IMMUNOLOGIC STUDIES OF AUTOIMMUNE DISEASE IN NZB/NZW F1 MICE : I. BINDING OF FLUORESCEIN-LABELED ANTINUCLEOSIDE ANTIBODIES IN LESIONS OF LUPUS-LIKE NEPHRITIS

For the past 3 years NZB and NZW mice have been maintained by sister-brother matings from English breeder stock. NZB/NZW F1 hybrids developed lupus-like nephritis during the 6th to 7th month and few survived beyond the 8th month. Renal tissues of these animals were examined with fluorescein-labeled antinucleoside sera, specific for thymine and cytosine, for the presence of denatured DNA in GCW, and with labeled antibody to mouse IgG for the presence of excess host globulin in the same areas. The following results have been obtained: (a) All 51 hybrids, over 5 months of age, had an excess of mouse globulin in GCW. 40 animals between the ages of 5 and 12 months showed, in the same areas, antigens which bound one or both of the antinucleoside antibodies. (b) Renal tissues of 19 NZB mice, 5–19 months old, and 27 NZW mice, 2–18 months old, were examined. Excess host globulin was seen in GCW of 13 NZB and 20 NZW animals. The tissues of only two old NZB mice, 14 months of age, bound antinucleoside antibody but none of the other animals did. The association of rapidly fatal lupus-like nephritis in NZB/NZW F1 mice with denatured DNA and mouse globulin in GCW supports the hypothesis involving this antigen-antibody complex in the pathogenesis of the disease

IMMUNOPATHOLOGICAL STUDIES OF ORTHOTOPIC HUMAN LIVER ALLOGRAFTS

Twenty-six specimens obtained from twenty human orthotopic liver allografts 10-968 days after transplantation were studied by light microscopy, electron microscopy, and immunofluorescence. The main lesions consisted of mononuclear-cell infiltration around the portal tracts, centrilobular cholestasis, liver-cell atrophy and reticulin collapse, obliterative intimal thickening of hepatic arteries, and fibrosis. Moderate amounts of IgG and/or IgM and complement (β1C/β1A globulin or C'lq) were observed in four of the liver samples and smaller deposits were present in another five. A further three specimens contained IgG without complement. IgA was detected in only one of the samples. The immunoglobulins were found in the walls of the portal and central veins and of the sinusoids in all thirteen positive liver samples, in the walls of branches of the hepatic artery in three, and in the cytoplasm of some of the mononuclear cells infiltrating the portal tracts in nine of the specimens. Fibrinogen was seen in eight of the samples, usually in the spaces of Disse. Accumulations of immunoglobulins and complement were less frequent in liver than in kidney and heart allografts. These findings suggest that in the failure of human liver allografts cell-mediated immunity and non-immunological factors may be more important than humoral antibody. © 1972

Homocysteine levels in preterm infants: is there an association with intraventricular hemorrhage? A prospective cohort study.

BACKGROUND: The purpose of this study was to characterize total homocysteine (tHcy) levels at birth in preterm and term infants and identify associations with intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and thrombocytopenia. METHODS: 123 infants \u3c 32 weeks gestation admitted to our Level III nursery were enrolled. A group of 25 term infants were enrolled for comparison. Two blood spots collected on filter paper with admission blood drawing were analyzed by a high performance liquid chromatography (HPLC) method. Statistical analysis included ANOVA, Spearman\u27s Rank Order Correlation and Mann-Whitney U test. RESULTS: The median tHcy was 2.75 micromol/L with an interquartile range of 1.34 - 4.96 micromol/L. There was no difference between preterm and term tHcy (median 2.76, IQR 1.25 - 4.8 micromol/L vs median 2.54, IQR 1.55 - 7.85 micromol/L, p = 0.07). There was no statistically significant difference in tHcy in 31 preterm infants with IVH compared to infants without IVH (median 1.96, IQR 1.09 - 4.35 micromol/L vs median 2.96, IQR 1.51 - 4.84 micromol/L, p = 0.43). There was also no statistically significant difference in tHcy in 7 infants with periventricular leukomalacia (PVL) compared to infants without PVL (median 1.55, IQR 0.25 - 3.45 micromol/L vs median 2.85, IQR 1.34 - 4.82 micromol/L, p = 0.07). Male infants had lower tHcy compared to female; prenatal steroids were associated with a higher tHcy. CONCLUSION: In our population of preterm infants, there is no association between IVH and tHcy. Male gender, prenatal steroids and preeclampsia were associated with differences in tHcy levels

Degenerative vascular disease and myocardial infarction in mice with lupus-like syndrome.

The pathogenesis of the degenerative vascular disease and myocardial infarction that develop in mice with lupus-like disease was studied by immunofluorescence, light microscopy, and electron microscopy. Medium and small coronary arteries and arterioles of both infarcted and noninfarcted hearts had focal degenerative lesions consisting of deposits of periodic-acid--Schiff (PAS)-positive or eosinophilic material in the intima and to a lesser extent in the media, degenerative changes in the media without accompanying cellular inflammation, and occasional proliferation or swelling of intimal cells. These lesions often narrowed and, together with platelet aggregation, occasionally occluded the vascular lumens. Granular deposits of mouse immunoglobulin, C3, and occasionally gp70 were present in the walls of medium and small arteries, arterioles, and venules of both infarcted and noninfarcted myocardium. Dense deposits of foreign material were found by electron microscopy in areas corresponding to the immune deposits. These findings are consistent with the interpretation that these noninflammatory vascular lesions are caused by local deposition of antigen--antibody complexes. The immune-complex--mediated injury appears to lead to thrombotic and/or obliterative vascular changes that contribute to decrease of the coronary blood flow and to the development of myocardial infarction