Peptide growth factors in the prostate as mediators of stromal epithelial interaction

Peptide growth factors play a role in the maintenance of normal prostatic growth and differentiation (Fig. 2). It seems likely that the androgen sensitivity of human prostate is mediated by the production of peptide growth factors from stromal cells which act as the direct intermediate of androgen action on epithelial cells. TGF-beta 1 inhibition of epithelial cells is opposed by the stimulatory action of EGF, IGF and FGFs to maintain an equilibrium of epithelial cell numbers. The indirect mitogenic action of androgens appear to act by down-regulation of TGF-beta 1 and possibly EGF receptors. There is also interaction with the effects of IGF-II, produced by prostatic stromal cells and acting on epithelial cells to increase proliferation. The growth of normal prostatic fibroblasts is under the control of bFGF and TGF-beta 1. However, although our understanding of the actions of these growth factors in the normal prostate has improved over the last decade, their role in the development and maintenance of prostate cancer is less clearly defined. TGF-beta 1, classically considered to be inhibitory for epithelial cells, may be up-regulated in prostatic tumours, stimulating growth. Alternatively, autocrine production of such growth factors by tumour cells may lead to loss of inhibitory effects from exogenous TGF-beta 1, a mechanism also witnessed with TGF-alpha and bFGF. The role of EGF in the development of prostate cancer is confusing because results from the use of different cell types and experimental conditions is contradictory. It may be that a switch in the production of the predominant EGFr ligand from EGF to TGF-alpha is an important feature in the development and maintenance of the malignant phenotype. The presence of TGF-alpha autocrine loops has been shown clearly in some tumour cell lines. This switch in the production of a particular ligand may also be a feature of IGFs in prostate cancer. IGF-II may be replaced by IGF-I during malignant progression, both of which are able to act via the type 1 receptor. This change in IGF expression appears to be accompanied by altered expression of the IGF-BP2, with less detectable within prostatic tissues but elevated serum levels [58]. Basic FGF is normally produced by prostatic fibroblasts but is also produced by some prostatic cancer cell lines [64]. However, as with all growth factors, the expression of the bFGF protein and its receptor is dependent on the cell line examined. The autocrine and paracrine control of normal and abnormal prostatic growth by growth factors is important in determining their role in the development and maintenance of prostate cancer. Better understanding of such mechanisms is essential for the development of novel therapeutic strategies in the control and treatment of prostate cancer.     

The Drug Evaluation Classification Program: using ocular and other signs to detect drug intoxication

BACKGROUND: A systematic approach to determining drug intoxication has been developed for use by police officers. By considering specific physiological signs, trained officers can detect the effects of seven major drug types. METHODS: Officers follow a 12-step testing sequence and evaluate signs such as pupil sizes and responses, eye movements, heart rate, body temperature, mental timing, and balance. A matrix is then used to compare that subject's signs to those that would be produced by the seven types of drugs. If a pattern match is found, the officer concludes that the subject is under the influence of a drug and specifies the drug type. RESULTS: Several field and laboratory validation studies have been conducted using these procedures. In general, officers were 70% to 90% accurate in determining intoxication status and drug classification, but poly-drug use and drug rebound effects can sometimes cause problems in interpretation. CONCLUSION: Ocular and other physiological signs can be used to detect drug intoxication and classify the type of drug taken. Knowledge of the procedures used in the Drug Recognition Program can enable optometrists to serve as consultants to the police and as expert witnesses in cases involving the use of ocular signs that indicate illicit drug use.     

<Superscript>1</Superscript>H NMR characterization of milk lipids: A comparison between cow and buffalo milk

Characterization of the lipid fraction of raw cow and buffalo milk samples, collected in different breeding areas in Apulia, a region of southern Italy, were performed by means of ¹H NMR. The aim of this work was to establish whether FA composition data obtained by ¹H NMR can be used in the differentiation of buffalo and cow milk samples according to species. A complete assignment of the signals present in the spectrum was attempted by COSY, heteronuclear coherence spectra. Quantification of FA was carried out by inserting the integrals of particular peaks in suitable calculations. Multivariate statistical analysis, conducted on the results of the quantification, permitted buffalo and cow milks to be distinguished.     

Electromyographic and neuromuscular variables in post-polio subjects

OBJECTIVE: Post-polio subjects experience functional deterioration many years after developing acute poliomyelitis and have been shown previously to have a deficit in strength recovery after isometric activity. This study characterized the size and stability of the motor units in a group of post-polio subjects with macro and single fiber electromyography (EMG) and correlated these variables with isometric strength, endurance, "work capacity," and strength recovery after fatiguing isometric exercise. DESIGN: A cohort of 12 post-polio subjects was tested for neuromuscular function. Electromyographic variables were determined on a separate day. SETTING: Volunteers were recruited from the community and tested in our neuromuscular research laboratory. SUBJECTS: A volunteer sample was obtained from advertisements. All subjects acknowledged post-polio syndrome symptoms. MAIN OUTCOME MEASURES: Neuromuscular variables were isometric knee extension peak torque, endurance (time to exhaustion) at 40% of maximal torque, tension time index, and recovery of torque at 10 minutes. Electromyographic variables were macro EMG and single fiber EMG (percent blocking and jitter). RESULTS: Macro EMG amplitude was ninefold the control value, and both jitter and blocking were greatly increased in comparison to control values. Isometric strength significantly (p < .05) correlated negatively with macro EMG amplitude. CONCLUSIONS: The weakest subjects had the greatest number of muscle fibers within the motor unit (as measured by macro EMG amplitude). Jitter and blocking did not correlate with neuromuscular function.     

Addressing a state''s physician workforce priorities through the funding of graduate medical education: the TennCare model

OBJECTIVE: To investigate differences in second-, third-, and fourth-year medical students' knowledge of bloodborne pathogen exposure risks, as well as their attitudes toward, and intentions to comply with, Universal Precautions (UP). DESIGN: Cross-sectional survey. PARTICIPANTS AND SETTING: Surveys about students' knowledge, attitudes, and intentions to comply with UP were completed by 111 second-year (preclinical), 80 third-year, and 60 fourth-year medical students at Washington University School of Medicine in the spring of 1996. RESULTS: Preclinical students knew more than clinical students about the efficacy of hepatitis B vaccine, use of antiretroviral therapy after occupational exposure to human immunodeficiency virus, and nonvaccinated healthcare workers' risk of infection from needlestick injuries (P<.001). Students' perceived risk of occupational exposure to bloodborne pathogens and attitudes toward hepatitis B vaccine did not differ, but preclinical students agreed more strongly that they should double glove for all invasive procedures with sharps (P<.001). Clinical students agreed more strongly with reporting only high-risk needlestick injuries (P=.057) and with rationalizations against using UP (P=.008). Preclinical students more frequently reported contemplating or preparing to comply with double gloving, wearing protective eyewear, reporting all exposures, and safely disposing of sharps, whereas students with clinical experience were more likely to report compliance. Clinical students also were more likely to report having "no plans" to practice the first three of these precautions (P<.001). CONCLUSIONS: Differences in knowledge, attitudes, and intentions to comply with UP between students with and without clinical experience may have important implications for the timing and content of interventions designed to improve compliance with UP.     

The flavin-containing monooxygenase 2 gene (FMO2) of humans, but not of other primates, encodes a truncated, nonfunctional protein

Flavin-containing monooxygenases (FMOs) are NADPH-dependent flavoenzymes that catalyze the oxidation of heteroatom centers in numerous drugs and xenobiotics. FMO2, or "pulmonary" FMO, one of five forms of the enzyme identified in mammals, is expressed predominantly in lung and differs from other FMOs in that it can catalyze the N-oxidation of certain primary alkylamines. We describe here the isolation and characterization of cDNAs for human FMO2. Analysis of the sequence of the cDNAs and of a section of the corresponding gene revealed that the major FMO2 allele of humans encodes a polypeptide that, compared with the orthologous protein of other mammals, lacks 64 amino acid residues from its C terminus. Heterologous expression of the cDNA revealed that the truncated polypeptide was catalytically inactive. The nonsense mutation that gave rise to the truncated polypeptide, a C --> T transition in codon 472, is not present in the FMO2 gene of closely related primates, including gorilla and chimpanzee, and must therefore have arisen in the human lineage after the divergence of the Homo and Pan clades. Possible mechanisms for the fixation of the mutation in the human population and the potential significance of the loss of functional FMO2 in humans are discussed.     

Treatment of pulmonary hypertension with inhaled nitric oxide during hepatic transplantation in an adolescent: reversibility of pulmonary hypertension after transplantation

Accusations of rape or sexual harassment are currently very high-profile in the military. This article discusses rape allegations in the military legal system from a psychiatric perspective. The original definition of "rape trauma syndrome" and subsequent psychiatric thinking about the diagnosis are briefly outlined. Common reactions seen in military victims in this era are described. A prototypical military case is presented. An adequate evaluation of an alleged victim is outlined. Credentials and preparation of an expert witness are also briefly discussed, with cautions about the use of expert testimony in cases of alleged sexual assault and rape trauma syndrome.     

Refractory head and neck pain. A difficult problem and a new alternative therapy

Mitral valve repair was performed in six patients by transferring the posterior tricuspid leaflet with its sub-valvular apparatus onto the mitral valve. This new technique considers the tricuspid valve as the patients own tissue bank where the posterior leaflet and eventually the adjacent part of the anterior leaflet is used as a "donor" valve, based on the knowledge that the right atrio-ventricular valve can be efficiently repaired with a very low risk of significant dysfunction. The mitral repair consists of incorporating the tricuspid autograft by securing the tricuspid papillary muscle to the mitral papillary muscle and by suturing the leaflet tissue where required. A mitral annuloplasty ring reinforces the repair. The tricuspid valve is subsequently repaired by annular plication and leaflet suture. A tricuspid ring is necessary to maintain efficient remodeling. The six patients ages ranged from 20 to 70 years. A etiology, was rheumatic in the first case and degenerative in the following. In three cases, sterilised endocarditis was responsible for ruptured chordae and leaflet destruction. The mitral insufficiency was located in a commissural area in 4 cases, and was due to a widespread posterior prolapse in 2. Post-operative control transesophageal echocardiography confirmed the excellent results of the repair and proved that, in selected cases, the tricuspid leaflet inserted onto the mitral apparatus is very efficient in correcting mitral insufficiency, without causing significant tricuspid impairment. With a 3 to 7 month follow-up, the results are stable.