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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 289 records · Page 16Linked to original sources

Relationship between the plasma levels of beta-carotene and lung functions in cigarette smokers.

Relationships between the plasma levels of beta-carotene (BC) and spirometry were studied in 30 asymptomatic male cigarette smokers and 34 age-matched non-smoking control subjects. Plasma BC-levels, determined by high performance liquid chromatography (HPLC), were decreased on average by 18% (p 0.1251) in the smokers relative to the non-smokers and by 28% (p 0.015) following correction for blood cholesterol. The spirometric values, FEV1 and FEF25-75, determined from the flow-volume loops of each subject, were decreased by 5% (p 0.095) and 12% (p 0.0072) respectively in the smokers relative to the non-smokers. In the smokers, but not in the non-smokers, the plasma levels of BC correlated significantly and positively with the spirometric values, FEV1 (r 0.48, p 0.01) and FEF25-75 (r 0.58, p 0.0008). The results suggest that BC-status may determine susceptibility to oxidant-mediated pulmonary dysfunction in cigarette smokers.

Adult↗

The WHO and why of HIV vaccine trials.

A World Health Organization (WHO) advisory committee meeting in Geneva at the end of last month approved phase III trials for HIV vaccines in developing countries. What is the justification for this decision?

AIDS Vaccines↗

The riminophenazine agents clofazimine and B669 reverse acquired multidrug resistance in a human lung cancer cell line.

The potential of the riminophenazine agents clofazimine and B669, at therapeutically relevant concentrations, to reverse P-glycoprotein-mediated multidrug-resistance (MDR) in a human lung cancer cell line (H69/LX4) has been investigated in vitro. Cyclosporin A, a well-documented MDR-modifying agent, was included for comparison. Clofazimine, B669 and cyclosporin A at minimally cytotoxic concentrations of 1, 0.5 and 5 micrograms/ml, respectively, were equally effective in restoring sensitivity to vinblastine, doxorubicin, daunorubicin and mitomycin C in the H69/LX4 cell line. All three chemosensitizing agents also increased the accumulation of [14C]vinblastine by H69/LX4 cells. Riminophenazines, which are relatively non-toxic, non-carcinogenic and non-myelosuppressive agents, are promising contenders for evaluation in experimental and clinical oncology as modulators of acquired MDR.

Anti-Infective Agents↗

Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) occur in pediatric patients; however, the incidence, associated morbidity, and mortality are unknown. A Canadian registry of DVT and PE in children (ages 1 month to 18 years) was established July 1, 1990 in 15 tertiary-care pediatric centers. One-hundred thirty-seven patients were identified prospectively and are the subject of this report. The incidence of DVT/PE was 5.3/10,000 hospital admissions or 0.07/10,000 children in Canada. Infants under 1 year old and teenagers predominated with equal numbers of both sexes. DVT were located in the upper (n = 50) and lower (n = 79) venous system, or as PE alone (n = 8). Central venous lines (CVLs) were present in approximately 33% of children with DVT (n = 45). Associated conditions were present in 96% of children and 90% of children had two or more associated conditions for DVT. DVT was diagnosed by venography (n = 83), duplex ultrasound (n = 37), and other combinations (n = 17). Twenty-two of the 31 ventilation/perfusion scans performed were interpreted as high-probability scans for PE. Therapy consisted of heparin (n = 115), thrombolysis (n = 15), surgical removal of a CVL or thrombus (n = 22), and oral anticoagulant therapy (n = 103). Significant bleeding complications did not occur. However, three (2.2%) children died as a direct consequence of their thromboembolic disease; DVT reoccurred in 23 children and postphlebitic syndrome (PPS) occurred in 26. In conclusion, DVTs occur in a significant number of hospitalized children with a mortality of 2.2%. Complications are not hemorrhagic, but thrombotic, and characterized by PE, recurrent disease, and PPS. In contrast to adults, the upper venous system is frequently affected because of the use of CVLs. The frequency of DVT/PE justifies controlled trials of primary prophylaxis in high-risk groups, and therapeutic trials to determine optimal treatment.

Administration, Oral↗

Does the MFB convey functionally different reward signals?

Pulse frequencies that sustain the same % of the maximum self-stimulation rate (equipotent frequencies) are equipreferred by rats because they elicit identical reward signals. However, when two equipotent frequencies are delivered through different electrodes, lack of equipreference can be expected if the resulting neural signals belong to different rewarding processes and if these signals are differentially ranked on the animal's decisional scale. We used this rationale to test the possibility that the MFB conveys functionally different signals. Rats were implanted with an electrode near the anterior MFB (aMFB) and another near the posterior MFB (pMFB). The rate of self-stimulation, as a function of the pulse frequency, was first obtained for each electrode, separately. Rats were then allowed to press for aMFB or pMFB stimulation in a double-lever box. One of the levers delivered a fixed aMFB frequency whereas the other delivered a variable pMFB frequency. In the following session, this situation was reversed. The time spent bar-pressing for each stimulus was plotted as a function of the variable frequency. Equipreference for equipotent stimuli (i.e. for frequencies that supported the same % of the maximum rate in the single-lever box) was noted for 6 out of 11 electrode pairs. However, in 3 cases, the subjects preferred the pMFB stimulus over an aMFB equipotent stimulus and in two other cases they preferred the aMFB stimulus. The data from these five subjects suggest the presence of functional heterogeneity within the MFB reward pathway, a view already supported by a variety of other studies.

Animals↗

TAP (transporter associated with antigen processing)-independent presentation of endogenously synthesized peptides is enhanced by endoplasmic reticulum insertion sequences located at the amino- but not carboxyl-terminus of the peptide.

Under most circumstances, cell surface MHC class I molecules display peptides derived from a cytosolic pool of proteins. The efficient presentation of such peptides requires the functioning of two MHC gene products [TAP1 and TAP2 (transporter-associated with Ag processing 1 and 2)] that form a complex that facilitates transmembrane movement of peptides from the cytosol to the endoplasmic reticulum, the site of peptide association with class I molecules. It has been previously shown that peptides can be presented in a TAP-independent manner in association with HLA A2.1 or H-2 Kd if they are expressed COOH-terminal to an endoplasmic reticulum insertion/signal sequence derived from the adenovirus E3/19K glycoprotein (Anderson et al., 1991. J. Exp. Med. 174: 489; Eisenlohr et al., 1992. Cell 71: 963). We show that: 1) the E3/19K signal sequence greatly enhances the presentation of each of four additional peptides tested in association with H-2 Kb or Kk, 2) the E3/19K signal sequence can be substituted by a signal sequence derived from beta-IFN, and 3) the E3/19K signal sequence does not function when located at the COOH terminus of antigenic peptides. These findings indicate that first, many peptides require TAP for efficient presentation to T cells, second, expression of peptides COOH-terminal to signal sequences is a generally applicable method of bypassing the TAP-dependence of peptide presentation and third, the leader sequence does not act to bypass TAP simply by increasing the hydrophobic nature of peptides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Psychosocial interest, medical interviews, and the recognition of depression.

OBJECTIVES: To measure primary care physicians' attitudes toward psychosocial issues, determine their relationship to the style of the medical interview, and assess whether attitudes and interview behaviors lead to correct diagnosis in patients with depression. DESIGN: Physicians were videotaped while interviewing four patients standardized with criteria symptoms of major depression. Physicians were unaware of the mental health focus of the study. SETTING: Patient examining rooms. PARTICIPANTS: Physicians were eligible for recruitment if they were board certified or eligible in family practice or internal medicine, practiced primary care medicine, and were listed in regional directories. Standardized patients were recruited from the community. MAIN OUTCOME MEASURES: Attitudes toward psychosocial issues (measured by the Physician Belief Scale), interview content (measured by review of the videotaped encounters), interview behaviors (measured by the Interaction Analysis System for Interview Evaluation), and a listing of depression in the differential diagnosis (determined by physician debriefing interviews). RESULTS: Forty-seven community-based practitioners participated. Forty-eight percent of interviews resulted in a diagnosis of depression. Physician Belief Scale scores were not significantly correlated with patient-centered interviewing, psychosocial questions, inquiry about depression symptoms, or a depression diagnosis. Longer interviews were more likely to result in a depression diagnosis. CONCLUSIONS: High interest in psychosocial issues was not associated with patient-centered interviewing behaviors, questions about psychosocial or depression symptoms, or depression diagnoses. However, certain patient-centered interviewing behaviors, particularly those defined as "affective," did lead to the recognition of depression.

Adult↗

The role of socioeconomic status and injury morbidity risk in adolescents.

OBJECTIVE: To examine the patterns of socioeconomic status and injury morbidity in adolescents. DESIGN: Prospective cohort study. SETTING: Metropolitan school district in Allegheny County, Pennsylvania. PARTICIPANTS: There were 1245 students (89%) recruited from 1400 aged 12 to 16 years. INTERVENTIONS: None. MEASURES AND RESULTS: Baseline variables of socioeconomic status used for this analysis included township of residence (from the 1990 census data ranked by the percentage of households below the poverty level) and employment status of the parents (student self-report). Life-table analysis revealed no differential risk of injury by socioeconomic status. Similar results were found when stratified by gender, race, injury type (sport vs nonsport), and injury place (school vs home). CONCLUSIONS: The results indicate that in this cohort of adolescents, socioeconomic status does not seem to be a contributing risk factor for injury.

Adolescent↗

Regeneration of HoxD expression domains during pattern regulation in chick wing buds.

The expression domains of genes located at the 5' end of the HoxD (formerly Hox-4) complex appear to correlate with pattern along both the proximal-distal (PrDi) and the anterior-posterior (AP) axes of the developing limb bud, and it has been suggested that the HoxD gene products are involved in the specification of positional information during limb development. The apical ectodermal ridge is required for limb outgrowth and is thought to influence mesodermal cells at the distal end of the limb bud in a region within which patterning events occur. In this paper, we examine the expression of 5' HoxD genes during PrDi pattern regulation in chick wing buds. In limbs undergoing pattern regulation, we demonstrate that the domains of HoxD11 and HoxD13 gene expression are "regenerated" within 24 hr of removal of the distal mesenchyme. In contrast, in limbs which will not form distal structures, HoxD13 expression becomes reduced.

Animals↗

Repeated sequence target sites for maternal DNA-binding proteins in genes activated in early sea urchin development.

This communication concerns a very highly conserved inverted repeat sequence element that serves as a target site for a sea urchin maternal DNA-binding factor. The maternal factor is present in relatively large amounts in unfertilized eggs, but is about 100 x less prevalent per embryo in 24-hr embryo nuclear extract. The inverted repeat target site is found in the regulatory domain of the CyIIIa cytoskeletal actin gene and also in two upstream genes encoding transcription factors that bind to a functionally important cis-regulatory element of the CyIIIa gene. There are about 460 copies of the inverted repeat target site per genome. About 15% of these sites occur in a nested arrangement together with a second inverted repeat that binds another previously characterized maternal transcription factor. This arrangement is the same as that which occurs in the CyIIIa gene, and it may be of regulatory significance with respect to activation of certain genes in oogenesis and early embryogenesis.

Actins↗

FGF-2 induces regeneration of the chick limb bud.

The chick limb bud is unable to mount a regenerative response following amputation at any stage of its development. Local application of heparan sulfate conjugated beads loaded with fibroblast growth factor-2 (FGF-2) onto an amputated stage 25 chick limb bud results in a high frequency (88%) of limbs in which the regeneration of digit-like structures was induced. The regenerative response is associated with the location of the FGF-2-loaded beads on the limb stump. This is the first report of the induction of a regenerative response in a higher vertebrate limb by a chemically defined agent.

Animals↗

Conversion of anterior limb bud cells to ZPA signaling cells in vitro and in vivo.

Following a graft of posterior (zone of polarizing activity or ZPA) cells into the anterior margin of the developing chick wing bud, anterior cells are induced to alter their developmental fate and form structures that are normally composed of posterior cells. When anterior cells are cultured under microdissociation conditions they develop ZPA signaling ability within 24 hr. ZPA signaling in these cultures is transient and once established the level of ZPA signaling declines with time in culture. ZPA signaling in anterior cells is sensitive to treatment with fibroblast growth factor-2 (FGF-2); the development of ZPA signaling is inhibited when nonsignaling anterior cells are cultured in the presence of FGF-2. Conversely, when anterior cells that have developed ZPA signaling are treated with FGF-2, ZPA signaling levels are maintained. Thus, our results suggest that FGF-2 maintains or stabilizes the positional character of anterior (nonsignaling) cells, as well as anterior ZPA signaling converted cells, and posterior (ZPA signaling) limb bud cells in vitro (R. Anderson, M. Landry, and K. Muneoka (1993) Development 117, 1421-1433). In addition, anterior cells will convert to ZPA signaling cells in vivo following apical ectodermal ridge (AER) removal, suggesting that a factor(s) localized to the AER prevents anterior cells from developing ZPA signaling capability during limb outgrowth. These findings indicate that nonsignaling anterior limb bud cells have the potential to become ZPA signaling cells and that FGF-2, or a related factor, functions in the maintenance of positional states in the developing limb.

Animals↗

Alpha-tocopherol prevents cyclosporin A-mediated activation of phospholipase A2 and inhibition of Na+, K(+)-adenosine triphosphatase activity in cultured hamster renal tubular cells.

At concentrations of 0.5 microM and upward, cyclosporin A (CsA) caused dose-related inhibition of the growth of a hamster renal tubular cell line (HAK ATCC; CCL15) in vitro. Inhibition of cell growth was due to the cytotoxic properties of CsA which were associated with enhancement of activity of phospholipase A2 (PLA2) according to the increased generation of arachidonic acid and lysophosphatidylcholine (LPC). Arachidonate per se, at concentrations of up to 20 microM, did not affect the growth of HAK cells, while cyclooxygenase and 5-lipoxygenase inhibitors failed to protect the cells against the antiproliferative effects of CsA. However, LPC caused dose-related inhibition of the growth of HAK cells. Moreover, coincubation with lysophospholipase or alpha-tocopherol (AT, vitamin E), a PLA2 inhibitory and lysophospholipid-complexing agent, protected the HAK cells against both CsA and LPC. The Na+, K(+)-ATPase activity of HAK cells was also inhibited by CsA, with the enzyme being protected by inclusion of AT or lysophospholipase. Increased activity of PLA2 and inhibition of Na+, K(+)-ATPase preceded cytotoxicity and cytolysis. Excessive production of lysophospholipids and consequent inhibition of Na+, K(+)-ATPase in renal tubular cells is a possible mechanism of CsA-induced nephrotoxicity. The protective effects of AT suggest that this agent may be clinically useful in preventing the renal side effects of CsA.

Animals↗