Molecular modelling of CYP4A subfamily members based on sequence homology with CYP102

1. Homology modelling of various members of the CYP4A subfamily based on the CYP102 template structure is reported. 2. The binding interactions of specific substrates to the CYP4A forms from rat (CYP4A1), human (CYP4A11) and rabbit (CYP4A4) are shown to be consistent with experimental evidence regarding regioselectivity of metabolism. 3. The differences in substrate specificity between CYP4A1, CYP4A11 and CYP4A4 towards fatty acids and prostaglandins respectively are rationalized in terms of variations in active site amino residues.     

Neutral lipid storage disease. Case report and lipid studies

A 9-year-old boy of Greek-Cypriot origin had been diagnosed at the age of 3 years as suffering from non-bullous ichthyosiform erythroderma. However, he also had hepatomegaly and abnormal liver function tests, biochemical evidence of myopathy, early cataracts, and lipid vacuoles in white blood cells and basal keratinocytes. A diagnosis of neutral lipid (triglyceride) storage disease was confirmed by lipid studies on cultured fibroblasts.     

Circumstances influencing umbilical-cord plasma catecholamines at delivery

Summary. Blood gases and plasma catecholamines were measured in umbilical arterial and venous blood samples after delivery. In all cases umbilical arterial noradrenaline concentrations were higher than venous levels. The lowest concentrations of noradrenaline were found after elective cacsarean section. Vaginal delivery, particularly when accompanied by instrumental manipulation, was associated with significantly higher concentrations of arterial noradrenaline. High concentrations of catecholamines were commonly recorded in those deliveries showing evidence of acid-base disturbance. Noradrenaline was the predominant catecholamine in all cases. A linear relation was demonstrated between arterial noradrenaline and arteriovenous noradrenaline difference.     

MYOPATHY WITH MINICORES IN SIBLINGS

Myopathy with minicores in siblings A muscle biopsy from a 5 year old boy with a myopathic disorder showed a wide range of fibre diameters, Type 1 fibre predominance and focal loss of ‘ATPase’ activity in some fibres. Electron microscopy showed, in about 10% of fibres, localized distortions and loss of Z-lines within compactly grouped myofibrils with preservation of glycogen and mitochondria. His younger sibling, aged 1 year, who was only mildly hypotonic, showed similar but less marked abnormalities on muscle biopsy. These changes are those described in ‘multicore disease’, but it is suggested that the term ‘minicore’ might be more appropriate to avoid confusion with central core disease in which multiple cores are often found. Because of the preservation of mitochondria and glycogen, and the slightly atypical staining of Type 1 fibres it is suggested that the disorder might be caused by an abnormality of myosin or actin.     

CONGENITAL AMAUROTIC IDIOCY -A PATHOLOGICAL, HISTOCHEMICAL, BIOCHEMICAL AND ULTRASTRUCTURAL STUDY

A case of congenital amaurotic idiocy, a subgroup of the neurovisceral lipidoses, is described. This is a rare condition of which only five cases have been reported previously. The brain was small and firm with marked neuronal loss and gliosis. Granular material with histochemical properties of the ceroid-lipofuscin group of lipopigments was found deposited within astrocytes, macrophages and residual brain stem neurons. Cells of the mononuclear phagocyte system within the liver, spleen, thymus and lungs contained similar material. Ultrastructurally this substance appeared as intracytoplasmic membranous and granular deposits within limiting membranes, and biochemical analysis of formalin-fixed tissue did not identify a specific material. Comparison is made with the Batten group of disorders.     

Antigenic expression of integrin α6β4 in junctional epidermolysis bullosa

Integrin α6β4 is a major component of hemidesmosomes, considered to play a central role in the adhesion of basal epidermal cells to the underlying dermis. It is therefore of considerable interest in the study of the aetiology of inherited blistering disorders. We have examined the immunohistochemical characteristics of skin from 16 patients with epidermolysis bullosa using two antibodies directed against epitopes on the β4 subunit of αβ4 integrin (G71, 3E1), one antibody directed against an epitope on the α6 subunit (GoH3), GB3 an antibody for nicein, and LH7.2, an anti-collagen type VII antibody. All 10 patients with junctional epidermolysis bullosa showed markedly reduced or no immunoreactivity with G71. These patients included two with GB3-positive junctional epidermolysis bullosa associated with pyloric atresia, and four with other subtypes. By contrast, five patients with dystrophic epidermolysis bullosa and one patient with epidermolysis bullosa simplex showed normal immunoreactivity with G71. In this study, G71 is shown to have a high specificity and sensitivity for the diagnosis of junctional epidermolysis bullosa. Immunoreactivity with 3E1 and GoH3 was normal in most patients, consistent with published reports showing normal immunoreactivity with other β4 and α6 subunit antibodies. The data suggest a modification of the β4 subunit of integrin α6β4 at the dermo-epidermal junction in junctional epidermolysis bullosa.     

Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine

OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocytegrowth and contractility in vitro. This study was designed toinvestigate the effect of exogenous IGF-II on regional myocardialfun ction at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anoesthetizedpigs by affigel blue beads, embolizing microvessels of the leftanterior descending coronary artery distribution. In the experimentalgroup (n=6), IGF-II (0·12 µg. kg^–1 in twoanimals and 0·6 µg. kg^–1 in four) was incorporatedinto the beads and delivered by them to the infarct area. Myocardialfunction was followed echocardiographically, and the excisedheart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to anechocardiographic segmental wall motion score (mean ±SEM), was similar between the two groups at baseline, but at4 weeks post-infarction was significantly (P=0·008) reducedin the control group (0·58± 0·38 vs 3·42± 0·84), in contrast to nearly baseline valuesin the experimental group (0·58 ± 0·33vs 1·17 ± 0·42, P=0·41). Cardiacperformance in injured segments was sign better after myocardialinjury in the experimental group (P=0·04). Tissue samplesfrom both groups (4 weeks post-infarction), stained with haematoxylinand eosin demonstrated pen-infarct myocyte hypertrophy, correspondingto regions selectively stained by an antibody for CD56, whichhighlights growing cardiac myocytes. By image analysis semi-quantification,staining for CD56 was significantly (P=0·04) higher inthe peri-infarct region of the experimental group, as comparedwith controls (106·5 ± 2·8 vs 92 ±4·4 gray level units). Microvessels stained for von-Willebrandfactor were similar in nwnber in both groups (P=0·8),as were mesenchymal cells stained for vimentin (P=0·7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area amelioratesregional cardiac function in the pig, perhaps by inducing peri-infarctmyocyte growth.