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Biomedical subjects

K P Mann

Publications and source records attributed to K P Mann.

14 recordsLinked to original sources
PubMed1999

Diagnosis of posttransplant granulocytic sarcoma by fine-needle aspiration cytology and flow cytometry.

We describe a patient who developed granulocytic sarcomas of the mesentery and breast approximately 4 yrs following an allogenic bone marrow transplantation for acute myeloblastic leukemia. The diagnosis was made by a combination of fine-needle aspiration cytology and flow cytometry. The differential diagnoses of localized masses in posttransplant patients and how the combination of fine-needle aspiration cytology and flow cytometry may be used are discussed.

Adult↗
PubMed1999

Post transplant CD8+ gammadelta T-cell lymphoma associated with human herpes virus-6 infection.

Gammadelta T-cell lymphoma is a rare T-cell lymphoproliferative disorder that has been reported in both immunocompetent and immunocompromised persons. This report describes a forty eight year old patient who developed gammadelta T-cell lymphoma four years after undergoing living-related kidney transplantation. The lymphoma expressed CD2, CD3, CD7, CD8 and CD56, and the gammadelta T-cell receptor and did not express CD5, CD4 and the alphabeta T-cell receptor. In addition, HHV-6 was cultured from the patient's bone marrow, marking the first time that this virus has been associated with gammadelta T-cell lymphoma. Since all patients with gammadelta T-cell lymphoma described to date have responded poorly to standard combination chemotherapies, the patient was treated with the purine analogue 2-chlorodeoxyadenosine. While he responded transiently to treatment, long term remission was not achieved indicating that additional therapeutic approches still need to be developed, for the management of this disorder.

Antigens, CD↗
PubMed1998

AIDS-related malignancies.

In the US over one million persons are currently infected with the HIV, over half a million have had AIDS, and over 300,000 have died from AIDS. Worldwide, it is estimated that more than 17 million people are currently infected with HIV, and over 1,200,000 cases of AIDS have been reported to the World Health Organization. By some estimates, up to 40% of patients with AIDS will ultimately develop some form of cancer. Non-Hodgkin's lymphoma, Kaposi's sarcoma and invasive cervical cancer have a higher incidence in persons with HIV infection and all three are AIDS-defining illnesses. In addition, several reports suggest that a number of other malignancies may occur at an increased incidence in persons with HIV infection, including squamous-cell carcinoma of the head, neck and anus, plasmacytoma, melanoma, small-cell lung cancer, basal-cell cancer, and germ-cell tumours. Clinicians should become familiar with HIV-related malignancies as their incidence is expected to further increase as more effective therapies for HIV and associated opportunistic infections allow patients to live longer in an advanced state of immunodeficiency. In the current article, we will review the clinical and therapeutic aspects of the most common AIDS-related malignancies including non-Hodgkin's and Hodgkin's lymphomas, Kaposi's sarcoma and anogenital epithelial neoplasias.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Rosai-Dorfman disease (extranodal sinus histiocytosis) in a patient with HIV.

Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy (SHML), is a rare histiocytosis of unknown etiology that most commonly involves the cervical lymph nodes. Extranodal involvement occurs in 30-40% of cases, most often in the head and neck. Characteristic histologic findings include emperiopolesis (engulfment) of lymphocytes and S-100 protein positivity. Treatment of Rosai-Dorfman disease is unnecessary unless the disorder becomes life- or organ-threatening, since the disease will resolve spontaneously in most patients. We present what, to the best of our knowledge, is the first reported case of Rosai-Dorfman disease limited to the skin in a patient infected with human immunodeficiency virus. SHML is described and diagnostic and therapeutic measures are reviewed.

Adult↗
PubMed1997

Neural cell adhesion molecule (CD56)-positive acute myelogenous leukemia and myelodysplastic and myeloproliferative syndromes.

The CD56 antigen is normally expressed on natural-killer cells but has additionally been shown to be present on a variety of hematologic malignancies, including a subset of acute myelogenous leukemia (AML). There is disagreement, however, about its prognostic significance and its association with specific cytogenetic abnormalities. All clinical samples from June 1994, through September 1995, with increased myeloblasts were analyzed by multiparameter flow cytometry for anomalous expression of CD56. Patients with CD56+ blast cells were selected, and morphologic review was performed. Clinical information was obtained, and cytogenetic data were reviewed. Southern blot analysis to detect rearrangement of the mixed lineage leukemia (MLL) gene was performed when possible. The samples from 23 of 114 patients studied demonstrated anomalous expression of CD56 on myeloblasts, including patients with AML, myelodysplastic syndromes (MDS), and chronic myelogenous leukemia in blast crisis. The samples from 10 of 15 patients with CD56+ AML demonstrated at least partial monocytic differentiation. Dysplastic features were displayed in the samples of 12 patients. Correlation with specific cytogenetic abnormalities was not found. The MLL gene was rearranged in five of 18 patients. Seventeen patients have died, with a median survival of 4.6 months for patients with AML. Three have sustained a complete remission. One has findings of high-grade myelodysplastic syndrome. Two were unavailable for follow-up. Expression of CD56 was found in 20% of patients with increased myeloblasts, including patients with high-grade MDS, chronic myelogenous leukemia in blast crisis, and AML. This phenotype was associated with dysplasia, monocytic differentiation, and rearrangement of the MLL gene.

Adolescent↗
PubMed1996

Establishing a pure lymphocyte gate for subset analysis by flow cytometry.

Development of a more cost-effective and efficient method of performing lymphocyte subset analysis is of continuing importance in clinical flow cytometry laboratories. Current two-color methods utilize forward and right angle light scatter and multiple tubes per sample and are thereby liable to gate contamination. Methods using three-color analysis with CD45 vs. right angle light scatter (RALS) gating cannot always exclude a contaminating nonlymphoid population. We have established a two tube approach to directly measure total T cells, T suppressor, and T helper subsets, total B cells and total natural killer cells. The technique involves staining of whole blood with a mixture of five monoclonal antibodies conjugated to three fluorochromes: CD4+CD19 fluorescein isothiocyanate (FITC), CD3+CD33 phycoerythrin (PE), CD45 peridin chlorophyll alpha protein (PerCP), CD8+CD16 FITC, CD3+CD33 PE, and CD45 PerCP. Analysis is performed using a single laser flow cytometer. This method has equivalent recovery to and improved purity of the lymphocyte gate when compared to well-established methods. These antibody combinations additionally allow clear separation of lymphocytes from other leukocytes and debris as well as separation of the T cell helper and suppressor subsets, natural killer cells and B lymphocytes. We additionally provide preliminary data that an accurate lymphocyte subset analysis can be performed on a single tube containing five antibodies (CD4+CD19 FITC, CD3+CD33 PE, and CD45 PerCP), although some measurements are performed deductively.

Antigens, CD↗
PubMed1995

Neutrophil-rich, Ki-1-positive anaplastic large-cell malignant lymphoma.

The presence of neutrophils, in the absence of necrosis, is uncommon in malignant lymphoma (ML). We identified a subgroup of Ki-1-positive anaplastic large cell ML (Ki-1 ALCL) in which neutrophils were a prominent component. Six of 20 cases of Ki-1 ALCL had a significant neutrophil infiltrate that varied from 5 to 10% to > 50% of cells per high power field. Neutrophils were not seen in 100 cases of other types of ML reviewed. Patients were first seen with skin lesions (four), localized lymphadenopathy (three), generalized lymphadenopathy (one), and localized extranodal disease (one). All had primary disease. Two patients had peripheral neutrophilia. Three of six patients had clinical stage IV disease. Four patients are currently in clinical remission; one died of recurrent disease; and one patient with acquired immunodeficiency syndrome (AIDS) died of Pneumocystis carinii pneumonia. Four cases demonstrated a T-cell phenotype, one of which arose in a patient with AIDS. Two had a B-cell phenotype. All cases were positive for CD30 (Ki-1). These observations expand the morphologic spectrum of Ki-1 ALCL to include a neutrophil-rich variant. We conclude that the presence of neutrophils is another morphologic feature shared by some cases of Ki-1 ALCL, lymphomatoid papulosis, and Hodgkin's disease, which suggests a possible pathogenetic link among them.

Adult↗
PubMed1993

Alternative poly(A) site utilization during adenovirus infection coincides with a decrease in the activity of a poly(A) site processing factor.

The recognition and processing of a pre-mRNA to create a poly(A) addition site, a necessary step in mRNA biogenesis, can also be a regulatory event in instances in which the frequency of use of a poly(A) site varies. One such case is found during the course of an adenovirus infection. Five poly(A) sites are utilized within the major late transcription unit to produce more than 20 distinct mRNAs during the late phase of infection. The proximal half of the major late transcription unit is also expressed during the early phase of a viral infection. During this early phase of expression, the L1 poly(A) site is used three times more frequently than the L3 poly(A) site. In contrast, the L3 site is used three times more frequently than the L1 site during the late phase of infection. Recent experiments have suggested that the recognition of the poly(A) site GU-rich downstream element by the CF1 processing factor may be a rate-determining step in poly(A) site selection. We demonstrate that the interaction of CF1 with the L1 poly(A) site is less stable than the interaction of CF1 with the L3 poly(A) site. We also find that there is a substantial decrease in the level of CF1 activity when an adenovirus infection proceeds to the late phase. We suggest that this reduction in CF1 activity, coupled with the relative instability of the interaction with the L1 poly(A) site, contributes to the reduced use of the L1 poly(A) site during the late stage of an adenovirus infection.

Adenoviridae Infections↗
PubMed1987

Posttranslational processing of the Epstein-Barr virus-encoded p63/LMP protein.

In this paper we describe the posttranslational processing of the p63/LMP (latent membrane protein) encoded by Epstein-Barr virus in transformed B cells. Specifically, we show that after synthesis, free LMP disappeared with a half-life of about 0.5 h. This was caused by the association of LMP with an insoluble complex. All detectable LMP in the plasma membrane was insoluble. This interaction was resistant to nondenaturing detergents but readily dissociated with 8 M urea or by boiling in 0.5% sodium dodecyl sulfate, suggesting that LMP may be associated with cytoskeletal elements. Most of the Nonidet P-40-insoluble LMP was phosphorylated (ppLMP) primarily on serine but also on threonine residues. No phosphotyrosine was detected. Furthermore, greater than 90% of the ppLMP resided in the Nonidet P-40-insoluble fraction, suggesting a strong correlation between complexing and phosphorylation. Additionally, ppLMP was found to be associated with a 53,000-molecular-weight phosphoprotein (pp53) of unknown origin. Finally, LMP turned over extremely rapidly, with a half-life of about 2 h. Taken together, these properties suggest that although LMP falls broadly within the category of phosphorylated, cytoskeleton-associated oncoproteins, it is nevertheless clearly different from any previously described member of this family.

Amino Acids↗
PubMed1985

Early events in Epstein-Barr virus infection provide a model for B cell activation.

We have used Epstein-Barr virus (EBV) infection in vitro to delineate two distinct stages in B cell activation. Previous studies have shown that the BLAST-2 (EBVCS) (EBV cell surface) activation antigen is expressed on a small fraction of B cells within 24 h of stimulation with a variety of agents, including mitogens and EBV. In this study, we have been able to isolate the BLAST-2 (EBVCS)+ cells early after activation/infection with EBV. These cells are small B cells that are actively synthesizing RNA but not DNA, and are, therefore, clearly distinct from large proliferating lymphoblasts. In addition, they contain multiple copies of the EBV genome, express the viral nuclear antigen (EBNA) and, most importantly, proceed to undergo transformation when placed back in culture. By comparison, the BLAST-2 (EBVCS)- population does not undergo transformation, even though a fraction of these cells are activated for RNA synthesis and express EBNA. Thus, using the EBV system, we have been able to show directly that an activated B cell first expresses the BLAST-2 (EBVCS) antigen concomitant with an increase in RNA synthesis, and then subsequently proceeds to differentiate into a proliferating lymphoblast.

Antigens, Viral↗
PubMed1985

Epstein-Barr virus-encoded protein found in plasma membranes of transformed cells.

We have developed monoclonal antibodies to a 63,000-molecular-weight protein (p63) which is the product of the most abundant messenger RNA in Epstein-Barr virus-transformed cells and shown that the protein is associated specifically with plasma membranes. It was also found to be associated with the other membrane fractions and was found in all Epstein-Barr virus-transformed cells tested. In addition, p63 was present in virions, resulting in transient, early appearance in newly infected cells. Newly synthesized p63 was detected at the time cells underwent blast transformation (48 to 72 h postinfection). The possible role of this protein in transformation and as a target for cell-mediated cytotoxicity is discussed.

Antibodies, Monoclonal↗
PubMed1982

Neural serotonin stimulates chloride transport in the rabbit corneal epithelium.

Evidence is presented that serotonin acts as a neurotransmitter in the cornea of the adult rabbit. Serotonin was localized to granules in a sparse population of subepithelial corneal nerves by an electron microscopic histochemical procedure. Significant endogenous levels of serotonin and its principal metabolite, 5-hydroxyindoleacetic acid, were detected in the central cornea by a fluorometric assay. Exogenous serotonin stimulated ion transport by corneal epithelium. This effect was potentiated by monoamine oxidase inhibition and was unaffected by an alpha-adrenergic receptor antagonist. Serotonin-stimulated ion transport was inhibited by the specific antagonist, methysergide, and by the replacement of Cl- with an impermeable anion. In tracer experiments, the serotonin-stimulated ion transport was shown to be caused by increased epithelial Cl- secretion. The serotonin response was partially inhibited by the beta-adrenergic antagonist, timolol. In a companion article, assay of corneal cyclic AMP showed stimulation of cyclic AMP synthesis by serotonin, inhibition by the specific antagonist, lysergic acid diethylamide, and potentiation by monoamine oxidase inhibition. We postulate that specific serotonergic receptors are present in the corneal epithelium and that activation of these receptors by serotonin released from serotonergic neurons increases the level of cyclic AMP, which stimulates active Cl- secretion by the corneal epithelium.

Animals↗
PubMedDate not supplied

Trilineage hematopoietic toxicity associated with valproic acid therapy.

PURPOSE: Sodium valproate is commonly used as an anticonvulsant for patients with refractory epilepsy. Hematopoietic toxicity involving platelets or erythrocytes has been previously described, as well as a few cases of generalized bone marrow suppression. PATIENTS AND METHODS: We report an infant receiving sodium valproate who developed severe anemia and thrombocytopenia, numerous circulating immature myeloid cells, and a coagulopathy. Bone marrow aspirate revealed approximately 40% abnormal promyelocytes, and the initial clinical and pathologic interpretation was consistent with the diagnosis of acute promyelocytic leukemia. RESULTS: Antineoplastic therapy was withheld while valproate was weaned. All hematopoietic abnormalities resolved after valproate therapy was discontinued. CONCLUSION: This report expands the clinical spectrum of hematopoietic toxicity associated with sodium valproate. Drug toxicity should be considered in any patient on valproate who develops hematopoietic abnormalities.

Cell Lineage↗