ABSTRACT
The aim of this study was to determine the differential effects of latent and activated transforming growth factor (TGF)-beta(1) in growth control of normal and proliferating hepatocytes in vivo. Rats were injected with adenoviruses expressing control transgenes (Ctrl), latent TGF-beta(1) [TGF-beta(L)], or activated TGF-beta(1) [TGF-beta(A)]. Additional animals underwent two-thirds partial hepatectomy (PH) 24 h after injection. Increased hepatocyte apoptosis was observed in TGF-beta(A)-injected but not TGF-beta(L)-injected animals 24 h postinjection (10.5%) compared with Ctrl animals (0.37%). The percent of apoptotic cells increased to 32.1% in TGF-beta(A)-injected animals 48 h after injection. Furthermore, TGF-beta(A)-injected rats did not survive 24 h after PH. Four hours after PH, 0.25 and 14.1% apoptotic hepatocytes were seen in Ctrl- and TGF-beta(A)-injected rats, respectively. TGF-beta(A)-induced apoptosis in primary rat hepatocytes was blocked with a pancaspase inhibitor. Thus autocrine expression of TGF-beta(A) but not TGF-beta(L) induces hepatocyte apoptosis in the normal rat liver. Rats overexpressing TGF-beta(A) do not survive two-thirds PH due to hepatic apoptosis. Thus activation of TGF-beta(1) may be a critical step in the growth control of normal and proliferating rat hepatocytes.
Subject(s)
Apoptosis/physiology , Autocrine Communication/physiology , Liver Regeneration/physiology , Liver/cytology , Liver/physiology , Transforming Growth Factor beta/genetics , Adenoviridae/genetics , Amino Acid Chloromethyl Ketones/pharmacology , Animals , Caspase Inhibitors , Caspases/metabolism , Cell Division/physiology , Collagen/genetics , Cysteine Proteinase Inhibitors/pharmacology , Gene Expression/physiology , Hepatectomy , Hepatocytes/cytology , Hepatocytes/enzymology , Hydrogen-Ion Concentration , In Situ Nick-End Labeling , Liver/surgery , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1 , Transgenes/physiologySubject(s)
Amitriptyline/pharmacology , Ethanol/pharmacology , Euphoria/drug effects , Adult , Drug Synergism , Humans , Male , Middle AgedABSTRACT
The medical school educational experience is very stressful for many students, prompting some to seek formal psychiatric care. The authors describe the Medical Student Support Services program of the University of Kentucky College of Medicine. From July 1983 to June 1985, this program served 66 patients, representing 417 visits. On the basis of retrospective chart review with the examining clinicians, the authors present DSM-III diagnoses, types of problems seen, descriptive profiles of the patients, duration of treatment, types of therapy used, and data on marital issues. They discuss the intricacies of providing psychiatric services to medical students and make recommendations for program development for such patients.
Subject(s)
Mental Disorders/therapy , Students, Medical/psychology , Female , Humans , Kentucky , Male , Mental Disorders/psychology , Stress, Psychological/therapy , Student Health ServicesABSTRACT
The genetic basis of a sexually dimorphic quantitative character in Drosophila melanogaster was investigated by means of two-way directional selection for increased and decreased differences between male and female wing length. The sex dimorphism (SD), defined as the mean wing length difference between the sexes, within families, provided the criterion for selection.-The two lines (High SD, Low SD) diverged rapidly during the 15 generations of selection, indicating the presence of extensive genetic variability for the genotype-sex interaction underlying the observed sexual dimorphism. There was evidence that genetic variability persisted in both lines when selection was relaxed. Most of the divergence between the two lines remained after 10 generations of relaxed selection.-The change in the level of sex dimorphism in the High line was due primarily to a decrease in male wing length; in the Low line most of the change in SD was the result of a decrease in female wing length. An overall reduction in wing length in both sexes in both lines is interpreted as an effect of inbreeding.-The distribution and nature of the genetic control underlying the SD characteristic of the two selection lines was investigated by chromosome substitution between selection lines using a marked inversion technique. The two lines differed by factors located on each of the three major chromosome pairs. Chromosome III had the greatest effect on the difference in SD level between lines, and showed an overall additive effect when present in homozygous versus heterozygous combination. Chromosome II had the least effect, with a significant dominance effect of the High II being evident when heterozygotes were compared with homozygotes. The effect of the X chromosome was intermediate. There was some evidence of interaction between non-homologous chromosomes.
