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Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 559 records · Page 31Linked to original sources
PubMed1983

A randomized comparison of melphalan versus melphalan plus hexamethylmelamine versus adriamycin plus cyclophosphamide in ovarian carcinoma.

A prospective randomized study was conducted in women with suboptimal (greater than or equal to 3 cm residual) Stage III, Stage IV, and recurrent ovarian adenocarcinoma to determine if combination chemotherapy is more effective than melphalan alone in achieving remission and improving survival. Of 233 evaluable patients with measurable disease, there were 64 treated with melphalan alone, of whom 20% achieved a clinical complete response and 17%, a partial response. Of the 97 patients receiving melphalan plus hexamethylmelamine, 28% achieved complete response compared with 32% of 72 patients given Adriamycin plus cyclophosphamide. The partial response rates for the combinations were 24% and 17%, respectively. The effect of these treatments was assessed in an additional 136 evaluable patients without measurable disease by progression-free interval and duration of survival. After statistically adjusting for distribution of cell type and grade, the clinical complete response rate for Adriamycin and cyclophosphamide (32%) in measurable cases was significantly higher (P = 0.04) than for melphalan alone. However, this combination did not improve median survival (12.3, 13.5, and 14.2 months, respectively, for M, M + H, and A + C). None of the other parameters showed a statistically significant advantage for combination chemotherapy, but the combinations caused more hematologic and gastrointestinal toxicity.

Adenocarcinoma↗
PubMed1983

Relationship between plasma desipramine levels and clinical outcome for RDC major depressive inpatients.

Depressed patients (N = 31), who met Research Diagnostic Criteria for major affective disorder-depressed, were severely ill and maintained drug-free for a 1-week period on inpatient status. They received a fixed dose (150 mg/day) of desipramine for a 4-week period with drug plasma level determination and clinical ratings performed at fixed time intervals throughout the study. Despite these rigid criteria for entrance and clinical outcome measures, no obvious relationship between plasma desipramine level and clinical outcome was found. The clinical implications of this finding are discussed.

Adult↗
PubMed1983

Effects of oral dipyridamole on coronary dynamics and myocardial metabolism at rest and during pacing-induced angina in patients with coronary artery disease.

The effects of oral dipyridamole administration (150 mg) on coronary hemodynamics, myocardial metabolism, and pacing threshold were studied in 10 patients with significant coronary artery disease (CAD). Following dipyridamole through 120 minutes, there was no significant change in resting heart rate, arterial pressure, coronary venous flow, coronary resistance, myocardial lactate extraction, or myocardial oxygen consumption. Rapid atrial pacing performed before and at 60, 90, and 120 minutes after dipyridamole failed to demonstrate any significant reduction in pacing threshold or evidence of increased ischemia after dipyridamole. Blood dipyridamole levels showed variable and slow absorption which probably explains the difference between intravenous and oral dipyridamole on coronary dynamics and myocardial response to pacing.

Administration, Oral↗
PubMed1983

Ventilatory failure due to asbestos pleurisy.

Seven patients are described who had a distinctive syndrome of chest wall restriction caused by asbestos-induced pleural fibrosis. All had severe dyspnea and predominant pleural disease on radiographic examination, with pulmonary function findings of reduced vital capacity, total lung capacity (measured in five patients), and maximal voluntary ventilation. Five patients had ventilatory failure with carbon dioxide retention; four of these have died and one is close to death. Examination of the thoracic organs in five patients showed minimal or no parenchymal fibrosis in three and less severe involvement of the parenchyma than of the pleura in the remaining two. Neoplasms were suspected in three patients because of extension of the pleural fibrosis into the lung. Two of these patients had pleural uptake of 67-gallium citrate attributable to the inflammatory reaction. With the increasing duration since onset of exposure in the nine million workers who have been exposed to asbestos, as well as in other exposed persons, it is expected that additional cases of ventilatory failure caused by asbestos-induced pleural fibrosis will be encountered.

Aged↗
PubMed1983

In vitro production of corticosteroid binder IB in the presence of proteolytic inhibitors.

The effect of proteolytic inhibitors on the temperature-dependent formation of corticosteroid binder IB in rat kidney cytosol was examined. Antipain increased the apparent binding of [3H]-triamcinolone acetonide in the cytosol. Leupeptin, chymostatin, soya bean trypsin inhibitor and lima bean trypsin inhibitor did not affect total binding, while L-1-tosylamide-2-phenylethyl chloromethyl ketone, N alpha-p-tosyl-L-lysine chloromethyl ketone and phenylmethylsulfonyl fluoride markedly reduced the charcoal resistant steroid binding. However, none of the inhibitors added during tissue homogenization, steroid binding or activation affected the extent of heat-dependent conversion of the [3H]-triamcinolone acetonide-receptor complexes to the IB form, which was characterized by its exclusion from DEAE-Sephadex ion exchanger. In contrast, sodium molybdate (10 mM) effectively inhibits IB formation without inhibiting protease activity of rat kidney cytosol. These observations indicate that the temperature-dependent formation of corticosteroid binder IB in vitro does not involve proteolytic transformation of unbound or steroid-bound cytosolic proteins. Addition of antipain (3 mM) to the cytosol markedly increased the radioactivity in the buffer prewash of DEAE-cellulose columns (apparent IB) only when the inhibitor was added prior to charcoal adsorption. However, a similar peak in the prewash also was obtained with receptor-free cytosol. Antipain had no effect on the rate of dissociation of performed [3H]-triamcinolone-acetonide-receptor complexes nor did it increase the amount of receptor adsorbed to hydroxylapatite. Chromatography on Sephadex G-25 and P-2 columns showed that the increased activity in the charcoal-resistant fraction in the presence of antipain is due to unbound steroid. Thus, antipain interferes with the ability of charcoal to remove unbound steroid from the cytosol.

Animals↗
PubMed1983

Comparison of corticosteroid binder IB with the alpha-chymotrypsin- and RNase-treated hepatic glucocorticoid receptors.

Rat liver and kidney cytosolic extracts contain the glucocorticoid receptor (binder II) and corticosteroid binder IB, both of which possess the steroid- and DNA-binding domains. Since it has been speculated that the smaller binder IB may be generated from binder II by proteolysis, the chymotrypsin-produced receptor fragment in rat liver cytosol has been compared with binder IB in terms of charge, size and DNA binding characteristics. The [3H]triamcinolone acetonide-receptor complex is converted to a smaller fragment by short term digestion (10 degrees C, 30 min) with 100 micrograms/ml alpha-chymotrypsin. Although the chymotrypsin fragment produced from previously heat-activated binder II and binder IB both exhibit DNA-binding capability, they differ in charge and size. Whereas the alpha-chymotrypsin-treated receptor has a Stokes radius of 30 A and elutes from DEAE-cellulose at 0.06 M potassium phosphate in a linear salt gradient, binder IB has a Stokes radius of 20 A and elutes in the buffer wash of the DEAE-cellulose column. Thus, while binder IB can be resolved from the heat-activated form of the [3H]TA-receptor on DEAE, the heat activated alpha-chymotrypsin product elutes from the anion exchange resin at the same ionic strength as intact activated binder II (i.e. at 0.05 M potassium phosphate), and the unactivated intact receptor elutes at about 0.20 M potassium phosphate. A more extended digestion with alpha-chymotrypsin (24 h, 0 degrees C) results in elimination of the DNA binding site without further reduction of the Stokes radius or change in the elution pattern from DEAE-cellulose. Furthermore, molybdate completely blocks formation of binder IB but does not inhibit the production of the receptor fragment by alpha-chymotrypsin. Treatment of the hepatic [3H]TA-receptor complex with RNase has no effect on the charge, size or DNA binding properties of the bound receptor. These results suggest that RNase does not activate the [3H]TA-receptor complex nor does it produce a IB-like component in the liver cytosol. The present results are consistent with the hypothesis that binder IB is formed in vitro by a process which may not involve proteolytic cleavage or RNase-induced modification of the glucocorticoid receptor (binder II).

Animals↗
PubMed1983

Intravesical thiotepa prophylaxis of superficial bladder cancer. A follow-up study.

Prophylactic intravesical instillations of thiotepa at 3-month intervals reduced the frequency of recurrences of superficial bladder tumors when compared with an untreated control group. Patients who developed frequent recurrences despite thiotepa instillations had a high risk of disease progression. These patients with progressive bladder carcinoma appeared to be unaffected by intravesical thiotepa in the dosage used. This raises the question as to whether such intravesical chemotherapy does anything to alter the underlying malignant process in the urothelium.

Drug Administration Schedule↗
PubMed1983

Correction of attenuation in whole-body determination of Co-57 B12 absorption: concise communication.

The use of Co-57-labeled B12 for whole-body measurement of B12 uptake in humans has the advantage over Co-58 of easy commercial availability and lower cumulative radiation to the liver, but the disadvantage of significant attenuation. Methods devised to correct for the attenuation have used inaccurate early 100% counts. A method is described here that uses a liver phantom, containing a dissolved Co-57 B12 capsule, in a water tank. The ratios of upper to lower detector counts is related to total counts; it varies at different depths in the tank, and with the overall tank depth that is selected to accord with measured body habitus. The ratio of detector counts in the final patient count is used to read off the appropriate 100% total count. With this technique there is a clear discrimination between normal patients and those with pernicious anemia.

Absorption↗
PubMed1982

Characterization of calcium binding to brush-border membranes from rat duodenum.

The Ca2+-binding properties of isolated brush-border membranes at physiological ionic strength and pH were examined by rapid Millipore filtration. A comprehensive analysis of the binding data suggested the presence of two types of Ca2+-binding sites. The high-affinity sites, Ka = (6.3 +/- 3.3) X 10(5) M-1 (mean +/- S.E.M.), bound 0.8 +/- 0.1 nmol of Ca2+/mg of protein and the low-affinity sites, Ka = (2.8 +/- 0.3) X 10(2) M-1, bound 33 +/- 3.5 nmol of Ca2+/mg of protein. The high-affinity site exhibited a selectivity for Ca2+, since high concentrations of competing bivalent cations were required to inhibit Ca2+ binding. The relative effectiveness of the competing cations (1 and 10 mM) for the high-affinity site was Mn2+ approximately equal to Sr2+ greater than Ba2+ greater than Mg2+. Data from the pH studies, treatment of the membranes with carbodi-imide and extraction of phospholipids with aqueous acetone and NH3 provided evidence that the low-affinity sites were primarily phospholipids and the high-affinity sites were either phosphoprotein or protein with associated phospholipid. Two possible roles for the high-affinity binding sites are suggested. Either high-affinity Ca2+ binding is involved with specific enzyme activities or Ca2+ transport across the luminal membrane occurs via a Ca2+ channel which contains a high-affinity Ca2+-specific binding site that may regulate the intracellular Ca2+ concentration and gating of the channel.

Animals↗
PubMed1982

Structural studies of collagen fibres from intervertebral disc.

A combined biochemical, X-ray and electron microscopic study is presented on the molecular structure of bovine and human intervertebral disc. Positively stained electron micrographs of Type I and Type II collagen are shown to have slightly but significantly different banding patterns. New low-angle meridional patterns from different anatomical parts of the intervertebral disc are reported from native and trypsin-extracted discs. Qualitative measurements of these intensities lead to the conclusion that in the nucleus pulposus of the disc, another molecule, probably proteoglycan, is ordered on the collagen fibrils at the axial level of the gap region.

Animals↗
PubMed1982

Immunological focusing by th mouse major histocompatibility complex: mouse strains confronted with distantly related lysozymes confine their attention to very few epitopes.

The gallinaceous lysozymes are a family of antigens that are distantly related to mouse lysozyme. A T cell-dependent proliferation assay was used to characterize the spectrum of reactivities to lysozyme determinants in B10-congenic mice. Cross-reactivity studies using a panel of species variant lysozymes to stimulate lymph node cells from chicken egg white lysozyme- and ring-necked pheasant egg white lysozyme-primed B10.D2 mice indicated a preferential focusing of T cell reactivity onto a single determinant containing amino acids 113-114. These data, in conjunction with results obtained by priming with cyanogen bromide cleavage fragments of lysozymes, suggested that a site commmon to the L3 region (amino acids 106-129) of all the lysozymes tested was a preferential anchorage site for I region-encoded Ia molecules on H-2d antigen-presenting cells, leading to the limited display of a determinant containing residues 113-114. Priming with L2H (amino acids 13-105), a peptide containing the major epitopes recognized by B10. A and B10 mice, failed to stimulate any T cell proliferation by B10.D2 lymph node cells. Thus, it appears the Ia molecules in any one mouse strain attach to very few sites on lysozyme to effectively display antigenic determinants for T cell activation. This result points to a model of limited determinant selection even on a very "foreign" antigen based upon a shortage of appropriate amino acid residues usable by Ia antigen-presenting structures of a strain.

Animals↗
PubMed1982

Imaging of acute arterial injury with 111In-labeled platelets: a comparison with scanning electron micrographs.

The relationship between degree of acute arterial injury, extent of platelet deposition, and ability to visualize arterial injury with Indium 111-labeled platelets was studied in 18 rabbits. An aortic lesion was made with a balloon catheter in each animal immediately after injection of autologously labeled platelets. Three nonlesioned rabbits with 111In-labeled platelets served as controls. An additional control study was performed in 12 lesioned rabbits in which nine were injected with 111In-labeled plasma protein and three with 111In-labeled red blood cells. A postmortem scanning electron microscope study of the aortae was made to determine the degree of injury to the intima and the amount of platelet deposition on the damaged arterial wall. The radionuclide scans and scanning electron micrographs were then compared. Lesions were seen in ten of 18 animals with labeled platelets that had extensive regions of denuded endothelium covered by a contiguous layer of platelets. Lesions consisting of patchy deendothelialization and platelet deposition could not be visualized on the scans. Red blood cells and fibrin were not conspicuous on micrographs of the lesions. No lesions were visualized in animals receiving 111In-labeled plasma protein or red blood cells before arterial injury, despite platelet deposition in the lesions.

Animals↗