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Biomedical subjects

A C Harris

Publications and source records attributed to A C Harris.

29 records · Page 2Linked to original sources

Staining for Bcl-2 protein helps to distinguish benign from malignant lymphoid aggregates in bone marrow biopsies.

Lymphoid nodules in a bone marrow biopsy may be either benign or malignant. Morphological clues may help to differentiate the benign from the malignant nodules. However, it is sometimes difficult, if not impossible, to make this distinction, especially in patients with a known low-grade lymphocytic malignancy. This study was undertaken to determine whether staining bone marrow biopsies with an antibody to the bcl-2 protein might aid in making this differentiation. Using a monoclonal antibody to bcl-2, we stained 26 bone marrows with benign lymphoid aggregates, 19 with a follicular lymphoma, 10 with small lymphocytic lymphoma/chronic lymphocytic leukemia, three with other non-Hodgkin's lymphomas, and three with other miscellaneous hematopoietic lesions. Only one of the 26 benign lymphoid aggregates had moderate to intense staining with this antibody; in contrast, 79% of the follicular lymphomas stained positively. Eight of the 10 small lymphocytic lymphoma/chronic lymphocytic leukemia cases stained with moderate to intense intensity; the other two cases had weak staining. No consistent pattern was seen with the other six lesions. Based on this data, we conclude that lack of staining of small lymphoid aggregates within the bone marrow with the antibody to the bcl-2 protein is suggestive of a benign aggregate, whereas moderate to strong staining intensity is most consistent with a malignant process.

Bone Marrow↗

Malignant lymphoma imitating hepatitis.

BACKGROUND: Involvement of the liver is common in low-grade lymphomas and usually occurs as disseminated disease. Less common causes include primary liver lymphoma, usually of B-cell origin, and hepatosplenic lymphoma, a recently described T-cell lymphoma. METHODS: The medical records of three patients with clinical features of hepatitis who were found at autopsy to have lymphoma involving primarily the liver and spleen were reviewed. Tissue sections were stained with hematoxylin and eosin after fixation. Immunohistochemistry evaluation was performed by the immunoperoxidase technique on tissue fixed in formaldehyde solution and embedded in paraffin. Frozen tissue was available for additional immunophenotypic studies in one patient (Patient 1). RESULTS: Presenting signs included fever, jaundice, hepatomegaly, and elevated liver enzyme levels, especially serum alkaline phosphatase and bilirubin. Palpable lymphadenopathy was absent. Clinical evaluation indicated hepatitis. Lymphoma was the unexpected finding at postmortem examination after a rapidly deteriorating clinical course. The entire liver in each patient showed a predominant portal lymphomatous infiltration. Two patients had small cleaved cell lymphomas, and one had a large cell lymphoma. Immunologically, one of the small cleaved cell lymphomas was of B-cell phenotype and one was of T-cell origin. The large cell lymphoma showed immunologic staining only with the CD15 antibody (LeuM1). CONCLUSIONS: Lymphoma diffusely involving the liver frequently is associated with splenic involvement and may present as primary hepatic dysfunction. In contrast to previous reports of hepatosplenic T-cell lymphoma, this series suggests that lymphoma involving primarily the liver and spleen can be diverse in cytologic and immunologic characteristics.

Aged↗

Novel isoforms of CaBP 33/37 (annexin V) from mammalian brain: structural and phosphorylation differences that suggest distinct biological roles.

Two calcium-dependent phospholipid- and membrane-binding proteins have been purified from bovine brain. These are termed CaBP33 and CaBP37. Complete sequence analysis has revealed that these two proteins are isoforms of annexin V. Despite an apparent difference of 4 kDa between the two proteins on SDS-PAGE, only two amino-acid substitutions were found. These are, in CaBP33, Ser-36 and Lys-125 and in CaBP37, Thr-36 and Glu-125. This corresponds to a mass difference of 15 Da. This was confirmed by electrospray mass spectrometric analysis. Both isoforms can be phosphorylated substoichiometrically in vitro by protein kinase C at residue Thr-22.

Amino Acid Sequence↗

Steroid cell tumor of the ovary in a child.

An 8-year-old girl exhibited severe, progressive virilization of 2 years' duration associated with markedly elevated circulating testosterone concentrations. Based on her initial clinical presentation and results of a chemical evaluation, she was originally thought to have non-classic 21-hydroxylase deficiency, but her condition did not respond to corticosteroid therapy. Further evaluation confirmed the presence of an ovarian neoplasm. The excised ovary contained an attached gray-brown mass. Light microscopic and ultrastructural examination revealed the mass to be a steroid cell tumor. Because Reinke's crystals were not present, it was designated to be a steroid cell tumor not otherwise specified. This case represents one of 22 reported cases of steroid cell tumor occurring in children described in the literature, most of which have been associated with heterosexual precocity. To our knowledge, steroid cell tumors are benign when they occur in prepubertal children. Although they are rare, steroid cell tumors of the ovary should be considered in cases of childhood virilization.

Adrenal Hyperplasia, Congenital↗

Muscarinic acetylcholine receptors. Peptide sequencing identifies residues involved in antagonist binding and disulfide bond formation.

Muscarinic acetylcholine receptors (mAChR) were purified from rat brain and labeled either with the site-directed affinity label [3H]propylbenzilylcholine mustard (PrBCM) or with the sulfhydryl-specific label [3H]N-ethylmaleimide (NEM), using a protocol designed to give selective incorporation of the label into disulfide-bonded cysteines. m1 mAChRs were purified from CHO-K1 cells stably expressing the cloned receptor sequence and labeled with [3H]PrBCM. The labeled receptors were cleaved with the lysine-specific protease Lys-C and, after fractionation of the products, subcleaved with cyanogen bromide. Two major CNBr cleavage products were found with a molecular mass of approximately 3.9 and approximately 2.4 kDa, labeled either by [3H]PrBCM or [3H]NEM. The results obtained from CNBr cleavage of purified forebrain receptors were consistent with those obtained from the purified cloned m1 mAChR. Edman degradation was applied to the CNBr peptides. The results were compatible with the attachment of the [3H]PrBCM label to a conserved aspartic acid residue in transmembrane helix 3 of the mAChR (corresponding to Asp-105, m1 sequence) and of [3H]NEM to a conserved cysteine residue (corresponding to Cys-98, m1 sequence). These results support the hypothesis that the cysteine residue participates in a disulfide bond on the extracellular surface of the mAChRs and related G-protein-coupled receptors, while the aspartic acid residue is involved in binding the positively charged headgroup of muscarinic antagonists.

Amino Acid Sequence↗

Sequence analysis of the cloned streptococcal cell surface antigen I/II.

The gene spa P (formerly designated as spa P1) encoding the Mr 185,000 surface antigen (I/II) of Streptococcus mutans, serotype c (NG5), has been sequenced. The gene (4683 bp) encodes a protein of 1561 amino acid residues including putative signal peptide (residues 1-38) and transmembrane (residues 1537-1556) sequences. The N-terminal region (60-550) has alanine-rich repeats and is predicted to be alpha-helical. However, the C-terminal region (800-1540) is proline-rich and favours an extended structure. Except for a short central variable region the sequences appear to be highly conserved for S. mutans serotype c. N-Terminal sequencing of separated antigen I and antigen II polypeptides suggests that the former represents the N-terminal and the latter the C-terminal portions of the intact antigen.

Amino Acid Sequence↗

Localization and structure of the muscarinic receptor ligand binding site.

A conserved aspartic acid residue in transmembrane helix 3 of the muscarinic acetylcholine receptors is important in binding the headgroup of muscarinic ligands. This acidic amino acid probably points into a relatively hydrophilic cavity whose walls are formed by the amphipathic transmembrane helices of the receptor. Amino acid side chains within this cavity contribute to ligand binding.

Binding Sites↗

Etiologic aspects of cold agglutinin disease: evidence for cytogenetically defined clones of lymphoid cells and the demonstration that an anti-Pr cold autoantibody is derived from a chromosomally aberrant B cell clone.

This study investigated the clonal nature of cold agglutinin disease in a series of nine patients, which included the benign or idiopathic form as well as cases with an underlying lymphoma. Surface marker phenotyping and karyotypic analysis were performed on peripheral blood lymphocytes. An increased proportion of B cells was found in four cases and in three of these patients a monoclonal B cell population was identified with a mu, kappa phenotype. In the same three cases, as well as an additional patient, an aberrant karyotype was demonstrated. The cytogenetic abnormality present in all four cases included trisomy 3; two patients also had a trisomy 12. One of these four patients had a well-differentiated lymphoma and underwent a splenectomy. Splenic lymphocytes were transformed with Epstein-Barr virus and cultured en masse. Eight clones were established producing the same cold agglutinin with identical specificity as that present in the patient's plasma. Five of these clones were studied cytogenetically, and all had the same abnormal karyotype (51,XX,+3,+9,+12,+13,+18) found in peripheral blood and splenic lymphocytes. Thus, in this case, the cold reactive autoantibody was produced by the chromosomally abnormal, neoplastic clone of lymphocytes. Our findings support the view that cold agglutinin disease represents a spectrum of clonal disorders.

Adult↗

Lactulose in vincristine-induced constipation.

Constipation which is resistant to the usual range of laxatives is a troublesome undesirable effect of vincristine. Lactulose in doses up to 25 ml thrice daily proved to be a simple and effective treatment in six patients with refractory vincristine-induced constipation, and a successful prophylactic in two other patients. Palatable, and without any serious undesirable effects, lactulose can improve the quality of life for patients with a malignant tumour which is responsive to vincristine.

Adult↗

Rhabdoid cells in peritoneal fluid. A case report.

BACKGROUND: Rhabdoid tumor is an aggressive, malignant renal neoplasm of infants. Many extrarenal sites have been documented. CASE: A poorly differentiated carcinoma of the ovary with rhabdoid features occurred in a 36-year-old woman. The peritoneal fluid contained numerous malignant cells with rhabdoid features. Electron microscopy and immunocytochemistry corroborated the rhabdoid nature of the cells. CONCLUSION: Rhabdoid cells can be distinguished from other neoplasms with similar cytologic features by ancillary studies and clinical history.

Adult↗