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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 559 records · Page 31Linked to original sources
PubMed1987

The structural basis of the inner blood-retina barrier in the eye of Macaca mulatta.

This is a morphological analysis of the inner blood-retina barrier in various segments of the retinal vasculature in the eye of Macaque monkeys. The primary aims of this study are to identify the components of the walls of the arteries, central capillaries, peripheral capillaries and veins of the retina using light and electron microscopy, and to compare and contrast junctional morphology as revealed by thin section electron microscopy and freeze-fracture. The walls of these vascular segments are composed of continuous endothelium, muscle cells or pericytes, and connective tissue. Endothelial cells are joined by tight and gap junctions. In freeze-fracture replicas, tight junctions consist of a continuous, complex network of branching and anastomosing strands which do not possess free endings. The intramembrane strands of tight junction remain preferentially associated with the outer membrane leaflet or E-face of the endothelial plasma membrane and sit at the bottom of linear strands or grooves. However, particles and fragments of the intramembrane strands may be avulsed from the E-face during the fracture process and are associated with ridges on the inner membrane leaflet or P-face. The total number of plasmalemmal vesicles per unit area of endothelial cell for each vascular segment in thin sections is less than non-barrier endothelium, but greater than barrier endothelium. The paucity of plasmalemmal vesicles and the complexity of the tight junctional network contribute to the barrier function of the retinal vascular endothelium.

Animals↗
PubMed1986

Purification of charybdotoxin, a specific inhibitor of the high-conductance Ca2+-activated K+ channel.

Charybdotoxin is a high-affinity specific inhibitor of the high-conductance Ca2+-activated K+ channel found in the plasma membranes of many vertebrate cell types. Using Ca2+-activated K+ channels reconstituted into planar lipid bilayer membranes as an assay, we have purified the toxin from the venom of the scorpion Leiurus quinquestriatus by a two-step procedure involving chromatofocusing on SP-Sephadex, followed by reversed-phase high-performance liquid chromatography. Charybdotoxin is shown to be a highly basic protein with a mass of 10 kDa. Under our standard assay conditions, the purified toxin inhibits the Ca2+-activated K+ channel with an apparent dissociation constant of 3.5 nM. The protein is unusually stable, with inhibitory potency being insensitive to boiling or exposure to organic solvents. The toxin's activity is sensitive to chymotrypsin treatment and to acylation of lysine groups. The protein may be radioiodinated without loss of activity.

Amino Acids↗
PubMed1986

Effect of middle ear modification on umbo vibration. Human temporal bone experiments with a new vibration measuring system.

The effects of aditus blockage, decrease of tympanic cavity volume, and resection of the tensor tympani muscle on umbo displacement were studied in human temporal bones using a new non-contacting video measuring system. This system, combined with stroboscopic illumination, allowed measurement of umbo vibration down to 0.3 micron in the 0.1- to 4.5-kHz frequency range for a constant 124-dB sound pressure level at the tympanic membrane. Aditus blockage caused a mean increase of 5.4 dB with a peak at 2.8 kHz and a mean decrease of 3.4 dB below 1.6 kHz. Decrease of the tympanic cavity volume by 30% to 42% showed an improvement of 2.2 dB in the 1.4- to 3-kHz range and a similar loss below 1 kHz. Resection of the tensor tympani muscle produced a slight improvement of 1.7 dB at 1.8 kHz.

Bone Conduction↗
PubMed1986

Energy expenditure in malnourished patients with colorectal cancer.

To evaluate energy expenditure in patients who have colorectal cancer with varying stages of disease and to examine the possible determinants of energy expenditure in a group of patients with cancer who have the same type of tumor, we studied 73 patients with biopsy proven and pathologically staged adenocarcinomas of the colon and rectum. Resting energy expenditure (REE) was measured by indirect calorimetry and compared with predicted energy expenditure (PEE), which was calculated from the Harris-Benedict formulas. Nutritional and tumor characteristics were examined. Forty-nine percent of patients had abnormal REE (normal = PEE +/- 10%). One quarter of the patients were hypometabolic (REE less than 90% PEE). The abnormalities persisted despite normalization of REE to metabolic body size (kg0.75) or predicted values based on weight, height, age, and sex. There were no differences in nutritional status, as judged by the percent of weight loss and visceral protein levels, between those patients in the hypometabolic, normometabolic, or hypermetabolic categories, and there were no significant relationships between energy expenditure and the tumor burden. The mean duration of disease in the normometabolic group was 4.5 months, while the hypometabolic and hypermetabolic groups had mean durations of 9.5 and 14.2 months, respectively. The tumor site and duration of the disease are important variables in studies of energy expenditure in patients with cancer.

Adenocarcinoma↗
PubMed1986

Duodenal delivery of levodopa for on-off fluctuations in parkinsonism: preliminary observations.

The pathogenesis of on-off motor fluctuations in parkinsonism remains incompletely understood, but slowed or erratic gastric emptying of orally administered levodopa may be involved. In 3 patients with resistant on-off fluctuations, direct duodenal continuous infusion of levodopa via a nasoduodenal tube resulted in a heightened therapeutic effect, including a reduction in motor fluctuations. In 1 of these patients, continuous duodenal levodopa infusion produced greater benefit than did intermittent duodenal levodopa administration. Direct duodenal delivery of levodopa lessens the problems with gastric emptying and may be suitable for long-term therapy in selected patients with resistant on-off motor fluctuations.

Adult↗
PubMed1986

Polymorphonuclear leukocyte response to stimulation in vitro during pregnancy.

Oxidative metabolism of polymorphonuclear leukocytes (PMNLs) isolated from pregnant women in the third trimester and from controls were studied using zymosan-induced chemiluminescence (CL) and f-Met-Leu-Phe-stimulated superoxide (O2-) generation. CL was significantly increased during pregnancy, but a decrease was noted in cytochrome c reduction. Total cellular levels of beta-glucuronidase and lysozyme were diminished in PMNLs from pregnant subjects, with unaltered concentrations of cytosol lactate dehydrogenase. The capacity of PMNLs from pregnant women to degranulate did not differ from controls. It is suggested that during pregnancy, in vivo stimulation of PMNLs may occur to account for these changes.

Adult↗
PubMed1986

Effects of peritoneovenous shunting on body composition.

The effect of peritoneovenous shunting on body composition has been studied in 7 cirrhotic patients undergoing a successful shunt and 3 patients in whom the shunt was unsuccessful. In the 7 patients with functioning shunts, their weight had decreased by a mean of 9 kg (p less than 0.001) by 6 wk after initial diuresis, natriuresis, and kaliuresis, and was associated with a decrease in total body potassium (TBK) but not total body nitrogen (TBN). This resulted in a significant decrease in the TBK/TBN ratio from 2.12 +/- 0.74 to 1.66 +/- 0.20 (p less than 0.01). By a mean of 14 mo, in these 7 patients there was a significant increase in mean TBN (from 1.54 +/- 0.10 to 1.84 +/- 0.10, p less than 0.005) associated with an improvement in the mean nitrogen index (from 0.74 +/- 0.04 to 0.88 +/- 0.04, p less than 0.005). These changes were associated with a significant increase in nonalcoholic calories, a nonsignificant increase in protein consumption, and a positive nitrogen balance. After the initial kaliuresis, mean potassium balance remained constantly positive (+22.7 +/- 3.4 mmol/day), serum aldosterone levels normalized, and TBK increased. In contrast, 3 patients with failed peritoneovenous shunting continued to lose weight significantly despite the presence of ascites; TBN and nitrogen index also decreased. In conclusion, body composition studies appear to have confirmed the clinical observation that cirrhotic patients with massive ascites have depleted body protein which is gradually repleted only after successful shunting. In this situation TBK, long used as a measure of lean body mass, is less satisfactory than TBN and nitrogen index. This improvement in body protein appears to be explained by an increased dietary intake associated with improved nitrogen balance, but these changes are not found in patients in whom the shunt failed.

Adult↗
PubMed1986

Multi-ion conduction and selectivity in the high-conductance Ca++-activated K+ channel from skeletal muscle.

Open-channel ion permeation properties were investigated for Ca++-activated K+ (CaK) channels in solutions of K+ and its analogues T1+, Rb+, and NH4+. Single CaK channels were inserted into planar lipid bilayers composed of neutral phospholipids, and open-channel current-voltage (I-V) relations were measured in symmetrical and asymmetrical solutions of each of these individual ions. For all concentrations studied, the zero-voltage conductance falls in the sequence K+ greater than T1+ greater than NH4+ greater than Rb+. The shape of the I-V curve in symmetrical solutions of a single permeant ion is non-ohmic and is species-dependent. The I-V shape is sublinear for K+ and T1+ and superlinear for Rb+ and NH4+. As judged by reversal potentials under bi-ionic conditions with K+ on one side of the bilayer and the test cation on the other, the permeability sequence is T1+ greater than K+ greater than Rb+ greater than NH4+ at 300 mM, which differs from the conductance sequence. Symmetrical mixtures of K+ or NH4+ with Rb+ show a striking anomalous mole fraction behavior, i.e., a minimum in single-channel conductance when the composition of a two-ion mixture is varied at constant total ion concentration. This result is incompatible with present models that consider the CaK channel a single-ion pore. In total, the results show that the CaK channel finely discriminates among K+-like ions, exhibiting different energy profiles among these species, and that several such ions can reside simultaneously within the conduction pathway.

Animals↗
PubMed1986

Increased expression of p53 protein in human leukemia cells.

We examined synthesis of the cellular phosphoprotein p53 in fresh bone marrow or peripheral blood cells from normal donors and from patients with leukemia, preleukemia, or other hematopoietic disorders. Lysates of cells labeled with [35S]methionine were immunoprecipitated with monoclonal antibodies to p53, and the immunoprecipitates were analyzed by NaDodSO4/polyacrylamide gel electrophoresis and autoradiography. Bone marrow or peripheral blood cells from 8 of 33 patients with hematopoietic disorders showed increased p53, seven of the eight occurring in cells of patients with preleukemia or acute myelogenous leukemia. Increased p53 synthesis was not associated with p53 gene amplification, as shown by Southern blot analysis. Synthesis of p53 was not increased in any of nine normal human bone marrow samples or eight normal human peripheral blood granulocyte, macrophage, and lymphocyte samples. The hematopoietic cells of patients in remission or with chronic forms of leukemia did not generally synthesize elevated levels of p53. In addition, we found negligible p53 mRNA and protein expression in a variety of human myeloid leukemia lines blocked at different stages of differentiation. Southern blot analysis showed that, except for the HL-60 cells, the p53 gene of the myeloid cell lines was intact. In view of recent evidence implicating p53 in transformation of cultured cells, our results using fresh leukemia cells suggest that p53 may contribute to the phenotype of certain leukemias in vivo.

Bone Marrow↗
PubMed1986

Piracetam in alcoholic organic mental disorder: a placebo controlled study comparing two dosages.

The following paper presents an investigation of the efficacy of piracetam in alcoholic organic mental disorder. A double-blind placebo-controlled study design was used to compare 2 dosages of the substance (2 X 3 g vs. 2 X 12 g). Cognitive function was assessed on days 0, 7, 14, 28, 42. Analysis of the results from 24 patients showed a clear-cut amelioration of cognitive functions in all 3 treatment groups. No difference could be demonstrated between the administration of placebo and the lower dose of piracetam. Patients on the higher dose showed an earlier improvement on one of the tests, but the final scores were similar in all three treatment groups.

Adult↗
PubMed1986

Double-blind assessment of potential pergolide-induced cardiotoxicity.

Possible pergolide-induced cardiotoxicity has been reported in open trials. Over a 6-month period of observation, we prospectively analyzed ECGs and 24-hour ambulatory ECG in 23 patients with Parkinson's disease who were randomized in a double-blind fashion to pergolide or placebo treatments. Pergolide therapy was associated with a mild and transient bradycardiac effect, but no clinically significant cardiotoxicity.

Aged↗
PubMed1986

Allosteric effects of Mg2+ on the gating of Ca2+-activated K+ channels from mammalian skeletal muscle.

Ca2+-activated K+ channels from rat muscle transverse tubule membranes were inserted into planar phospholipid bilayers, and the activation of these channels by Ca2+ was studied. On the cytoplasmic side of the channel, calcium ions (in the range 10-100 mumol l-1) increase the opening probability of the channel in a graded way. This 'activation curve' is sigmoid, with an average Hill coefficient of about 2. Magnesium ions, in the range 1-10 mmol l-1, increase the apparent affinity of the channel for Ca2+ and greatly enhance the sigmoidicity of the Ca2+ activation curve. In the presence of 10 mmol l-1 Mg2+, the Hill coefficient for Ca2+ activation is about 4.5. This effect depends upon Mg2+ concentration but not upon applied voltage. Mg2+ is effective only when added to the cytoplasmic side of the channel. The results argue that this high-conductance, Ca2+-activated K+ channel contains at least six Ca2+-binding sites involved in the activation process.

Allosteric Regulation↗
PubMed1986

Effects of dietary supplementation of fish oil on neutrophil and epidermal fatty acids. Modulation of clinical course of psoriatic subjects.

Findings from an eight-week fish oil-supplemented diet given to 13 psoriatic patients demonstrated that eicosapentaenoic acid (20:5,n3 [EPA]) and docosahexaenoic acid (22:6,n3 [DCHA]) are rapidly incorporated into the sera, neutrophils, and epidermis of participating patients, and that the incorporation of EPA and DCHA into epidermal lipids increased with weeks of supplementation with minimal alteration of arachidonic acid (AA) in the epidermal lipids. Global clinical evaluation showed that eight patients demonstrated mild to moderate improvement in their psoriatic lesions. Improved clinical response correlated with high EPA/DCHA ratios attained in epidermal tissue specimens. These findings underscore the need for further investigations into the role of dietary n3 fatty acids, particularly the possibility of pentaenoic acid as a potential protective agent and/or therapeutic adjunct for the clinical management of psoriasis.

Adult↗
PubMed1986

Tuberculous esophagitis with erosion into aortic aneurysm.

An 87-year-old woman with a known atherosclerotic thoracic aneurysm died suddenly from a massive esophageal hemorrhage. Prior to death, tuberculous esophagitis was diagnosed by biopsy. At autopsy, a fistulous tract was found extending from the esophagus to the aortic aneurysm; this fistula proved to be the site of fatal hemorrhage. The tract was surrounded by a granulomatous inflammatory reaction, in which acid-fast bacilli were found. To our knowledge, this is the first reported case of tuberculous esophagitis extending to an aortic aneurysm resulting in hemorrhage and death.

Aged↗