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Biomedical subjects

M E Conrad

Publications and source records attributed to M E Conrad.

At least 19 recordsLinked to original sources
PubMed1979

Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation.

IgA myeloma proteins of kappa- and lambda-types were isolated from two patients. These were used to produce and purify anti-idiotype antibodies of both broad (myeloma-related) and narrow (individual myeloma) specificities. The anti-idiotype antibodies were conjugated with fluorochromes and used as immunofluorescent probes to trace in the patients clonal expansion at different levels of B-cell differentiation. Our results (a) confirm that B lymphocyte precursors in IgA plasma-cell myelomas are involved in the malignant process, (b) show that B lymphocytes of the malignant clone include those expressing each of the major heavy-chain isotypes, mu, delta, gamma, and alpha, and (c) provide strong circumstantial evidence that pre-B-cell members of the malignant clone are also increased in frequency. T cells expressing idiotypic determinants were not detected. These findings argue that the initial oncogenic event may occur in a B-stem cell and is not influenced through stimulation by antigen. An interesting association was the increased frequency of related clones of B lymphocytes as detected by their reactivity with anti-idiotype antibodies of broad specificity. Neither plasma cell nor pre-B-cell members of these related clones were increased in frequency. Anti-idiotype antibodies or helper T cells reactive with myeloma-related idiotypes could be responsible for this phenomenon. We discuss other implications of these findings and speculate that all of the various phenotypes of B-lineage malignancies may result from oncogenic processes affecting stem cell targets.

Antibodies, Neoplasm↗
PubMed1979

The aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome.

Occasionally it is difficult to differentiate paroxysmal nocturnal hemoglobinuria (PNH) from idiopathic aplastic anemia in patients who present with pancytopenia and an aplastic bone marrow. Patients with PNH may not have an abnormal acid hemolysis test, and patients with aplastic anemia may present with evidence of abnormal sucrose lysis, acid hemolysis, and antibody-mediated complement hemolysis. Demonstration of a population of red blood cells which are highly susceptible to antibody-mediated complement lysis makes a diagnosis of PNH probable. Donor red blood cell survival studies, which distinguish intracorpuscular from extracorpuscular hemolytic disorders, permit differentiation of the two disorders.

Adult↗
PubMed1979

Bone marrow necrosis.

Bone marrow necrosis has been regarded as a rare entity in specimens obtained from living patients and has been associated with poor prognosis. In contrast, we believe that it is a commonplace finding in bone marrow specimens which is frequently overlooked and which occurs in patients with multiple acute and chronic disorders. It is postulated that bone marrow necrosis eventuates from vascular occlusion of small blood vessels as a result of a number of causes. When bone marrow necrosis is prolonged, it may be associated with the development of bone marrow fibrosis and serve as a predisposing lesion for idiopathic myelofibrosis. Additional investigation of this phenomenon is required to determine its usefulness in the diagnosis of disease states and its role in the pathophysiology of a number of disorders.

Animals↗
PubMed1979

Beneficial effects of hepatitis in patients with acute myelogenous leukemia.

Of 50 consecutive patients admitted with acute myelogenous leukemia, 30 developed complete remissions on antileukemic therapy. Nineteen of the 30 repeatedly had elevated serum glutamic oxalacetic transaminase (SGOT) concentrations 3 to 14 weeks after the start of therapy. Patients with SGOT elevations had a significantly greater chance of remission and a longer survival (76 +/- 11 weeks) than those with normal SGOT levels (39 +/- 5 weeks), suggesting that hepatitis may have a beneficial effect in acute myelogenous leukemia. The hepatitis was mild in all patients. Review of patients at this institution alive 2 years after the diagnosis of acute myelogenous leukemia showed that they repeatedly had elevated SGOT levels. We believe that most had non-A, non-B post-transfusion hepatitis, which may have a beneficial effect on the leukemia or serve as an indicator of patients who have greater immunocompetence and thus a better prognosis.

Adolescent↗
PubMed1979

Pseudochloroma: extramedullary hematopoietic nodules in chronic myelogenous leukemia.

Five patients with chronic myelogenous leukemia had multiple hemorrhagic soft tissue lesions at the time of diagnosis. Histologic examination of tissue removed by biopsy and at autopsy revealed extramedullary hematopoietic nodules with associated hemorrhage and necrosis. No evidence of either blastic transformation or systemic bleeding diathesis was found. Pseudochloroma is a treatable although potentially fatal complication of uncontrolled chronic myelogenous leukemia and should not be confused with myeloblastomas occurring with blastic transformation. Early recognition of the syndrome, prompt treatment with intensive chemotherapy, and radiation therapy of intracranial lesions seem to provide effective control of this complication and reversion to a status that is responsive to conventional treatment of chronic myelogenous leukemia.

Adult↗
PubMed1979

Ultrastructural radioautography and cytochemistry of lead absorption.

Lead is a universal environmental contaminant absorbed largely through the gastrointestinal tract by unknown mechanisms. Because lead absorption is influenced by iron content in the body and diet, we used ultrastructural radioautography and cytochemistry to study absorption of physiologic lead doses in the rat duodenal epithelial cell and compared these findings to those previously reported for iron absorption. Rat duodenal loops exposed in vivo to 210Pb for 1 minute demonstrated the majority of labels on the microvilli, terminal web, and apical cytoplasm. Specimens exposed to radiolead for 10 minutes demonstrated more abundant labeling with a relative increase in labeling of epithelial cell mitochondria, nuclei and basal cytoplasm, as well as phagocytic cells, endothelial cells, and circulating erythrocytes of the lamina propria. Timm's sulfide-silver method localized trace metals in epithelial cells. After administration of lead, a significant increase in staining was observed in microvilli, mitochondria, non-membrane-bound cytoplasm, and nuclear chromatin. The rapid appearance of absorbed lead in epithelial cell mitochondria and nuclei, as well as phagocytic cells in the lamina propria, was distinctly different from that reported for absorbed iron and suggests different mechanisms for the subcellular transport of these cations. The combination of radioautography and Timm's sulfide-silver staining provides the specificity and resolution needed for ultrastructural evaluation of lead absorption and should be useful in further studies of lead metabolism.

Animals↗
PubMed1979

Bone marrow necrosis and degeneration.

Bone marrow necrosis, regarded as a rare finding in specimens from living patients, has been associated with a poor prognosis in patients with serious hematologic diseases and metastatic carcinoma. Two patients with extensive idiopathic bone marrow necrosis and a relatively benign course of illness were found. Therefore, we examined 500 consecutive bone marrow biopsy specimens that were obtained in a university hospital complex. Review of this material showed evidence of necrosis and degenerative changes of variable severity in one third of the biopsy specimens. It was found with approximately the same incidence in patients who underwent bone marrow biopsy for either neoplastic or nonneoplastic disorders; an increased prevalence was not observed in the group of patients who had received chemotherapy. Based on these observations, we believe necrosis and degeneration of the bone marrow is a commonplace finding that is frequently overlooked in a wide variety of acute and chronic disorders, and that requires further investigation to determine its clinical importance.

Aged↗
PubMed1978

Association of presenile cataracts with heterozygosity for galactosaemic states and with riboflavin deficiency.

Red cells and the lens of the eye are non-nucleated cells; moreover, they have metabolic similarities. Cataracts develop in childhood in homozygotes for galactosaemic abnormalities, which can be detected by biochemical measurements in red blood-cells. It has not been determined whether heterozygotes for these defects are at greater risk for cataract development later in life. Similarly, riboflavin deficiecy for which the erythrocyte is a sensitive indicator, has been associated with cataracts in animals. Red-cell studies were carried out in 22 patients, aged under 50, with cataracts. Heterozygosity for galactokinase deficiency was detected in 5 patients, for galactose-uridyl transferase in 2, and evidence of an erythrocytic deficiency of riboflavin in 8. Even when Black subjects were excluded from analysis because of their high incidence of polymorphism for galactokinase, these findings are significantly different from those expected from population surveys and suggest that many patients with presenile cataracts have a biochemical abnormality which can be detected by examination of red blood-cells and which may be corrected by dietary restrictions or supplements.

Adolescent↗
PubMed1978

Effects of calcium on the absorption and retention of lead.

An inverse relationship between lead retention and dietary calcium content has been known to exist for many years, but the reasons for this association remained unknown. In rats, the manipulation of dietary calcium had no significant effect upon the absorption of lead, but calcium-deprived animals had decreased excretion and thus increased body retention of lead. Intraluminal calcium decreased the absorption of test doses of lead from the small intestine in a dose-related manner. We postulated that this occurred because the two metals competed for similar binding sites on intestinal mucosal proteins which were important in the absorptive process. In vivo, lead bound to two heat-stable intestinal mucosal fractions which have been shown to bind calcium. Although more lead bound to the higher molecular weight fraction and more calcium bound to the lower molecular weight vitamin D-induced CaBP, substantial amounts of lead and calcium were found in both fractions. Further, the addition of calcium to test doses of lead markedly diminished the amount of lead bound by both fractions. Shared binding sites on absorptive proteins would explain why dietary calcium decreases lead absorption.

Animals↗
PubMed1977

von Willebrand's disease and hemorrhagic telangiectasia: association of two complex disorders of hemostasis resulting in life-threatening hemorrhage.

The clinical and laboratory findings in a patient with uncontrolled gastrointestinal bleeding secondary to combined hemostatic defects (von Willebrand's disease and hemorrhagic telangiectasia) are described. Evidence for von Willebrand's disease was found in five family members, but no other affected relative was found to have hemorrhagic telangiectasia. Complete assestivity, factor VIII antigen and von Willebrand factor levels. The patient described also was evaluated for her response to transfusion utilizing these same measurements. Previous reports of the coexistence of hemostatic defects with hereditary hemorrhagic telangiectasia are reviewed. The importance of complete hemostatic evaluation of patients with mucocutaneous bleeding is stressed in light or current knowledge of the diagnostic specificity of available laboratory tests.

Blood Coagulation Tests↗
PubMed1977

Tissue factor generation by human mononuclear cells: effects of endotoxin and dissociation of tissue factor generation from mitogenic response.

The effects of the presence of endotoxin in a mononuclear cell culture system have been assessed. Endotoxin was shown to be mitogenic for human peripheral blood lymphocytes and capable of stimulating the generation of tissue factor. Concentrations of endotoxin, found to contaminate many commercial mitogens and antigens, activated mononuclear cells in a time-dependent manner. Generation of tissue factor was detected in cultures harvested from 2 to 72 hours following stimulation with endotoxin. Dose-response curves relating concentrations of endotoxin to mononuclear cell stimulation were determined; as little as 0.001 microng/ml. of E. coli endotoxin was capable of stimulating the generation of tissue factor in the cell cultures. The mitogenic effect of endotoxin was modest, however, and appeared to be unrelated to the ability of endotoxin to active tissue factor. Inhibition of DNA synthesis in the cell cultures by cytosine arabinoside or nonlethal irradiation failed to impair the generation of tissue factor. Endotoxin contamination of various reagents used in cell culture was evaluated with the Limulus assay, which detected as little as 1 X 10(-4) microng/ml. of endotoxin. Endotoxin was detected in preparations of phytohemagglutinin, purified protein derivative of the tubercle bacillus, mumps vaccine, tetanus toxoid, concanavalin A, and pokeweed mitogen. Because of the broad implications of contamination by endotoxin of various reagents, we assessed the specificity of the Limulus assay for the detection of endotoxin in the lectin, concanavalin A, and determined that the reaction was specific for endotoxin. Contamination by endotoxin of mononuclear cell culture systems should be considered as a possible factor in the production of various biological effects attributed to some commonly used mitogens and antigens.

Cytarabine↗