Protein C Osaka 10 with aberrant propeptide processing: loss of anticoagulant activity due to an amino acid substitution in the protein C precursor

We studied the molecular basis of protein C deficiency in a family with a history of thromboembolic disease. An approximately 50% reduction in anticoagulant activity despite normal levels of protein C amidolytic activity and antigen was detected in plasma from the proband. All the exons and intron/exon junctions of the protein C gene were studied using a strategy that combined polymerase chain reaction amplification with DNA sequencing of the amplified fragments. We identified a C-to-A change at nucleotide number 1387 of the protein C gene in the proband and his mother, and this mutant was designated protein C Osaka 10. The C-to-A change resulted in the substitution of Ser for Arg at position -1, which is the processing protease cleavage site. The mutant protein C was partially purified from plasma of the patient's mother using barium adsorption followed by ion-exchange column chromatography. It eluted at the same sodium chloride concentration as normal protein C, and thus gamma-carboxylation of the mutant protein appeared to be normal. The apparent molecular weight of this mutant protein C was the same as that of the normal protein on immunoblotting. Amino-terminal sequence analysis showed that the light chain of the mutant protein C had an additional Ser at position-1. Thus, the loss of anticoagulant activity of protein C Osaka 10 can be explained by alteration of the conformation of the Gla domain by the additional Ser in the mutant molecule.     

Neonatal hyperthyroidism caused by TSH receptor antibodies in maternal autoimmune hyperthyroidism

Between July 1993 and December 1994 five term infants of mothers with Graves' disease were hospitalised at the Frühgeburtenstation of the Univ.-Frauenklinik Graz. Four Mothers had elevated TSH-receptor-antibody (TRAb)--levels during pregnancy, one had normalised TRAb-titers. In one case hyperthyroidism was first diagnosed during pregnancy. Three newborns had elevated TRAb-titers; in one of them thyrotoxicosis was diagnosed clinically and biochemically at the second day of life, one newborn had mild hyperthyroidism with tachycardia at the end of the first week of life and one newborn was asymptomatic by immediately initiated therapy. The two other newborns had normal thyroid hormone and antibody levels and no symptoms or signs of hyperthyroidism. The cases are reported and discussed in detail and our overall approach to diagnosis and treatment of neonatal hyperthyroidism in case of maternal Graves' disease will be given.     

Citrullinemia: management and clinical course. Apropos of a familial case

The authors report two cases of citrullinemia in siblings which add to 68 observations from the literature. They overview the clinical presentation, diagnosis and therapeutic management of the disease. The prognosis of severe neonatal form remains poor but an early adequate management may contribute to an acceptable outcome.     

Expressed emotion, social skill, and response to negative affect in schizophrenia.

Examined social skills and social perception of 48 schizophrenia/schizoaffective disorder patients (aged 18–55 yrs) in response to negative affect as a function of family expressed emotion (EE). Ss participated in a role-play test, a social perception test, and a problem-solving discussion with a family member and were assessed on several measures of symptomatology. EE of family members was evaluated with the Camberwell Family Interview. On the role-play test, Ss with less critical relatives became more assertive in response to increased negative affect from a confederate portraying either a family member or friend, but Ss with highly critical relatives did not. Ss with highly critical relatives were also less assertive when confronted with negative affect from a confederate portraying a family member rather than a friend. The behaviors of both relatives and Ss during a family problem-solving interaction were related to the EE dimensions of criticism, emotional overinvolvement, and warmth. Patient gender was also related to family problem solving but was independent of EE. S's ratings of affect on a videotaped social perception task were not related to family EE, and there were few differences in psychopathology between Ss with high and low EE relatives.… (PsycINFO Database Record (c) 2010 APA, all rights reserved)