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.     

Facially generated occlusal vertical dimension

Facial height has a profound effect on attractiveness. Occlusal vertical dimension (OVD) determines facial proportion at maximum intercuspation and influences facial dimension at rest. Deficient facial height visibly compromises optimal facial beauty. This article explores the dependent relationships between the OVD and facial esthetics, and discusses the role of facial analysis in determining an optimal OVD.     

The incidence, morbidity, and mortality of surgical procedures after orthotopic heart transplantation

OBJECTIVE: The authors present their experience with patients having undergone orthotopic heart transplantation (OHT) in whom surgical conditions subsequently developed that required operative intervention. The incidence, morbidity, and mortality of these procedures are reported. SUMMARY BACKGROUND DATA: Several studies have evaluated the management options of biliary tract disease after OHT. Multiple reports of patients having undergone OHT who subsequently underwent peripheral vascular reconstructions, plastic reconstructive, and thoracic procedures also have been published. METHODS: A chart review of 349 patients who underwent OHT between 1985 and 1996 was conducted to identify surgical procedures that were required in the post-transplant period. Their outcomes are reported. RESULTS: Of 349 patients who underwent OHT, conditions requiring 94 surgical procedures developed in 54 patients (15%). Biliary tract disease developed in 17 patients (5%) who required cholecystectomy, 2 of the 5 patients with acute cholecystitis died. Eight patients (2%) underwent orthopedic procedures with no operative mortality. Flap advancements for sternal wound infections were performed in five patients and four deaths occurred. Seventeen thoracic procedures were performed in 11 patients with an overall mortality of 45%. Twenty-one vascular procedures were performed on 17 patients with 1 delayed death due to a malignancy. Seven patients underwent procedures of the colon and rectum with no mortality. Seven patients underwent repair of inguinal or incisional hernias with no mortality. Various infections occurred with one resultant death after operative intervention. Six procedures were performed for diseases of the small intestine with no resultant mortalities. CONCLUSIONS: Patients having undergone OHT and chronic immunosuppression are at increased risk of having complications develop from infection. Acute cholecystitis and sternal wound infection caused an inordinate risk of complications and death. Malignancies developed in four patients who required surgical intervention. A heightened awareness of coexisting peripheral vascular disease in patients transplanted for ischemic cardiomyopathy should exist. Close screening before surgery and surveillance after surgery to identify risk factors for infection and vascular disease and to screen for malignancies are essential.