Cardiovascular magnetic resonance evaluation of paediatric patients with systemic lupus erythematosus and cardiac symptoms.

OBJECTIVES: To evaluate the cardiovascular magnetic resonance (CMR) findings in a paediatric population with systemic lupus erythematosus (SLE) and cardiac symptoms. METHODS: Twenty-five SLE children, aged 10.2 ± 2.6 years, with cardiac symptoms and normal routine non-invasive evaluation were examined by CMR, using a 1.5 T system and compared with sex-matched SLE adults. Left ventricular (LV) volumes, ejection fraction, T2 ratio, early (EGE) and late (LGE) gadolinium enhancement were assessed. Acute and chronic lesions were characterised as LGE-positive plus T2 > 2, EGE > 4 or T2 < 2, EGE < 4, respectively. According to LGE, lesions were characterized as: (a) diffuse subendocardial, (b) subepicardial and (c) subendocardial/transmural, due to vasculitis, myocarditis and myocardial infarction, respectively. RESULTS: LV ejection fraction (LVEF) was normal in all SLEs. T2 > 2, EGE > 4 and positive epicardial LGE wall was identified in 5/25 children. Diffuse subendocardial fibrosis was documented in 1/25. No evidence of myocardial infarction was identified in any children. In contrast, in SLE adults, LGE indicative of myocardial infarction was identified in 6/25, myocarditis in 3/25, Libman-Sacks endocarditis in 1/25 and diffuse subendocardial fibrosis in 2/25. The incidence of heart disease in SLE children was lower compared to SLE adults (p < 0.05), with a predominance of myocarditis in children and myocardial infarction in adults. A significant correlation was documented between disease duration and CMR lesions (p < 0.05). CONCLUSION: CMR identifies a predominance of myocarditis in paediatric SLE with cardiac symptoms and normal routine non-invasive evaluation. However, the incidence of cardiac lesions is lower compared to SLE adults, probably due to shorter disease duration. SIGNIFICANCE AND INNOVATION: CMR identifies heart involvement in a significant percentage of SLE children with cardiac symptoms and normal routine noninvasive evaluation.The incidence of heart disease is lower in SLE children compared with SLE adults.Predominance of myocarditis and myocardial infarction is observed in SLE children and SLE adults, respectively.

Light deprivation slows but does not prevent the loss of photoreceptors in taurine transporter knockout mice.

UNLABELLED: Taurine transporter knockout mice show severe retinal degeneration at an early age. The study was designed to determine whether degeneration also takes place in the absence of light. Mice were maintained up to 6 weeks of age in cyclic lighting or in total darkness. Degeneration took place in both groups, but was more rapid in animals exposed to standard cyclic illumination. At the ultrastructural level the retinas showed features characteristic of apoptosis but not of necrosis. CONCLUSIONS: Cell differentiation is not seriously affected by the lack of a functional taurine transporter but mature photoreceptor cells do not survive without an intact transporter, even in the dark.

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-A(g7) mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes.

AIMS/HYPOTHESIS: In the NOD mouse model, attempts to show MHC class II expression by pancreatic beta cells were unsuccessful so far. We readdressed this question by analysing I-A(g7) expression in single pancreatic beta cells. METHODS: Single-cell multiplex RT PCR and single-cell immunofluorescence were used to study MHC class II expression in NOD and NOD/SCID beta cells. RESULTS: Pancreatic beta cells from NOD mice express the I-A(g7) protein as well as the corresponding mRNA. The frequency of MHC class II mRNA-expressing beta cells is drastically increased during the progression to overt diabetes. MHC class II protein is accumulated intracellularly, and invariant chain is co-expressed. Beta cells from 9- to 10-week-old NOD/SCID mice express MHC class II at the same low frequency as beta cells from 3-week-old NOD mice. CONCLUSION/INTERPRETATION: NOD beta cells express I-A(g7) and could be a direct target of autoreactive CD4+ T cells. This MHC class II expression is triggered by infiltrating lymphocytes.

Ultrastructure of peritubular tissue in association with tubular hyalinization in human testis.

Testicular peritubular tissue, also known as the tunica propria, surrounds the seminiferous tubules and is responsible for contractile, paracrine and transport functions. The aim of the present report is to describe the pathomorphology of peritubular tissue in association with tubular hyalinization in human testis. Twenty-seven testicular biopsies from 21 subfertile and infertile men were studied with the electron microscope. Biopsies from five patients showed complete or nearly complete tubular hyalinization. In addition to changes described earlier, the following new ultrastructural features were observed: 1. loss of polarity and configuration of myoid cells; 2. protrusion of myoid cells towards the tubule and evagination of basal lamina surrounding the tubule towards the interstitial direction leading to 'bridge' formation. These 'bridges' of myoid cells often created completely separated small compartments within the tunica propria; 3. vacuolization and fragmentation of myoid cell nuclei; 4. a balloon-like swelling of myoid cell containing phagolysosomes and lipid droplets. We conclude that disorganization and loss of vital functions of the extracellular matrix and myoid cells contribute to the pathogenesis of tubular hyalinization.

Inhibition of collagen IV deposition promotes regeneration of injured CNS axons.

Scarring impedes axon regrowth across the lesion site and is one major extrinsic constraint to effective regeneration in the adult mammalian central nervous system. In the present study we determined whether specific biochemical or immunochemical modulation of one major component of the scar, the basal membrane (BM), would provide a means to stimulate axon regeneration in the mechanically transected postcommissural fornix of the adult rat. Basal membrane developed within the first 2 weeks after transection in spatiotemporal coincidence with the abrupt growth arrest of spontaneously regrowing axons. Local injection of anticollagen IV antibodies or alpha, alpha'-dipyridyl, an inhibitor of collagen triple helix formation and synthesis, significantly reduced lesion-induced BM deposition. This treatment allowed massive axon elongation across the lesion site. Anterograde tracing provided unequivocal evidence that regenerating axons follow their original pathway, reinnervate the appropriate target, the mammillary body, and become remyelinated with compact myelin. Presynaptic electrophysiological recordings of regenerated fibre tracts showed recovery to nearly normal conduction properties. Our results indicate that lesion-induced BM is an impediment for successful axonal regeneration and its reduction is a prerequisite and sufficient condition for regrowing axons to cross the lesion site.

Ultracytochemistry of 3beta-hydroxysteroid dehydrogenase in Leydig cell precursors and vascular endothelial cells of the postnatal rat testis.

In the biosynthesis of steroid hormones 3beta-hydroxysteroid dehydrogenase (3beta-HSD) is a key enzyme. The present report describes the subcellular localization of the enzyme in the fetal-type Leydig cells, the fibroblast-like precursors of adult-type Leydig cells and in endothelial cells of interstitial capillaries. Histochemical methods for light microscopy and ultracytochemical methods for electron microscopy were used on rat testes of postnatal day 15. 3beta-HSD reactivity was located at subcellular levels by means of the ferricyanide method. A specific, distinct localization of reaction product in the form of copper ferrocyanide precipitates was observed on the membranes of the smooth endoplasmic reticulum not only in the fetal-type Leydig cells and the fibroblast-like precursors of adult-type Leydig cells, but also focally in the endothelial cells of interstitial blood capillaries. Topographically, the 3beta-HSD-positive precursors were most often found in the outer layer of the boundary tissue and surrounding interstitial blood vessels. The capillaries with 3beta-HSD-positive endothelial cells were usually located in the vicinity of 3beta-HSD-positive Leydig cells. For the first time, 3beta-HSD has been located at the subcellular level in precursors of adult-type Leydig cells and focally in capillary endothelial cells associated with them. Due to the close association between 3beta-HSD-positive vascular endothelial cells and Leydig cells a paracrine relationship between the two cell types may be involved in the acute regulation of steroidogenesis by blood-borne luteinizing hormone.

Electron microscopic evidence for deep invaginations of the lamina propria towards the seminiferous tubule lumen in a patient with varicocele.

Ultrastructural studies on biopsy tissue from the right testis of a 39-year old patient with varicocele revealed 2.5-5 microns thick invaginations of the lamina propria towards the lumen of the seminiferous tubules. These invaginations were of various lengths. The presence of invaginations was confirmed through examination of serial semi-thin sections. In some seminiferous tubules two neighbouring deep invaginations were joined together thus completely encircling and thereby separating the basal compartment, and in some cases even the adluminal compartment, of the seminiferous tubule. The invaginations were surrounded continuously by the basement membrane and contained collagen fibres, cell processes of myoid cells and in some cases also their nuclei.

The embryotoxicity of cyclophosphamide in rabbits during the histiotrophic phase of nutrition.

After iv injection of cyclophosphamide (CP; 80 mg/kg) and dechlor-CP (60 mg/kg) on the 9th day of gestation (histiotrophic phase of nutrition) in rabbits, the concentrations of activated CP and activated dechlor-CP were determined fluorometrically in the maternal blood and in the yolk sac fluid. Activated CP and dechlor-CP could be measured in the maternal blood but not in the yolk sac fluid. This holds true for both the free as well as the protein bound form. During the histiotrophic phase of nutrition on the 9th day of gestation, the yolk sac wall seems to be a barrier for activated CP and dechlor-CP. This phenomenon has to be traced back on the oxazaphosphorinring activated in position C4 and not on the alkylating activity. Therefore, a direct effect of activated CP can be excluded as the main reason for the embryotoxicity of CP. Consequently, the effects of iv-injected CP on the entoderm of the visceral layer of the yolk sac placenta were investigated. Three, 6, 12, and 24 hours after CP injection, the maternal animals were laparotomized and the entoderm of the visceral layer of the yolk sac placenta in the mesometral parts of the blastoderms were prepared for electron microscopy. Like in the control group, 3 hours after CP injection no differences are found. Six hours after CP injection, a relatively flat cell-type can be observed, which is probably based on the reduced absorptive capability of the entoderm. Twelve hours after CP injection the entoderm cells are nearly uniformly of the columnar type; this is interpreted as a restored absorptive activity. Twenty-four hours after CP injection the columnar form of the entoderm cells and the reduced pinocytotic activity are interpreted as a state of secretion. During the histiotrophic phase of nutrition (9th day of gestation in rabbits), CP-induced inhibition of the absorptive activity of the entoderm cells might lead to a quantitatively and/or qualitatively changed nutrition of the developing embryo. This changed nutrition may be the source of the embryotoxic effects of CP.