Molecular genetic survey of 16 kindreds with hereditary antithrombin III deficiency

Molecular genetic techniques were utilized to examine antithrombin III (ATIII) gene status in 16 independently ascertained kindreds with hereditary ATIII deficiency. In one of these families antithrombin III deficiency is caused by hemizygosity of the ATIII locus. In the remaining 15 kindreds, two copies of the ATIII gene are present and appear to be grossly normal at the level of whole genome Southern blotting, suggesting that small deletions, insertions or limited nucleotide substitution(s) in the antithrombin III gene, or "trans- acting" defects at other loci involved in the processing, modification, and secretion of biologically active ATIII are responsible for the observed anticoagulant disorders.     

Synthesis of cobalamin coenzymes by human lymphocytes in vitro and the effect of folates and metabolic inhibitors

The uptake of 57Co-cyanocobalamin (CN-Cbl) and its conversion to 5- deoxyadenosylcobalamin (Ado-Cbl), methylcobalamin (Me-Cbl), and hydroxocobalamin (OH-Cbl) has been studied in phytohemagglutinin (PHA)- transformed lymphocytes from normal subjects and patients with patients with pernicious anemia. Uptake and conversion were much greater by PHA- stimulated lymphocytes than by mature non-transformed lymphocytes. In normal cells, uptake of 57Co-CN-Cbl and synthesis of the cobalamin coenzymes were approximately linear between 3 and 48 hr incubation. Ado- Cbl was the major cobalamin formed, and after 72 hr the cells contained about twice as much Ado-Cbl as Me-Cbl. Uptake by lymphocytes from patients with untreated pernicious anemia (PA) was greater than that by normal lymphocytes, but the proportions of Ado-Cbl and Me-Cbl synthesized by each were similar. Folic acid and methyltetrahydrofolate enhanced synthesis of Me-Cbl both in normal and in PA cells, while methotrexate and 5-fluorouracil depressed it. This depression was overcome by 5-formyltetrahydrofolate, suggesting that an uninterrupted folate cycle may play an important role in Me-Cbl synthesis.     

A profile of cortical gray matter volume deficits characteristic of schizophrenia

Quantitative magnetic resonance imaging (MRI) studies from our laboratory have reported that patients with schizophrenia show a widespread cortical gray matter volume deficit, which is especially pronounced in the prefrontal and anterior superior temporal cortices. The present study compared two separate samples of schizophrenic patients -- 71 men from a Veterans Administration (VA) hospital and a sample of 57 severely ill men from a state hospital (SH) -- in an effort to test whether the pattern of brain volume abnormalities previously observed in VA schizophrenic patients can be generalized to other groups of schizophrenic patients. MRI-derived brain volumes of gray matter, white matter and sulcal cerebrospinal fluid (CSF) in six cortical regions, and CSF in the lateral and third ventricles were computed. All MRI volumes were adjusted for normal variation in head size and age and were expressed as standardized Z-scores, which also permitted structures of different sizes to be compared directly. The two schizophrenic groups displayed similar patterns of volume abnormalities: cortical gray matter but not white matter volume deficits that were widespread but especially notable in the prefrontal and temporal regions. The regional gray matter deficits in the SH group were generally greater than those in the VA group, particularly in the prefrontal and posterior superior temporal regions. Both schizophrenic groups had abnormally large volumes of the cortical sulci and lateral and third ventricles; however, the SH group showed greater enlargements, the most prominent occurring in the ventricles and temporal sulci. The overlapping patterns of cortical gray matter deficits in the two groups provide evidence for generality of this pattern of regional brain volume abnormalities in schizophrenia.