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Biomedical subjects

L M Weiss

Publications and source records attributed to L M Weiss.

At least 235 records · Page 13Linked to original sources
PubMed1992

Lymphoproliferative lesions in patients with common variable immunodeficiency syndrome.

We reviewed our experience with 30 nodal and extranodal lymphoid lesions from 17 patients with common variable immunodeficiency (CVID). Immunohistochemical studies were performed on biopsies from 15 patients, in situ hybridization for Epstein-Barr virus in nine cases, and gene rearrangement analysis on seven lesions. The biopsies were classified into four groups: malignant lymphoma (two cases); atypical lymphoid hyperplasia (eight cases); reactive lymphoid hyperplasia (14 cases); and chronic granulomatous inflammation (six cases). The two malignant lymphomas were diagnosed using histologic criteria; tissue was not available for the assessment of clonality. In one neoplasm, Epstein-Barr virus was identified in the tumor cells by in situ hybridization. The cases of reactive lymphoid hyperplasia and chronic granulomatous inflammation had no atypical architectural, cytologic, or immunohistochemical features. The cases of atypical lymphoid hyperplasia were of particular interest, as these patients had either widespread involvement or massive disease. The diagnosis of lymphoma was considered likely by the clinicians and, in three cases, the histologic slides were originally interpreted as malignant lymphoma by the referring pathologists. Although the architecture of these lesions appeared to be effaced on hematoxylin and eosin-stained sections, immunohistochemical analysis demonstrated preserved architecture with florid expansion of B-cell and T-cell compartments. In addition, clinical follow-up of these patients was benign, and gene rearrangement analysis in three lesions revealed no evidence of clonality. We conclude that the majority of lymphoid lesions in patients with CVID are benign. Immunohistochemical and gene rearrangement studies are particularly helpful in the assessment of cases of atypical lymphoid hyperplasia.

Adolescent↗
PubMed1992

Chagas' disease.

Chagas' disease, caused by Trypanosoma cruzi, is an important cause of morbidity in many countries in Latin America. The important modes of transmission are by the bite of the reduviid bug and blood transfusion. The organism exists in three morphological forms: trypomastigotes, amastigotes, and epimastigotes. The mechanism of transformation and differentiation is currently being explored, and signal transduction pathways of the parasites may be involved in this process. Parasite adherence to and invasion of host cells is a complex process involving complement, phospholipase, penetrin, neuraminidase, and hemolysin. Two clinical forms of the disease are recognized, acute and chronic. During the acute stage pathological damage is related to the presence of the parasite, whereas in the chronic stage few parasites are found. In recent years the roles of tumor necrosis factor, gamma interferon, and the interleukins in the pathogenesis of this infection have been reported. The common manifestations of chronic cardiomyopathy are arrhythmias and thromboembolic events. Autoimmune, neurogenic, and microvascular factors may be important in the pathogenesis of the cardiomyopathy. The gastrointestinal tract is another important target, and "mega syndromes" are common manifestations. The diagnosis and treatment of this infection are active areas of investigation. New serological and molecular biological techniques have improved the diagnosis of chronic infection. Exacerbations of T. cruzi infection have been reported for patients receiving immuno-suppressive therapy and for those with AIDS.

Animals↗
PubMed1992

Detection of enteroviral RNA in idiopathic dilated cardiomyopathy and other human cardiac tissues.

Enteroviruses have been considered to be a possible cause of idiopathic dilated cardiomyopathy. We used a polymerase chain reaction methodology for the identification of enteroviral RNA in an attempt to provide evidence of a role for enteroviruses in the pathogenesis of idiopathic dilated cardiomyopathy. The methodology was shown to identify a wide variety of enteroviruses with a sensitivity up to 0.1-1 plaque-forming units/gram of tissue. 5 of 11 cases (45%) of idiopathic dilated cardiomyopathy, as well as 9 of 24 cases (38%) of a wide variety of other cardiac conditions (including normal heart), were positive for enteroviral nucleic acid sequences; all eight control cases of breast carcinoma tested were negative. These results suggest that both the normal and abnormal heart may represent a site of latent or low-grade persistent enteroviral infection, and that the mere presence of enteroviral nucleic acid sequences is not specifically associated with idiopathic dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1992

Pyrimethamine concentrations in serum during treatment of acute murine experimental toxoplasmosis.

Central nervous system toxoplasmosis is a major opportunistic infection in patients with acquired immunodeficiency syndrome. The standard therapy for this infection is pyrimethamine (PYR) and sulfonamides. To assess in vivo if PYR alone could adequately treat toxoplasmosis, a murine model of acute toxoplasmosis was used. The CD1 strain of mice was infected intraperitoneally with 10(4) parasites of the RH strain of Toxoplasma gondii. Pyrimethamine was administered in mouse chow at concentrations of 0, 0.03125, 0.0625, 0.125, 0.25, or 1.0 mg of PYR/g of food, which provides the following daily PYR dosages: 0, 6.25, 12.5, 25, 50, and 200 mg/kg/day. No sulfonamides were administered. Serum PYR levels proved more accurate than mg of PYR/g of food in predicting survival. Mice with serum PYR levels greater than or equal to 500 ng/ml (2 microM) survived and had no parasites present on peritoneal lavage. Mice with serum PYR levels less than 100 ng/ml (0.4 microM) had a 100% mortality rate and the average parasite count was 3 x 10(7) organisms in the lavage fluid. At a PYR level of 370 ng/ml, six of 11 mice survived and the lavage fluid contained 2.5 x 10(5) organisms. Previously, using 3H-uracil in an in vitro assay, PYR at a concentration of 500 ng/ml was shown to be as effective in inhibiting Toxoplasma growth as the combination of PYR (100 ng/ml) and sulfonamides 25 micrograms/ml). These data suggest the potential usefulness of PYR for monotherapy of toxoplasmosis and are consistent with previously described in vitro assays.

Acute Disease↗
PubMed1992

Diagnosis of Encephalitozoon cuniculi infection by western blot and the use of cross-reactive antigens for the possible detection of microsporidiosis in humans.

Microsporidia are very primitive, eukaryotic, obligate, intracellular, protozoan parasites. Encephalitozoon cuniculi, a microsporidian originally described from a rabbit infection, has been described in humans as well as in many species of laboratory animals. We report the detection of E. cuniculi by Western blotting in a rabbit with torticollis that was obtained from an Encephalitozoon-free colony. Cross-reactivity of this serum was observed with antigens prepared from several genera of microsporidia. Identical Western blotting patterns were obtained with sera obtained from a rabbit immunized with E. cuniculi that was purified from tissue culture cells. In addition, we were able to demonstrate cross-reactivity between E. cuniculi rabbit antisera and Enterocytozoon bieneusi antigens by indirect immunofluorescent assay techniques in human intestinal biopsy samples. These cross-reactions between microsporidia may be useful in developing diagnostic tests for non-cultivatable microsporidia such as Enterocytozoon bieneusi.

Animals↗
PubMed1992

Epstein-Barr virus-associated gastric adenocarcinoma.

The Epstein-Barr virus (EBV) has been detected in certain types of lymphoma and some epithelial neoplasms including nasopharyngeal lymphoepithelioma, and rare lymphoepithelioma-like carcinomas occurring in a variety of organs including, most recently, the stomach. The authors investigated the possibility that EBV may be present not only in the rare gastric cancers that resemble nasopharyngeal lymphoepithelioma, but also in typical gastric adenocarcinoma. EBV sequences were detected in 22 of 138 (16%) cases of typical gastric adenocarcinoma by polymerase chain reaction and in situ hybridization (ISH) techniques. The EBV genomes were specifically present within the gastric carcinoma cells in an even distribution. The EBV genomes were also present in adjacent dysplastic epithelium but were absent in surrounding lymphocytes, other normal stromal cells, intestinal metaplasia, and normal gastric mucosa. The EBV genomes in the infected gastric carcinoma cells are expressed as EBV RNA was detected by ISH. EBV was most often detected in gastric tumors from men (21%) compared with women (3%). Thus some cases of gastric adenocarcinoma are EBV-associated.

Adenocarcinoma↗
PubMed1992

Detection of Epstein-Barr virus genome in Ki-1 (CD30)-positive, large-cell anaplastic lymphomas using the polymerase chain reaction.

Ki-1 (CD30)-positive, large-cell anaplastic lymphoma (LCAL) is a distinctive subset of non-Hodgkin's lymphoma; morphologically, the neoplastic cells of LCAL may closely resemble Reed-Sternberg cell variants of Hodgkin's disease. The neoplastic cells in Hodgkin's disease are often CD30-positive, as are some of the transformed lymphocytes in infectious mononucleosis. Recent evidence suggests an etiologic role for the Epstein-Barr virus (EBV) in Hodgkin's disease. Because of the phenotypic similarities between Hodgkin's disease and LCAL, we used the polymerase chain reaction (PCR) to analyze eight specimens of LCAL for EBV genome. Diagnoses were established by paraffin section morphology and immunohistochemistry. For comparison, we also analyzed nine non-Hodgkin's lymphomas other than the LCAL type, three Hodgkin's disease specimens, and nine non-neoplastic lymph nodes. PCR was performed using DNA extracted from frozen tissue; DNA was amplified using two sets of oligonucleotide primers corresponding to the BamH1 W-fragment of the EBV genome. Amplified EBV genome was obtained from all specimens except for one mantle zone lymphoma, one diffuse mixed-cell lymphoma, and six non-neoplastic lymph nodes. EBV terminus region probing and in situ hybridization techniques, each less sensitive than PCR, were performed in selected cases in an attempt to corroborate our PCR results. Only 2 of 13 specimens contained EBV detectable by these other techniques, and neither specimen was a LCAL. In view of the high incidence of latent EBV infections in humans, the biologic significance of our PCR results is uncertain. Despite the detection of EBV genome by PCR in a high percentage of lymphomas, we were unable to substantiate an etiologic role for EBV in LCAL. The PCR technique may be too sensitive to provide meaningful data on the possible role of EBV in lymphomagenesis.

Antigens, CD↗
PubMed1992

Criteria for the definition of Epstein-Barr virus association in Hodgkin's disease.

There is a clear association between the Epstein-Barr virus (EBV) and Hodgkin's disease (HD). EBV is not, however, detectable within the affected tissues of all cases. The proportion of positive cases varies from 15-79% depending on the assay used to detect EBV. The techniques utilised vary not only in sensitivity but in their ability to detect viral DNA, RNA, or protein and in their ability to demonstrate the cellular localisation of the virus. Thus, the biological significance of a positive result will vary depending on the method of analysis. In the present study, four different methods of detecting EBV were compared. RNA in situ hybridization was found to be the most practical method of detecting EBV in tumour cells. Using this assay EBV was detected in the Reed-Sternberg cells of 33% and 45% of the two series of HD cases examined in this study. We believe that these cases should be considered EBV-associated.

Adolescent↗
PubMed1992

Molecular biologic studies of Hodgkin's disease.

There has been intense interest in applying the techniques of molecular biology to further our understanding of Hodgkin's disease. Numerous studies of the status of lymphocyte antigen receptor genes have been performed, with conflicting results. There is more uniformity in the results of Epstein-Barr viral (EBV) studies; evidence of EBV can be identified in the Reed-Sternberg cells of approximately 40% to 50% of cases. There is no consensus on whether the t(14;18) is present in tissues involved by Hodgkin's disease.

Chromosomes, Human, Pair 14↗
PubMed1992

Description of an in situ hybridization methodology for detection of Epstein-Barr virus RNA in paraffin-embedded tissues, with a survey of normal and neoplastic tissues.

The authors describe a highly sensitive and practical in situ hybridization method using an oligonucleotide probe for EBER1 RNA for the detection of Epstein-Barr virus (EBV) in formalin-fixed, paraffin-embedded tissue sections. Paraffin-embedded tissues from 793 cases of normal and neoplastic tissues were studied. Nuclear staining for EBV RNA was uniformly present in all or virtually all neoplastic cells in a variety of known EBV-positive tumors. We also demonstrate rare EBV-infected cells in normal lymphoid tissues. RNAase predigestion, competitive inhibition, and control probe studies confirmed the specificity of the staining. In addition, cross-reactivity of EBV RNA staining with other viruses was not present. Additionally, the distribution of EBV in a wide variety of other normal and neoplastic tissues is reported.

Base Sequence↗
PubMed1992

Characterization of the topography of Epstein-Barr virus infection in human immunodeficiency virus-associated lymphoid tissues.

A highly sensitive in situ hybridization methodology for Epstein-Barr virus (EBV) RNA was used to determine the topography of EBV infection in 16 cases of human immunodeficiency virus-associated lymphoid tissues. Four lymphomas, 11 persistent generalized lymphadenopathy (PGL) lymph nodes, and one lymphoepithelial cyst were studied. The pattern of EBV infection was diffuse in all lymphoma cases and predominantly interfollicular in PGL nodes. No discernable pattern of infection was present in the lymphoepithelial cyst. Germinal center cells were also infected in seven of the PGL cases, and this pattern predominated in one case. Double labeling immunohistochemistry/in situ hybridization studies on four cases of PGL indicated that the EBV infection was primarily involving B-lymphocytes, but rare infected T-lymphocytes were also identified. These studies further clarify the pattern and cellular site of EBV infection in human immunodeficiency virus-related lymphoid disease.

AIDS-Related Complex↗
PubMed1992

Lymphoepitheliomalike carcinoma of the skin. A case report with immunophenotypic analysis and in situ hybridization for Epstein-Barr viral genome.

Lymphoepithelioma is a malignant epithelial neoplasm of the nasopharynx. Similar malignancies--lymphoepitheliomalike carcinomas--of salivary glands, thymus, larynx, lung, stomach, and uterus have been described. We present here a case of lymphoepitheliomalike carcinoma of the skin in an 84-year-old woman. Histologically this neoplasm presented as a fairly discrete dermal aggregate of syncytial nests of epithelioid-appearing cells that displayed no squamous or glandular differentiation, surrounded by a dense lymphocytic infiltrate. Results of immunophenotypic studies showed expression of high molecular weight cytokeratins and increased density of dermal dendrocytes within and adjacent to the tumor. No Epstein-Barr viral genomic sequences were detected by in situ hybridization, which suggests that cutaneous neoplasms may have different etiologic agents compared with similar tumors, found to be associated with this DNA-containing virus, arising in extracutaneous sites. The combined light microscopic and immunohistochemical assessment of this rate cutaneous neoplasm permits distinction of lymphoepitheliomalike carcinoma from benign/malignant lymphoproliferative disorders or neuroendocrine carcinomas.

Aged↗
PubMed1992

Detection of HIV-1 protein and nucleic acid in enterochromaffin cells of HIV-1-seropositive patients.

Diarrhea contributes significantly to the morbidity and mortality of patients with the acquired immunodeficiency syndrome (AIDS). Up to 50% of AIDS patients have diarrhea, and an etiologic agent for this cannot be identified in all of them. Recent evidence suggests that enterochromaffin cells may be infected by the human immunodeficiency virus type 1 (HIV-1) and may contribute to the unexplained diarrhea. To test this hypothesis further, endoscopic biopsies of duodena from 22 HIV-1 seropositive patients [17 with diarrhea (> 500 g/day and > 3 bowel movements/day), five without diarrhea] and from 15 normal controls (no HIV risk factors) without diarrhea were studied. Formalin-fixed and paraffin-embedded 5-microns sections were examined by immunocytochemistry, using a monoclonal antibody to the HIV-1 gp41 protein, and by in situ hybridization with a full-length biotinylated HIV-1 DNA probe. Positive staining for gp41 was detected in crypt cells, consistent with the location, size, and morphology of enterochromaffin cells, in 11 of 17 HIV-1-seropositive patients with diarrhea, and in none of five without diarrhea. Nucleic acid hybridization staining was performed in five of the 11 patients who had positive gp41 staining; all showed HIV nucleic acid sequences in similar cells. All three of the five patients with positive staining for HIV nucleic acid sequences had diarrhea for which no etiologic agent for diarrhea could be found, and one each had cryptosporidia or microsporidia. No staining was observed in any of the samples from normal control tissues. These results suggest that HIV-1 may infect enterochromaffin cells and possibly alter their function. This, in turn, may contribute to the diarrhea associated with AIDS.

Adult↗
PubMed1992

Treatment options for AIDS-related esophageal and diarrheal disorders.

Gastrointestinal involvement is extremely common in the acquired immunodeficiency syndrome (AIDS), and the vast majority of such afflicted patients manifest disease in the esophagus, or in the small and/or large intestine. A great deal of interest is currently under way to discover the most efficient therapies for the various disorders complicating AIDS, and therapeutic recommendations change frequently. This paper will review the current treatment options of AIDS-related esophageal and diarrheal disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Blastocystis hominis in hospital employees.

Several reports have appeared that either support or deny the importance of the protozoan Blastocystis hominis as an intestinal pathogen in humans. In this report, we describe the clinical characteristics of B. hominis and its response to therapy in hospital employees found to have the parasite on routine screening of stools. During the study, 49 patients with B. hominis were identified, and 413 stools were examined from these patients. Twenty-nine patients were asymptomatic (59%), and 20 had symptoms of bloating, flatulence, soft/loose stools, or constipation. Of these 20 patients, 10 had symptoms that correlated with the presence or absence of B. hominis, four had symptoms that were independent of B. homonis, and six had other intestinal parasites that could account for their symptoms. Nineteen percent of patients without treatment had eradication of B. hominis from stool on follow-up examination. Metronidazole did not increase this rate. Iodoquinol treatment eradicated the organism in 41% of patients (p less than 0.05), and resulted in the reduction or eradication of the parasite in 62%, as determined by follow-up examination.

Adolescent↗
PubMed1991

Clinical significance of morphologic subdivision in diffuse large cell lymphoma.

Although diffuse large cell lymphomas can be morphologically divided into large cell (DLC) and immunoblastic (IBL) subtypes, the clinical significance of this subdivision remains controversial. The initial diagnostic materials from 85 patients with recorded diagnoses of diffuse large cell lymphoma who were treated at Stanford between 1975 and 1986 with cyclophosphamide, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP); methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M-BACOD); or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were retrospectively reviewed by a panel of hematopathologists and classified according to morphologic criteria of the Working Formulation. Based on the criterion of agreement of two of three observers, 60 patients were classified as having DLC, 19 as having IBL, and the lymphomas in 6 patients could not be additionally classified. No significant differences in complete response (CR) rate, freedom from disease progression (FFP), or overall survival were found between the DLC and IBL groups. There was also no significant difference in prognosis between DLC cases additionally subclassified as large cleaved cell (16 patients) and those with large non-cleaved cell (36 patients). Although IBL is considered to be a high-grade lymphoma, the authors concluded that it does not differ significantly in prognosis from DLC lymphoma and, therefore, does not justify a modified treatment selection based on IBL morphologic type alone. Definitive evaluation of the prognostic significance of morphologic subdivision may require a larger cohort of uniformly treated patients.

Actuarial Analysis↗
PubMed1991

Epstein-Barr virus in benign lymph node biopsies from individuals infected with the human immunodeficiency virus is associated with concurrent or subsequent development of non-Hodgkin's lymphoma.

Individuals infected with the human immunodeficiency virus (HIV) have an increased incidence of high-grade B-cell lymphoma. In many instances, these lymphomas contain Epstein-Barr viral (EBV) genomes. To investigate the role of EBV in development of HIV-related lymphoma, benign fixed lymph node biopsies from normal individuals and HIV-infected individuals with persistent generalized lymphadenopathy (PGL) were analyzed for EBV sequences by polymerase chain reaction and in situ DNA hybridization techniques. EBV DNA was not detected in any of 16 benign lymph node biopsies from normal individuals, but could be detected from 13 of 35 PGL biopsies. The EBV-infected cells were present in both follicular and interfollicular areas and in both small and large lymphoid cells. The presence of detectable amounts of EBV DNA in the 13 PGL biopsies was associated with an increased incidence of concurrent lymphoma at another site (n = 3) or development of lymphoma in time (n = 2). In contrast, only 1 of 22 individuals with EBV-negative PGL biopsies developed lymphoma in time (P less than .05). EBV was detected in all five lymphomas in which tissue was available for subsequent analysis, including the lymphoma that developed in the individual without EBV in his previous PGL biopsy. These findings support the hypothesis that EBV plays a role in development of some HIV-related lymphomas. Detectable EBV lymphoproliferations occur in a few PGL biopsies and are associated with a significant risk of EBV DNA-positive non-Hodgkin's lymphoma.

Antigens, Viral↗