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Biomedical subjects

L Miller

Publications and source records attributed to L Miller.

At least 253 records · Page 14Linked to original sources

Brain and self: toward a neuropsychodynamic model of ego autonomy and personality.

Principles derived from neuropsychology can begin to be applied to the development of heuristic models of complex psychological processes and can thereby contribute to theories of personality and psychopathology. Applications of neuropsychological concepts to the problems of self-knowledge, ego autonomy, and personality integration are discussed. Special reference is made to the role of the frontal lobes in the recursive modulation of behavior and to the verbal functions of the left hemisphere in self-awareness and self-control. Caution against a narrow localizationist conceptualization of human behavior is urged, and suggestions for interdisciplinary rapproachment are offered.

Brain↗

Signal requirements for the acquisition of tumoricidal competence by chicken peritoneal macrophages.

The present study was conducted to determine the tumoricidal potential of chicken macrophages. Sephadex-elicited peritoneal macrophages from 6-wk-old Cornell K-strain White Leghorn females (B15B15) were used as effector cells against three different 51Cr-labeled tumor cell targets: LSCC-RP9 (B15B2), MDCC-CU14 (B19, C2), and MDCC-CU25 (B17B17). Quantification of tumoricidal activity was done in a 16-h, Cr-release assay. Macrophages collected at 12, 24, and 42 h post-Sephadex stimulation failed to kill any of the tumor cell targets. However, macrophages treated with concanavalin A stimulated splenic cell supernatants (lymphokines, LK) and lipopolysaccharide (LPS) were able to kill all three tumor cell targets in coculture experiments. Cell-free supernatants collected from LPS and LK alone or combination-treated macrophages demonstrated cytolytic activity for both RP9 and CU25 tumor cell targets. The results of the study, therefore, suggest that chicken macrophages acquire tumoricidal competence if treated with macrophage activation signals such as LK, or LPS or both.

Animals↗

Comparison of macrophage function in several commercial broiler genetic lines.

The present study was conducted to establish baseline profiles of various macrophage functions in four commercial broiler genetic lines designated as Lines 1, 2, 3, and 4. All experiments were carried out between 2 to 3 wk of age. Total numbers of peritoneal exudate cells per bird collected 42 h after a single i.p. injection of Sephadex-G50 were comparable among the lines. Line 1 produced fewer macrophages along with reduced phagocytosis of opsonized SRBC, whereas Line 4 macrophages were depressed in unopsonized SRBC phagocytosis. Macrophages from Lines 2 and 4 killed internalized Escherichia coli earlier than macrophages from Lines 1 and 3. Supernatants from lipopolysaccharide-treated macrophages from Lines 1 and 2 exhibited significantly higher cytolytic activity against LSCC-RP9 tumor cells when compared with supernatants from Line 3 and 4 macrophages. The current study demonstrates genetic variation among the four broiler lines for mononuclear phagocytic system functions.

Animals↗

Economic analysis in health care antitrust.

The Federal Trade Commission (FTC or Commission) has been very active in enforcing antitrust laws in the health care field for the past two decades. The staff has investigated a wide variety of cases covering a broad range of restrictions on competition. These cases can be divided into three basic types of cases in health care: (1) mergers and acquisitions, (2) horizontal restraints cases or agreements among competitors, and (3) input market monopolization cases, such as hospital privileges cases. The Commission relies on both legal and economic analysis in all of these cases. As Chairman Steiger of the Federal Trade Commission has stated, antitrust policy has been "increasingly reshaped by analysis based on economic theory." This article attempts to explain the economic analysis used in antitrust enforcement as applied to the first two of the three types of health care cases. Section I presents the basic economic framework that is used to assess the competitive implications of health care mergers and acquisitions. Section II describes the analysis applied to other agreements among competitors in the health care field and briefly explains how this analysis differs in other health care cases.

Antitrust Laws↗

C5a structural requirements for neutrophil receptor interaction.

A number of C5a modifications were tested to determine effects on receptor binding to polymorphonuclear leukocyte (PMNL) membrane receptors and triggering of PMNL chemokinesis and myeloperoxidase (MPO) release. Site-directed mutagenesis was used to probe relationships of key C-terminal residues, and suggested a role for additional sites, particularly Lys19-20. A synthetic peptide based on C5a 19-30, weakly inhibited C5a binding. Potency of the C-terminal octapeptide, a full agonist, was markedly improved by a single Phe substitution for His67, and a Phe point mutation at this site was shown to enhance activity of the full recombinant protein.

Cells, Cultured↗

Tidal peritoneal dialysis: a pediatric experience.

The objective of this study was to assess whether eight hours of nightly tidal peritoneal dialysis (TPD) can provide uremia control equal that of CCPD/CAPD. A pilot study collected data from patients who volunteered to use TPD at home. Six children, ages 5 to 16, who required regular dialysis and lived within a 175 miles of the training center volunteered to use home TPD. These subjects were trained and followed at the University of Iowa Hospitals and Clinics. Dialysate creatinine and urea nitrogen were measured during both CCPD and TPD. Clearances were measured for tidal dialysis using multiple dialysate flow rates. Dialysate urea clearance (KU - ml/min normalized to 70 kg.) increased with dialysate flow (QD - ml/kg/H) [KU = 9.566 + 0.251 X (QD)], and dialysate urea nitrogen losses equaled those of CCPD. Eight hours of tidal dialysis can provide dialysis efficiency equal that of CAPD/CCPD.

Adolescent↗

Patient profile.

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Adult↗

Surveillance for rejection by echocardiographically guided endomyocardial biopsy in the infant heart transplant recipient.

Echocardiographically guided endomyocardial biopsy via percutaneous right internal jugular vein puncture has been performed 98 times in six patients 5-16 years of age at our institutions. The use of this approach was extended for rejection surveillance in seven infants transplanted at 2 weeks to 15 months of age (median, 2 months; mode, 2 weeks). A total of 35 consecutive biopsies were performed under heavy sedation in these infants (lowest weight, 3.0 kg) with the use of a 5F semirigid bioptome through a 5.0-cm 5F sheath. There was no case of entrance failure. A median of four biopsies was performed on each child (range, one to 14). Four to seven tissue pieces per biopsy were obtained using an apical four-chamber view for bioptome guidance. Ten instances of clinically suspected rejection were not confirmed by biopsy, and two cases of unsuspected rejection were found. The only complication was one instance of new mild tricuspid regurgitation in this group compared with one instance of increased tricuspid regurgitation after biopsy in the older child group. These preliminary results suggest that echocardiographically guided endomyocardial biopsy from the right internal jugular approach is a reliable and safe means for rejection surveillance in the infant and young child.

Biopsy↗

Orthostatic hypotension in human immunodeficiency virus infection may be the result of generalized autonomic nervous system dysfunction.

We used an autonomic nervous system (ANS) testing battery to determine if generalized ANS dysfunction was present in five human immunodeficiency virus-positive (HIV+) patients presenting with severe orthostatic hypotension (OH). All five patients had abnormal ANS testing, which demonstrated both sympathetic and parasympathetic defects, i.e., generalized ANS dysfunction. Treatment with fludrocortisone effectively reversed the OH in four of the five patients. The OH was transient in these four patients. We believe it is important to recognize that OH may be the result of generalized ANS dysfunction in HIV-positive patients and that it can be effectively treated.

Autonomic Nervous System↗

Enhanced stability of subtilisin by three point mutations.

This study was undertaken to characterize the effect of three point mutations made on aprA-subtilisin on the stability of the protein to both heat- and detergent-induced denaturation. Asparagine residues at positions 109 and 218 were replaced with serine residues to prevent the possible cyclization between these asparagines and the adjacent glycine residues and hence to increase the long-term stability. The effect of these substitutions on conformational stability was examined by thermal denaturation. At high calcium concentrations, the Ser109-substituted analog showed a 3 degrees C higher transition temperature than that of aprA-subtilisin, while the Ser218 substituted analog had a 4 degrees C higher transition temperature. The analog with both changes had a 7 degrees C higher transition temperature than that of the original aprA-subtilisin, indicating that the contributions of the individual mutations were additive. The analog with both mutations also exhibited increased stability in the presence of sodium dodecyl sulfate (SDS) when compared to aprA-subtilisin. In addition to the above two mutations, the asparagine at position 76, located in the high affinity Ca(2+) binding loop of subtilisin, was changed to aspartic acid. The effect of this mutation on the thermal stability of the protein was examined at different calcium concentrations. The analog with all three mutations exhibited little dependence on calcium concentration below 1 mM levels, while the proteins without the mutation at asparagine-76 displayed a strong dependence of melting temperature on Ca(2+) concentration in this range. At much higher calcium concentrations, the analog with three mutations showed an increase in stability similar to that observed with aprA-subtilisin. The analog with three mutations also exhibited greater stability to SDS-induced denaturation than both aprA-subtilisin and the Ser109- and Ser218-substituted analogs. The activation energy barrier for loss of structure in 1% SDS for the analog with all three mutations was increased over that for aprA-subtilisin by 16 kcal/ml. These results suggest that the mutation of asparagine-76 to aspartic acid increases the affinity of the primary Ca(2+) binding site.

Circular Dichroism↗

Eosinophilia-myalgia syndrome. Results of national surveillance.

Eosinophilia-myalgia syndrome, a newly recognized disorder that occurred in epidemic proportions during 1989, is associated with ingestion of manufactured tryptophan. A case is defined by debilitating myalgias and absolute eosinophilia greater than or equal to 1.0 x 10(9) cells/L. As of July 10, 1990, a total of 1531 cases had been reported nationwide, including 27 deaths. The highest rates of reported illness are concentrated in the western states, 68% are non-Hispanic white women aged 35 years and older, and data on associated clinical findings suggest a multisystemic disorder. The most frequent features include arthralgia (73%), rash (60%), cough or dyspnea (59%), peripheral edema (59%), elevated aldolase level (46%), and elevations in the results of liver function tests (43%). Neuropathy or neuritis, resulting in paralysis and death in some patients, was seen in 27%, and chest roentgenogram abnormalities were noted in 21% of those tested. Ninety-one percent reported onset of symptoms during or after May 1989, and 97% reported having taken tryptophan before the onset of symptoms. Since the recall of over-the-counter preparations of tryptophan in November 1989, the number of new cases of this potentially fatal disorder has fallen dramatically.

Adolescent↗

Azelastine and desmethylazelastine suppress acetylcholine-induced contraction and depolarization in human airway smooth muscle.

We examined the effects of a new anti-asthmatic drug, azelastine, and its principal metabolite, desmethylazelastine, on the in vitro electromechanical response of human airway smooth muscle during cholinergic stimulation. Membrane potential and isometric force were simultaneously measured using an intracellular microelectrode and a microforce transducer. Desmethylazelastine significantly suppressed acetylcholine-induced depolarization and contraction at 10(-6) M, whereas azelastine produced similar results at 10(-4) M, suggesting that the metabolite may be the principal compound acting upon the airway smooth muscle cell.

Acetylcholine↗

Transmembrane signaling in P815 mastocytoma cells by transfected IgE receptors.

In order to delineate structural-functional relationships of the mast cell receptor for IgE (Fc epsilon RI) by molecular-genetic analysis, a transfectable cell must be identified which resembles mast cells except for being deficient in receptors. We have found that the well known murine mastocytoma P815 is suitable. These cells express no Fc epsilon RI, lack mRNA for the alpha and beta subunits of the receptor, but contain some mRNA for gamma chains. After transfection with the cDNA for each of the subunits, stable clones could be isolated which expressed several hundred thousand normal Fc epsilon RI and synthesized large amounts of mRNA for alpha, beta, and gamma, the last at 3-fold higher levels than in the untransfected cells. Aggregation of the transfected receptors led to opening of presumptive calcium channels and to activation of phospholipase C, phospholipase A2, and protein kinase C. The kinetics and other characteristics of the signals were similar to those observed after stimulation of the rat tumor mast cells from which the receptor genetic material had been derived but were smaller in magnitude. These weaker signals most likely result from an overall reduced reactivity exhibited by the P815 cells since stimulation by other ligands led to weaker or even no responses. The cells failed to degranulate after either receptor aggregation or reaction with ionophores with or without phorbol ester. Both the transfected and untransfected P815 cells express Fc receptors for IgG (Fc gamma RII) which, interestingly, independently triggered similar responses despite their apparently simpler subunit structure.

Animals↗

Eosinophilia-myalgia syndrome associated with exposure to tryptophan from a single manufacturer.

Although eosinophilia-myalgia syndrome has been linked to use of tryptophan, it has been unclear whether tryptophan itself or a contaminant causes illness. In Oregon, we compared the brand and source of tryptophan used by 58 patients with eosinophilia-myalgia syndrome with the brand and source of tryptophan used by 30 asymptomatic controls identified through a random telephone survey and 63 asymptomatic controls who contacted the Oregon Health Division voluntarily. Although a single brand/retail lot of tryptophan was statistically associated with the development of eosinophilia-myalgia syndrome, there was no common importer, wholesaler, tablet maker, encapsulator, or distributor. However, 45 (98%) of 46 cases had taken a product made by one manufacturer, compared with three (30%) of 10 telephone survey controls and 15 (48%) of 31 volunteer controls. Retail lots of tryptophan from this manufacturer that were associated with cases were significantly more likely to have been produced from January through June 1989 than lots from this manufacturer that were taken by controls. These findings indicate that the recent epidemic of eosinophilia-myalgia syndrome was caused by a contaminant or an alteration in a subset of tryptophan manufactured by a single company in Japan shortly before the outbreak began.

Adult↗

Analytical and preparative resolution of enantiomers of prostaglandin precursors and prostaglandins by liquid chromatography on derivatized cellulose chiral stationary phases.

Analytical methods were developed for the separation of the enantiomers of four cyclopentenone precursors of prostaglandins. The resolution obtained is correlated with the chemical environment around the chiral center of the cyclopentenones. The analytical methods were scaled up to preparative loadings and the chromatographic parameters were varied to determine their effect on the preparative separations. The correlation between analytical resolution and preparative resolution was also investigated. In addition to the precursors, the preparative resolution of the enantiomers of a synthetic prostaglandin analogue was investigated.

Alprostadil↗