Platelet-derived growth factor beta-receptors can both promote and inhibit chemotaxis in human vascular smooth muscle cells

The effect of the three platelet-derived growth factor (PDGF) isoforms AA, AB, and BB on migration was investigated in cultured human saphenous vein smooth muscle cells. The modified Boyden chamber technique yielded efficacies BB > AB, AA = 0. However, the BB concentration-response relationship displayed a pronounced peak, occurring between 1 and 10 ng/mL, with no response above this range. Checkerboard analysis showed that the promotion of migration at low concentrations was chemotactic in nature but that the downturn was independent of gradient. Furthermore, at high concentrations BB was able to prevent chemotaxis induced by fetal calf serum and epidermal growth factor (EGF). Experiments using low concentrations of BB in combination with high concentrations of AA to saturate PDGF alpha-receptors in the presence and absence of a neutralizing antibody to alpha-receptors revealed that alpha-receptor activation induced partial inhibition of chemotaxis but this did not account for the inhibition of migration by high concentrations of BB. Despite possessing no significant chemotactic action itself, high concentrations of the AB isoform completely inhibited BB induced chemotaxis. Taken together these results suggest that the chemotactic signal induced by PDGF is dominated by PDGF beta-receptors and switches from positive at low concentrations to negative at higher concentrations. Stimulation of DNA synthesis by the three isoforms (as measured by [3H] thymidine incorporation) yielded saturable responses for the AB and BB isoforms, with similar efficacy and weak or no response for the AA isoform. Concentration-dependent patterns of tyrosine phosphorylation of certain proteins mirrored the form of the chemotactic response and suggest one possible underlying regulatory mechanism to account for the disparity between PDGF-induced chemotaxis and DNA synthesis.     

Psychologic factors and oral lichen planus. A psychometric evaluation of 100 cases

OBJECTIVE: The purpose of this study was to analyze the importance of psychologic factors in patients with oral lichen planus, and attempts were made to identify possible personality features characteristic of patients with oral lichen planus. STUDY DESIGN: The study involved 100 patients with oral lichen planus (group 1) and 50 control subjects (group 2). We applied the following psychometric tests to both groups: Spielberger State-Trait Anxiety Inventory, Cattell Personality Questionnaire 16PF, Hassanyeh Rating of Anxiety-Depression-Vulnerability, Beck Depression Inventory, Raskin Depression Screen, and Covi Anxiety Screen. RESULTS: The patients with oral lichen planus were found to exhibit greater anxiety, as reflected by statistically significant scores with the anxiety tests that were used (Spielberger State-Trait Anxiety Inventory, Cattell Personality Questionnaire 16PF, Hassanyeh Rating of Anxiety-Depression-Vulnerability, and Covi Anxiety Screen). The patients with oral lichen planus likewise exhibited greater depression than the controls in all 3 depression tests applied (Beck Depression Inventory, Hassanyeh Rating of Anxiety-Depression-Vulnerability, and Raskin Depression Screen) and were more vulnerable to psychic disorders on the basis of the PD subscales (vulnerability) of the Hassanyeh questionnaire. Three features (conformity to the group, astuteness, and rebelliousness) defined the personalities of our patients with oral lichen planus, according to the Cattell 16PF questionnaire. Finally, those patients with erosive lichen planus exhibited higher depression scores than patients with nonerosive lichen planus. CONCLUSIONS: Despite the higher anxiety scores observed in patients with oral lichen planus, it was not established that the observed psychologic alterations constitute a direct etiologic factor of oral lichen planus; nor was it established that such alterations are a consequence of oral lichen planus and its lesions.     

The evolution of a successful liver transplant program in 1996: the clinical and administrative role of the anesthesiologist

The establishment of a new liver transplant program requires enormous planning and resources. Extensive negotiations must take place to ensure institutional and departmental commitments to obtain the proper equipment, personnel, and other resources. The formation of a well-trained multidisciplinary team of physicians and nurses becomes the next step. Finally, ample time must be provided to adequately deploy resources, lobby referring physicians, recruit patients, and troubleshoot problems as they arise.     

Genetic analysis with hierarchical models

Apoptosis is a genetically programmed series of events that results in cell death. As a consequence, it is difficult to identify dominant genes that play a role in this process using genetic selections in conventional cell culture systems. Accordingly, we have established an efficient expression screen to isolate dominant, apoptosis-inducing genes. The assay is based on the apoptotic morphology induced in the human kidney cell line 293 after transient transfection of small plasmid pools from normalized cDNA expression libraries. Using this assay, we isolated a novel isoform of the proto-oncogene Neu differentiation factor (NDF), a ligand for erbB receptor tyrosine kinases. Several lines of experimental evidence indicate that this gene kills in a cell-autonomous fashion and independently of known erbB receptors. This apoptotic property of an NDF isoform is readily contrasted with NDF's transforming potential and might balance the tendency to tumorigenesis in cells that overexpress NDF.     

Cardiac output and mixed venous oxygen content measurements by a tracer bolus method: theory

We present a bolus method of inert-gas delivery to the lungs that facilitates application of multiple inert gases and the multiple inert-gas-exchange technique (MIGET) model to noninvasive measurements of cardiac output (CO) and central mixed venous oxygen content Reduction in recirculation error is made possible by 1) replacement of sinusoidal input functions with impulse inputs and 2) replacement of steady-state analyses with transient analyses. Recirculation error reduction increases the inert-gas selection to include common gases without unusually high (and difficult to find) tissue-to-blood partition coefficients for maximizing the systemic filtering efficiency. This paper also presents a practical method for determining the recirculation contributions to inert expired profiles in animals and determining their specific contributions to errors in the calculations of CO and from simulations applied to published ventilation-perfusion ratio (V/Q) profiles. Recirculation errors from common gases were found to be reducible to the order of 5% or less for both CO and whereas simulation studies indicate that measurement bias contributions from recirculation, V/Q mismatch, and the V/Q extraction process can be limited to 15% for subjects with severe V/Q mismatch and high inspired oxygen fraction levels. These studies demonstrate a decreasing influence of V/Q mismatch on parameter extraction bias as the number of inert gases are increased. However, the influence of measurement uncertainty on parameter extraction error limits improvement to six gases.     

Severe prepartum ketosis in an obese beef cow

A beef cow was examined to find the cause of decreasing appetite of 2 weeks' duration. The cow was obese (body condition score, 8 of 9), and multiple fetuses were identified on palpation per rectum. Urinalysis revealed > 160 mg of ketones/dl. Abnormal serum biochemical data included high concentrations of bilirubin, creatinine, sodium, and chloride; low concentrations of total CO2 and calcium; and high activity of aspartate transaminase. Treatment included administration of dextrose solution, i.v.; propylene glycol, PO; and insulin, i.v. and SC. The cow's appetite improved gradually over 8 days of treatment. Concentration of ketone bodies in urine decreased to trace amounts by day 4. The cow was discharged on day 10 and gave birth to twins 4 days after discharge (duration of gestation, 279 days). The clinical history of this cow differed from the history of other cattle with ketosis, but mimicked pregnancy toxemia in ewes. Multiple fetuses have not been implicated as a predisposing factor in severe prepartum ketosis of cows.     

Multiple repetitive DNA sequences in the paracentromeric regions of Arabidopsis thaliana L

An efficient purification protocol for infectivity causing a transmissible spongiform encephalopathy (TSE) is described. From fractions purified by this protocol about 3 x 10(8) LD50 but only 3 ng of nucleic acids per gram of brain material can be isolated from all TSE-affected brains (hamster, human, sheep, cattle). By PAGE such fractions from brains of infected and control hamsters contained only one distinct nucleic acid band of 1.5 kg together with some broader smear of nucleic acid material. Although distilled water was used for such purifications, quite often a similar nucleic acid band was isolated from blanks containing no brain material. In all instances this material proved to be DNA. The result challenges the potentially important claim that purified infectious preparations of TSE-specific amyloid are free of nucleic acids of viral size. Nucleic acids isolated by other groups from diseased brain were not detected in preparations isolated by the new protocol. The application of this purification protocol in future studies will be helpful to decide whether TSEs are caused by agents containing nucleic acid or by protein only.