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Biomedical subjects

C Peterson

Publications and source records attributed to C Peterson.

At least 253 records · Page 14Linked to original sources

Meclofenomate inhibition of UV-induced erythema--a randomized, placebo-controlled, double-blind study.

Systemic intradermal and topical inhibitors of eicosanoid synthesis have been shown to decrease the intensity delay the onset of erythema produced with a single exposure to ultraviolet (UV) light. We studied the effect of single and multiple doses of meclofenomate on erythema induced by single and multiple doses of UV light. Thirty Caucasian subjects took either meclofenomate 100 mg t.i.d. or matching placebo for 5 days, crossing over to the alternative for 5 more days after a 2-day washout period. A statistical analysis was made of erythema response immediately prior to the study and then on 8 successive days during the study. Analysis of single and multiple exposure data revealed a statistically significant inhibition of erythema from meclofenomate therapy as compared with placebo.

Adult↗

D-verapamil and L-verapamil are equally effective in increasing vincristine accumulation in leukemic cells in vitro.

Leukemic cells isolated from peripheral blood from 6 patients with chronic lymphocytic leukemia, immunocytoma and prolymphocytic leukemia were incubated with vincristine (10 nM) with and without racemic verapamil and its L- and D-isomers (6.6 microM). Verapamil increased vincristine accumulation in all cells, the increase varying between 100 and 700%. Racemic verapamil and the L- and D-isomer increased cellular vincristine accumulation to the same extent. The verapamil effect could not be reversed by increasing the calcium concentration in the incubation medium (final concentration 2.5-5.0 mM). The results indicate that the mechanism behind the effect of verapamil on cellular accumulation of vincristine does not depend upon changes in calcium transport.

Calcium↗

High molecular weight microtubule-associated proteins bind to actin lattices (Hirano bodies).

Hirano bodies are filamentous, paracrystalline inclusions that are found in dendrites and cell bodies of neurons in Alzheimer's and other neurodegenerative diseases. Actin appears to be a major component of these structures. We present evidence that tropomyosin and high molecular weight microtubule-associated proteins (MAPs) are also components of Hirano bodies. Although an association between actin and MAPs has been noted in vitro, interactions in vivo have not heretofore been demonstrated. Since microtubules are not present in Hirano bodies, and anti-tubulin and anti-neurofilament antibodies do not bind to Hirano bodies, the association between MAPs and these inclusions is likely a result of interactions between MAPs and actin, and not MAPs and microtubules or neurofilaments.

Actins↗

6-Mercaptopurine in cerebrospinal fluid during oral maintenance therapy of children with acute lymphoblastic leukemia.

In three children receiving oral remission maintenance therapy for acute lymphoblastic leukemia, the concentrations of 6-mercaptopurine (6-MP) in cerebrospinal fluid (CSF), plasma and red blood cells were compared. CSF samples were obtained from an Ommaya reservoir previously inserted for treatment of CNS relapse. At the time of the study, the children were all in remission and had been on oral 6-MP (42-63 mg m-2) once daily for at least 24 weeks. Immediately before dose intake on the day of study (about 24 h after last dose), the concentrations of 6-MP in CSF, plasma and red blood cells were rather similar and below 20 ng ml-1 in all patients. After dose intake, the concentrations in plasma and in red blood cells increased to 40-200 ng nl-1 within 0.5-4 h. In contrast, the concentration of 6-MP in the CSF remained fairly constant around 4-10 ng ml-1 throughout the time period studied (up to 4 h). It is concluded that 6-MP can be detected in CSF during oral maintenance therapy and that the drug has different pharmacokinetic profile in CSF to that in plasma and red blood cells. Further studies are necessary to evaluate the significance of the 6-MP concentrations obtained in CSF for the prevention of CNS relapse.

Administration, Oral↗

A hyperthermia study of differential sensitivity and thermotolerance in AKR murine leukemia and normal bone marrow cells.

It has been previously demonstrated that AKR leukemia (lymphoma) cells are more sensitive than normal bone marrow cells to hyperthermic killing at 41.8 degrees C and 42.5 degrees C in vitro. This differential heat sensitivity might be explained by a greater ability to induce thermotolerance (TT) in normal versus neoplastic hematopoetic cells. We tested this hypothesis using the spleen colony methodology in the AKR murine model. A greater heat sensitivity of leukemia in comparison to normal bone marrow cells was observed at 42.5 degrees C; this observation agrees with previous reports. However, using a preincubation temperature of 40.0 degrees C for 120 min did not result in the induction of TT in either normal bone marrow (AKR) cells or AKR leukemia cells. The rationale for the choice of preincubation temperatures and times, as well as the clinical implications of these results are discussed.

Adaptation, Physiological↗

Hemodynamic, renal and endocrine effects of atrial natriuretic peptide infusion in severe heart failure.

The cardiac release and total body and renal clearances and the hemodynamic, renal and endocrine effects of increasing doses of atrial natriuretic peptide were investigated in 12 patients with severe chronic congestive heart failure. Immunoreactive arterial plasma levels of atrial natriuretic peptide were 10-fold higher than normal and there was no correlation between aortic atrial natriuretic peptide and cardiac filling pressures. The heart released atrial natriuretic peptide into the coronary sinus. The kidney, though a major clearance site, accounted for only 33% of the total body clearance. Administration of 0.3 micrograms/kg per min atrial natriuretic peptide produced significant changes in heart rate (95 +/- 4 to 85 +/- 4 beats/min) and mean arterial (92 +/- 8 to 77 +/- 9 mm Hg), right atrial (13 +/- 3 to 8 +/- 2 mm Hg) and mean pulmonary artery occluded (27 +/- 3 to 14 +/- 3 mm Hg) pressures. Atrial natriuretic peptide increased cardiac index (2.25 +/- 0.18 to 2.83 +/- 0.3 liters/min per m2) and stroke work index (21 +/- 1.5 to 29 +/- 3.4 g/m2), whereas systemic vascular resistance (1,424 +/- 139 to 1,033 +/- 97 dynes.s.cm(-5)) decreased. Infusion of 0.1 microgram/kg per min atrial natriuretic peptide increased urinary flow 128%, fractional excretion of sodium 133% and fractional excretion of potassium 35%. The filtration fraction increased from 29 +/- 2 to 31 +/- 4%. This represented a disproportionate rise in glomerular filtration rate over renal plasma flow. Plasma aldosterone and norepinephrine decreased whereas plasma renin activity remained unchanged. In association with these hemodynamic, excretory and endocrine changes, the urinary excretion of cyclic guanosine monophosphate doubled. Placebo had no effect. These results showed that, despite high circulating levels of atrial natriuretic peptide, administration of this hormone in heart failure is associated with potentially beneficial hemodynamic, renal and endocrine effects.

Adult↗

Pessimistic explanatory style is a risk factor for physical illness: a thirty-five-year longitudinal study.

Explanatory style, the habitual ways in which individuals explain bad events, was extracted from open-ended questionnaires filled out by 99 graduates of the Harvard University classes of 1942-1944 at age 25. Physical health from ages 30 to 60 as measured by physician examination was related to earlier explanatory style. Pessimistic explanatory style (the belief that bad events are caused by stable, global, and internal factors) predicted poor health at ages 45 through 60, even when physical and mental health at age 25 were controlled. Pessimism in early adulthood appears to be a risk factor for poor health in middle and late adulthood.

Adult↗

Atrial natriuretic peptide and the renal response to hypervolemia in nephrotic humans.

To elucidate the abnormality of body fluid homeostasis that attends the nephrotic syndrome, we compared the atrial hormonal and renal excretory and vasomotor responses to water immersion of nephrotic patients (N = 10) with those of healthy controls (N = 9). Nephrotics exhibited depressed baseline levels of atrial natriuretic peptide (ANP, P less than 0.05) and lower rates of urine flow and sodium excretion (P less than 0.01). Although immersion-induced hypervolemia increased plasma ANP to equivalent levels (75 +/- 19 vs. 60 +/- 6 pg/ml), the disparity in corresponding urinary flow (5 +/- 1 vs. 13 +/- 2 ml/min, P less than 0.01) and sodium excretion (171 +/- 42 vs. 540 +/- 65 muEq/min, P less than 0.01) grew larger. In contrast, immersion caused an equivalent reduction of renal vascular resistance by 16 and 17%, respectively (P less than 0.01). Despite higher renal plasma flow and lower oncotic pressure of plasma, the glomerular filtration rate remained constant during immersion in both groups. Similar constancy of fractional clearances of dextrans of graded size suggests that immersion may have lowered the glomerular transcapillary hydraulic pressure difference (delta P). We conclude that renal vasomotor responsiveness to hypervolemia is preserved in nephrotics, but that the mediatory role of ANP in this response is uncertain. By contrast, diminished responsiveness of the distal nephron to the natriuretic action of endogenous ANP could contribute to edema formation in the nephrotic syndrome.

Adolescent↗

The relation between young children's cognitive role-taking and mothers' preference for a conflict-inducing childrearing method.

In this study, we examined children's cognitive role-taking in relation to their mothers' choices of techniques to solve domestic dilemmas involving children's misbehavior, social skills, and logical reasoning. Results showed that a mother's preference for the childrearing strategy known as distancing, which uses a Socratic or dialectical inquiry to create cognitive conflict in the child, bore a significant association to her child's advancement in cognitive role-taking skill. This finding is discussed in relation to theories of cognitive development that postulate that mental conflict or tension stimulates cognitive growth. Practical factors that might inhibit mothers from making effective use of the distancing technique are also considered.

Adult↗

Acute myelogenous leukemia with eosinophilic differentiation and trisomy-1.

A 50-year-old woman presented with anemia and eosinophilia. Her bone marrow biopsy, peripheral blood, and clinical features were consistent with a diagnosis of an evolving acute myelogenous leukemia. Striking dysplastic eosinophilic differentiation associated with trisomy-1 was evident, and eosinophil granule major basic protein was detected in involved tissue. Trisomy-1 has not been previously reported in association with acute myelogenous leukemia showing eosinophilic differentiation. Intensive cytotoxic chemotherapy produced a short-lived clinical and cytogenetic remission. At autopsy multiple tumor nodules composed of dysplastic eosinophil precursors and myeloblasts were evident in multiple organs.

Bone Marrow↗

Rapid increases in glial fibrillary acidic protein mRNA and protein levels in the copper-deficient, brindled mouse.

The brindled mouse (MObr/y) carries an X-linked mutation that produces severe copper deficiency. Affected males suffer profound deficits in oxidative metabolism. We have examined astrocyte pathology in MObr/y during development and have found marked changes in the metabolism of glial fibrillary acidic protein (GFAP). Immunocytochemistry with anti-GFAP antisera revealed a marked increase in staining at postnatal day 12 (P12), compared to heterozygous female and unaffected male littermates, particularly in neocortex and thalamus. Septum, hypothalamus, and striatum showed little change. Western blot analysis revealed increased levels of GFAP in MObr/y forebrain and cerebellum. Levels of GFAP mRNA were determined by Northern blotting with a mouse GFAP cDNA probe. At P10, mRNA levels were normal, but increased to 8-10 times normal by P12. Levels at P15 remained similarly elevated. Thus, immunostaining and protein determinations correlate with mRNA elevations. Astrocytes can alter GFAP mRNA and protein levels over a relatively short time. Counts of neocortical cells did not reveal differences in cell numbers between MObr/y and controls, indicating that the observed changes reflect increased cellular levels and not a large increase in the numbers of astrocytes.

Animals↗

Role of cardiac atria in the human renal response to changing plasma volume.

We examined the role of cardiac atria in the renal response to sequential volume expansion and contraction, during and directly following water immersion. In immersed healthy volunteers (group 1, n = 9) atrial diameter, plasma levels of atrial natriuretic peptide (ANP), and natriuresis increased, whereas renal vascular resistance (RVR) and filtration fraction declined. Each parameter changed in an opposite direction postimmersion. An analysis of transglomerular dextran transport suggests that transglomerular hydraulic pressure difference (delta P) changed in parallel with filtration fraction. Baseline atrial diameter, plasma ANP, RVR, and filtration fraction were significantly elevated in nine recipients of denervated cardiac allografts (group 2). Atrial diameter and plasma ANP changed in parallel with group 1 during and after immersion. However, corresponding reciprocal changes in RVR were smaller and filtration fraction remained constant throughout. From transglomerular dextran transport, we compute that delta P increased progressively during and after immersion, suggesting predominant efferent arteriolar tone. The postimmersed state was associated also with enhanced sodium retention despite sixfold higher plasma ANP than in group 1. These findings are consistent with an effect of cardiac denervation to leave unopposed efferent sympathetic nervous traffic to the kidney. They suggest that the latter is an important modulator of the renal response to changing plasma volume in humans.

Atrial Function↗

Effects of project versus parallel groups on social interaction and affective responses in senior citizens.

Using activity analysis, occupational therapists structure group activities to meet the needs and goals of group members. This study compared the effects of project group structure (subjects participate together on a common task) with parallel group structure (subjects each have a task) in a sample of healthy seniors (32 women and 9 men). Subjects randomly assigned to either experimental condition made creative and imitative collages in a counter-balanced order. Time-sampled observations revealed that project group subjects talked and looked at others significantly more than parallel group subjects. On-task and laughing behaviors were also measured, but results were inconclusive. Project group subjects rated their activities higher on the action factor of the Osgood semantic differential (OSD) than did parallel group subjects, but there were no other differences on the OSD or on MacKenzie's Group Climate Questionnaire. Nor were there significant main effects between the creative collage and the imitative collage. Results are discussed both in terms of group task structure as an occupational therapy tool and in terms of methodologies for future activity analysis research.

Affect↗

Initiation events in in-vitro packaging of bacteriophage phi 29 DNA-gp3.

Initiation events in the packaging of bacteriophage phi 29 DNA-gp3 (DNA-gene product 3 complex) were studied in a completely defined in-vitro system that included purified proheads, DNA-gp3 and the DNA packaging protein gp16. In the sequential interactions, gp16 first bound to, and was modified by, the prohead. The prohead-gp16 complex then bound to DNA-gp3, resulting in a second modification of gp16 that permitted binding of ATP. DNA-gp3 aggregates were produced, and the hydrolysis of ATP accompanied DNA-gp3 packaging. Binding and hydrolysis of ATP by gp16 was both prohead- and DNA-gp3-dependent. Interruption of packaging by DNase I addition revealed filled heads but few particles containing partial lengths of DNA, suggesting that following a rate-limiting initiation, the translocation of DNA-gp3 into the prohead was much faster in the defined in-vitro system than in extracts.

Adenosine Triphosphate↗

Prohead and DNA-gp3-dependent ATPase activity of the DNA packaging protein gp16 of bacteriophage phi 29.

The ATPase activity of the DNA packaging protein gp16 (gene product 16) of bacteriophage phi 29 was studied in the completely defined in-vitro assembly system. ATP was hydrolyzed to ADP and Pi in the packaging reaction that included purified proheads, DNA-gp3 and gp16. Approximately one molecule of ATP was used in the packaging of 2 base-pairs of phi 29 DNA, or 9 X 10(3) ATP molecules per virion. The hydrolysis of ATP by gp16 was both prohead and DNA-gp3 dependent. gp16 contained both the "A-type" and the "B-type" ATP-binding consensus sequences (Walker et al., 1982) and the predicted secondary structure for ATP binding. The A-type sequence of gp16 was "basic-hydrophobic region-G-X2-G-X-G-K-S-X7-hydrophobic", and similar sequences were found in the phage DNA packaging proteins gpA of lambda, gp19 of T7 and gp17 of T4. Having both the ATP-binding and potential magnesium-binding domains, all of these proteins probably function as ATPases and may have common prohead-binding capabilities. The phi 29 protein gp3, covalently bound to the DNA, may be analogous in function to proteins gpNul of lambda and gpl of phi 21 that bind the DNA.

Adenosine Triphosphatases↗