Hereditary Hemolytic Anemia Associated With Abnormal Membrane Lipids: Mechanism of Accumulation of Phosphatidyl Choline

In order to study the mechanism of theaccumulation of phosphatidyl choline(PC) in erythrocytes with abnormal erythrocyte phospholipids from patientswith a hereditary hemolytic anemia, thephospholipids of the erythrocytes werelabeled radioactively. Labeling of phosphatides was achieved by both passiveequilibration with preformed phosphatides, and active "acylase"-mediated incorporation of fatty acid (FA) in thepresence of glucose, ATP and coenzymeA. The labeled cells were then reincubated in fresh compatible sera and thecatabolism of the labeled erythrocytephospholipids was followed. In addition,total acylase capacity of erythrocytestroma was determined under optimalconditions in a system with excesslysophosphatide, FA, ATP, CoA, andMg⁺⁺. No differences in passive uptakeor release of phosphatides were found between the patients’ erythrocytes andcomparable reticulocyte-rich controls. Onthe other hand, overall active incorporation of FA into PC was abnormally increased in the patients’ erythrocytes,whereas incorporation of FA intophosphatidyl-ethanolamine (PE) was decreased. However, acylase capacity forboth lysophosphatidylcholine (LPC) andlysophosphatidylethanolamine (LPE) wasnormal in the patients’ cells. This apparent paradox could be explained by thesubsequent turnover of actively incorporated PC-FA which was found to bereduced. A brief labeling experiment designed to approximate pulse-chase conditions and to label primarily PC showed aconsiderable inhibition of the subsequenttransfer of PC-FA to PE upon reincubation in fresh serum. This transfer haspreviously been shown to be responsiblefor a significant portion of PC-FA catabolism. Reincubation in hyperlipemicsera obtained from patients with liverdisease or artificially enriched with PCdid not influence the abnormal outflow ofphosphatide-FA in actively labeled cells.The findings were consistent with theconcept that PC accumulated in thesecells because of a defect in the catabolismof actively incorporated PC-FA. This defect appeared to be in the transfer ofPC-FA to PE prior to final release fromthe cell. Passive exchange pathways andthe active anabolic acylase pathway werenot abnormal in these patients’ erythrocytes.

Submitted on March 4, 1971 Revised on May 4, 1971 Accepted on May 10, 1971     

EFFECT OF PROLONGED ADMINISTRATION OF RANITIDINE ON PITUITARY AND THYROID HORMONES, AND THEIR RESPONSE TO SPECIFIC HYPOTHALAMIC-RELEASING FACTORS

We have studied, in a double blind controlled trial, 30 male patients with duodenal ulcer to evaluate the effect of prolonged oral administration of ranitidine (150 mg bd for 4 weeks), a new H2-receptor antagonist, on basal PRL, LH, FSH and TSH concentrations, on their response to specific releasing hormones, and on basal and TRH-stimulated levels of thyroid hormones. Neither the basal levels of PRL, FSH, LH and TSH, nor their response to stimulation with appropriate releasing hormone were affected by ranitidine. Basal concentrations of T4 and its levels after TRH stimulation at 40 min (but not at 20, 60 and 120 min) were lower after ranitidine treatment (P < 0·05); basal and stimulated T3 and rT3 were unaffected. These results could suggest a possible role of histamine in thyroxine regulation but further studies are required.     

The value of bacteriology and serology in the diagnosis of cellulitis and erysipelas

Patients diagnosed as suffering from erysipelas or cellulitis were subjected to bacteriological and serological investigations. The serological tests used included the anti-streptolysin O reaction (ASO), the anti-deoxyribonuclease B test (ADB) and the anti-hyaluronidase tests (AHT) that are specific both for the group A streptococcus (Streptococcus pyogenes) and for the human pyogenic streptococci of group C or group G. Antibody tests to the alpha-lysin and the nuclease of Staphylococcus aureus were also employed. Conventional bacteriological culture methods were used plus needle aspiration of injected saline in most patients with erysipelas, but recognized pathogens were isolated in only 42% of cases. Our results indicate the limitations of these tests for making initial diagnoses and deciding treatment. Serial serological testing was very successful in differentiating cellulitis due to group A, C or G haemolytic streptococci, or occasionally Staphylococcus aureus, but was positive in only 40% of cases of erysipelas.     

Increased Activity of Some Folic Acid Enzyme Systems in Infectious Mononucleosis

Increased levels of activity for the formate activating enzyme and N⁵,N¹⁰-methylene FH₄ dehydrogenase have been found in the leukocytes from patients with infectious mononucleosis; in addition dihydrofolic reductase, anenzyme not found in mature circulating leukocytes, has been detected in infectious mononucleosis cells. Glucose-6-phosphate dehydrogenase activity isless in infectious mononucleosis leukocytes than in normal leukocytes.

These findings are similar to the results obtained in acute and chronic myelogenous leukemia and indicate that the leukocytes seen in infectious mononucleosis have the enzymatic apparatus associated with synthesis of DNA.

Submitted on November 6, 1961 Accepted on January 12, 1962     

Fish and Amphibian Embryos -- A Model System for Evaluating Teratogenicity

Fish and Amphibian Embryos—A Model System for EvaluatingTeratogenicity. Birge, W.J., Black, J.A., Westerman, A.G. andRamey, B.A. (1983). Fundam. Appl. Toxicol. 3: 237–242.Developmental stages of fish and amphibians were used to evaluatereproductive impairments produced by environmental contaminants.Using static-renewal and flow-through procedures, exposure wasinitiated at, or soon after, fertilization and maintained through4 days posthatching. Trace concentrations of many environmentaltoxicants produced high frequencies of mortality and teratogenesis.When developmental stages of the trout were exposed to inorganicmercury, 10% control-adjusted mortality was observed at 1 µg/Land frequencies of terata in hatched populations ranged from8% to 43% for exposure concentrations of 2 to 25 µg/L-In similar tests with the narrow-mouthed toad, 45% mortalityoccurred when mercury was administered at 1 µg/L; frequenciesof teratogenesis ranged from 8% to 17% at exposure concentrationsof 1 to 5 µg/L; and complete mortality occurred at 7 µg/L.Boron-induced teratogenesis in trout ranged from 5% at 1 µg/Lto 51% at higher exposure levels. When catfish embryos wereexposed to atrazine at 0.06, 4.8, and 46.7 mg/L, terata appearedin surviving populations at frequencies of 4%, 69%, and 100%,respectively. Fish and amphibian developmental stages constitutesimple and effective models for 1) investigating mechanismsof teratogenesis, 2) evaluating the impact of environmentaltoxicants on aquatic biota, and 3) identifying environmentalteratogens which may be of concern to human health.     

Erythropoietin in Children I. Findings in Various Types of Anemia

Erythropoietin assays were carried out on the plasma of 39 children with various blood dyscrasias. Increased erythropoietin activity was found primarily in those patients with depressed bone marrow function and severe anemia. No direct relationship could be found between the severity of the anemia and the erythropoietin level. No erythropoietin was found in the plasma of patients with hemolytic anemia or renal disease with the exception of one patient with bilateral Wilm's tumor.     

Change in Nutrient Intakes, Number of Servings, and Contributions of Total Fat from Food Groups in 4- to 10-Year-Old Children Enrolled in a Nutrition Education Study

Objective To determine change in nutrient intakes, number of servings, and contributions of total fat from food groups in children who lowered their dietary fat intake.Design A research and demonstration study designed to lower plasma low-density lipoprotein cholesterol level. There were four study groups: two intervention and two control groups. All children had hypercholesterolemia except for those in one control group. Three 24-hour dietary recalls were collected on randomly assigned days over a 2-week period at baseline and 3 months after the intervention.Subjects Three hundred three 4- to 10-year old children from suburbs north of Philadelphia, Pa.Interventions One intervention involved a home-based, parent-child autotutorial program (PCAT group) with audiotaped stories and print materials for the children and their families; the other intervention involved one face-to-face counseling session with a registered dietitian (counseling group).Outcome measures Change in mean nutrient intakes compared with the Recommended Dietary Allowance (RDA); change in number of servings and mean grams of total fat contributed from 10 different food groups.Statistical analyses performed Analyses of variance and χ² analyses.Results Children in every study group had mean intakes of all nutrients (except vitamin D) greater than 67% of the RDA 3 months after the baseline measurement. Several food groups (ie, meats, dairy products, fats/oils, and desserts) provided less total fat to the diets of children who reduced their dietary lipid intake after 3 months (ie, PCAT and counseling groups). These children also reduced the mean number of servings selected from these food groups. Within these same food groups, some children consumed fewer servings of higher fat foods and more servings of lower fat foods.Applications/conclusions Children who lowered their dietary fat intake after intervention reported both quantitative and qualitative changes in food choices from several food groups. These choices did not significantly reduce their nutrient intakes. J Am Diet Assoc. 1996; 96:865-873.