A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family.

A sibship is reported of three generations of a Jordanian family of normal intelligence with a complex malformation of upper extremity, shoulder and thorax, which is combined with variously expressed congenital heart disease. The deformity consists of a flat glenoid fossa, a hypoplastic scapula, aplasia of the humerus and/or radius, bony spurs of the elbow joint and in the shoulder region, hypoplasia of the carpal joints and hypodactyly with aplasia of the thumb. The claviculae are short, thick and abnormally curved and there are kyphoscoliosis and pectus excavatum. Four siblings show congenital heart disease. Pelvis and lower extremity are normal. The condition is inherited as a Mendelian autosomal dominant.

Turcot syndrome (glioma polyposis). Case report.

A case of Turcot syndrome (glioma polyposis) is described in a 22-year-old woman. The patient initially presented with a frontoparietal glioma, and was subsequently found to have segmental colonic polyposis with adenocarcinomatous changes. Her colonic polyposis was nonfamilial.

Monoamine oxidase activities in human brain microvessels.

Microvessels can be easily isolated from human brain samples obtained at autopsy. Human frontal cortex MAO type A and B activities are similar in microvessel and microvessel-free preparations. In microvessels, enzyme activities and the ratio of MAO type A to type B vary among the areas studied and could selectively regulate the passage of certain amines though the blood vessel wall.

Protracted form of Canavan's disease: case history and protein kinase activity of membrane fractions.

Clinical and morphological findings in an 8-year-old Jewish girl with spongy leukodystrophy are presented. Ultrastructural changes indicated that this may be a form of Canavan's disease with some atypical features. Biochemical measurements indicated that synaptosomal membranes prepared from the striatum but not from the cerebral cortex were deficient in protein kinase activity based on incorporation of 32P into proteins. Both areas contained the same spectrum of proteins. Cyclic AMP (cAMP) measurements indicated no significant differences between brain areas, or when compared to tissue obtained from a stillborn and a 5-year-old child.

Liver in cerebrotendinous xanthomatosis (CTX)--a histochemical and EM study of four cases.

Cerebrotendinous xanthomatosis (CTX) is a rare inherited lipid storage disease. The primary biochemical defect in CTX is a block in hepatic bile acid synthesis with consequent accumulation of two bile pentols in the liver. Hence specimens of liver from four affecteds were examined by light and electron microscopy. These revealed perisinusoidal fibrosis, bile canalicular alterations and hepatocellular alterations including the appearance of fat droplets, proliferation of the smooth endoplasmic reticulum, accumulation of lipofuscin-like pigment, foci of cytoplasmic degeneration, proliferation of microbodies and prominent mitochondrial changes. In one untreated patient crystalloid cores were noted in the microbodies. These disappeared on therapy.

On the neurochemistry of an adult form of ceroid lipofuscinosis (Kuf's disease).

Little progress has been made in procedures for diagnosis of this baffling group of diseases known as ceroid lipofuscinoses (CL), which exhibit infantile, juvenile, and adult forms. Although these have been shown for the most part to be genetic in origin, the enzymatic or other defects leading to accumulation of lipopigments in tertiary lysosomes of neurons or astrocytes re unknown. Among the more commonly discussed theories is the role of peroxy radicals or their products formed by lipoperoxidation of polyunsaturated fatty acids. Although peroxy radicals are damaging to tissues and biological processes, no differences were observed in levels of leucocyte peroxidase (metabolizing H2O2) for Kuf's patients in comparison to age-matched controls. Also, no differences were observed in levels of blood factors that affect the rates of lipoperoxidatin by rat or human brain homogenates in vitro (measured by formation of MDA or other TBA positive materials).

Mitigation of experimental allergic encephalomyelitis by cathepsin D inhibition.

Intraperitoneal treatment with the enzyme inhibitor, pepstatin, of BSVS mice, guinea pigs and Lewis rats which were sensitized with guinea pig spinal cord and pertussis vaccine resulted in complete or partial suppression of paralysis dependent on the species studied and alterations of histological signs of experimental allergic encephalomyelitis (EAE). The effect was dose-dependent but had no relationship to the age of the experimental animal at the time of the experiment.

Protein phosphorylation in human synaptosomal membranes: evidence for the presence of substrates for cyclic nucleotide guanosine 3'-5'-monophosphate dependent protein kinases.

Synaptosomal membranes prepared from different anatomical regions of postmortem human brain readily incorporate phosphate when incubated with labelled ATP in vitro. Separation of proteins on SDS slab gels indicated up to 30 protein bands stained by Coomassie blue of which ten incorporated label, as detected by radioautography (mol. wt. range 16-110 K with a major double band at 49-50 K). Incorporation into the 110 K region appeared to increase in older persons, and that into the 49-50 K region decreased. Human but not rat membranes subjected to similar conditions of treatment failed to respond to the addition of cAMP at 10(-5) - 10(-7) M but were highly sensitive to the addition of cGMP at 10(-6) M, which led to intensification of existing bands and the appearance of a major band at 60 K. The 110 K band present in high concentration in white matter striatum, caudate nucleus, and putamen was insensitive to cGMP addition. The presence of cGMP-dependent protein kinase substrates has not previously been reported in synapses, and it may be of significance in view of the known sensitivity of this system to biological regulatory agents.

Treatment of experimental allergic encephalomyelitis with an inhibitor of cathepsin D (pepstatin).

Intraperitoneal administration of pepstatin (2 mg/day for 5 weeks) to Lewis rats subjected to experimental allergic encephalomyelitis (EAE) (induced by guinea pig spinal cord and pertussis vaccine) suppressed the appearance of clinical signs of disease, and reduced the severity and incidence of CNS lesions normally associated with this disease. Administration of pepstatin for shorter periods to Lewis rats, or BSVS mice, or guinea pigs challenged with myelin basic protein delayed, but did not prevent clinical signs of EAE, but was accompanied in all cases by a less severe histopathology.

Lipoperoxidation in human and rat brain tissue: developmental and regional studies.

Lipoperoxidation in human and rat brain was studied on the basis of formation in vitro of thiobarbituric acid positive (TBA) materials. In rats aged 1--540 days, the endogenous pools of reactive material were unchanged but on subsequent incubation of their homogenates the level of TBA-positive materials fell by 3 fold (fresh weight basis) and 5.4 fold (protein basis). In human brain, there was a distinct regional distribution of reactive materials in the endogenous pools with highest levels in the cerebellar vermis, and lower levels in thalamus, cortical regions, substantia nigra, caudate nucleus, pallidum, putamen, and hypothalamus. Only trace levels were detected in the pineal gland. On incubation all values rose 13--25 fold within 3 h at 37 degrees C except for cerebellar vermis which was increased 6 fold, and pineal gland 9 fold. Four TBA-positive materials were separated from rat brain by TLC, three of which were identical to malonyldialdehyde and its polymers. Lipoperoxidation in rat homogenates was inhibited 75--90% by sera from several different sources. The inhibitory properties were unaffected by dialysis and were not reproduced by addition of a large number of low and high mol. wt. components including vitamin E when added in concentrations equal to or exceeding that of native serum.

Glycine levels in the degenerated human spinal cord.

Tissues from non-degenerated tissue of 18 patients were assayed for glycine concentration in grey and white matter in the thoracic, cervical and lumbar regions. Confirming earlier results, glycine concentration was found to be maximal in the grey matter of the lumbar segments of the lateral column. Analysis of tissue from 11 human spinal cords showing unilateral Wallerian degeneration, 4 cords with amyotrophic sclerosis and 4 cords with bilateral Wallerian degeneration failed to show statistically significant differences when compared with control values. The results argue against a supraspinal origin of glycine and suggest that glycine levels are regulated locally or at a segmental level in the spinal cord in man.

Leukocyte peroxidase deficiency in a family with a dominant form of Kuf's disease.

Use of a spectrophotomtetric assay of peroxidase with p-phenylenediamine as cosubstrate demonstrated deficient enzymne activity in leukocytes from two patients with a dominantly inherited form of ceroid lipofuscinosis (Kuf's disease) and a clinically hlealthy unaffected sibling. When the reaction was performned in the absence of added hydrogen peroxide, oxidation of the p-phenylenediamnine cosubstrate (indicating the presence of endogenous peroxide) occurred only with enzyme samnples from the three siblings but not with those from a large number of unrelated, unaffected controls. This demonstrates that the deficiency of peroxide) found previously in the recessively inherited infantile and juvenile formns of ceroid lipofuscinosis (Batten-Spielmeyer-Vogt disease) is also present in an adult form with dominant inheritance.