The unexpected finding of high incidence of 30-bp deletion in LMP1 gene in reactive lymphoid tissue and HD without EBV-positive Reed-Sternberg cells suggests that this deletion may not be relevant to HD pathogenesis in most cases.

Adolescent↗