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Biomedical subjects

J A Knight

Publications and source records attributed to J A Knight.

At least 19 recordsLinked to original sources
PubMed1992

Lipid peroxidation in stored red cells.

Lipid peroxidation is initiated by the production of oxygen-free radicals; it is increased in a wide variety of diseases, including various hemolytic anemias, and in hemoglobin disorders. Increased lipid peroxidation occurs in red cells in the presence of reactive iron species and some heme moieties. In this study, greatly reduced concentrations of malondialdehyde, an indicator of lipid peroxidation, were observed in stored blood upon the addition of both deferoxamine mesylate and diethylenetriaminepentaacetic acid (p less than 0.001). The antioxidant glutathione was much less effective (p less than 0.01 or less than 0.05, depending on incubation time). On the other hand, the addition of dimercaptosuccinic acid and ascorbic acid both significantly increased malondialdehyde production over controls (p less than 0.001 and p less than 0.05, respectively). Ascorbic acid, in the presence of deferoxamine mesylate, added no red cell protection over that of deferoxamine mesylate alone. The addition of metal chelators and, possibly, certain antioxidants to stored blood may be effective in increasing the viability and longevity of transfused red cells.

Blood Component Transfusion↗
PubMed1991

Acetylcholine receptors from normal human muscle: concentration, purification, and use in radioreceptor assays for autoantibodies.

We measured the concentration of acetylcholine receptor (AChR) in various normal human muscles, obtained at autopsy, in order to find a more reliable and convenient source than the amputated leg muscle from diabetic patients for the isolation of AChR. We found that human calf muscle contains the highest concentration of AChR, approaching the concentration of receptor required for the radioreceptor assay for autoantibodies in myasthenia gravis (MG). Because the amount of contaminant proteins in the receptor preparations affect the sensitivity and precision of the assay, various chromatographic techniques were tested to improve the purity of the receptor preparation. We found that both G-100 Sephadex and DEAE Sephacel chromatographies were effective in removing contaminant proteins. DEAE Sephacel chromatography is particularly useful because the procedure provides higher recovery of receptor. Against the same pool of autoantibodies from patients with MG, AChRs from diabetic and normal leg muscle exhibit similar affinities. We conclude that AChR from normal human calf muscle can be used in radioreceptor assays for measuring autoantibodies in patients with myasthenia gravis.

Autoantibodies↗
PubMed1990

Carcinogenesis bioassays of nickel oxides and nickel-copper oxides by intramuscular administration to Fischer-344 rats.

Five nickel oxides and nickel-copper oxides, with chemical compositions, physicochemical properties, and biological characteristics that were previously reported, were tested for carcinogenicity by administration to groups of male Fischer-344 rats as a single im injection (20 mg Ni/rat). Two additional groups of rats received injections of the glycerol vehicle (Negative Controls) or nickel subsulfide (alpha Ni3S2, 20 mg Ni/rat, Positive Controls). Within the observation period of 2 yr post-injection, the following numbers of sarcomas developed at the injection site: Negative Controls, 0/15; Positive Controls, 15/15; Compound A (INCO black NiO, prepared at less than 650 degrees C), 6/15; Compound B (grey NiO, calcined at 735 degrees C), 0/15; Compound F (green NiO, calcined at 1,045 degrees C), 0/15; Compound H (oxidized Ni-Cu matte, Ni/Cu = 2.5:1, calcined at 850 degrees C), 13/15; Compound I (oxidized Ni-Cu matte, Ni/Cu = 5:1, calcined at 850 degrees C), 15/15. The Ni- and Ni/Cu-oxides that induced sarcomas (Compounds A, H, and I) had measurable dissolution rates in body fluids and were strongly positive in an erythrocytosis stimulation assay, demonstrating Ni bioavailability. Compound A contained detectable Ni[III] and Compounds H and I contained Cu, plus traces of Fe, Co and S, which may all promote oxygen free-radical reactions. In contrast, the compounds that did not induce sarcomas (Compounds B and F) were essentially insoluble in body fluids, did not stimulate erythrocytosis, and were practically devoid of Ni[III], Cu, Fe, Co, or S. Thus, the bioavailability of nickel and the presence of constituents that promote oxygen free-radical reactions evidently influence the carcinogenicity of nickel oxides and related compounds.

Animals↗
PubMed1990

Cerebrospinal fluid lipoperoxides quantified by liquid chromatography, and determination of reference values.

Cerebrospinal fluid lipoperoxides, measured as the malondialdehyde-thiobarbituric acid (MDA-TBA) adduct, were quantified by adapting the plasma liquid-chromatographic method of Wong et al. (Clin Chem 1987;33:214-20) to cerebrospinal fluid. Reference values for spinal fluid specimens from 91 adults, ages 17 to 95 y, and 37 children, ages 8 d to 8 y, were determined. Their concentrations were not significantly different (P = 0.222), adults having a mean (and SD) of 0.11 (0.06) mumol and children 0.10 (0.04) mumol of MDA per liter. Their ranges were 0.02-0.26 and 0.04-0.21 mumol of MDA per liter, respectively. We found concentrations in cerebrospinal fluid to be increased in several central nervous system disorders, including seizures, cerebral infarction, alcoholic encephalopathy, and, perhaps, prematurity. The presence of other thiobarbituric acid-reactive substances in cerebrospinal fluid stresses the importance of using highly specific techniques when lipoperoxides are measured in body fluids.

Adolescent↗
PubMed1989

Generalized beta 2-microglobulin deposition. A preamyloidosis disorder?

Generalized beta 2-microglobulin deposition in the tissues of a 64-year-old man with idiopathic end-stage renal disease was determined post mortem by the use of immunoperoxidase and radial immunodiffusion techniques. He developed progressive organ failure secondary to beta 2-microglobulin deposition, requiring dialysis for the last two years of his life. His immediate cause of death was severe bronchopneumonia. The extensive tissular deposits were shown to be congophilic but not birefringent by alkaline Congo red stains. Immunochemical studies showed that the deposits were beta 2-microglobulin-positive but AA amyloid-, P-component-, prealbumin-, and kappa and lambda light chain-negative. We suggest that this patient had a primary beta 2-microglobulin dyscrasia in which beta 2-microglobulin deposited in tissues but did not undergo complete amyloidogenic change.

Amyloidosis↗
PubMed1988

Improved specificity of the CA 125 enzyme immunoassay for ovarian carcinomas by use of the ratio of CA 125 to carcinoembryonic antigen.

We found that ovarian cyst fluids contained carcinoembryonic antigen (CEA) and CA 19-9 and CA 125 tumor markers. However, only the ratio of CA 125 to CEA concentrations provided sufficient specificity to differentiate serous from mucinous cysts. For CEA measurement, our results suggested the use of a monoclonal CEA kit. When CEA was determined with a Hybritech monoclonal CEA kit, all ratios in mucinous ovarian cysts were less than 10 and most of the ratios were greater than 1000 in serous ovarian cysts. We also found that the ratio of CA 125 to CEA in serum could be used to differentiate ovarian from nonovarian malignant diseases when both sera contain increased CA 125 concentrations. The nonovarian malignancies consisted of colorectal, breast, lung, and pancreatic carcinomas. The mean ratio for serum from patients with nonovarian cancers was 0.94 (n = 19); for ovarian-cancer patients (n = 45), 916. Therefore, determining this ratio will greatly improve the specificity of the CA 125 test for ovarian cancer.

Antibodies, Monoclonal↗
PubMed1987

Right ventricular blood temperature profiles for rate responsive pacing.

To establish the efficacy of a temperature-based pacemaker control algorithm, right ventricular temperature and heart rate were measured for 12-70 hours in eight patients (51 +/- 17 years) and in one normal volunteer (28 years) during a variety of activities including exercise, rest, sleeping, eating, drinking, and bathing. A diurnal variation in heart rate and temperature was observed. Drinking caused transient temperature changes (less than one minute); during eating, increases of 0.07-0.36 degrees C over 3-12 minutes were observed. An increase of 0.24 degrees C over 8.5 minutes was observed in one patient during bathing. An abrupt drop in temperature was typically observed at the onset of exercise, followed by a steady temperature rise. During treadmill exercise, after a drop (0.13-0.48 degrees C, Bruce n = 4; 0.16-0.34 degrees C, Naughton, n = 3) during the first 1-2 minutes, temperature rose steadily through the end of peak exercise (0.45-1.01 degrees C, Bruce; 0.28-0.47 degrees C, Naughton). A temperature dip was also observed when a patient was told exercise would start but the treadmill failed to turn on. The dip is probably secondary to changes in blood flow from the peripheral circulation to the central system at the onset of exercise. Repeated exercise separated by short rests caused progressive blunting of the initial dip. Right ventricular temperature changes in a predictable manner with daily activity, allowing a temperature algorithm to detect rest and exercise.

Adult↗
PubMed1985

Primary pulmonary hypertension in childhood: a report of two brothers.

We report 2 cases of primary pulmonary hypertension in brothers, 6 and 3 years old. Their lungs contained numerous plexiform vascular lesions. The literature is reviewed involving familial cases, especially those in which siblings were affected. Several of these cases lack the pathological verification necessary for acceptance as examples of plexogenic pulmonary arteriopathy.

Cardiomegaly↗
PubMed1985

In-vitro stability of human alpha-fetoprotein.

We assessed the stability of alpha-fetoprotein (AFP) in clinical specimens in the presence and absence of serum and albumin, at different temperatures and concentrations. We find it depends on both AFP concentration and incubation temperature. Dilution of most specimens with either phosphate buffer or phosphate-buffered saline or by immunoelectrodiffusion resulted in some loss of AFP. Attempts to stabilize AFP during either sample dilution or incubation by use of albumin in concentrations up to 1 g/L did not protect it from inactivation unless normal human serum was also included. Frozen AFP solutions were less stable than solutions stored at 4 degrees C. AFP was most stable when lyophilized and stored desiccated. The AFP-inactivation curves were usually nonlinear. Apparently both polymerization and degradation occur simultaneously as AFP loses its activity. Proteolytic enzyme inhibitor and sulfhydryl reagent not only failed to protect it from inactivation, they appeared to speed it.

Amniotic Fluid↗
PubMed1979

Neutral protease inhibitors from human intervertebral disc and femoral head articular cartilage.

Assays of several proteases, incorporating guanidinium chloride extracts of human femoral head cartilage and intervertebral disc, demonstrated that both tissues contain inhibitors of certain serine proteases. Trypsin, chymotrypsin and a granule extract of human polymorphonuclear leukocytes containing elastase and cathepsin G activities, were inhibited by low molecular weight fractions prepared by Sephadex G-75 chromatography. Using a radioassay, it was further shown that these fractions inhibit proteolysis of cartilage proteoglycan. The inhibitor in intervertebral disc is concentrated in the nucleus pulposus, with a decreasing gradient to the periphery of the annulus fibrosus. It is proposed that these inhibitors confer at least partial protection against pathological proteolysis of the proteoglycans in human articular cartilage and nucleus pulposus.

Animals↗
PubMed1979

Suppression of mitochondrially-determined resistance to chloramphenicol and paromomycin by nuclear genes in Saccharomyces cerevisiae.

Phenotypic "revertants" of a drug resistant strain of Saccharomyces cerevisiae were induced by mutgenesis with manganese. Several of these drug sensitive mutants have been shown to result from mutations in the nuclear genome that cause phenotypic modification (suppression) of the mitochondrially-determined drug resistant genotype. Four mutants carrying a single recessive nuclear gene capable of modifying mitochondrial chloramphenicol resistance are described; these may be assigned to three complementation groups. Chloramphenicol resistant mutants mapping at five separate mitochondrial loci are described. At least two of the nuclear genes cause modification of mitochondrial chloramphenicol resistance determined by mutations at three of these loci, but the other two loci are apparently non-suppressible by these nuclear alleles. This indicates that these modifiers do not act by causing a general decrease in cellular or mitochondrial permeability to the drug. A single dominant nuclear modifier of mitochondrial paromomycin resistance has been identified. It is non-allelic to and does not interact with the genes modifying mitochondrial chloramphenicol resistance.

Chloramphenicol↗