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Biomedical subjects

P O Anderson

Publications and source records attributed to P O Anderson.

At least 19 recordsLinked to original sources
PubMed2001

Inhibition of the transcription factors AP-1 and NF-kappaB in CD4 T cells by peroxisome proliferator-activated receptor gamma ligands.

The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear hormone receptor superfamily, is essential for adipocyte differentiation and glucose homeostasis. PPARgamma has been found recently to regulate macrophage activation in response to mitogens and inflammation. Our study shows PPARgamma to be preferentially expressed in the nuclei of resting T cells and to increase upon activation of T cells by either anti-CD3 and anti-CD28 or phorbol myristyl acetate (PMA). We also found the PPARgamma ligand ciglitizone to attenuate the activation of T cells by inhibiting cytokine gene expression and anti-CD3 and anti-CD28 or PMA-induced proliferative responses. Inhibition of both the proliferative response and inflammatory cytokine expression in CD4 T cells was correlated with suppression of the activated transcription factors AP1 and NF-kappaB. PPARgamma ligands also strongly inhibited SEA-induced Vbeta3 T cell activation in vivo. These results, together with previous findings of the inhibitory effect of PPARgamma ligands on activated macrophages, provide clear evidence for PPARgamma as a negative regulator of the inflammatory activation of both macrophage and T cells. PPARgamma may thus be a potential therapeutic target for the treatment of autoimmunity.

Animals↗
PubMed2001

Assembly of tapasin-associated MHC class I in the absence of the transporter associated with antigen processing (TAP).

The assembly of MHC class I molecules is regulated by a multi-protein complex in the endoplasmic reticules (ER) termed the loading complex. Tapasin is suggested to be one of the molecules forming this complex on the basis of its interaction with both the transporter associated with antigen processing (TAP) and MHC class I molecules. To address whether TAP is indispensable for the processing of the assembly of tapasin-associated MHC class I molecules, we studied the association of MHC class I molecules with tapasin, the assembly of tapasin-associated MHC class I with peptides and the peptide-mediated dissociation of MHC class I from tapasin in TAP-mutant T2 cells. In the absence of TAP, MHC class I heavy chain and beta(2)-microglobulin dimers were found to be properly associated with tapasin. The stable MHC class I dimer was required for its association with tapasin in the ER. In the absence of TAP, tapasin retained MHC class I molecules much longer in the ER than in the presence of TAP. This low off-rate of MHC class I from tapasin was due to the absence of high-affinity peptides in the ER of TAP-mutant cells but not to the absence of TAP per se. The introduction of peptides into permeabilized microsomes of TAP-mutant cells led to effective loading of the peptides onto tapasin-associated MHC class I and to the subsequent dissociation of MHC class I from tapasin. These results demonstrate that regulation of the assembly of tapasin-associated MHC class I is independent of the interaction of tapasin with TAP, but is dependent upon the peptides transported by TAP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Distinct differences in association of MHC class I with endoplasmic reticulum proteins in wild-type, and beta 2-microglobulin- and TAP-deficient cell lines.

In this study we have compared the interaction of human MHC class I molecules with IgG heavy chain (HC) binding protein (BiP), calnexin, calreticulin, tapasin and TAP in beta(2)-microglobulin (beta(2)m)- or TAP-deficient cells, as well as in wild-type B-LCL cells. Distinct differences between the association of HC and these endoplasmic reticulum (ER) proteins were found in the three cell lines. In the absence of beta(2)m (Daudi cells), HC associated with both BiP and calnexin. A prominent portion of HC was complexed simultaneously to both chaperones, as indicated by co-precipitation with either anti-calnexin or anti-class I antisera. In the presence of beta(2)m, but absence of TAP (T2 cells), HC could be co-precipitated with calnexin, whereas no detectable interaction with BiP could be demonstrated. This suggests that calnexin interacts with HC at a later stage than BiP. In B-LCL cells, HC-beta(2)m associated with calreticulin and tapasin, whereas no interaction with calnexin and BiP was observed. In the absence of beta(2)m, HC were rapidly degraded in the ER, while the ER retained HC were stabilized in the presence of beta(2)m, even in the absence of TAP. The dissociation of class I molecules from TAP in B-LCL cells correlated with the kinetics of appearance of class I molecules on the cell surface, suggesting that TAP retains peptide-free class I molecules in the ER. Taken together, our results suggest the model that BiP and calnexin sequentially control the folding of MHC class I, before MHC class I molecules associate with the loading complex.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Weight gain in infants breastfed by mothers who take fluoxetine.

OBJECTIVE: Despite the manufacturer's recommendation that fluoxetine not be used by women while breastfeeding, many women choose to do so. There is little information available in the literature to suggest that this practice is or is not safe. The purpose of this study was to examine weight gain in infants who are breastfed by mothers who take fluoxetine, compared with weight gain in infants who are breastfed by mothers who do not take any psychotherapeutic medication. A secondary goal was to assess the frequency of reported side effects in infants who are breastfed by mothers who take fluoxetine. METHODOLOGY: A retrospective cohort study design was used. Subjects were identified from an ongoing pregnancy outcome study conducted through the California Teratogen Information Service and Clinical Research Program. A total of 64 women were interviewed who had taken fluoxetine during a pregnancy between the 1989 and 1997; 26 of these women breastfed their infants and continued to take the medication, and 38 breastfed their infants but did not take the medication. Postnatal weight gain was taken from pediatric records, and the frequency of side effects was measured by maternal response to the interview questionnaire. RESULTS: Using linear regression analysis, the infants who were breastfed by mothers taking fluoxetine demonstrated a growth curve significantly below that of infants who were breastfed by mothers who did not take the drug. The average deficit in measurements taken between 2 weeks and 6 months of age was 392 g (95% confidence interval: -5, -780). Using a repeated measures analysis of covariance for those infants with more than one postnatal weight measurement available, the difference between the two groups was similar, approximately 1.2 standard deviations (P =.005). In response to interview questions regarding side effects, no mother who breastfed her infant while taking fluoxetine reported any unusual symptoms that could be attributed to the medication. CONCLUSIONS: These data do not suggest that women who breastfeed while taking fluoxetine are likely to note unusual behavior in their infants that they consider related to use of the medication. However, although there was no excess of infants in the fluoxetine group with postnatal weight measurements >2 standard deviations below the mean, these data indicate that breastfeeding while taking fluoxetine is associated with reduced growth that may be of clinical importance in situations in which infant weight gain is already of concern.

Antidepressive Agents, Second-Generation↗
PubMed1994

Establishment of a 900 telephone number at a university-based drug information service.

Effects of converting a free drug information service at a university medical center to a 900 telephone number are described. Calls to a university medical center drug information service had increased beyond the capacity of staff. A telephone survey to recent users of the service indicated that callers outside the institution would be willing to pay a fee for the service, so a 900 number was instituted for outside calls in January 1993. Staff recorded data on all questions they answered; data for 1993 were compared with those from 1992. Question volume decreased by 48% after the 900 number was instituted, with questions from outside the institution dropping by 55%, questions from outside health care professionals dropping by 72%, and questions from the lay public increasing slightly. One severe impediment to callers from local hospitals was that many hospitals block access to 900 numbers from their telephone systems. The average length of a call was three minutes and the average cost per call was $6. Net income during the first year of operation was $6698. The 900 number provided some income, but it did not completely offset operating costs. A 900 telephone number is a workable, but imperfect, method of providing drug information to outside callers. Early notification of users before implementing a 900 number is essential to allow time for them to arrange telephone access.

California↗
PubMed1991

Drug use during breast-feeding.

The physicochemical and pharmacokinetic factors involved in transfer of drugs into breast milk are reviewed. Passage of drugs into milk can best be viewed as a two-compartment system. Various ratios of the drug concentration values in the two compartments and ratios of maternal-to-infant intake have been described. Knowledge of the limitations of these methods is necessary to properly interpret and apply the literature on drug excretion into breast milk. Factors involved in choosing a drug for a nursing mother are listed, a stepwise approach to minimizing transfer of drug to the infant is presented, and the literature on the excretion of specific drugs into milk is reviewed. Generally, drugs given to nursing mothers reach infants in much smaller amounts than drugs given to pregnant women. Decisions about nursing during drug therapy and the choice of drug therapy in a nursing mother should be based on the dosage and duration of therapy, age of the infant, quantity of milk consumed, experience with the drug in infants, degree of oral absorption of the drug by the infant, potential long-term effects, possible interference with lactation, and non-dose-related toxicities (e.g., potential allergic reactions). Too often, the mother's need for a medication is perceived as a reason to discontinue nursing. By understanding the principles of drug passage into breast milk and systematically evaluating the mother's needs, infant factors, and the data on specific drugs, clinicians can usually devise treatment plans that allow nursing while minimizing the risks to the infant.

Breast Feeding↗
PubMed1987

Evaluation of prenatal vitamin-mineral supplements.

Nutritional requirements of pregnancy are reviewed, and guidelines for evaluating prenatal vitamin-mineral supplements are provided. Daily antepartum supplementation of 0.4-0.8 mg of folic acid and 30-60 mg of elemental iron is currently recommended, although the lower ends of these ranges may be most appropriate. Dietary intake of these nutrients is likely to be inadequate without supplementation, and their importance is well established. Requirements for other minerals and vitamins are not well established, and there is no consensus on the need for supplementation. However, available data suggest that prenatal supplements should probably contain other nutrients; pyridoxine hydrochloride, cholecalciferol, vitamin E, pantothenic acid, calcium, magnesium, zinc, copper, and possibly selenium should be considered. Interactions among the minerals and vitamins commonly found in prenatal supplements may affect the absorption of various nutrient components. Thus, very high or low levels of certain nutrients should be avoided. The chemical form of minerals should also be considered. Products should have demonstrated bioavailability for iron, zinc, and other components that are subject to bioavailability problems. Use of low-potency product that contains a wide range of vitamins and minerals appears to be the most prudent approach to prenatal vitamin and mineral supplementation.

Absorption↗
PubMed1987

Effect of a pharmacy-based cost-containment program on cimetidine costs and use.

A program developed by the University of California at San Diego Medical Center to curb over-prescribing of cimetidine is described. Guidelines for cimetidine use were approved in September 1985. Pharmacists undertook physician education and enforced the guidelines by monitoring patients through a specially designed documentation form. When use of cimetidine was not in compliance with the guidelines, the pharmacists contacted the physicians to recommend changes. Use of cimetidine hydrochloride injection declined 49% between September 30 and December 6, 1985. Extrapolated to an entire year, this reduction would result in cost savings of +12,000 to +16,000. However, after pharmacists stopped enforcing the guidelines in December 1985, use of cimetidine hydrochloride injection gradually increased to near control levels. In February 1986, the review of patients receiving cimetidine was reinstituted, resulting in another decline in use. Periodic review and reinforcement by pharmacists appear necessary to ensure that cimetidine continues to be prescribed appropriately.

California↗