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Biomedical subjects

C Graham

Publications and source records attributed to C Graham.

At least 109 records · Page 6Linked to original sources

Effects of methanol vapor on human neurobehavioral measures.

Methanol could become an important motor fuel. The objective of this exploratory study was to provide preliminary information about whether or not acute exposure to methanol at 250 mg/m3 for 75 minutes would have adverse effects on human neurobehavioral functions important in everyday life. This concentration level was selected because it is at the upper limit of the traffic scenario estimates provided by the U.S. Environmental Protection Agency (EPA)2 (86 to 240 mg/m3), but is below the maximum concentrations for eight-hour average exposures currently recommended by the National Institute of Occupational Safety and Health (NIOSH) and the American Conference of Government and Industrial Hygienists (ACGIH) (260 mg/m3). Although traffic scenario exposure estimates suggest that such high levels of exposure last less than 15 minutes, we used a 75-minute exposure to increase the probability of identifying dependent measures that should be studied in more detail in a future confirmatory study. Twelve healthy young men, each serving as his own control, participated in two sham exposures and two methanol exposures under counterbalanced, double-blind control conditions. Because methanol is present in many foods, and because high preexposure levels of methanol or formate might obscure exposure effects, subjects were required to strictly limit their diets for 12 hours before each experimental session. The following endpoints were examined before, during, and after exposure to methanol and sham vapors: blood and urinary methanol; plasma formate; oral temperature; blood pressure; subjective mood, alertness, fatigue, workload, and symptom scales; spectral analysis of the electroencephalogram; visual- and auditory-event-related potentials; contingent negative variation; respiration; cardiac interbeat interval; Symbol Digit substitution task; three-choice reaction time; Stroop color-word test; simple reaction time; visual function; critical flicker fusion frequency; hand steadiness; visual search task; Gamberale reaction time task; visual tracking task; Sternberg memory task; interval production task; and speeded addition task. Two dual tasks were also included in the task batteries. These endpoints were selected from those indicated in the literature to be sensitive to solvents, and from those that are widely used in other neurobehavioral test batteries to identify the effects of environmental pollutants. Because the number of endpoints examined was large and the number of subjects was small, procedures designed to reduce the number of statistical tests performed were used. Mean methanol concentration in the exposure room during methanol exposures was 249 mg/m3 (SD +/- 7 mg/m3). Exposure produced significant increases in blood and urine methanol concentration. As expected, no changes in plasma formate were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

A superfamily of NADPH-dependent reductases in eukaryotes and prokaryotes.

Aldose reductase (AR) is implicated in some of the disabling complications of diabetes, including neuropathy, retinopathy and cataracts. Our studies are aimed at further clarifying the role of AR in diabetes and facilitating the design of new classes of potent, specific AR inhibitors by gaining an understanding of the protein structure of AR. To this end, we have determined the complete protein sequence of rat lens AR using cDNA analysis and primer extension of mRNA. By comparing protein sequences, we have found that the structural relatedness (41% to 57%) among the vertebrate proteins, aldose reductase, aldehyde reductase, prostaglandin F synthase and the frog lens protein rho-crystallin can now be extended to prokaryotes by the inclusion of Corynebacterium 2,5-diketo-D-gluconate reductase. This more distantly related protein shares 30-40% identity with the vertebrate enzymes. Sequence alignments reveal that 18% of the amino acids are completely conserved in all members of the superfamily, many of them in clusters, suggesting that they mark important structural features such as the nucleotide binding site and substrate binding site. rho-Crystallin, which is structurally related to this superfamily of NADPH-dependent reductases, does not appear to reduce PGH2, PGD2, xylose or glyceraldehyde to any appreciable extent. It does, however, bind NADPH.

Aldehyde Oxidoreductases↗

Small bowel obstruction in the elderly.

The records of 56 consecutive patients, age 70 years or older, who were operated on for mechanical small bowel obstruction were reviewed to determine the effect of early operation versus delayed operation. Delayed operation was defined as a laparotomy performed more than 48 hours after admission. Excluding the 13 patients with hernias, there were no significant differences between the early operation and delayed operation groups in regard to age, cause of small bowel obstruction, duration of prehospitalization symptoms, degree of underlying disease, or physical findings on presentation--with the exception of a significantly higher number of patients in the early operation group who had abdominal tenderness. There were no differences between mortality and small bowel infarction rates in the two groups. There was an increase in the complication rate (60 vs 24%, P less than .05) and the mean length of stay (29.6 vs 20.0 days, P less than 0.05) in the delayed operation group. This increased mean length of stay was directly related to the higher number of complications caused by delay in operation. Advanced age in a patient with complete small bowel obstruction should not stay the surgeon's hand because delay only leads to a prohibitive increase in complications and length of hospitalization.

Aged↗

Characterization of mRNA and genes for aldose reductase in rat.

Aldose reductase (AR; E.C. 1. 1. 1. 21) has been implicated in a variety of diabetic complications. To investigate the expression of this enzyme in target tissues susceptible to such complications, mRNA encoding AR was characterized by Northern blot hybridization in various tissues and cultured cell preparations. The size of mRNA for AR (approximately 1500 bases) was in good agreement with the size determined by sequence analysis. A cDNA probe for AR from rat lens hybridized to the same size species of RNA isolated from cultured dog lens epithelial cells, cultured human retinal capillary pericytes (mural cells), and Y 79 human retinoblastoma cells. In rat tissues, a substantial amount of mRNA was expressed not only in lens, but also in retina, sciatic nerve and kidney medulla. AR mRNA seemed to be less abundant in rat skeletal muscle and brain, and was scarcely present in liver. Furthermore, Southern blot analysis of rat genomic DNA indicated that there are multiple sequences related to that for AR, probably indicating the existence of a multi-gene family.

Aldehyde Reductase↗

Dynamic monitoring of corneal carbohydrate metabolism using high-resolution deuterium NMR spectroscopy.

Glucose metabolism in rabbit corneas was monitored with deuterium (D or 2H) NMR spectroscopy. The corneas were incubated in 5.5 mM deuterated glucose (glucose-6, 6-D2). A 2.5 micrograms change in lactate and a 4.1 micrograms change in glucose could be detected by the NMR method. The mean rates of glucose utilization and lactate production in intact rabbit corneas were 248- and 151 micrograms h-1, respectively. The lactate production/glucose utilization ratio of 0.60, i.e. 60% of total glucose is metabolized to lactate, confirms that glycolysis is the principal pathway for glucose catabolism. Further, based on enrichment of the HDO signal (which refers to the naturally abundant deuterium signal arising from deuterons in water), glucose oxidation through Krebs cycle and its associated pathways is estimated to be 90 micrograms h-1 or 36% of total consumption. The significant advantages of deuterium NMR spectroscopy over other NMR techniques (e.g. 13C spectroscopy) are: (1) shorter acquisition times because of the short relaxation times of deuterated metabolites; (2) the HDO signal can be used as the internal reference; and (3) significant reduction in cost and high availability of 2H-labeled compounds. Deuterium NMR spectroscopy is therefore a reliable and effective means with which the corneal glycolytic activity prior to transplantation can be readily assessed.

Animals↗

Exercise testing in the evaluation of human responses to powerline frequency fields.

The present study used exercise testing to examine the effects of 60-Hz electric and magnetic field exposure. Eleven males, 21-29 years, were tested during four experimental sessions (counterbalanced order and double-blind design). These included either 45-min exercise (50% of VO2 max) or no-exercise periods followed by either real field (9-kV/m, 16-A/m) or sham exposure for 2 h in a 60-Hz human exposure facility. Exercise produced a decrease in plasma volume and increases (p less than 0.05) in lactic acid, cortisol, growth hormone and testosterone levels, but these were not different under real and sham field conditions during the 2-h recovery periods. During no-exercise sessions, cardiac interbeat interval was increased (p less than 0.05), i.e., heart rate was slower, when subjects were exposed to real fields. Our results suggest that future studies should focus on evaluation of the effects of 60-Hz fields on the entire process of exercise-induced activation and recovery.

Adult↗

Effects of variation in physical effort on frontalis EMG activity.

The physiological mechanisms underlying forehead muscle biofeedback for stress reduction are not well understood. A common hypothesis considers the frontales to be "key muscles" uniquely indexing the degree of tension present in the general musculature. We tested this hypothesis under conditions ranging from relaxation to maximum physical effort. The hypothesis was not supported. Changes in forehead muscle activity were limited primarily to reflecting changes in head and neck muscle tension.

Adult↗

Neuronal differentiation of cloned human teratoma cells in response to retinoic acid in vitro.

We have analysed immunocytochemically the differentiation in vitro of clones of the human teratoma cell line Tera-2. The proliferating stem cells expressed Thy-1 and N-CAM/D2-CAM antigens. On treatment with 5 X 10(-5) M retinoic acid in either monolayer or aggregate cultures they began to express receptors for tetanus toxin and McAb A2B5. Three weeks after initiating retinoic acid treatment, the cultures contained a variety of cell morphologies, including about 3% of cells with a neuron-like morphology. These cells were reactive with tetanus toxin, McAb A2B5, and antibodies against Thy-1 and N-CAM/D2-CAM. They also expressed 55 000 and 210 000 Da neurofilament subunits.

Animals↗

Inhibition of human lymphocyte transformation by tomato lectin.

The lectin from tomato (Lycopersicon esculentum) fruits was found to be non-mitogenic for human lymphocytes in culture and actually suppressed spontaneous DNA synthesis. It also inhibited the transformation of human peripheral blood lymphocytes induced by recall antigens or allogeneic cells in vitro. This inhibition was most effective when the lectin was present from the beginning of the culture period, and could be abolished by the simultaneous addition of oligomers of N-acetylglucosamine. The tomato lectin was able to bind to several major lymphocyte cell surface glycoproteins, but not to the major histocompatibility (HLA) antigens. The binding of tomato lectin to lymphocytes could be inhibited by wheat germ agglutinin (WGA), but not by concanavalin A. Tomato lectin could agglutinate monocytes and B lymphocytes as well as T lymphocytes. Human serum used to supplement the culture medium supporting lymphocyte transformation was equally effective after passage through a tomato lectin-Sepharose column. The inhibition of lymphocyte transformation brought about by tomato lectin was not stopped by exogenously added interleukin 1 and/or interleukin 2, even at very high concentrations.

Binding, Competitive↗

Tomato lectin resists digestion in the mammalian alimentary canal and binds to intestinal villi without deleterious effects.

Experiments were designed to investigate whether orally consumed tomato lectin could resist the digestive process and function as a lectin within the alimentary canal. Rats fed on a tomato lectin-rich diet passed faeces containing serologically detectable tomato lectin, and the lectin could be shown by immunoperoxidase staining bound to intestinal villi. Moreover, radioactivity was mainly recovered from the alimentary canal 3h after 125I-labelled tomato lectin administration with only traces in the circulation or internal organs. Radioactivity absorbed into the human circulation after consumption of 125I-labelled tomato lectin was also less than that expected for a digestable protein.

Administration, Oral↗

Bovine serum eliminates rapid nonspecific toxic reactions during bioassay of stored fish for Clostridium botulinum toxin.

When stored fish or some fish products were tested for the presence of Clostridium botulinum toxin, nonspecific toxic reactions in mice often occurred, rendering the bioassay inconclusive. The nonspecific toxic reactions were mediated by the gram-negative microbiota, inherent to the fish, which were the source of lethal, heat-stable endotoxins. The treatment of assay samples with bovine serum eliminated nonspecific reactions through the interaction of constituent serum immunoglobulin M (IgM) with endotoxic material. Removal of IgM from bovine serum through treatment with protein A or concanavalin A resulted in a loss of protective activity.

Animals↗

A comparison of tomato (Lycopersicon esculentum) lectin with its deglycosylated derivative.

A deglycosylated derivative of tomato (Lycopersicon esculentum) lectin was prepared with the use of trifluoromethanesulphonic acid. Its properties were generally similar to those of the native lectin, but differences were evident in terms of relative agglutinating activity towards sheep, (untreated) human and trypsin-treated human erythrocytes. The two forms of tomato lectin were used in conjunction with a battery of specific antisera to investigate structural relatedness among solanaceous lectins. Immunological cross-reactivity between tomato, potato and Datura lectins depends on the integrity of the glycosylated region of those lectins; that between Datura lectin and other seed lectins, however, has a separate structural basis.

Cross Reactions↗

Solubilization studies on the epicuticular antigens of Strongyloides ratti.

Antigens on the epicuticular surface of Strongyloides ratti infective third-stage larvae (L3) were demonstrated by both ferritin-conjugated antibody and indirect fluorescent antibody techniques. The rat antibodies from immune serum that bind to these antigens were chiefly of the IgG2a subclass. Solubilization of these antigens by extraction with detergents, hypertonic salt, organic solvents and by freezing and thawing was limited as measured by the reduction in antibody binding to the epicuticle. The epicuticular antigens were resistant in situ to degradation by a variety of proteases, carbohydrases and lipase. Infectivity of the L3 in the rat was not reduced by prior sensitization with rat antibody. The epicuticular antigens are not completely species-specific since antibody from S. ransomi-infected pigs cross-reacted well with S. ratti L3 antibody. However, high levels of resistance to S. ratti could be induced in rats only by multiple inoculations of heat-killed S. ratti L3.

Animals↗