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Biomedical subjects

L M Weiss

Publications and source records attributed to L M Weiss.

At least 199 records · Page 11Linked to original sources

Absence of Epstein-Barr viral RNA in lymphomatoid papulosis.

Epstein-Barr virus (EBV) recently has been implicated in the pathogenesis of Hodgkin's disease (HD). Lymphomatoid papulosis (LyP) is a premalignant cutaneous lymphoproliferative disorder which shares several characteristics with HD. The hypothesis has been made that EBV may be associated with the pathogenesis of LyP. We therefore examined 17 skin biopsy specimens and two lymph nodes from nine patients with LyP for EBV RNA using the highly sensitive and specific EBER method. In all specimens, the large atypical cells were negative for EBV while poly T studies confirmed the presence of adequate RNA for detection of EBER. The negative EBER results were confirmed in seven LyP patients whose biopsies were also stained for latent membrane protein (LMP-1). Interestingly, one patient with clonally related LyP and HD had no EBV RNA detected in any specimen. We conclude that EBV is unlikely to be an important aetiological agent in LyP. If confirmed in other patients, HD associated with LyP may have a different aetiology from HD arising de novo.

Adult↗

Lack of evidence of Epstein-Barr virus in hairy cell leukemia and monocytoid B-cell lymphoma.

An association between the Epstein-Barr virus (EBV) and hairy cell leukemia (HCL) has been reported. Due to the similarities between HCL and monocytoid B-cell lymphoma (MBCL), an association between EBV and MBCL has been postulated. To address these issues we studied 27 spleens from cases with HCL and 13 tissue specimens from cases with MBCL from various sites for evidence of EBV DNA and RNA by in situ hybridization. Using a genomic EBV internal repeat probe and an oligonucleotide probe directed against the EBER1 gene, we were unable to identify EBV DNA or RNA, respectively, in the tumor cells of any of the cases. The results of our study suggest that EBV may not be strongly linked with either HCL or MBCL.

DNA, Viral↗

Cytogenetic studies of composite lymphomas: monocytoid B-cell lymphoma and other B-cell non-Hodgkin's lymphomas.

Monocytoid B-cell lymphoma (MBCL) is a newly recognized, morphologically and immunologically distinct, low-grade B-cell neoplasm that may exist as a pure morphologic entity or as a component of a composite lymphoma. To determine whether cytogenetic abnormalities exist in cases of MBCL, fresh tissue from four lymphoma specimens in which MBCL was a substantial component were analyzed by classic cytogenetics; no pure MBCL cases were available for study. One monoclonal neoplastic population was found in each case by immunophenotyping studies and classic cytogenetics. Clonal cytogenetic abnormalities included -X or +X, t(14;18)(q32;q21), del(6q), t(11;14)(q13;q32), dup(12q), dup(1q), t(2;3)(q13;q29), and der(8)t(8;9)(p11.2;q13). The abnormal clone usually reflected the underlying lymphomatous process, namely, follicular lymphoma [t(14;18)], mantle cell lymphoma [t(11;14)], or small lymphocytic lymphoma (partial trisomy 12). There were no cytogenetic abnormalities common to all neoplasms. Taken together, the cytogenetic and immunologic data suggest that although MBCL may exist as a pure entity, it also may commonly represent a morphologic variant or a component of other primary lymphomatous processes.

Adult↗

The relationship of Epstein-Barr virus to infection-related (sporadic) and familial hemophagocytic syndrome and secondary (lymphoma-related) hemophagocytosis: an in situ hybridization study.

Many cases of hemophagocytic syndrome have been associated with viral infections, particularly Epstein-Barr virus (EBV), but the pathogenesis of the syndrome remains unclear. We have examined lymph node, spleen, liver, and bone marrow sections from 12 cases, including four cases of proven or probable infection-related hemophagocytic syndrome (IHPS), three cases of familial hemophagocytic syndrome (FHPS), and five cases of secondary hemophagocytosis associated with T-cell malignant lymphoma (SHPC), for EBV RNA using a sensitive and specific in situ hybridization technique. Epstein-Barr virus RNA was detected in seven of 12 cases (58%), including three cases of IHPS, one case of FHPS, and three cases of SHPC. Numerous EBV-positive cells were detected in two cases of IHPS (in multiple anatomic sites) and in one case of FHPS (in the spleen). Diffuse EBV positivity also was noted within the neoplastic cells of one case of SHPC. Rare to occasional EBV-positive cells were found in multiple sites in another case of IHPS and within admixed, reactive lymphoid cells in two cases of SHPC. The results indicate that numerous EBV-positive cells can be identified in some cases of IHPS, FHPS, and SHPC, suggesting a pathogenetic role for the virus. However, the absence of EBV from a proportion of cases of IHPS and FHPS in this study suggests that other infectious agents also play a role in the pathogenesis of this syndrome.

Adolescent↗

bcl-2 expression in Hodgkin's disease. Correlation with the t(14;18) translocation and Epstein-Barr virus.

In a prior study from our laboratory using the polymerase chain reaction (PCR) technique, the t(14;18)(q32;q21) translocation was detected in low copy number in 32% of Hodgkin's disease cases. The cell of origin of the t(14;18), however, was not determined. To further investigate the role of bcl-2 in Hodgkin's disease and the possibility that the translocation resides in Reed-Sternberg and Hodgkin's (RS-H) cells, we analyzed selected cases of Hodgkin's disease immunohistologically using a monoclonal antibody reactive with bcl-2. Because Epstein-Barr virus (EBV) has been reported to upregulate bcl-2 expression, we also used an in situ method for detecting EBV in these tissues. Thirteen cases of Hodgkin's disease were studied, including seven cases with the t(14;18) translocation and six cases without it, as determined by PCR in a prior study. bcl-2 protein was detected immunohistologically in the RS-H cells in eight cases: three with the t(14;18) translocation and five in which the translocation was not detected. EBV RNA was detected in the RS-H cells of four patients, including two in which the RS-H cells also were bcl-2 positive. The presence of bcl-2 staining of the RS-H cells in this series of cases did not correlate with clinical features, histologic subtype, the presence of the t(14;18) translocation, or EBV-positivity. The lack of consistent bcl-2 protein expression in RS-H cells, including EBV-positive RS-H cells, may suggest that the t(14;18) translocation does not reside in RS-H cells in at least a subset of cases of Hodgkin's disease. If this is true, the t(14;18) translocation may not play an important role in the pathogenesis of Hodgkin's disease.

Adolescent↗

Efficacy of azithromycin for treating Babesia microti infection in the hamster model.

Because of its prevalence and severity, Babesia microti infection is an important public health problem. The current treatment of choice is clindamycin plus quinine. However, in some cases other treatments are needed because of drug intolerance or relapse. The activity of azithromycin was investigated for treatment of babesiosis in the hamster model. All animals received vancomycin to prevent antibiotic-associated colitis. Quinine (250 mg/kg/day), azithromycin (150 mg/kg/day), and the combination of azithromycin and quinine were compared. A significant suppression of parasitemia was found in all treatment groups (combination had the greatest effect, followed by azithromycin, then quinine; P < .05). The mean survival was significantly prolonged in the combination group (P < .05). Azithromycin as monotherapy in a higher dose (300 mg/kg/day) also resulted in a significant prolongation of survival (P < .05). Spirogermanium and ciprofloxacin, which have been reported to have antimalarial activity, had no effect on parasitemia or survival in this experimental babesiosis model.

Animals↗

Small subunit rRNA sequence of Enterocytozoon bieneusi and its potential diagnostic role with use of the polymerase chain reaction.

In the past several years, microsporidia have become recognized as another important group of opportunistic infections of immunocompromised patients, especially those with AIDS. Enteric infections with the noncultivatable microsporidian parasite Enterocytozoon bieneusi have been diagnosed from AIDS patients with chronic diarrhea, malabsorption, and wasting. The incidence of infection and mechanism of transmission of these organisms in humans is unknown. Several recent tests for human pathogens have been developed using rRNA genes as diagnostic probes. Using the polymerase chain reaction and conserved regions of the small subunit rRNA (SSU-rRNA) gene, the SSU-rRNA gene of E. bieneusi was successfully cloned and subsequently sequenced. Amplification of E. bieneusi rRNA could be demonstrated from intestinal biopsies from HIV-1-infected patients infected with E. bieneusi but not from intestinal biopsies from noninfected patients. This cloned SSU-rRNA gene was used to develop improved probes for detection of E. bieneusi in tissue of infected patients.

AIDS-Related Opportunistic Infections↗

Stage I renal cell carcinoma. A clinicopathologic study of 82 cases.

Stage has been established as the most important predictor of prognosis in renal cell carcinoma. The predictive value of other morphologic features is less well established. Therefore, in this study we assessed morphologic parameters in 82 Robson stage I renal cell carcinomas. Insufficient numbers of T1 lesions were present in this series to permit a confident comparison of Robson staging with the Union Internationale Contre le Cancer-American Joint Committee on Cancer TNM (tumor, node, metastasis) staging. Morphologic parameters--including size, character of cytoplasm, nuclear grade, and pelvic invasion--were studied. Both univariate survival analysis and multivariate or tree-structured survival analysis (TSSA) were employed, with disease-free survival and actuarial survival as end points. Nuclear grade was the most important predictor of prognosis in stage I neoplasms by TSSA. Nuclear grade greater than 2 correlated with significantly shorter survival (p = 0.018). Stage I tumors measuring less than 5.0 cm by survival analysis (or 6.0 cm by TSSA) were associated with improved disease-free survival (p = 0.040), although TSSA indicated that the effect was pronounced only in low-grade neoplasms. The character of cell cytoplasm was not independent of nuclear grade (Kruskal-Wallis test, p = 0.028). The contingency table indicated disproportionate numbers of grade 4 mixed cell tumors, grade 3 granular cell tumors, and low-grade clear cell tumors. By TSSA, younger patients with low-grade but larger tumors had a poor clinical outcome. Elderly patients with high-grade tumors had the worst overall survival. None of the other clinical parameters or architectural pattern correlated with survival or disease-free survival. When nuclear grade was combined with tumor size and age at diagnosis in a decision tree, patients with stage I neoplasms were separated into favorable, intermediate, and poor prognosis groups.

Adult↗

Diagnosis and treatment of intestinal helminths. I. Common intestinal cestodes.

Increase in travel and immigration has led to a heightened awareness of parasitic diseases among health professionals. Intestinal helminths are important human parasites. Cestodes or tapeworms comprise an important group of helminths. The diagnosis of tapeworm infections requires a skilled laboratory because serological tests are unavailable. In this first part of our review of intestinal helminths, we describe the salient features of the diagnosis and treatment of several important intestinal cestodes, including Diphyllobothrium latum, Taenia, Hymenolepis, and Dipylidium caninum. Niclosamide and praziquantel are the drugs of choice for tapeworm infections.

Adult↗

Parasitic infections in AIDS patients. Cryptosporidiosis, isosporiasis, microsporidiosis, cyclosporiasis.

AIDS is characteristically associated with several intracellular enteric protozoan infections that often cause chronic and sometimes fatal intractable large-volume diarrhea. Until the AIDS epidemic, several of these parasitic infections were almost unknown as causes of human disease. This article reviews the diseases produced by cryptosporidia, isospora, cyclospora, and microsporidia in humans.

AIDS-Related Opportunistic Infections↗

Taeniasis and cysticercosis.

This article focuses on clinical issues of taeniasis and cysticercosis, including a comprehensive review of the clinical data, standard and latest chemotherapy, modern concepts of pathogenesis, conventional and advanced diagnostic tests, current epidemiology, and effective means of control. Fundamental parasitology is covered to familiarize physicians and scientists with the latest concepts of parasites.

Adrenal Cortex Hormones↗

Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance.

Fifty-two infiltrating breast carcinomas with medullary features (BCMF) were studied immunohistochemically to determine the immunophenotype of the mononuclear tumor inflammatory cells (MTIC) in formalin-fixed, paraffin-embedded material. The neoplasms were also examined for Epstein-Barr virus (EBV) DNA by the polymerase chain reaction (PCR). BCMF were independently classified as medullary carcinoma (MC) or infiltrating ductal carcinoma (IDC) by six observers according to the criteria of Pedersen et al. DNA from 35 BCMF was successfully amplified using PCR, but all were negative for EBV DNA. These included, by 4/6 consensus diagnosis, 16 MC, 18 IDC, and one BCMF which failed to achieve consensus diagnosis. MTIC were present to a mild degree in 19 BCMF (37%) and to moderate to severe degrees in 33 (63%). MTIC were predominantly (> or = 75%) lymphocytic in 31 BCMF (13 MC, 16 IDC, two without consensus diagnostic agreement), and plasmacytic in 10 (six MC, four IDC); equal proportions of lymphocytes and plasma cells occurred in 11 (six MC, five IDC). Lymphocytic MTIC were mostly CD45RO+/CD3+ T-cells in nearly all cases, and showed a predominant CD3+/CD4+ and CD3+/CD4- immunophenotype in 36% and 64% of cases, respectively. Natural killer cells (CD57+) and histiocytes (MAC 387+) were virtually absent. The number, cell type, and T-cell subsets of the MTIC were unrelated to consensus diagnosis, axillary lymph node status, or overall survival. EBV is unassociated with MC, despite the histologic similarities of MC to EBV-associated lymphoepithelial lesions of other organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Epstein-Barr virus distribution in nonneoplastic lymph nodes.

Epstein-Barr virus (EBV) has been associated with a wide variety of neoplastic conditions including nasopharyngeal carcinoma, gastric carcinoma, lymphoproliferative disorders in immunocompromised hosts, Hodgkin's disease, and non-Hodgkin's lymphomas of either B or T-cell phenotype. Although the presence of EBV in neoplastic lymph nodes has been well studied, very few studies have examined the distribution of EBV in normal or reactive lymph nodes. We studied normal or reactive lymph nodes from patients in Peru, a geographical region with a relatively high prevalence of EBV infection as compared with the United States or Europe. EBV DNA-RNA in situ hybridization was performed using a 30-base biotinylated oligonucleotide complementary to the EBER1 gene of EBV. Ten cases showed the presence of EBV RNA in scattered cells (less than 50 per section) and were utilized in the study. Most of the cells labeling for EBV RNA were small lymphocytes although some large lymphocytes also labeled. These cases were then subjected to double-labeling immunohistochemical/in situ hybridization studies using monoclonal antibodies L26(CD20), Leu22(CD43), Leu7(CD57), and the polyclonal antibody CD3. In their respective sections, of those cells that showed positive labeling for EBV RNA, 44% double labeled for L26, 24% double labeled for CD3, and 23% double labeled for Leu22. No cells double labeled for Leu7. This study shows that EBV RNA is expressed in both B and T-cells in nonneoplastic lymph nodes. These findings are compatible with other studies that have shown the presence of EBV in both B and T-cell non-Hodgkin's lymphomas.

Adolescent↗

High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of HIV-associated Hodgkin's disease.

The Epstein-Barr virus (EBV) has been implicated in the pathogenesis of Hodgkin's disease, with an frequency of 15 to 50% in the immunocompetent host. We studied 12 formalin-fixed, paraffin-embedded cases of Hodgkin's disease occurring in human immunodeficiency virus-infected individuals to determine the frequency of EBV in Hodgkin's disease from this population. EBV DNA-RNA in situ hybridization was performed using a 30-base biotinylated anti-sense oligonucleotide complementary to the EBER1 gene of EBV. EBV RNA was found in the Reed-Sternberg cells and variants in 11 of 12 cases. Double-labeling studies confirmed the presence of EBV RNA in CD15-expressing Hodgkin's cells in all 11 cases, although rare B lymphocytes coexpressing EBV RNA and CD20 were also noted in these cases. The Hodgkin's cells in all 11 EBER-positive cases expressed latent membrane protein. The one case negative for EBV RNA showed the histology of nodular, lymphocyte predominance, a subtype thought to be distinct from other types of Hodgkin's disease.

Adult↗

Nasal lymphomas in Peru. High incidence of T-cell immunophenotype and Epstein-Barr virus infection.

The incidence of non-Hodgkin's lymphoma of the nasal region is much higher in Peru than in the United States and is similar to the incidence of sinonasal lymphomas in Asian countries. To characterize these lymphomas, we evaluated the clinical, morphologic, and immunohistochemical features of 14 cases and also analyzed the cases for Epstein-Barr virus (EBV) RNA using a sensitive and specific in situ hybridization method. Morphologically, the cases consisted of nine large cell immunoblastic lymphomas, one diffuse mixed cell lymphoma, one diffuse small cleaved lymphoma, one small noncleaved lymphoma, and two cases unclassifiable in the Working Formulation. Eleven cases demonstrated evidence of T lineage, two were of B lineage and one of indeterminate immunophenotype. In 13 of the lymphoma cases including all of the T-cell lymphomas, EBV RNA was detected in a high percentage of cells. Double-labeling immunohistochemical and in situ hybridization studies identified CD43 positivity in the cells labeling for EBV RNA. Much smaller amounts of EBV RNA were detectable in six of eight control benign nasopharyngeal biopsy specimens, and two were completely negative. These findings are similar to the prevalence of EBV-positive T-cell lymphomas in Asian countries and differ from the findings of the more common EBV-negative B-cell nasal lymphomas in the United States. These findings suggest that EBV plays a role in the development of nasal T-cell lymphomas and that the incidence of EBV infection may explain the reported "East-West" difference in the incidence of nasal T-cell lymphomas.

Adolescent↗

Brain lymphomas of immunocompetent and immunocompromised patients: study of the association with Epstein-Barr virus.

The Epstein-Barr virus (EBV) has been described in association with lymphomas of the central nervous system. To test if the association between EBV and central nervous system lymphomas was limited to patients with immunosuppression or whether the association also held for patients who were immunocompetent and to determine the true prevalence of any association, we studied 37 formalin-fixed, paraffin-embedded cases of central nervous system lymphomas occurring in immunocompromised and immunocompetent patients. EBV DNA-RNA in situ hybridization was performed using a 30-base biotinylated antisense oligonucleotide complementary to the EBER1 gene of EBV. Immunohistochemistry was also performed, using a monoclonal antibody to the latent membrane protein of EBV. The most common histologic subtypes of lymphoma were high grade immunoblastic (57%), diffuse large cell (22%), and small, noncleaved, non-Burkitt's (11%). Eighty-six percent of all tumors in our series were of B-cell lineage, as confirmed by CD20 expression, but only 37% of the primary tumors showed restricted CD20 expression. EBV RNA was identified in all or virtually all of the malignant lymphoid cells in 11 of the 37 cases (30%), including 10 primary brain lymphomas and one metastasis from systemic disease. Latent membrane protein expression was identified in 64% of the EBER1-positive cases. All 10 patients who had a history of immunosuppression had tumors that expressed EBV RNA. We confirm the strong association of EBV with brain lymphomas occurring in immunocompromised patients, whether due to AIDS or to the immunosuppression associated with organ transplantation. Our findings also demonstrate a low rate of EBV-positivity in immunocompetent patients.

Adolescent↗