Lack of association between antiphospholipid antibodies and first-trimester spontaneous abortion: prospective study of pregnancies detected within 21 days of conception

OBJECTIVE: To determine the role of antiphospholipid antibodies and anticardiolipin antibodies in first-trimester losses, addressing experimental pitfalls that preclude excluding the possibility that these antibodies reflect merely the selection bias of studying couples only after they have already experienced losses. DESIGN: Given that retrospective studies cannot exclude the possibility that such antibodies arise as a result of the fetal death, blood samples were obtained either before pregnancy or very early in pregnancy. Sera were obtained within 21 days of conception. SETTING: Multicenter university-based hospitals (National Institute of Child Health and Human Development collaborative study). PATIENT(S): Subjects for the current study were 93 women who later experienced pregnancy loss (48 diabetic; 45 nondiabetic), matched 2:1 with 190 controls (93 diabetic and 97 nondiabetic) who subsequently had normal live-born offspring. INTERVENTION(S): Sera from these 283 women were analyzed for antiphospholipid antibodies by enzyme immunoassay. In 260 of the 283 women (87 with pregnancy losses; 173 with live-born infants), sera were also available to perform assays for anticardiolipin antibodies by enzyme immunoassay. MAIN OUTCOME MEASURE(S): Pregnancy losses. RESULT(S): No association was observed between pregnancy loss and the presence of antiphospholipid antibodies or anticardiolipin antibodies. Levels of antiphospholipid antibodies were 6-19 PL/mL in 62.4% of the pregnancies that ended in losses and > or = 20 PL/mL in 5.4%; among pregnancies resulting in live-born infants, the percentages were 56.8% and 6.8%, respectively. Of the pregnancies that ended in a loss, 5.7% had anticardiolipin antibodies > or = 16 GPL/mL, compared with 5.2% of those ending in a live birth. CONCLUSION(S): This prospective study suggests that anticardiolipin antibodies and antiphospholipid antibodies are not associated with an increased risk for first-trimester pregnancy loss.     

Constitutive expression of mature transforming growth factor beta1 in the liver accelerates hepatocarcinogenesis in transgenic mice

Transforming growth factor beta-1 (TGF-beta1) is a potent inhibitor of hepatocyte growth both in vivo and in vitro. In this study, we analyzed the effects of TGF-beta1 on both naturally occurring and diethylnitrosamine-induced hepatocarcinogenesis using single transgenic TGF-beta1 and double transgenic c-myc/TGF-beta1 mice in which the expression of both transgenes was targeted to the liver. Hepatocellular tumors developed spontaneously in 59% (10 of 17) of the TGF-beta1 mice by 16-18 months of age. Coexpression of TGF-beta1 and c-myc transgenes in the liver accelerated hepatic tumor growth in both the presence and absence of carcinogenic treatment. Moreover, diethylnitrosamine-initiated tumors in the c-myc/TGF-beta1 mice showed a high rate of malignant conversion associated with a reduced expression or lack of TGF-beta receptor type II. The results suggest that overexpression of TGF-beta1 may contribute to liver carcinogenesis and that loss of TGF-beta receptor type II transduced inhibitory growth signals and up-regulation of c-myc are critical steps in liver tumor progression.     

The neurobiology of anxiety disorders

The use of pharmacologic challenges and the application of new brain imaging technologies in the study of patients with anxiety disorders have led to an improvement in the understanding of the neurobiologic basis of these disorders. Abnormal function of noradrenergic, serotonergic, GABAergic, and dopaminergic neural systems as well as abnormal chemoreceptor reactivity have all been implicated in the pathophysiology of anxiety. Functional imaging data have revealed abnormal patterns of cortical and subcortical activity in anxiety patients. These data have allowed significant improvements in the available anatomic models of the anxiety disorders. Further improvements in research technique and technology likely will lead in the near future to a significantly clearer image of the neurobiologic processes involved in anxiety disorders.     

Structural characterization of the maltose acceptor-products synthesized by Leuconostoc mesenteroides NRRL B-1299 dextransucrase

The glucooligosaccharides (GOS), produced by Leuconostoc mesenteroides NRRL B-1299 dextransucrase through an acceptor reaction with maltose and sucrose, were purified by reverse phase chromatography. Logarithmic plots of retention time vs. dp of the GOS gave three parallel lines suggesting the existence of at least three families of homologous molecules. The structure (13C and 1H NMR spectroscopy) and reactivity of the purified molecules of the three families were investigated. All the products bear a maltose residue at the reducing end. The GOS in the first family (named OD) contained additional glucosyl residues all alpha-(1-->6) linked. The smallest molecule in this first series was panose or alpha-D-glucopyranosyl-(1-->6)-D-maltose (dp 3). All the OD molecules were shown to be good acceptors for dextransucrase in the presence of sucrose. The second family, named R, was composed of linear GOS containing alpha-(1-->6)-linked glucosyl residues and a terminal alpha-(1-->2)-linked residue at the non-reducing end of the molecule; the smallest molecule in this family was alpha-D-glucopyranosyl-(1-->2)-D-panose (dp 4). The third family, R', was formed of GOS containing additional residues linked through alpha-(1-->6) linkages that constitute the linear chain, and an alpha-(1-->2)-branched residue located on the penultimate element of the chain, near the non-reducing end. The smallest molecule in this series is alpha-D-glucopyranosyl-(1-->6)-[alpha-D-glucopyranosyl-(1-->2)]-alpha-D- glucopyranosyl-(1-->6)-D-panose, dp 6. R and R' GOS are very poor acceptors for L. mesenteroides NRRL B-1299 dextransucrase. This study makes it possible to suggest a rather simple reaction scheme, where molecules Ri, R'i and ODi of the same dp all result from the glucosylation of the same GOS: ODi-l.