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Biomedical subjects

J A Edwards

Publications and source records attributed to J A Edwards.

At least 55 records · Page 3Linked to original sources
PubMed1986

Response variability of human brain tumors to AZQ in tissue culture.

In a series of 28 glioma-derived cell cultures and 6 non-gliomatous CNS tumors, AZQ has been found to have varying degrees of growth inhibiting or cytotoxic activity in nearly all lines tested at doses greater than 100 mcg/ml. At dose levels comparable to the clinically achieved levels (1 mcg/ml), AZQ was found to have a cytotoxic effect in 8 of 28 glioma-derived and 2 of 6 non-gliomatous cell lines tested. These findings suggest that AZQ has activity against certain glioma-derived cells in culture at a response ratio similar to that seen in vivo. There, appear to be significant differences in the degree of responsiveness in different patients' tumor cells which can be detected in vitro prior to clinical treatment.

Antineoplastic Agents↗
PubMed1986

Reproductive toxicity studies with oxybutynin hydrochloride.

Oxybutynin hydrochloride, an anti-cholinergic/anti-spasmodic agent, was examined for its effect on fertility and peri-post natal development in the rat and its embryotoxic potential in the rat and rabbit. In the rat effects on reproductive performance included a slight increase in the incidence of foetal malformations, extended gestation period and impaired post natal performance of offspring. These findings occurred at dosages clearly associated with maternal toxicity. Oxybutynin hydrochloride did not exert an effect on reproductive processes in the rat at lower dosages or on embryonic and foetal development in the rabbit.

Animals↗
PubMed1986

Hemoglobin deficit: an inherited hypochromic anemia in the mouse.

The character and pathogenesis of hemoglobin deficit (gene symbol, hbd), an autosomal recessive trait in the mouse, were studied. The main hematological features of hemoglobin deficit are anemia, red cell hypochromia and microcytosis, and reticulocytosis. The absence of raised fecal urobilinogen excretion and frank hyperbilirubinemia and bilirubinuria suggests that excess hemolysis is not the primary cause of the anemia. The raised plasma iron concentration and the failure of the anemia to respond to parenteral iron treatment indicate that the anemia is not due to iron deficiency. The absence of siderocytes and sideroblasts suggests that anemia is probably not due to ferrochelatase deficiency. Thalassemia is excluded by the finding of balanced reticulocyte globin chain synthesis. The markedly elevated levels of free red cell protoporphyrin taken together with the other findings already noted suggest that the anemia of hemoglobin deficit is due to a defect in the erythroid cell iron procurement mechanisms leading in turn to diminished heme and hemoglobin synthesis.

Alleles↗
PubMed1985

Evidence of more rapid stimulus evaluation following cigarette smoking.

Experienced male smokers (greater than 15 cigarettes daily) performed a rapid visual information processing (RVIP) task requiring the detection of sequences of three consecutive odd or even digits in a series presented singly on a TV screen, at a rate of 100 digits/minute. Approximately 80 targets occurred every 10 minutes. All subjects took part in three test sessions: (a) Baseline of 10 minutes on the RVIP task, (2) treatment phase of 10 minutes smoking one cigarette (0.9mg or 1.5mg standard machine delivery of nicotine) or not smoking (NS), (3) posttreatment phase of 20 minutes on the task. Before these morning sessions subjects abstained from smoking for at least 12 hours. Smoking increased the number of correct detections and decreased response time compared with pre-smoking baseline and NS sessions. Analysis of vertex Event-Related Potentials to correct detections revealed a significant reduction in P300 latency following smoking compared to NS sessions. It is suggested that smoking has speeded up stimulus evaluation processes in these individuals. These data are consistent with the common self-report by smokers that smoking aids concentration.

Adult↗
PubMed1985

Study of the HLA gene and antigen frequency from a Saudi Arabian hospital.

The HLA-A, -B, -C and DR loci antigen frequencies were determined, respectively, on 1145, 558 and 352 healthy nonrelated Saudi family members. B21, CW4, CW7, and Dr7 showed the highest gene frequencies, of 14.6%, 28.3%, 7.4% and 19.5%, when compared to other populations. Haplotypes A2-B5, A32-B51, A26-B8, A2-B21, A28-B35, Aw19-B21 and B21-CW4 showed the highest frequencies when compared to other populations. Gene frequencies of 14.6% and 20.2% for B21 and Aw19 antigens, respectively, are highest among Middle East populations. Gene frequencies for A1 (10.5%), A2 (24.9%), A3 (8.9%), A9 (16.7%) and A28 (7.9%) are similar to the 10.1%, 24.9%, 8.3%, 16.8% and 7.7%, respectively, reported for the Turkish population. Also, gene frequencies for B5 (18.5%), B21 (14.6%) and B35 (10.2%) are very close to 17.1%, 14.0% and 10.2%, respectively, reported in the Yemenite population. The above results suggest some influence of other populations on the 'pure' Arab population.

Gene Frequency↗
PubMed1985

Transmural distribution of isomyosin in rabbit ventricle during maturation examined by immunofluorescence and staining for calcium-activated adenosine triphosphatase.

Mammalian ventricle contains two major isomyosins, V1 and V3, which differ in the primary structure of their heavy chains (HC alpha alpha and HC beta beta, respectively) and in their adenosine triphosphatase activity. The distribution of the HC alpha isomyosin in the left ventricle of the rabbit was followed as a function of age and transmural location. HC alpha was detected with a monoclonal antibody found to be specific for the hinge region of V1 myosin molecules when viewed in the electron microscope after low-angle rotary shadowing. Frozen sections were observed with indirect immunofluorescence developed to this anti-HC alpha hinge antibody. Serial sections were observed with the histochemical assay for calcium-activated myosin adenosine triphosphatase, using preincubation at various pH levels. Results show that all the ventricular myocytes in baby rabbits (2 weeks) are stained by the HC alpha-antibody from the epi- to endocardium. The isomyosin content of myocytes varies through the epi- to endocardium of the right ventricular wall of the adult (1-year-old) rabbit, with the HC alpha form predominating in the outer epicardial third of the wall and the lowest amount of HC alpha in the middle third of the wall. A mixture of stained and unstained myocytes is seen in the endo- and subendocardial regions. The spatial distribution of HC alpha in 4-month-old rabbits varies between that of the baby and adult. There is good agreement between myocyte classifications made by histochemical and antibody staining methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

Differential expression of HLA class II antigens on human fetal and adult lymphocytes and macrophages.

A panel of monoclonal antibodies to monomorphic determinants of the MHC class II subregion locus products: DP, DR and DQ, was used to investigate the expression of these antigens on early lymphocytes and macrophages from human fetal liver (13-20 weeks), placenta (16 weeks and term) and cord blood, in relation to the class II phenotype of cells from adult tonsil and peripheral blood. Fetal liver sections and cell suspensions showed differential expression of class II antigens. DP was expressed at a higher frequency (11.0% of nucleated cells) than DR on lymphoid cells and macrophages from fetal liver, and DQ was either absent or expressed on less than 0.3% of nucleated cells. Consistent with this finding, DP but not DR or DQ antigens were observed on vascular elements and macrophages in the villi of 16-week placenta. At term, all three subregion locus products were expressed. Adult tonsil and peripheral blood B lymphocytes expressed DP, DR and DQ antigens with similar frequency; however, DQ was expressed at a lower frequency than DP and DR on cord blood B lymphocytes. In contrast, 30-50% macrophages from cord blood and adult peripheral blood expressed DP and DR, but fewer (5% and 18%, respectively) expressed DQ. These data suggest that class II antigens are expressed in the sequence DP, DR, DQ on developing lymphocytes. A similar sequence is suggested for macrophages.

Adult↗
PubMed1983

Effects of hypophysectomy on acetylcholinesterase and butyrylcholinesterase in the rat.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities were examined in several tissues of normal and hypophysectomized male and female rats. Significant sex differences in the mean AChE activities of normal rats were observed in the superior cervical ganglion (three times more activity in males) and in serum (50% more activity in females). Sex differences in the BuChE activity of serum and liver were even larger (ten times more activity in females), but the activity of other tissues was similar in both sexes. Hypophysectomy had little effect on the mean activity of AChE but did alter BuChE activity in certain tissues. Most of the effects of hypophysectomy on mean BuChE activity were opposite in direction in the two sexes. For example, in males hypophysectomy caused increases in the BuChE activity of serum (300%) and liver (43%), while in females it caused decreases in both tissues (25 and 30% respectively). In rats of a given group, the AChE activity of each tissue appeared to be regulated independently of the activity in other tissues. By contrast, BuChE activity showed statistically significant correlations in more than half of the tissue-pairs examined in control rats of either sex. These correlations can be considered to reflect a tendency toward body-wide regulation. In female rats, the cross-tissue correlations were largely eliminated by hypophysectomy. This finding indicates that the regulation of BuChE may be strongly affected by hormones under the control of the pituitary gland. However, in male rats, only the correlations involving atria were altered by hypophysectomy. Therefore, the effects of hormones on BuChE are probably both sex and tissue dependent.

Acetylcholinesterase↗
PubMed1983

Thermal inactivation of the molecular forms of acetylcholinesterase and butyrylcholinesterase.

To compare acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) and butyrylcholinesterase (acylcholine acylhydrolase, EC 3.1.1.8), we utilized the physical parameter of thermolability. In serum or muscle extracts from mouse and rat, butyrylcholinesterase was inactivated as a unimodal function of temperature. Inactivation began at 51 degrees C and was complete at 54-57 degrees C (depending upon time of incubation). Acetylcholinesterase was inactivated in two stages. A 60% decrease in activity from 42 to 48 degrees C was followed by a plateau. The second stage of inactivation began at 51 degrees C and was complete at 57-60 degrees C (depending upon time of incubation). Sucrose density gradients revealed that the partial loss of acetylcholinesterase activity at 48 degrees C was due to inactivation of the monomeric 4 S enzyme, which was the most thermolabile molecular form in each tissue examined. When heated after isolation on density gradients, most of the forms of acetylcholinesterase and butyrylcholinesterase lost activity as a single exponential function of time. The monomers of both enzymes were inactivated fastest. Inactivation of the larger froms was slower and required higher temperatures. Tetrameric 10 S acetylcholinesterase was unique in following a time course that could only be fitted by a double exponential equation (i.e., when this form was heated to 55 degrees C, almost 60% of the activity showed a short half-life while the remainder showed a long half-life). This behavior did not reflect differences in the thermolability of soluble and membrane-derived tetramers.

Acetylcholinesterase↗
PubMed1983

Asthma induced myocardial infarction in a patient with normal coronary arteries: a case report and a pathogenetic hypothesis.

A 57 year old white woman is reported who developed a myocardial infarction during an attack of allergic asthma and was subsequently found to have a normal coronary arteriogram. The literature on myocardial ischemia and infarction associated with structurally normal coronary arteries is reviewed with particular reference to prostaglandin production, histamine release, platelet activation and the induction of coronary vasospasm. A hypothesis is constructed to explain asthma induced myocardial infarction in terms of interrelated pathogenetic mechanisms.

Asthma↗
PubMed1982

Rapidly transported proteins released from nerve and isolated with myelin.

An in vitro preparation was used to determine if rapidly transported radiolabeled protein which is isolated with the myelin fraction of frog sciatic nerves is similar to rapidly transported radiolabeled protein released from sciatic nerves. Sciatic nerves along with their eighth and ninth dorsal root ganglia were placed in modified Warburg flasks. The center well of the flasks contained 100 microCi [3H]leucine. The preparation was incubated for 24 h, the sciatic nerve removed and the myelin isolated. The solution in which the sciatic nerve portion of the preparation incubated was removed, dialyzed and lyophilized. The radiolabeled proteins isolated from myelin and those released from the nerve were separated on 10% SDS polyacrylamide gels. Results of this separation revealed that a radiolabeled protein of 100,000 daltons was isolated with myelin and released from sciatic nerves. Incubating isolated myelin in 10 mM EDTA for 14-16 h brought about the release of a protein of 100,000 daltons.

Animals↗
PubMed1982

Divergent regulation of acetylcholinesterase and butyrylcholinesterase in tissues of the rat.

Investigating the possibility that acetylcholinesterase (AchE) and butyrylcholinesterase (BuChE) are regulated in a coordinated manner, we have examined the natural variation in activity of these two enzymes in several tissues of adult male Sprague-Dawley, Fischer-344, and Wistar-Furth rats. Both enzymes varied greatly in mean activity among brain, diaphragm, atria, serum, superior cervical ganglia, and liver. In Sprague-Dawley rats there were also large individual variations with up to a fivefold range of AChE activities and up to a 100-fold range of BuChE activities in a given tissue. Individual variations in cholinesterase activities appeared to be smaller in the inbred Fischer-344 or Wistar-Furth rats. Experiments with internal standards of partially purified AChE and BuChE indicated that the individual variations probably reflected differences in the intrinsic content or specific activity of the tissue enzymes. Comparison of the AChE activities in different tissues of a given group of rats failed to reveal statistically significant correlations in any strain (i.e., the relative activity of any one tissue was no guide to the relative activity of any other tissue in the same rat). This result indicates that the regulation of AChE is tissue-specific. By contrast, BuChE activity showed highly significant correlations among the majority of the tissues examined in the Sprague-Dawley rats, implying that widely dispersed factors can affect the regulation of this enzyme. Body-wide regulation is not necessarily the rule, however, since only a single tissue pair in the inbred Fischer rats and none of the pairs in the Wistar-Furth rats showed significant correlations of BuChE activity. In general, AChE and BuChE activities were not correlated with each other to a statistically significant degree. We conclude that the control of these enzymes normally involves different mechanisms and is strongly affected by the genetic background of the sample population.

Acetylcholinesterase↗
PubMed1982

The kinetics of iron uptake by isolated intestinal cells from normal mice and mice with sex-linked anemia.

No significant differences of Km or Vmax could be demonstrated for the initial rate (0-3 min) of iron uptake by preparations of isolated duodenal mucosal epithelial cells from normal or sex-linked anemic (sla) mice. Isolated cells from sla mice do, however, take up significantly more iron than normal cells after 20-min incubation. Upon reincubation with various types of mobilizing agents, the amount of iron released from, and the amount of iron remaining in, cells from sla mice was significantly elevated compared to control values. The percentage of iron released was the same for both types of cells, for all mobilization media employed. The current data, in conjunction with previous studies that showed deficient mucosal to serosal transport of iron in everted duodenal sacs from sla mice, suggest that the lesion in these mice may be located between the mucosal cell and the vascular compartment rather than in the mucosal cell.

Anemia↗
PubMed1980

Defective delivery of iron to the developing red cell of the Belgrade laboratory rat.

Erythroid cell iron and transferrin uptake and release was studied in the anemia of the Belgrade laboratory rat (gene symbol, b), an autosomal recessive trait characterized by hypochromia and hyperferrinemia. When reticulocyte-rich red cells were incubated in vitro with doubly (59Fe, 125I) labeled transferrin, b/b cells demonstrated a significantly higher uptake of transferrin (164% of control at 60 min), and a significantly lower uptake of iron (21% of control at 60 min) than control cells. These findings with b/b cells were simulated by sodium-fluoride-treated control cells, but not by trypsin-treated control cells. When reticulocytes exposed to doubly labeled transferrin were incubated in normal rat plasma, there was a substantial loss of 125I from both the b/b cells (mean 71%) and control cells (mean 49%), but only a loss of 59Fe from the b/b cells (mean 21%). These findings suggest a defect in the delivery of iron to the b/b reticulocyte, which is distal to the binding of transferrin to its cell surface receptor.

Anemia, Hypochromic↗
PubMed1979

A simple method for the intravenous fat-tolerance test.

A simple method for measuring intravenous fat tolerance with an artificial fat emulsion (intralipid) was studied and compared with the currently used method of Carlson and Rossner [J. Lab. Invest. 29, 271-280 (1972)]. The proposed method uses as little as 3 mL of whole blood to follow, by nephelometry, the elimination of intravenously administered fat emulsions. There is a high correlation between the K2 values obtained by the current method for plasma and those obtained by the proposed method (r = 0.903). The latter is simpler, quicker, and more acceptable to patients.

Adult↗