Biomedical subjects
Publications and source records attributed to D West.
A patient, who proved to have a chylous cyst of the colon, presented with bright red rectal bleeding and an abnormality on barium enema suggesting a colonic polyp. We review such an unusual presentation and other reported cases.
We have previously reported that intravenous administration of the octapeptide of cholecystokinin (CCK-8) is more effective in reducing single meal size in baboons at noontime than in the morning. We have also reported that immunoreactive insulin levels in the cerebrospinal fluid (CSF) are elevated after animals have recently eaten. To test whether elevated CSF insulin levels can alter the efficacy of intravenous CCK to reduce meal size we administered subthreshold doses of CCK-8 to baboons infused with either synthetic CSF or CSF and insulin (100 microU X kg-1 X day-1) via the cisterna magna. Intravenous CCK-8 alone reduced 30-min meal size from 504 +/- 121 to 378 +/- 113 kcal (n = 7, P = NS). Chronic intracisternal insulin infusion enhanced CCK-8's suppressive effects such that 30-min meal size was reduced from 544 +/- 74 to 240 +/- 108 kcal (n = 7, P less than 0.005). Intracisternal insulin infusion had no significant effect on total food intake, basal plasma insulin and glucose levels, or postprandial plasma insulin and glucose levels. These findings suggest that central insulin may contribute to food intake regulation by modulating the ability of brain-gut peptides to alter single meal size.
The use of a radioimmunoassay (RIA) demonstrated that angiogenic factors from human and animal tumours, normal bovine retinas, myocardial infarcts, synovial fluid from patients with joint diseases and wound fluid shared common antigenic determinants. Values for angiogenesis factors expressed as microgram Walker tumour TAF/mg protein varied from 0.8 (wound fluid) to 207 (myocardial infarct). Activated macrophages produced an angiogenic factor which did not cross-react. Normal tissue extracts which were non-angiogenic by the chicken chorioallantoic membrane assay also failed to cross-react in the RIA. The antigenic similarity of angiogenic factors from such a wide variety of sources suggests that, in order to minimize therapeutic side effects, it would be best to use angiogenic agonists and antagonists locally.
The interrupted T4 phage td gene, which encodes thymidylate synthase, is the first known example of an intron-containing prokaryotic structural gene. Analysis of td-encoded transcripts provides evidence in favor of maturation at the RNA level. Northern blotting with T4 RNA and with region-specific probes revealed three classes of RNA: diffuse premessage (ca. 2.5 kb), a low-abundance mature mRNA (ca. 1.3 kb), and an abundant free intron RNA (ca. 1.0 kb). The existence of covalently joined mature mRNA was suggested by hybridization and S1 protection experiments and was confirmed by primer extension analysis of the splice junction. In analogy to expression of interrupted eukaryotic genes, these results are consistent with an RNA processing model that would account for the direct gene transcript serving as precursor for both free intron RNA and a spliced mRNA that is colinear with the thymidylate synthase product.
The authors conducted a study of 404 melanoma patients and 521 control patients of both sexes at Roswell Park Memorial Institute. As have previous investigators, they found that higher risk attaches to upper socioeconomic status, as measured by occupation and education, lightness of complexion and hair, and amount of blue in the admixture of eye color. The authors also found a higher risk among individuals who reacted to sun exposure by burning, blistering, or freckling rather than by tanning. A particular concern was to measure risk associated with exposure to the sun. As have two other investigators, they found that risk decreased with increasing exposure, suggesting either that individuals continually exposed to the sun have less risk because of tanning, or that susceptibles purposely avoid sun exposure, or both. The fact that melanoma occurs with greater frequency on sites exposed to the sun suggests that sun exposure plays a part. These studies showed a dose-response increase in risk (odds ratios of up to 4 for males and over 6 for females) with increases in number of traits possessed, such as light complexion, and burning or freckling in response to sun exposure. This is consistent with the authors' earlier finding of a strong familial aggregation of melanoma.
The cytochrome P-450-dependent aryl hydrocarbon hydroxylase (AHH) metabolizes a wide variety of endogenous and exogenous compounds to nontoxic metabolites and/or toxic products. We have utilized a series of 18 flavone modulators of AHH to distinguish and probe for different cytochrome P-450 isozymes in liver microsomes from control and 3-methylcholanthrene (MC)-injected rats. some flavones (maackiain acetate, flavanone, mollisacacidin, embinin, sciadopitysin) activated, while most of the tested compounds inhibited the MC-induced type of AHH. Although all flavones either inhibited or had little effect on the constitutive AHH in microsomes from control rats, the degree of inhibition varied greatly: some flavones (chrysin, chrysoeriol, baicalein, maackiain acetate, isoliquiritigenin, sciadopitysin) inhibited over 75% of the AHH. The various flavones we screened may prove useful in defining the cytochrome P-450 content of tissues and for probing the active sites of individual isozymes. The modulatory effects of the naturally occurring flavones assume additional importance in that they may be factors in animal and human responsiveness to cytochrome P-450 substrates.
The cytochromes P-450 of the mixed function oxidase system metabolize a wide variety of endogenous compounds to either nontoxic products or toxic metabolites. A number of natural products, such as flavonoids, influence this metabolism. Exposure to these compounds may therefore be a factor in animal and human responsiveness to cytochrome P-450 substrates. We have examined the effect of the pterocarpan medicarpin on the cytochrome P-450-dependent aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin deethylase (ECD) activities of rat liver microsomes. Medicarpin and maackiain and two of their biosynthetic precursors inhibit the constitutive and phenobarbital (PB)-induced types of AHH, but have little effect on the 3-methylcholanthrene (MC)-induced type of AHH. This is in contrast to the effect of the commonly used cytochrome P-450 inhibitor 7,8-benzoflavone, which inhibits the hepatic AHH of MC-treated rats and has no effects on the AHH of control or PB-treated rats. However, medicarpin inhibited the constitutive as well as the PB- and MC-induced ECD. The specific modulatory effect as well as its relative availability suggests the utility of medicarpin as a probe for different forms of cytochrome P-450 in animal tissues.
The Self-Care Rehabilitation in Pediatric Asthma (SCRPA) project was designed to ascertain the level to which children with asthma are able to acquire the asthma knowledge and skills presented in a self-management training program conducted by the American Lung Association of Utah and the effect of such training on the asthma experience. The preschool SCRPA Curriculum (ages 2-5) consisted of six 1-hour classes scheduled twice a week for 3 weeks. The first and last classes were for one or both parents only, and the middle four sessions were for the child and parent(s). The school-age SCRPA curriculum (ages 6-14) consisted of eight 90-minute classes for both child and parent(s) scheduled twice a week for 4 weeks. Private physicians referred 21 preschool children and 38 school-age children into the program. The school-age children were randomly assigned to a study or control group, and the preschool children served as their own controls. A comparison of asthma episodes during the 3 months before and after training showed a statistically significant decrease in the number of episodes but no change in severity in the preschool, school study, and school control groups. The decrease in episodes for the control groups suggest that the family record keeping required of all subjects may have a beneficial effect, a phenomenon worth further investigation. Also, the school-age group, in pre- and posttesting, demonstrated that the SCRPA curriculum increased knowledge and skills in the study group, changes not found in the control group.
Acetylated low density lipoprotein (Ac-LDL) is taken up by bovine aortic and adrenal capillary cells but not by brain capillary cells. This indicates that the uptake of Ac-LDL is not a feature of all types of endothelial cell. A quantitative examination of lipoprotein uptake by flow cytometry showed cells in G2M took up 45% more Ac-LDL than those in G1S. Compared with confluent cultures, sub-confluent bovine aortic cells took up three times as much LDL but Ac-LDL uptake was increased by only 34%. This indicates that the Ac-LDL receptor is not down-regulated to the same extent as that for LDL.
The distribution of cytochromes P-450 that catalyze aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase were studied with monoclonal antibody (MAb) 1-7-1 which completely inhibits these activities of a purified 3-methylcholanthrene-induced rat liver cytochrome P-450. The degree of inhibition by MAb 1-7-1 quantitatively assesses the contribution of different cytochromes P-450 in the liver, lung, and kidney microsomes from untreated, 3-methylcholanthrene- and phenobarbital (PB)-treated rats, mice, guinea pigs, and hamsters. Enzyme sensitivity to MAb 1-7-1 inhibition defines two types of cytochrome P-450 contributing to aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase. The MAb 1-7-1-sensitive cytochrome P-450 is a major contributor to aryl hydrocarbon hydroxylase in rat liver, lung, and kidney of 3-methylcholanthrene-treated rats, C57BL/6 mice, guinea pigs, and hamsters; this type is also present in lesser amounts in the extrahepatic tissues of the control and PB-treated animals, and in the lungs of the relatively "noninducible" DBA/2 mice treated with 3-methylcholanthrene. This form however makes little or no contribution to liver aryl hydrocarbon hydroxylase of control or PB-treated animals. 7-Ethoxycoumarin O-deethylase is also a function of both the MAb 1-7-1-sensitive and insensitive classes of cytochrome P-450. The ratio of the classes contributing to aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase differs in the various tissues and species and after inducer treatment. All of the 7-ethoxycoumarin O-deethylase activity in guinea pigs and hamsters is a function of cytochromes P-450 different than the MAb 1-7-1-sensitive cytochrome P-450 responsible for aryl hydrocarbon hydroxylase activity. Thus, the MAb 1-7-1 antigenically defines the type of cytochromes P-450 contributing to each reaction. Cytochromes P-450 can be viewed as paradigmatic for enzyme systems in which the nature and amount of product is regulated by multiple isoenzymic forms. Analyses using monoclonal antibodies to specific isoenzymes may thus have broad application to a variety of other complex systems which are composed of multiple isoenzymes.
A radiochemical assay for glucose-6-phosphatase, which depends on the absorption of radiolabelled substrate on to a nascent precipitate of BaSO4 and Zn(OH)2, can give rise to erroneously high activities. Adsorption on to a Fe(OH)3 precipitate does not expose the incubation medium to extreme alkaline conditions and provides a satisfactory and simple assay. This method demonstrates a very low activity of the enzyme in mammalian muscle, in contrast with previous findings.
Monoclonal antibodies (MAbs) to cytochrome P-450 isozymes can be used to phenotype tissues for epitope-specific cytochrome P-450 content. MAbs that inhibit specific cytochrome P-450 dependent drug or carcinogen reactions are useful tools for quantitative measurement of the individual or classes of cytochromes P-450 that catalyze these reactions. This method has been applied successfully to animal as well as human tissues. Radioimmunoassays based on MAbs have been developed and provide a rapid and efficient means for detecting cytochromes P-450 independent of functional enzyme activity. In addition, MAbs coupled to a Sepharose support can be used to immunopurify cytochromes P-450 in a procedure that is more rapid and efficient than conventional purification schemes. MAbs add a new dimension to analyses of cytochrome P-450 multiplicity and will find numerous applications in elucidation of the relationship between cytochrome P-450 phenotype and carcinogen or drug metabolism.
We conducted a case-control study in ten areas of the United States in which a total of 2,982 bladder cancer patients and 5,782 population controls were interviewed. We employed a variety of existing and new techniques to reduce bias and to monitor the quality of data collected. We review here many of the design elements and field methods that can be generally applied in epidemiologic studies, particularly multi-center interview studies, and explain the reasons for our selection of the methods, instruments, and procedures used.
Cytochromes P-450 are a family of enzymes responsible for metabolism of drug and xenobiotics, such as carcinogen, and certain physiological compounds, such as steroids and prostaglandins. We prepared a monoclonal antibody (MAb 1-7-1) to a polycyclic hydrocarbon-induced rat cytochrome P-450 that antigenically defines and inhibits a type of cytochrome P-450 responsible for aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin deethylase (ECD) activity in human placenta. We examined the placentas from single and twin births from mothers who smoked cigarettes and nonsmokers. The MAb 1-7-1 inhibited the smoking-induced AHH activity of essentially the entire population of placentas by 70 to 95%. Thus, up to 95% of the AHH in a population of human placentas is catalyzed by a type of cytochrome P-450 that contains an antigenic site recognized by MAb 1-7-1. A second type of cytochrome P-450, which is insensitive to MAb 1-7-1, is responsible for the ECD activity in the placentas of nonsmokers. In the placentas from smokers, both types of P-450 contribute to ECD activity. Their ratios can be determined by the amount of inhibition by MAb 1-7-1 which ranges from 0 to 70%. The placentas from both dizygotic and dichorionic monozygotic twins show extraordinarily high intrapair concordance for both the absolute amounts of AHH and ECD and their inhibition by MAb 1-7-1 compared with unrelated individuals, indicating that interindividual differences in these parameters of biological activity are not due to random variation or experimental error. Our results show that the amount of activity of antigenically unique types of cytochrome P-450 responsible for different drug and carcinogen reactions can be measured in different individuals by the amount of their inhibition by highly specific monoclonal antibodies. These findings may have general application to studies on the relationship cytochrome P-450 phenotype to population differences in drug and carcinogen biotransformation.
For most patients, one of the last steps in the subjective determination of the refractive error is the equalization of their accommodative stimuli. Several previous authors have stated that the preferred method of balancing is by some form of binocular stimulation, either with a Turville infinity balance or a polarizing technique [Miles, P. (1948) Am. J. Ophthal . 31, 1460-1466; Morgan, M. W., Jr (1949) Am. J. Optom . 26, 231-239; Goodwin, H. E. (1966) Optom . Wkly 57, 28, 47-51; Grentsch , L. W. and Goodwin, H. E. (1966) Am. J. Optom . 43, 658-663]. This experiment looks at a slightly different aspect: how repeatable a given technique is. We performed five common methods of balancing: vectographic , equal acuity through low plus blur, red-green equalization, Jackson cross-cylinder, and equal loss of acuity with plus blur. We find no significant differences in the variation of any of these techniques; they are all equally reliable. In addition, there seems to be no difference in their mean values, contrary to previous reports.
A human lung tumour cell line has been grown in serum-free medium for 12 months and during this period cells were subcultured every 4 days. The culture medium contained an angiogenesis factor which has been purified and shown to be similar to that isolated from other sources including solid tumours. This is the first report that demonstrates de novo synthesis and secretion of angiogenesis factor by a cell line adapted to grow in a serum-free medium.
5 of 8 infarcted human myocardial tissues were shown to contain an angiogenesis factor which resembles that obtained from solid tumours. The concentration of angiogenesis factor, measured by radioimmunoassay, was similar to that in tumours. It is suggested that the myocardial-infarct angiogenesis factor modulates collateral enlargement or ingrowth of new blood vessels in the infarcted tissues.
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