Energy Metabolism in the Erythrocytes of Premature Infants Compared to Full Term Newborn Infants and Adults

1. The following aspects of energy metabolism have been compared in theerythrocytes of premature infants, full term newborn infants, and adults:levels of activity of the enzymes involved in the generation and utilization ofATP, and measurements of the content of ATP and of ADP.

2. The levels of activity of hexokinase, phosphoglyceric acid kinase andpyruvate kinase are significantly increased in the erythrocytes of prematureand full term newborn infants compared to adults.

3. The level of activity of phosphofructokinase is significantly decreasedin the erythrocytes of premature and full term newborn infants compared toadults.

4. In the erythrocytes of premature infants the content of ATP is significantly increased compared to both full term newborns and adults. The content of ADP is not increased. The percentage content of ADP is significantlybelow the values found in full term newborn infants and adults.

5. In the erythrocytes of full term newborn infants the content of bothATP and ADP is significantly greater than in adults. The ratio of ADP tothe total amount of ATP plus ADP does not differ from the adult value.

Submitted on December 6, 1962 Accepted on February 1, 1963     

Inflammatory Response of Mouse Skin Exposed to the Very Potent Carcinogen Dibenzo[a,l]pyrene: A Model for Tumor Promotion

The potent carcinogenicity of dibenzo[a,l]pyrene in mouse skinis associated with an inflammation unique among polycyclic aromatichydrocarbons and expressed as erythema. The time course of erythemaand the associated histological events in the skin of femaleSENCAR mice were determined after a single application of 6.25–200nmol dibenzo[a,l]pyrene or selected metabolites. Dibenzo[a,l]pyreneand dibenzo[a,l]pyrene-11,12-dihydrodiol, precursor to the bay-regiondiol epoxide, induced an erythema first present 5–6 daysafter treatment Dibenzo[a,l]pyrene-8,9-dihy-drodiol and otherdibenzo[a,l]pyrene metabolites, however, did not induce erythema.These findings suggest a central role for the bay-region diolepoxide in the induction of the observed inflammation. The intensityand duration of erythema were dose-dependent, whereas the delayedappearance of erythema was constant and dose-independent. Theseresults suggest induction of an immune hypersensitivity by dibenzo[a,l]pyreneand its 11,12-dihydrodiol. Histological changes in the skinwere consistent with a contact hypersensitivity reaction andincluded, in association with erythema, epidermal hyperplasiaand the presence of mononuclear leukocytes in the dermis. Animalswere tested for dibenzo[a,l]-pyrene-induced contact hypersensitivity.Female SENCAR mice were treated with a single dermal applicationof dibenzo[a,l]pyrene or 7,12-dimethylbenz[a]anthracene. Fivedays later, the animals were challenged with a single applicationof dibenzo[a,l]pyrene or 7,12-dimethylbenz[a]anthracene to theear pinna. Ear swelling exhibited features of a contact hypersensitivityreaction, including (1) delayed appearance after challenge,(2) noninducibility in animals not previously exposed to chemicalsensitizer, and (3) chemical specificity. The results suggestthat dibenzo[a,l]pyrene induces, via its bay-region diol epoxide,a contact hypersensitivity reaction that may promote tumor developmentand thereby enhance carcinogenic potency.     

Characterization and Genetic Studies of Microcytic Anemia in House Mouse

Microcytic anemia, inherited as a unit autosomal recessive, is the first of thetwelve known single-gene induced hereditary anemias of the mouse whichresults entirely from alteration of individual erythrocytes rather than from reduction in number of red cells. At all ages where mk/mk individuals could berecognized, from the fifteenth day of gestation to adulthood, the erythrocytecount of mk/mk individuals was at least as high as that of normal counterparts.At all ages, the hemoglobin concentration in these small erythrocytes was alsoreduced, so that the total available hemoglobin was markedly reduced at allages. The higher than normal numbers of erythrocytes in adult microcyticmice demonstrate that the cell-producing mechanisms operate efficiently.Genetic tests have shown that the mk single-gene defect has no relation tostructure of either the -chain or the -chain of the hemoglobin molecule. Themk microcytosis and hypochromia must then result from a metabolic or structural defect independent both of the factors responsible for regulating red cellnumber and of those controlling hemoglobin structure.

This mk/mk microcytic anemia shows some similarities to human thalassemias: hypochromia, microcytosis and presence of target cells, combined withsplenomegaly, reticulocytosis, and higher than normal erythrocyte counts (likethalassemia minor). As in thalassemia, hemoglobin structure is normal, although the amount per cell is subnormal. Human hemolytic anemias also sharesome of these characteristics. The similarities of mk/mk microcytic anemia ofthe mouse to certain human anemias are sufficient to warrant its further investigation as an animal model for understanding of human hereditary disease.

Submitted on October 9, 1969 Accepted on January 15, 1970     

The Antigenicity of the Rho (Du) Blood Factor

The antigenicity of the Rh variant Rh_o(D^u) was investigated by the transfusion of 45 Rh negative (cde/cde) patients with 68 units of "low grade"Rh_o (D^u) blood of the phenotypes Rh_o(ccD^uee) or Rh₂(ccD^uE). The donorred cells had normal viability; none of the patients made antibodies to Rh_o(D)or Rh_o(D_u).

The results indicate that the inherited, "low grade" Rh_o(D^u) factor is farless antigenic than Rh_o(D). It was also less antigenic than Kell or rh' (E) inthis study. It remains possible that this variant will prove to be antigenic insome recipients, but the hazard from this is undoubtedly much less than hasbeen expected.

Submitted on January 17, 1962 Accepted on April 17, 1962     

Heterogeneity in the expression of surface-exposed epitopes among larvae of Ascaris lumbricoides

Quantitative immunofluorescence was used to examine differences in the binding of antibody to the surfaces of individual living infective stage larvae of Ascaris lumbricoides. Using rabbit antisera, it was first established that larvae cultured for 48 h after artificial hatching were relatively uniform in their levels of antibody binding and in minimal exposure of epitopes expressed by later larval stages. Aliquots from a pool of larvae were probed with serum from individual infected people living in an endemic area of Nigeria. The larvae used were derived from parasites collected in the same geographical area in which serum donors were living. Two principal points emerged. First, serum donors varied considerably in the degree to which their antibody bound to the larvae. Secondly, the binding of antibody from a given donor revealed remarkable heterogeneity in surface epitope expression. Such intra-specific variability in antigen expression has considerable implications for the development of immunity to parasitic nematodes.     

Oral features and dental health in Hurler Syndrome following hematopoietic stem cell transplantation

International Journal of Paediatric Dentistry 2010; 20: 322–329 Background. Hurler Syndrome is associated with a deficiency of a specific lysosomal enzyme involved in the degradation of glycosaminoglycans. Hematopoietic stem cell transplantation (HSCT) in early infancy is undertaken to help prevent the accumulation of glycosaminoglycans and improve organ function. Aim. To investigate the oral features and dental health of patients with Hurler Syndrome who have undergone successful HSCT. Materials and methods. Twenty‐five patients (median age 8.6 years) post‐HSCT (mean age 9.4 months) underwent oral assessment (mean of 7.5 years post‐HSCT). Results. Dental development was delayed. Numerous occlusal anomalies were noted including: open‐bite, class III skeletal base, dental spacing, primary molar infra‐occlusion and ectopic tooth eruption. Dental anomalies included hypodontia, microdontia, enamel defects, thin tapering canine crowns, pointed molar cusps, bulbous molar crowns and molar taurodontism. Tooth roots were usually short/blunted/spindle‐like in permanent molars. The prevalence of dental caries was low in the permanent dentition (mean DMFT 0.7) but high in the primary dentition (mean dmft 2.4). Oral hygiene instruction with plaque and or calculus removal was indicated in 71% of those that were dentate. Conclusion. Patients with Hurler Syndrome post‐HSCT are likely to have delayed dental development, a malocclusion, and dental anomalies, particularly hypodontia and microdontia.