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Biomedical subjects

D Faust

Publications and source records attributed to D Faust.

At least 19 recordsLinked to original sources
PubMed2001

Involvement of protein kinase Cdelta in contact-dependent inhibition of growth in human and murine fibroblasts.

There is evidence that protein kinase C delta (PKCdelta) is a tumor suppressor, although its physiological role has not been elucidated so far. Since important anti-proliferative signals are mediated by cell-cell contacts we studied whether PKCdelta is involved in contact-dependent inhibition of growth in human (FH109) and murine (NIH3T3) fibroblasts. Cell-cell contacts were imitated by the addition of glutardialdehyde-fixed cells to sparsely seeded fibroblasts. Downregulation of the PKC isoforms alpha, delta, epsilon, and mu after prolonged treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA, 0.1 microM) resulted in a significant release from contact-inhibition in FH109 cells. Bryostatin 1 selectively prevented TPA-induced PKCdelta-downregulation and reversed TPA-induced release from contact-inhibition arguing for a role of PKCdelta in contact-inhibition. In accordance, the PKCdelta specific inhibitor Rottlerin (1 microM) totally abolished contact-inhibition. Interestingly, immunofluorescence revealed a rapid translocation of PKCdelta to the nucleus when cultures reached confluence with a peak in early-mid G1 phase. Nuclear translocation of PKCdelta in response to cell-cell contacts could also be demonstrated after subcellular fractionation by Western blotting and by measuring PKCdelta-activity after immunoprecipitation. Transient transfection of NIH3T3 cells with a dominant negative mutant of PKCdelta induced a transformed phenotype. We conclude that PKCdelta is involved in contact-dependent inhibition of growth.

3T3 Cells↗
PubMed2001

[Diagnostic imaging in liver cirrhosis].

For the diagnosis of liver cirrhosis ultrasound, computed tomography, magnetic resonance imaging, and angiography are recommended as imaging modalities. Ultrasound of the liver is used as a screening imaging tool in cases of patients suspicious for diffuse liver disease and is helpful in the term of follow-up examinations. Computed tomography is mainly performed to clarify the presence of liver disease detected by ultrasound. In this context, accurate examination of the vascular structures of the liver as well as extrahepatic situation, is of the essence. Diagnosis of diffuse liver disease and characterization of morphologic changes is improved using contrast-enhanced MR imaging with liver specific contrast media. Combined magnetic resonance imaging can provide comprehensive evaluation of cirrhosis. An improved detection rate and characterization of regenerating nodules can be achieved compared to imaging modalities such as ultrasound and computed tomography. MR imaging can be performed in a one-stop-technique using unenhanced and liver-specific-contrast-enhanced sequence protocols to evaluate the liver parenchyma itself, MR cholangiography to verify the bile duct system, and MR angiography to specify the vascular situation. This technique is the optimal protocol for diagnostic imaging in patients suffering from liver cirrhosis and the method of choice to reach the final diagnosis.

Diagnostic Imaging↗
PubMed2001

Permeability characteristics of polyamines across intestinal epithelium using the Caco-2 monolayer system: comparison between transepithelial flux and mitogen-stimulated uptake into epithelial cells.

The polyamines putrescine, spermidine, and spermine are present in foods in high amounts, and are used for cell growth throughout the body. Surprisingly little is known about the mechanisms of polyamine absorption in the gut. To elucidate the mechanisms, transepithelial transport of polyamines was studied in human enterocytelike Caco-2 cells, grown on permeable filter supports. Transport of all three polyamines across Caco-2 cell monolayers was linear; intraepithelial accumulation of polyamines was higher in confluent than in differentiated Caco-2 cells, but still negligible in comparison with the overall transport across the monolayers. Epidermal growth factor (EGF) enhanced polyamine accumulation in Caco-2 cells four-fold, and basolateral uptake was higher than apical uptake if the cells were stimulated to grow. The amounts of polyamines taken up by the cells were nevertheless negligible in comparison with the net polyamine flux across the monolayers. Basolateral excretion of polyamines was in the picomolar range, whereas their transepithelial transport, occurring presumably by passive diffusion through the paracellular pathway, contributed hundreds of micromoles of polyamines to the basolateral chamber. We conclude that transepithelial transport of polyamines occurs by passive diffusion, and that it is not influenced when epithelial cells are stimulated to proliferate by a potent mitogen such as EGF.

Biological Transport↗
PubMed2001

Determination of alpha1-proteinase inhibitor by a new enzyme linked immunosorbant assay in feces, serum and an enterocyte-like cell line.

Although alpha(1)-proteinase inhibitor (alpha(1)-PI), the main serine proteinase inhibitor in human plasma, is predominantly liver-derived, the proof of fecal alpha(1)-PI is a maker for intestinal protein loss. Furthermore, alpha(1)-PI is synthesized locally by human intestinal epithelial cell lines (e. g. Caco-2). Therefore, we investigated the diagnostic value of a new enzyme-linked immunosorbent assay (ELISA) to detect alpha(1)-PI in serum, feces, and Caco-2 supernatants in comparison with radial immunodiffusion (RID). alpha(1)-PI concentrations assessed by ELISA were on an average 30 % higher than those measured by RID. Only the ELISA system detected alpha(1)-PI in supernatants of Caco-2 cells. Our data imply first that this ELISA system is more sensitive to assess alpha(1)-PI than other methods, and second that it obviously determines locally synthesized alpha(1)-PI which can not be liver-derived. However, further examinations are necessary to distinguish between enterocyte-derived or systemic alpha(1)-PI and its diagnostic relevance in bowel disease.

Adolescent↗
PubMed2000

Errors in scoring objective personality tests.

Given the paucity of previous research, we examined the occurrence of scoring error on widely used objective personality tests and examined its possible relation to two factors: scoring procedure complexity (SPC) and commitment to accuracy (CTA). We double-checked the scoring of three tests (MMPI, Beck Depression Inventory, Spielberger State/Trait Anxiety Inventory) across three settings. Each of the tests were misscored at a surprisingly high rate in at least one setting, and some such errors altered major interpretive implications. Tests of higher SPC showed greater error rates, but high CTA greatly reduced the occurrence of error across levels of SPC. Unexpected sources of error were also uncovered, such as commercial computer scoring errors and disagreement in scoring standards among test publishers. Practical suggestions for improving scoring accuracy are offered.

Bias↗
PubMed1999

p16INK4 mediates contact-inhibition of growth.

Growth of non-transformed cells in vitro is regulated by density-dependent mechanisms via cell-cell contacts, leading to arrest in late G1-phase at confluency (contact-inhibition of growth). In the present study it is shown that this results from p16INK4-mediated dissociation of the complex cdk4-cyclin D1, which is responsible for the inactivation of the gate keeper of G1-S transition, the retinoblastoma protein pRb. As a consequence of the inactivation of cdk4, downstream the activation of cdk2 and hyperphosphorylation and thus inactivation of pRb was impaired. Direct evidence for the central role of p16INK4 in growth control comes from the observation that a competitive inhibitor of p16INK4 repressed contact inhibition of growth. These findings provide an explanation for the high incidence of mutation or loss of INK4 in human tumours.

Amino Acid Sequence↗
PubMed1999

Hypospadiac or intact foreskin graft for syndactyly repair.

BACKGROUND/PURPOSE: Syndactyly is one of the most common malformations of the hands and feet. Repair may necessitate the use of a full-thickness skin graft. The prepuce is an excellent choice for grafting because of its lack of hair, elasticity, and degree of thickness. The authors report 4 cases of syndactyly repair using foreskin for grafting. METHODS: The authors reviewed 4 cases of syndactyly repaired at Children's Hospital, where foreskin was used for grafting. There was one congenital band syndrome and 3 cases of simple syndactyly. Three patients had a normal prepuce and underwent simultaneous circumcision. One patient presented with coronal hypospadias and underwent simultaneous meatal advancement and glanuloplasty. RESULTS: All patients experienced a satisfactory outcome with no graft loss and no complications. No grafts showed hair, and 3 grafts showed slight relative hyperpigmentation. Excess foreskin was available in all cases of simple syndactyly. Concominant hypospadias repair did not increase the morbidity of the surgery. CONCLUSION: The intact or hypospadiac foreskin is an excellent choice for a free graft in syndactyly repair when available.

Child, Preschool↗
PubMed1999

Effects of the label "schizophrenia" on causal attributions of violence.

We investigated the relation between the label of "schizophrenia" and causal attributions of violence. Undergraduates read 1 of 10 scenarios in which two variables were manipulated: a psychiatric label and environmental stress. The scenario described an employee who acted violently toward his boss. Subjects made causal attributions for the employee's behavior by completing an adapted version of the Causal Dimension Scale II. Subjects also completed a questionnaire designed to explore several issues concerning the effects of the schizophrenia label on perceptions of behavior. Contrary to the primary hypothesis, the schizophrenia label did not lead subjects to make significantly more personality causal attributions for violent behavior. With increasing environmental stress, subjects did make significantly fewer personality attributions. A follow-up study using practicing clinicians as subjects yielded similar findings. The results of these studies are discussed in light of perceived stereotypes of persons with schizophrenia and conceptual issues in attribution research.

Adult↗
PubMed1997

Maintaining theophylline compliance/adherence in severely asthmatic children: the role of psychologic functioning of the child and family.

BACKGROUND: Noncompliance with asthma therapy by asthmatic children and their families is a common cause of treatment failure. Psychologic factors have been reported to influence adherence patterns. OBJECTIVE: To evaluate the relationship of psychologic function of severely asthmatic children and families with theophylline compliance during a 1-year follow-up period after inpatient asthma rehabilitation. METHOD: Thirty-seven severely asthmatic children with a median age of 9 years (range, 2 to 17 years) were treated in an inpatient rehabilitation program (median, 15 days). Established clinical rating scales of psychologic adjustment were used for children (Child Global Assessment Scale) and families (Family Global Assessment Scale) at the time of admission. Patients were defined as noncompliant if 30% or more of theophylline levels obtained during the 1-year follow-up period were less than 5 mg/L (mumol/L). RESULTS: Compliant children had higher scores on the Child Global Assessment Scale than noncompliant children (64 versus 48, P = .09). Families of compliant children had significantly higher scores on the Family Global Assessment Scale than did families with noncompliant children (63 versus 54, P < .05). There was no statistical relationship between compliance status and parent-reported behavior problems, demographic factors (age, race, sex, and number of parents at home), health insurance, specialty referral at admission, measures of medical morbidity (days hospitalized, number of emergency care visits, and number of corticosteroid bursts), or length of rehabilitation stay. Both compliant and noncompliant children had comparable reductions in morbidity (hospital and emergency care, number of corticosteroid bursts required). CONCLUSION: Psychologic functioning of the child and family may be related to theophylline compliance.

Adolescent↗
PubMed1997

Caring for the severely asthmatic child and family. I. The rationale for family systems integrated medical/psychological treatment.

Comprehensive care for the severely asthmatic child includes psychological as well as medical treatment. Family therapy is a recognized modality of therapy. Investigations have examined the role of emotion and asthma as well as psychosomatic asthma. Pharmacological treatment of beta 2-agonist and cromolyn prior to disciplining the child prevents psychosomatic asthma secondary to crying or shouting. Adherence to multiple asthma therapeutic modalities is imperative, and a psychological and medical team can address these important clinical issues in a high-risk population.

Asthma↗
PubMed1996

An economic evaluation of short-term inpatient rehabilitation for children with severe asthma.

BACKGROUND: The cost of asthma care in the United States in 1990 has been estimated to be 6.2 billion dollars. The greatest proportion is due to hospital care. OBJECTIVE: We report changes in estimated medical charges of 59 children with severe asthma 1 year before inpatient rehabilitation and over a 4-year follow-up period. METHODS: Asthma resource use (e.g., hospital, physician, medication) was identified before and after inpatient rehabilitation. Estimated charges were assigned. This was done retrospectively for the 1-year period before rehabilitation, prospectively during rehabilitation, and over a 4-year follow-up period. Patients served as their own controls. There was no control group. RESULTS: When median asthma resource use 1 year before rehabilitation was compared with that during the first, second, third, and fourth years of follow-up, there was a reduction in median hospitalization and median emergency care. Compared with mean total medical charges the year before rehabilitation, reductions in mean total medical charges were 56.7% at the completion of the first year (excluding charges for rehabilitation), 70.5% at second year, 74.6% at third year, and 77.5% at fourth year. Over the 4-year postrehabilitation period, the discounted cumulative net savings was $29,605. The discounted cumulative net savings surpassed the mean rehabilitation charge during the early months of the fourth year of the postrehabilitation period. CONCLUSION: Inpatient rehabilitation was significantly associated with a reduction in estimated total medical charges over a 4-year follow-up period.

Adolescent↗
PubMed1995

Density-dependent regulation of cell growth by contactinhibin and the contactinhibin receptor.

BACKGROUND: The number of cells within mammalian tissues is maintained by growth-stimulating and growth-inhibiting mechanisms, with inhibitory signals being superimposed over growth stimuli. This is reflected, in the culture of normal adherent cells, by the phenomenon of density-dependent inhibition of growth: cells cease proliferation after becoming a confluent monolayer. We have shown previously that a plasma membrane glycoprotein, contactinhibin, is a major effector of negative growth regulation. Although transformed cells express contactinhibin in a functionally active form, they are not growth-inhibited, suggesting that the defects that lead to their aberrant growth are located 'downstream' of contactinhibin. RESULTS: Here, we provide evidence that a 92 kD plasma membrane protein, which we call CiR, binds specifically to contactinhibin and acts as a receptor mediating the contact-dependent inhibition of growth of cultured human fibroblasts. When polyclonal antibodies against CiR were introduced into cells using liposomes, confluent cells were released from density-dependent growth control. By contrast, cross-linking CiR that is localized to the plasma membrane, using anti-CiR antibodies, led to growth inhibition, suggesting that CiR is a signalling molecule and implicating CiR oligomerization in signal generation. This conclusion is supported by the finding that binding of contactinhibin by CiR is strongly dependent on the local concentration of both molecules and has a sharp threshold. When CiR was isolated by immuno-precipitation under conditions favouring phosphorylation, it was hyperphosphorylated on serine and threonine residues and had reduced contactinhibin-binding capacity; the binding capacity of CiR was restored after treatment with potato acid phosphatase. Fibroblasts transformed with simian virus 40 had reduced CiR expression, higher CiR phosphorylation levels, and a strongly reduced capacity of CiR to bind to contactinhibin. Phosphatase treatment of the CiR isolated from transformed cells only partially restored its contactinhibin-binding capacity. CONCLUSIONS: Homeostasis is the net result of a highly balanced network of growth-stimulating and growth-inhibitory signals. We have shown that density-dependent inhibition of growth in vitro is mediated by the interaction of contactinhibin with a 92 kD plasma membrane glycoprotein, CiR, the contactinhibin-binding capacity of which is regulated by phosphorylation.

Cell Count↗
PubMed1995

The detection of deception.

In clinical situations patient honesty and self-interest usually coincide; however, in legal circumstances patients may be motivated to deceive and may be skilled in doing so. Research raises doubts about the capacity of health professionals to detect malingering, particularly when there is less known about conditions or expected symptom patterns, more definitive tests are lacking or require patient cooperation, and diagnosis depends substantially on patient self-report. Given the lack of systematic feedback about our judgmental accuracy when deciding the presence or absence of malingering, clinical experience per se provides an inadequate means for identifying and correcting erroneous practices and for determining just how confident we ought to be in our subjective impressions. Thus, in the appraisal of malingering, it is dangerous to place too much dependence on subjective confidence. Methods are discussed that can supplement medical examination and increase the accuracy of malingering detection.

Diagnosis, Differential↗
PubMed1995

Modulation of mRNA expression and secretion of C1q in mouse macrophages by anti-inflammatory drugs and cAMP: evidence for the partial involvement of a pathway that includes cyclooxygenase, prostaglandin E2 and adenylate cyclase.

Isolated BALB/c mouse thioglycollate-elicited (inflammatory) peritoneal macrophages release at least 10 times more C1q than do isolated resident peritoneal macrophages. Addition of non-steroidal anti-inflammatory drugs (NSAID) to thioglycollate-elicited macrophages in culture inhibited the release of C1q and reduced levels of C1q-specific mRNA. Contrastingly, the NSAID were found to enhance C1q-specific mRNA levels in resident macrophages, although no increase in C1q levels secreted was observed. This suggests that the response of macrophages to NSAID, with respect to C1q synthesis, reflects the developmental stage of the macrophage. The gold salt auranofin (AFN) was found to enhance markedly C1q synthesis at both transcriptional and secretory levels in thioglycollate-elicited macrophages whilst, conversely, AFN reduced mRNA levels in resident macrophages. This indicates that AFN and the NSAID may work via the same or similar biochemical pathway, but with opposing effects. The glucocorticoid hydrocortisone (HC) greatly enhanced C1q-specific mRNA levels in both thioglycollate-elicited and resident macrophages, although no parallel increases in C1q secreted were observed. The data on inhibition of C1q biosynthesis by NSAID in thioglycollate-elicited macrophages are supported by the enhancement of C1q biosynthesis following addition of prostaglandin E2 (PGE2) or dibutyryl cyclic AMP (dBcAMP) to the cultures. From these experiments, it is concluded that C1q biosynthesis is controlled, at least in part, by a pathway involving cAMP.

Adenylyl Cyclases↗
PubMed1992

Integrating the cognitive mental status examination into the medical interview.

The frequency of cognitive deficits in medical patients makes the cognitive mental status evaluation an important component of the medical interview. This paper helps delineate the clinical situations in which formal cognitive mental status questioning is indicated. We address the critical issues involving the doctor-patient interaction in order to facilitate the evaluation of mental status without alienating the patient or introducing artificial and unnecessary questions. We review more specifically the areas of attention, memory, language, constructional ability, and higher cognitive functions. Finally, we address issues of referral for further evaluation.

Attention↗
PubMed1991

Forensic neuropsychology: the art of practicing a science that does not yet exist.

Despite its future promise, neuropsychological evidence generally lacks scientifically demonstrated value for resolving legal issues, and thus, if admitted into court, should be accorded little or no weight. In support of this contention, examples of problems and limits in forensic neuropsychology are described. These include contrasts between the clinical and forensic context; the base-rate problem; lack of standardized practices; problems assessing credibility or malingering; difficulties determining prior functioning, limits in the capacity to integrate complex data; and the lack of relation between judgmental accuracy and education, experience, or credentials. Some possible counterarguments are also addressed.

Activities of Daily Living↗
PubMed1990

To say it's not so doesn't prove that it isn't: research on the detection of malingering. Reply to Bigler.

Research that directly examines clinicians' capacity to detect malingering creates doubt about their success in this endeavor and about confident self-appraisals of detective abilities. We argue that Bigler's counterassertions lack supportive evidence or conflict with research on such topics as clinicians' level of training and experience and their judgmental accuracy. We further note that lack of both base rate information and definitive outcome information compound doubts about clinicians' capacity to detect malingering.

Child↗