Studies on the H-Y antigen in rats

The H-Y antigen has been studied under a variety of experimental conditions in BN and Lewis rats. The results indicate that 1. graft size is crucially important in determining the fate of male skin isografts on females; 2. H-Y incompatible ear skin grafts survive significantly better than those of trunk origin; 3. prior exposure of females to male lymphoid cells greatly increases their capacity to reject male skin isografts; 4. neonatal castration has no influence on the expression of H-Y; 5. multiparity can induce unresponsiveness to H-Y; and 6. although BN females respond better than do Lewis females to H-Y, the antigen is stronger in Lewis males. These findings are compared with the results of similar experiments conducted with mice.Submitted in memory of Dr. Joy Palm, member of the Wistar Institute, who pioneered the genetic analysis of histocompatibility in rats.     

The long-term fate of neurons in allografts of ganglia in AG-B-compatible normal and immunologically tolerant rats

Neurons in Ag-B-incompatible allografts of ganglia are acutely rejected while those in Ag-B-compatible grafts are able to survive the immune reaction directed against them. The present study was undertaken to determine the long-term fate of neurons in allografts of ganglia in Ag-B-compatible rats. Isogenic strains of Ag-B-compatible adult Lewis (LE) and Fischer (FR) rats were used. The sensory nodose ganglia were reciprocally exchanged between normal LE and FR and between LE and FR animals rendered immunologically tolerant of each other's histocompatibity antigens. The findings were similar in both rat strains and revealed that although neurons and glial cells (i.e., satellite and Schwann cells) could survive for prolonged periods they were nevertheless eventually rejected by normal (nonimmunosuppressed) recipients. On the other hand, neurons and glial cells survived indefinitely in allografts in tolerant rats. Moreover, these neurons were functional because they regenerated nerve fibers into cotransplanted isografts of tongue and exerted the neurotrophic influence of inducing taste bud regeneration. The results demonstrate that, unlike kidney and heart, neurons in ganglia allografts cannot survive indefinitely without immunosuppression in Ag-B-compatible animals. Nevertheless, the permanent survival and function of neurons in Ag-B-compatible grafts can be achieved, as it is in Ag-B-incompatible ganglia grafts, by rendering the recipient immunologically tolerant.     

Effect of neurotensin on pancreatic function in man

The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs.     

Skeletal muscle protein and amino acid metabolism in hereditary mouse muscular dystrophy. Accelerated protein turnover and increased alanine and glutamine formation and release

Interactins between skeletal muscle protein and amino acid metabolism were investigated using C57BL and 129ReJ mice with hereditary muscular dystrophy. On incubation, hind limb muscle preparations from dystrophic mice released large quantities of amino acids, particularly alanine and glutamine which were increased 70% and 40% compared to muscles from carrier or control mice. The increased alanine release did not result from altered alanine oxidation to CO2 or reincorporation into protein. Alanine and glutamine formation from added amino acids were equal with dystrophic and control muscles. Incorporation in vitro of leucine, alanine, and glutamate into proteins of dystrophic muscle was 3- to 7-fold greater than control muscle, and the incorporation in vivo of [3H]- or [14C]arginine into muscle proteins was greater in extent and earlier in time with dystrophic as compared to control muscle. Proteins were also labeled in vivo using [guanido-14C]arginine. On incubation of these muscles in vitro, a 100% greater loss of label from protein was observed with dystrophic as compared to control preparations, and the appearance of label in the media was correspondingly increased. Sodium dodecyl sulfate-gel electrophoresis of dystrophic skeletal muscle showed numerous protein bands to be reduced in density, but autoradiographic studies demonstrated that these same bands were more highly labeled in vitro by [35S]methionine in dystrophic than in control muscle. Although insulin stimulation of glucose uptake was markedly blunted in dystrophic muscle, insulin inhibited alanine and glutamine release equally from both control and dystrophic muscle. These data indicate that alanine and glutamine formation and release are increased in hereditary mouse muscular dystrophy. An accelerated degradation and an increased resynthesis of many muscle proteins were also observed in dystrophic compared to control animals. This increased proteolysis may account for the increased alanine and glutamine formation in dystrophic muscle.     

Capacity of adult steel (SI/SId) and dominant spotting (W/Wv) mouse skin to support melanogenesis.

Utilizing skin grafting techniques, melanocytes were incorporated into adult steel ($\text{Sl}\text{Sl}{}^{\mathrm{d}}$) and dominant spotting ($\text{W}\text{W}{}^{\mathrm{v}}$) hair follicles, where they survived and pigmented a number of hair generations. Previous investigations have indicated that the steel alleles act on the embryonic skin to prevent the survival of melanocytes. The present study suggests that this gene action mechanism may be temporary and does not continue into adult life. In addition, the study demonstrates that some hair bulb melanocytes can pigment more than one hair generation.     

Characterization and the broad cross‐species applicability of 20 anonymous nuclear loci isolated from the Taiwan Hwamei (Garrulax taewanus)

We isolated 20 anonymous nuclear loci (8556 bp in total) from the Taiwan Hwamei (Garrulax taewanus), an endemic songbird of Taiwan. A panel of nine to 15 individuals with unknown relationship was used to characterize polymorphism of these loci. We identified 46 single nucleotide polymorphic sites (SNPs) in 15 polymorphic loci. Frequency of SNPs was one per every 186 bp in average. Nucleotide diversity, θ, ranged from 0.00054 to 0.00371 per locus. We also tested cross‐species applicability of these loci on 17 species from eight different passerine families. All 20 loci could be successfully amplified (ranged from one to 16 species, mean = 7.9 species).     

Varicella-zoster virus proteins in skin lesions: implications for a novel role of ORF29p in chickenpox

Skin biopsy samples from varicella-zoster virus (VZV)-infected patients examined by immunohistochemistry demonstrated VZV replication in nonepithelial cell types. ORF29p, a nonstructural nuclear protein, was found in nerves of two of six patients with chickenpox. In tissue culture, ORF29p was secreted by VZV-infected fibroblasts. Extracellular ORF29p can be taken up through endocytosis by human neurons, implying a novel role for this protein in pathogenesis.     

The Use of Multiple Outcomes Analysis in Neurotoxicity: An Example from the New Zealand Study of Offspring of Mothers Exposed to Methyl Mercury

Neurotoxicity has become an important area in the study of the risk to children of noncarcinogens. Many of the tests used to evaluate neurotoxic effects in neurotoxic studies are psychometric tests to assess cognitive, motor, and perceptual performance in individuals in order to determine the presence of psychological problems, impaired educational achievement, or neurological abnormalities. The underlying assumption of these procedures are that a test performance deficit is indicative of a neurological disability, and that such disability derives from the prenatal exposure to an offending substance. The usual analytic paradigm for discerning environmental impacts is to analyze the scores of a particular subtest in a battery taken separately as the dependent variable with regression analysis, which adjusts for cultural background, educational level, and socioeconomic status. The impact of this analysis is to determine the correlation of each of the psychometric test results to exposure. We show a statistical method to simultaneously analyze the multiple outcomes of many tests using General Estimating Equations (GEE) to determine if a correlation exists between the global measure of all these tests and exposure adjusted for covariates of interest and the correlation among the dependent psychometric variables. We show the application of this method to the results of children whose mothers were exposed to mercury during pregnancy.