Verle E. Headings

FAMILIAL SARCOIDOSIS WITH MULTIPLE OCCURRENCES IN ELEVEN FAMILIES: A POSSIBLE MECHANISM OF INHERITANCE

Among 80 Black patients with sarcoidosis, 11 families were identified as containing multiple cases. Monogenic modes of inheritance were reasonably excluded by informal inspection of pedigree patterns and by poor fit of corrected ratios within sibships to the expected ratio for all sibships at risk. The observed familial distribution conforms in several respects to properties that are descriptive of multigenic traits. Additionally, heritability based only on female probands was estimated to be between 60% and 70%. A larger sample size should permit analysis of additional multigenic properties.

Decreased total carbonic anhydrase esterase activity and decreased levels of carbonic anhydrase 1 isozyme in erythrocytes of type II diabetic patients

In this exploratory study, we investigated total erythrocyte carbonic anhydrase (CA) estrase activity as well as CA I isozyme concentration in patients with diabetes mellitus type II (DM) and healthy individuals of Howard University Hospital community. Total estrase activity of CA was measured spectrophotometrically using p-nitrophenol acetate before and after inhibition with acetazolamide. CA I isozyme was measured by radial immunodiffusion using monoclonal antibody (CA I) in agarose plates. The study involved 20 consented participants; 10 normal (N) and 10 (DM), 21 to 84 years of age. The study was approved by the Howard University Institution Review Board. The CA activity was measured following lysis of cells as U/min/mL and CA I concentration as mg/l. We observed CA activity as 46.3±4(N) and 25±2.1 (DM) whereas CA I concentration as 1896±125 (N) and 1104 ±63 (DM). We speculate that the change in the CA activity may of fundamental importance in the regulation of intracellular; pHi for the basic control of metabolism in diabetes mellitus. Further, we propose that CA activity is a good candidate for a biomarker of diabetes mellitus for the early detection of insulin resistance because the CA activity variation was proportional to the severity of the diabetes.

Multiple molecular forms of serum ?1-antitrypsin

The pattern of multiple electrophoretic types associated with the M genetic variant of α1-antitrypsin (α1-AT) was examined for changes associated with development and pregnancy. Serum specimens from nonpregnant and pregnant adults and newborn infants, amniotic fluid, and serum treated with neuraminidase were subjected to electrophoresis in acid starch gel and antigen-antibody crossed electrophoresis. Quantitative measurements on each of six electrophoretic forms of this variant show that in serum from infants and in serum treated with neuraminidase a greater proportion of the total α1-AT antigen is found in the more cathodally migrating forms. This supports the hypothesis that the phenomenon of multiple molecular forms of this protein is associated in some manner with the degree of complexing with sialic acid. It also suggests that the enzyme systems concerned with constructing this glycoprotein complex are relatively immature in the liver of the infant. These observations potentially provide a basis for differentiating between some of the genetic variants of α1-AT.

Biological Variation in the Heterogeneous Distribution of Haemoglobin F among Erythrocytes

Summary. The development of highly specific fluorescent labelled antibodies against haemoglobin F presented an opportunity to investigate variables which might influence distribution of this haemoglobin among individual erythrocytes. Earlier investigations revealed heterogeneous distribution within healthy individuals and in individuals with sickle cell disease and other haemoglobinopathies. The current study demonstrates quantitatively that there are normal biological determinants of variability in the frequency of F‐containing erythrocytes in individuals who have a haemoglobin A electrophoretic phenotype. It also is shown that the frequency of F‐containing erythrocytes during the early recovery phase of sickle cell crisis is significantly higher than when there is no recent history of crisis. The mean quantity of haemoglobin F per F‐containing erythrocyte appears to be lower after a crisis than in individuals without recent history of crisis. This suggests that following a crisis there may either be biochemical constraints on haemoglobin F synthesis per erythrocyte precursor cell or else there is limited opportunity for selective removal of low F‐containing erythrocytes from the circulation.

Quantitation of hemoglobins by immunodiffusion: Specific antibodies to hemoglobins A1, S and F

Abstract A simple and sensitive immunochemical method for quantifying hemoglobins A1, S and F is described. Antibodies to human hemoglobins A1, S and F were obtained in goats and after cross absorption were shown to be specific for thei corresponding hemoglobins. These specific antisera were employed in a radial immunodiffusion method to quantify hemoglobins A1, S and F in hemoglobin specimens of known phenotype as ascertained by electrophoresis on cellulose acetate. The method accurately quantifies hemoglobins in purified hemoglobin mixtures designed to simulate expected proportions in newborn infants who have sickle cell trait or sickle cell anemia. Principal application of this methodology currently under consideration are in diagnosis of hemoglobin SS in the infanct and studies on rates of development change in hemoglobins A1, S and F.

Identification of inherited protein variants in individual erythrocytes

Inherited electrophoretic variants of hemoglobin, carbonic anhydrase, and glucose-6-phosphate dehydrogenase in individual erythrocytes were separated by electrophoresis in ultrathin agar gels. By staining the electropherograms with specific fluorescein-conjugated antibodies against hemoglobins, relative proportions of two hemoglobins within individual erythrocytes can be estimated. The findings suggested that the intracellular proportions of HbA and HbS in heterozygotes are heterogeneous within a given population of cells. By this method cells containing hemoglobin F (F cells) as well as a minor variant of hemoglobin F were identified. This tool potentially offers an approach to monitoring distribution of inherited variants in individual erythrocytes for a large number of proteins.

Toxoplasma gondii: survival time and variability in mouse host strains.

Abstract The survival time of four strains of mice, namely Turk, Glaxo, Balb-C, and C 57 Black, inoculated with the RH strain of Toxoplasma gondii, was determined. Results obtained were analyzed to show how the “number of Toxoplasma” is related to the strain of mice and its survival time. All three effects and the interaction term were significant at level p = 0.05. The regression of the number of Toxoplasma per inoculum on log of host survival time differed significantly between Turk-Glaxo strains, and both Balb-C and C 57 Black strains. At a dose of 10,000 Toxoplasma/mm3 no difference in host strain susceptibility was apparent. The relatively superior survival time of Glaxo and Turk at increasing doses is interpreted as reflecting genetic resistance to the lethal effect of Toxoplasma. Specific evidence on this point, as well as the magnitude of the genetic effect, must await further examination.

Genetic aspects of quantitative variation in the carbonic anhydrases of the pig-tailed macaque, Macaca nemestrina. I. Response to thyroxine

Effects of thyroxine on incorporation of l-serine-C14 into four carbonic anhydrase isozymes (CA II, CA Ia, CA Ib, CA Ic) and hemoglobin were quantified in reticulocytes of Macaca nemestrina in vitro. Response to thyroxine differed significantly between CA Ia and two allelic variants (CA Ib and CA Ic) and the nonallelic isozyme (CA II). The effects of thyroxine on serine incorporation into hemoglobin and three of the carbonic anhydrase isozymes were shown to be nonlinear with thyroxine concentration.

Erythrocyte total carbonic anhydrase esterase activity in african american obese children: reduction starts at a young age.

A previous study from this laboratory showed that patients with diabetes mellitus type 2 (type 2 diabetes) have significantly lower values (P \ 0.05) of carbonic anhydrase (CA) activity and its isozyme (CAI) concentration compared with their healthy counterparts. Furthermore, the values varied with the severity of the diabetes or insulin resistance (Gambhir et al. 2007). Kondo et al. (1975) reported contradictory results, however, as they found increased levels of both CAI and CAII in patients with diabetes. A study involving hypertensive human subjects reported 63% of hypertensive patients with decreased CA activity compared with the normotensive population, and 37% showed CA activity significantly higher than that of normotensives. Glucose intolerance, insulin resistance, and hyperinsulinemia

Models of the relationship between genetic counselor and client

Three alternative models of the relationship between genetic counselors and clients are typified by the paternalistic professional, the expert consultant, and the autonomous client. Kants principle of autonomy stipulates that the agent with rational will is to be treated as an end in itself rather than merely as a means to an end. Mutual respect between two such autonomous agents, in our case a genetic counselor and a client, will dictate elements of the clinical encounter.