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Biomedical subjects

G L Anderson

Publications and source records attributed to G L Anderson.

At least 73 records · Page 4Linked to original sources

Skeletal muscle arteriolar constriction to ANG II: evaluation of a myogenic component.

This study addressed the hypothesis that an increase in blood pressure contributes to the overall constrictive response of skeletal muscle arterioles to angiotensin II (ANG II). Diameters of second-order arterioles (2A) and third-order arterioles (3A) in the rat cremaster muscle were quantitated after intravenous administration of ANG II. Hindquarter blood pressure was either allowed to increase or was maintained at normal levels. Constriction of 3A to bolus injection of ANG II was the same whether hindquarter pressure increased or not. However, the total vascular constrictive response of the cremaster muscle (based on 2A blood flow) and of the entire hindquarter (based on iliac arterial blood flow) to bolus ANG II was greater when hindquarter pressure was held constant. During slow infusion of ANG II, 3A constriction was unaffected by an abrupt decrease or increase in hindquarter pressure. However, an abrupt reduction of hindquarter pressure caused a significant decline in hindquarter vascular resistance. Thus an increase in blood pressure, whether rapid or gradual, does not influence 3A constriction to ANG II. However, in the entire hindquarter, a rapid rise in blood pressure opposes constriction to ANG II, whereas a gradual pressure rise evokes a mechanism that enhances constrictive response to the peptide.

Angiotensin II↗

Long-term maintenance of a low-fat diet: durability of fat-related dietary habits in the Women's Health Trial.

The Women's Health Trial (WHT) was a feasibility study for a randomized trial of a low-fat diet for the prevention of breast cancer. One year after the WHT was terminated, a random sample of 894 participants who had been active in the WHT for an average of 16 months (range = 5 to 37) completed questionnaires about their dietary habits (a 21-item instrument that measures five dimensions of low-fat dietary habits) and food intake (a food frequency questionnaire). Women who participated in the intervention program maintained most of the low-fat dietary habits adopted during the study: mean total fat intake increased from 37.8 g to 41.0 g and scales describing substitution of specially manufactured low-fat foods and modification of meats to be lower in fat increased only slightly (by 0.11 and 0.14, respectively, on a scale of 1 = always to 4 = never). Scales describing avoiding meat and avoiding fats as a flavoring increased by 0.23 and 0.22, respectively, which suggests some recidivism. Women in the control group lowered their dietary fat intake from 65.0 to 57.5 g, but all differences in fat intake and fat-related dietary habits scales between women in the control and intervention groups remained highly statistically significant. In multiple regression models, all five low-fat dietary habits scales were independently associated with percentage of energy from fat, but the strongest association was for avoiding fats as flavorings. These results suggest that substitutions of specially manufactured low-fat foods are easily adopted and maintained dietary changes, but that maintenance of new habits related to avoiding fats as flavorings and avoiding meat will require long-term reinforcement strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Microcirculatory disturbances following the passage of emboli in an experimental free-flap model.

Following completion of arterial repair in an experimental free-flap model, platelet emboli have been observed passing through the microcirculation downstream. The purpose of this experimental study was to observe and quantitate changes in capillary perfusion occurring subsequent to these events. The isolated rat cremaster model was used. For 6 hours subsequent to surgical injury of the main artery in this model, the number of emboli and the number of perfused capillaries downstream were counted. In eight rats having an intentional arterial wall injury, emboli were consistently seen during the first hour of reflow. In the nine control animals having no arterial injury, no emboli were seen. The presence of emboli in the cremaster muscle, resulting from the arterial injury, was associated with a significant reduction in the number of perfused capillaries. We suggest that the observed decrease in capillary perfusion was associated with microemboli that produced an adverse effect for several hours after their initial presence in the circulation.

Analysis of Variance↗

Reduced neutrophil superoxide generation and plasma lipoperoxide levels in pigs fed with cod liver oil.

Circulating neutrophils, isolated from pigs fed for 8 weeks with a diet supplemented with CLO, had an accentuated n-3 fatty acid incorporation into the plasma membrane, as evidenced by an approximately four-fold greater n-3/n-6 ratio as compared with the control diet group. Moreover, the neutrophils of the CLO fed pigs produced less superoxide when stimulated with PMA or f-MLP, as well as showing a more prolonged latency period before O2(-)-generation. In the plasma of pigs fed with CLO there were higher levels of thiobarbituric reactive material and lipofuscin, while the content of GSSG was similar in both dietary groups. The results of this study indicate that dietary supplementation with CLO reduces the activation of circulating neutrophils and favours the presence in the plasma of lipoperoxides.

Animals↗

Small artery resistance increases during the development of renal hypertension.

Vascular pressures were measured in the principal (A1) arteriole and in upstream small arteries of the rat cremaster muscle to investigate vascular resistance changes associated with one-kidney, one clip Goldblatt hypertension. Pressure measurements were made at a proximal and distal site of each vessel using a servonull micropipette system. Vessel diameters were measured using video microscopy. A1 arteriole and external spermatic artery diameters were both decreased after 2 and 4 weeks of hypertension. Mean arterial pressure was elevated after 2 weeks of hypertension (106 +/- 4 mm Hg versus 140 +/- 5 mm Hg). Likewise, vascular pressures were elevated at every site: pudicepigastric artery (36%), external spermatic artery (47%), and A1 arteriole (38%). The pressure drop along the external spermatic artery was increased (87%) after 2 weeks of hypertension. Mean arterial pressure was further elevated from 2-4 weeks of hypertension (105 +/- 4 mm Hg versus 162 +/- 7 mm Hg) but only the proximal pudic-epigastric artery pressure was further elevated during this time from 2 to 4 weeks (131 +/- 5 mm Hg versus 147 +/- 7 mm Hg) of hypertension development. This was associated with an increased pressure drop (87%) along the artery compared with the situation at 2 weeks. These data indicate that small arteries upstream from the microcirculation contribute significantly to the increase in vascular resistance during hypertension. In addition, these data indicate that the increases in small artery resistance do not develop uniformly throughout all vessel branches.

Animals↗

Lack of correlation between mast cell response and active anaphylaxis in mice.

Mast cell-competent mice, sensitized to lysozyme, were examined for their mast cell and anaphylactic responses to determine whether anaphylactic shock could occur independent of mast cell participation. Tissues (cremaster muscle, subdermal connective tissue and mesentery), taken a short time after intravenous antigenic challenge, showed no evidence of mast cell degranulation above control tissues. Data obtained from a quantitative comparison of the onset and increase in local and systemic anaphylactic and mast cell sensitivities to the antigen provide strong support for the view that mast cells are not the major effector cells for systemic anaphylaxis in mice. The significant increase in blood pressure that occurred immediately after infusion with the antigen also indicates that other cells within the blood stream are involved.

Anaphylaxis↗

MMPI special scale clinical correlates for adolescent inpatients.

Little research has focused on the clinical correlates of adolescents' Minnesota Multiphasic Personality Inventory (MMPI) special scale responses. We investigated the clinical correlates of the MacAndrew Alcoholism Scale (MAC), Anxiety (A), Repression (R), and Ego Strength (Es) scales, based on self-reported data from 68 inpatient adolescents and ratings by their nursing staff and individual therapists. Parametric and nonparametric analyses revealed patterns of clinically relevant descriptors for these scales in a manner largely consistent with findings derived from studies of adult respondents. Results are discussed in terms of implications for interpretation of each of these special scales and in relation to a general approach to understanding adolescents' MMPI profiles.

Adolescent↗

The effect of photodynamic therapy on tumor oxygenation.

Oxygen microelectrodes were used to measure tumor partial pressure of oxygen (PO2) before and after photodynamic therapy (PDT) in a rat transplantable subcutaneous chondrosarcoma. Before PDT there was a gradient of PO2 from the superficial layers of the tumor (PO2 = 46 +/- 6 mm Hg) toward the center of the tumor (PO2 = 10 +/- 1 mm Hg). Mean tumor PO2 (21 +/- 2 mm Hg) was significantly reduced to 3 +/- 1 mm Hg 1 hour after PDT, and this reduction in PO2 persisted 4 hours (8 +/- 2 mm Hg) and 24 hours (6 +/- 1 mm Hg) after PDT. The largest percentage decrease in PO2 occurred at a depth of only 50 microns into the tumor. Inasmuch as PDT has been shown to decrease blood flow, our data suggest that PDT actions on blood vessels in the peripheral areas of the tumor are of major importance for eliciting the tumor hypoxia that contributes to tumor necrosis after PDT.

Animals↗

Vascular isolation of the rat cremaster muscle.

The vascular supply to the rat cremaster muscle was completely isolated to provide a microvascular preparation with a controllable blood flow. The anatomy of the cremaster vascular supply and the surgical approach to isolate the cremaster muscle on its neurovascular pedicle are described. The functional integrity of this isolated cremaster preparation was tested using intravital video microscopy to evaluate the tissue's response to vasoactive agents and to peripheral nerve stimulation. The isolated cremaster muscle was positioned in situ in a controlled tissue bath and concentration response curves to the topical application of norepinephrine (NE) and acetylcholine (Ach) were determined. Vasoconstriction elicited by the topical application of NE or by stimulation of the genitofemoral nerve trunk was similar for both the isolated and standard cremaster preparations. Application of 10(-5) M Ach caused maximal vasodilation equal to that produced by 10(-3) M papaverine in both preparations. In summary, the isolated cremaster muscle of the rat is an acceptable model of a skeletal muscle microcirculation which can be used to investigate microvascular function when precise monitoring or control of perfusion to the entire muscle is needed.

Acetylcholine↗

Postrenal modification of urine in birds.

The role of the cloaca and lower intestine in the postrenal modification of urine was studied in conscious normally hydrated desert quail. The birds were studied for a period of 12 days during which they were in intake-output balance. It was calculated that of the combined mixture of urine-feces entering the lower intestine, 47% water, 62% sodium, and 49% potassium were reabsorbed. If this material is considered as coming from the ureteral urine, then the composition of the ureteral urine entering the lower intestine was changed as follows: 77% water, 72% sodium, and 82% potassium were reabsorbed. For urate, 68% of the total present in ureteral urine was degraded in the lower intestine. In terms of the filtered load produced by the kidneys, the lower intestine reabsorbed 1.5% filtered water, 0.4% filtered sodium, and 46% filtered potassium. The total filtered loads reabsorbed by the combined efforts of the kidney and lower intestine were 99.5% water, 99.8% sodium, and 88% potassium. It appears that the cloaca and lower intestine of birds may serve a similar function to that of the distal nephron in mammals, making the fine adjustments in water and sodium reabsorption from the urine.

Absorption↗

Reactions with the oxidized iron protein of Azotobacter vinelandii nitrogenase: formation of a 2Fe center.

The Fe-S center of oxidized Fe protein from Azotobacter vinelandii nitrogenase is decomposed by alpha,alpha'-dipyridyl in a biphasic process. In the presence of MgATP, 2 Fe are immediately removed by chelation while the additional irons are removed only after several hours. A slower biphasic Fe release also was observed in the presence of chelator alone. MgADP prevented the Fe release by chelator. An intermediate in the reaction was isolated containing 2 Fe. The visible spectrum of the intermediate was similar to that of 2Fe-2S ferredoxins (epsilon max at 325, 416, and 460 nm of 16.1, 11.3, and 9.0 mM-1 cm-1). The 2Fe form was electron paramagnetic resonance (EPR) silent until partially reduced with sodium dithionite. The EPR spectral properties were similar to 2Fe-2S ferredoxins; namely, the Fe center had resonances at g = 2.00, 1.94, and 1.92 which were detectable, essentially unbroadened at 70 K. The results suggest that in the oxidized (2+) state Fe protein can undergo a 4Fe to 2Fe conversion.

2,2'-Dipyridyl↗

Inhibition of histamine-induced protein leakage in rat skeletal muscle by blockade of prostaglandin synthesis.

The effects of two prostaglandin synthesis blockers, indomethacin and mefenemic acid, on both histamine-induced extravasation of albumin and arteriole dilation were studied using intravital fluorescent microscopy. Sprague-Dawley rats (140-180 g) were anesthetized with pentobarbital (50mg/Kg) and the cremaster muscle was positioned in a Krebs bath (pH = 7.4, PCO2 = 40 mm Hg, PO2 = 35 mm Hg, temp = 34 degrees). Fluorescein isothiocyanate-labeled albumin was injected intravascularly and the fluorescent image of the cremaster microcirculation was produced by illumination from an argon laser (488 nm). Videotape analysis of the experiments showed that increasing concentrations of histamine in the bath produced both a concentration-dependent arteriole dilation and a concentration-dependent leakage of labeled albumin into the interstitium. Adding indomethacin (10 or 100 micrograms/ml) or mefenemic acid (10 micrograms/ml) to the Krebs bath significantly diminished the protein leakage induced by histamine but did not alter the arteriole dilation. These results indicate that prostaglandins may be directly involved in the histamine-induced increase in vascular permeability to macromolecules but not in the arteriole dilation histamine produces.

Animals↗

Cecae of desert quail: importance in modifying the urine.

The importance of the digestive ceca in the modification of ureteral urine was evaluated in conscious, unrestrained desert quail. Cecaectomized (Cx) birds took in slightly more food and water and excreted more solids and water than did sham operated controls. The percent utilization of food for the Cx birds was 76 and 79% for the sham operated controls. Urate output was 47 ml/kg day for Cx and 41 ml/kg day for the sham operated controls. Water content of the excrement was 90% for the Cx and 85% for the sham operated controls. There was a slight but insignificant increase in uric acid excretion in the droppings of cecaectomized birds.

Animals↗

Protein loss induced by complement activation during peritoneal dialysis.

A variable loss of macromolecules during peritoneal dialysis has been noted in both humans and experimental animals. We investigated the potential role of the complement system for inducing protein loss during peritoneal dialysis, both to shed light on clinical variability of protein loss and to develop a model for quantitatively studying complement-induced microvascular protein leakage. Rats received intra-arterial injections of a fluorescent dye conjugated to rat serum albumin and underwent a 3.5-hr series of 15-min peritoneal dialysis exchanges. After the control exchanges, rats received either intra-arterial zymosan-activated rat serum, saline, unactivated rat serum, or endotoxin; other rats received an intraperitoneal injection of endotoxin, histamine, phenylephrine, or nitroprusside. The drainage volume from each exchange was measured, and the concentrations of labeled albumin, total protein, and urea were determined by spectroscopy. Zymosan-activated rat serum and endotoxin injections (both intraperitoneal and intra-arterial), each of which may activate the alternative pathway of complement, produced a dramatic increase in dialysate protein concentrations. In addition, histamine, which is a vasodilator but which may also be involved as a mediator of the activated complement system and/or endotoxemia, also produced an increase in dialysate protein concentrations. On the other hand, drugs which may alter peritoneal blood flow such as the vasodilator nitroprusside or the vasoconstrictor phenylephrine, did not affect dialysate protein concentrations. These data suggest that activation of the alternative pathway of complement may cause variation in protein loss during peritoneal dialysis and that in some situations, pharmacological control of this system could be an important therapeutic consideration.

Animals↗

Total luminescence spectroscopy of fluorescence changes during aging in Caenorhabditis elegans.

Total luminescence spectroscopy was employed to characterize and quantitate age-related changes in fluorescence in the nematode Caenorhabditis elegans, an established model for aging research. The excitation wavelength was varied between 250 and 590 nm in 10-nm increments. At each excitation wavelength, the emission wavelength was varied between 300 and 600 nm. Contour plots of corrected spectra were made. All fluorescence increased severalfold with age, except for that ascribed to tryptophan of soluble protein fractions. This general increase included fluorescence due to flavins, which is not expected to increase with age but has previously been observed to do so in this species. Blue emission peaks that approximated Schiff base product fluorescence were detected in whole aqueous homogenates, chloroform/methanol extracts, and detergent-cleaned cuticle preparations. Age-related increases in emission intensities of these peaks were demonstrated in aqueous homogenates and isolated cuticles. Cuticle preparations, known to be rich in collagenous protein, exhibited a fluorescence peak that approximated the recently described pyridinoline cross-link of vertebrate collagen. This peak, as well as the entire cuticle emission spectrum between 300 and 500 nm, increased dramatically with age. A fluorescence peak tentatively identified as cuticle tyrosine, characteristic of collagenous protein, also increased in older worms. The effectiveness of the spectroscopic technique in distinguishing individual fluorescence peaks in complex mixtures was demonstrated, and the potential of the nematode cuticle for age-related collagen studies was identified.

Animals↗

Pyrrol[1,4]benzodiazepine antibiotics. Proposed structures and characteristics of the in vitro deoxyribonucleic acid adducts of anthramycin, tomaymycin, sibiromycin, and neothramycins A and B.

The pyrrol[1,4]benzodiazepine antibiotics anthramycin, tomaymycin, sibiromycin, and neothramycins A and B are potent antitumor agents that bind to DNA in a unique manner, resulting in some unusual biological consequences. This paper describes results on which the points of covalent linkage between the drugs (carbinolamine carbon atom) and DNA (N-2 of guanine) are deduced, as well as Corey-Pauling-Koltun (CPK) models for the various drug-DNA adducts. Predictions based upon these CPK models have been tested, and the results are reported in this paper. These tested experimental predictions include (1) instability of the drug-DNA adducts to denaturation of DNA, (2) saturation binding limits, (3) effect of drug binding on the structure of DNA, (4) lack of unwinding and in vitro strand breakage of closed-circular supercoiled simian virus 40 (SV-40) DNA, (5) sensitivity of the secondary structure of DNA to drug binding, (6) hydrodynamic properties of the drug-DNA adducts, (7) hydrogen bonding of the 9-phenolic proton in anthramycin to DNA, (8) structure-activity relationships, and (9) biological consequences of DNA damage, including cumulative damage and slow excision repair, double-strain breaks in DNA in repair-proficient cells, and the selective inhibition of H-strand DNA synthesis in mitochondria. The results are completely in accord with our postulated space-filling models.

Aminoglycosides↗