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R A Norman

Publications and source records attributed to R A Norman.

At least 19 recordsLinked to original sources
PubMed1992

Hemodynamic studies in DOCA-salt hypertensive rats after opening of an arteriovenous fistula.

We determined the cardiovascular responses in normal and deoxycorticosterone acetate (DOCA)-salt hypertensive rats with reduced total peripheral resistance due to an arteriovenous (a-v) fistula. Animals were divided into four groups: control, fistula, DOCA-salt, and DOCA-salt fistula. The fistula was made by anastomosing the aorta and vena cava below the renal arteries. Four weeks after the creation of the fistula both DOCA-salt and DOCA-salt fistula animals received DOCA and salt for 6-8 wk. At the end of 10-12 wk we measured mean arterial pressure, cardiac output, tissue flows, and right atrial pressure. Flow measurements using radioactive microspheres were made in anesthetized animals. Cardiac index (CI) was 202% higher in the fistula group than in the control animals and 165% higher in the DOCA-salt fistula than in the DOCA-salt animals. There was no difference in cardiac output between the control and DOCA-salt animals. The increase in cardiac output was due to the fistula flow as evidenced by a significant increase in the number of microspheres in the lung. Mean arterial pressure was 115 +/- 4 mmHg (control) and 108 +/- 5 mmHg (fistula) in non-DOCA rats but increased in both DOCA groups, 159 +/- 3 mmHg (DOCA-salt) and 145 +/- 5 mmHg (DOCA-salt fistula). Right atrial pressure was increased above control in both fistula animals but was normal in DOCA-salt animals. Total peripheral resistance (TPR) was higher than control in DOCA-salt animals, but TPR in both the fistula and DOCA-salt fistula animals was lower than control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Mutation analysis of the cystic fibrosis transmembrane regulator gene in Native American populations of the southwest.

We report DNA and clinical analyses of cystic fibrosis (CF) in two previously unstudied, genetically isolated populations: Pueblo and Navajo Native Americans. Direct mutation analysis of six mutations of the CFTR gene--namely, delta F508, G542X, G551D, R553X, N1303K, and W1282X--was performed on PCR-amplified genomic DNA extracted from blood samples. Haplotype analyses with marker/enzyme pairs XV2c/TaqI and KM19/PstI were performed as well. Of the 12 affected individuals studied, no delta F508 mutation was detected; only one G542X mutation was found. None of the other mutations was detected. All affected individuals have either an AA, AC, or CC haplotype, except for the one carrying the G542X mutation, who has the haplotype AB. Clinically, six of the affected individuals examined exhibit growth deficiency, and five (all from the Zuni Pueblo) have a severe CF phenotype. Four of the six Zunis with CF are also microcephalic, a finding not previously noted in CF patients. Our DNA data have serious implications for risk assessment of CF carrier status for these people.

Adolescent↗
PubMed1992

Molecular analysis of cis-regulatory sequences at the alpha-amylase locus in Drosophila melanogaster.

The Amylase locus in Drosophila melanogaster contains duplicate, divergently transcribed structural genes for alpha-amylase, AmyA and AmyB. A sensitive and reliable transient expression assay was developed for testing amylase activities produced by exogenous Amy genes in somatically transformed larvae of an amylase-null strain of flies. Alleles tested, AmyA and AmyB, came from recombinant clone lambda Dm65, which contains genomic DNA from a Canton-S strain. The transient assay was used in a deletion analysis aimed at locating cis-regulatory sequences within the 5' region of AmyB. Results suggest that upstream regulatory sequences for correct spatial expression of AmyA and AmyB in third-instar larvae are located within 446 and 430 bp of their respective starts for transcription. A sequence required for high levels of AmyB expression was located within its 5' upstream region between the base pairs at -332 and -219. AmyA does not appear to have a comparable regulatory element in its 5'-flanking sequence. Barely detectable expression of AmyB was observed when it was flanked by only 92 bp of upstream sequence. A model is proposed for incomplete coordinate control of the duplicate Amy genes.

Amino Acid Sequence↗
PubMed1990

Dosage compensation and dietary glucose repression of larval amylase activity in Drosophila miranda.

The functional locus for alpha-amylase (Amy) in Drosophila miranda is in the evolutionarily new X2 chromosome. X2 evolved from an autosome in response to an ancestral autosome-Y translocation that gave rise to the "neo-Y" chromosome of this species. Y-linked Amy, if still present in the ancestrally translocated element, is unexpressed. Dosage compensation for amylase activity was examined in larvae of the S 204 strain. Since dietary glucose is known to repress Amy expression in Drosophila melanogaster, dosage compensation of amylase activity in male larvae of D. miranda was tested by rearing larvae of both sexes on yeast diets with or without a glucose supplement. The WT 10 strain of Drosophila persimilis, a sibling species in which Amy is autosomally linked, was used as a reference for tests of amylase activity differences between the sexes. On the diet with glucose, Amy expression was repressed in both WT 10 and S 204 larvae and male larvae of S 204 displayed dosage compensation for amylase activity. On the nonrepressing diet consisting of yeast alone, S 204 continued to display dosage compensation.

Animals↗
PubMed1990

Amylase gene expression in intraspecific and interspecific somatic transformants of Drosophila.

The Amylase locus in Drosophila melanogaster normally contains two copies of the structural gene for alpha-amylase, a centromere-proximal copy, Amy-p, and a distal copy, Amy-d. Products of the two genes may display discrete electrophoretic mobilities, but many strains known to carry the Amy duplication are characterized by a single amylase electromorph, e.g., Oregon-R, which produces the mobility variant AMY-1. A transient expression assay was used in somatic transformation experiments to test the functional status of the Amy genes from an Oregon-R strain. Plasmid constructs containing either the proximal or distal copy were tested in amylase-null hosts. Both genes produced a functional AMY-1 isozyme. Constructs were tested against an AMY-3 reference activity produced by a coinjected plasmid that contains the Amy-d3 allele from a Canton-S strain. With reference to the internal control, the Amy-p and Amy-d genes from Oregon-R expressed different relative activity levels for AMY-1 in transient assays. The transient expression assay was successfully used to test the functional status of Amy-homologous sequences from strains of other species of Drosophila characterized by a single amylase elctromorph, namely, Drosophila pseudoobscura ST and Drosophila miranda S 204. The amylase-null strain of D. melanogaster provided the hosts for these interspecific somatic transformation experiments.

Amylases↗
PubMed1990

Molecular genetics of a three-gene cluster in the Amy region of Drosophila.

Analysis of amylase RNA levels in the anterior and posterior midgut regions of flies from the Amy1,6 mapA and c Amy2,3 mapC strains of D. melanogaster, reared on yeast and on yeast supplemented with glucose, indicates that the trans-acting map gene controls the abundance of amylase RNA tissue-specifically, i.e., in the adult posterior midgut. This is consistent with the view that its role in controlling Amy expression is that of a transcription factor. Dietary glucose represses Amy expression in the anterior and posterior midgut regions of adults, reducing the abundance of amylase RNA, which suggests that it also controls Amy transcriptional activity. However, the mechanism for glucose repression appears to act systemically in the midgut, in a manner that is independent of the effects of map on Amy expression. A new glucose repressible TU was identified that is located just proximal to the Amy locus in region 54A of polytene chromosome 2R. It is transcribed in the direction opposite to that of the proximal Amy gene and encodes an RNA about 1500 bases long. Its RNA is expressed in both larvae and adults of the above strains of D. melanogaster, but the nature of the product it encodes is unknown. We speculate that all three genes in the cluster at 54A, namely the two Amy gene copies and the new glucose repressible TU, are coordinately controlled by the same mechanism that regulates Amy gene expression in response to dietary glucose. Somatic transformation experiments suggest that 5' cis-regulatory mechanisms required for the correct spatial expression of the proximal and distal Amylase genes from a Canton-S strain of D. melanogaster, Amy-p1 and Amy-d3, are located within 450 bp and 463 bp of their respective translation start sites. These regions also contain sequences responsive to dietary glucose repression, which is mediated at the DNA level of exogenous Amy genes in somatically transformed larvae reared on a yeast + glucose diet. A positive activator is located in the upstream region of Amy-d3 between the nucleotide pairs at -365 and -252 from the translation start site, but a comparable activator does not appear to exist in the upstream region of Amy-p1. Deletion analysis of the 5' sequence flanking the coding region of Amy-d3 indicates 125 nucleotide pairs of flanking DNA is sufficient for its functional activity. A model is proposed for coordinate control, in part, of the duplicated Amy genes.

Amylases↗
PubMed1989

"Skin is in".

Explore the source record for details and available documents.

Dermatology↗
PubMed1988

Mechanisms of partial renal infarct hypertension.

Contributions of both the renin-angiotensin and immune systems to the aetiology of renal infarct hypertension were examined in Sprague-Dawley rats. Partial renal infarction was produced by ligating and sectioning two out of three branches of the left renal artery. The right kidney remained intact. Renal infarction resulted in rapid development of stable hypertension. One week following infarction, the plasma renin activity (PRA) increased more than threefold. However, PRA returned to control levels 4 weeks after infarction. Chronic immunosuppressive therapy with cyclophosphamide at most only attenuated the development of renal infarct hypertension associated with this transient renin elevation. However, cyclophosphamide prevented the later maintenance phase of the hypertension, and could also completely reverse established infarct hypertension. Activation of the renin-angiotensin system plays a role in the onset of partial renal infarct hypertension, but an intact immune system is required for maintenance of the hypertension. It is hypothesized that immunological reactions against renal tissue maintain renal infarct hypertension.

Animals↗
PubMed1987

Structural organization of the alpha-amylase gene locus in Drosophila melanogaster and Drosophila miranda.

Chromosomal sites belonging to the alpha-amylase gene family have been identified in D. melanogaster and D. miranda and in the sibling species of miranda, pseudoobscura, and persimilis. Two sites occur in chromosome 2 of melanogaster; one contains the Amy gene locus (54A) and the other an amylase "pseudogene" (53CD). Two sites of homology exist at 73A and 78C and perhaps another at 81BC in chromosome 3 of pseudoobscura and persimilis and in the homologous regions of the X2 chromosome in miranda. The active Amy locus is apparently at 73A. The structural organization of cloned sequences from this multigene family in melanogaster and miranda is under analysis, with emphasis on the functional Amy gene region. Electrophoretic variants of amylase have served as invaluable tools in these studies. For melanogaster, their use as genetic markers enabled us to positively identify our lambda Dm65 clone of the Amy locus and to show that it contains two functional copies of the structural gene for alpha-amylase. Amylase isozymes are now being used in P element-mediated transformation experiments aimed at defining regulatory elements for the temporal and spatial control of amylase expression during development and in response to dietary glucose. In miranda, electrophoretic variants of amylase were useful in assigning the Amy locus to chromosome X2, and they continue to serve as essential markers in our study of the evolution of dosage compensation for amylase expression in males of this species. Restriction maps of the Amy locus in 7 strains of D. melanogaster indicate that despite the worldwide origins of the chromosome samples, all contain a duplication of the amylase structural gene at this locus regardless of whether they produce two alpha-amylase isozymes, a single variant, or none. We have aligned these maps with the genetic and cytological maps of chromosome 2R in melanogaster and assigned alleles for different amylase isozymes to either the proximal or distal Amy gene copy in a number of strains. Restriction site polymorphism is relatively limited at the Amy locus, but some strain-specific rearrangements exist. The locus of two strains with reduced amylase activity, Amy1 (CA 1) and Amy "null", contain anomalies--an insertion in the former and an inversion in the latter. Causal relationships are being sought between the level of amylase expression in these strains and the position of their respective anomalies.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Spontaneous hypertension is primarily the result of sympathetic overactivity and immunologic dysfunction.

Overactivity of the sympathetic nervous system and immunologic dysfunction have been shown to contribute to development and maintenance of hypertension in the Okamoto spontaneously hypertensive rat (SHR). In this study, the combined effects of reduction in sympathetic activity and immunologic manipulation on spontaneous hypertension have been determined. Neonatal SHRs received sham implants or implants of thymic tissue from Wistar donor rats. In addition, the thymus-implanted SHRs underwent bilateral renal denervation when they were 6 weeks old. At the same time, the sham-implanted SHRs underwent sham renal denervation. The denervations or sham operations were repeated when the SHRs were 9, 12, 15, and 18 weeks old. Wistar-Kyoto (WKY) rats also underwent serial sham renal denervations. Tail-cuff pressure measurements indicated that approximately 75% of the chronic hypertension in the SHRs was prevented by the combination of thymic implants and renal denervations. Direct arterial pressure measurements confirmed these results; when the rats were 21 weeks old, mean arterial pressure averaged 177 +/- 5.5 mm Hg in sham-operated SHRs, 134 +/- 2.7 mm Hg in implanted, denervated SHRs, and 121 +/- 2.1 mm Hg in sham-operated WKY rats. These data indicate that overactivity of the sympathetic nervous system and immunologic dysfunction account for the majority of the hypertension in the Okamoto SHR.

Animals↗
PubMed1986

Immunological dysfunction and enhanced sympathetic activity contribute to the pathogenesis of spontaneous hypertension.

Chronic elimination of renal sympathetic nerve activity will prevent one-third of the hypertension in spontaneously hypertensive rats (SHR), and manipulations of the immune system will block one-half of the spontaneous hypertension. In the present study the combined role of enhanced sympathetic activity and immunological dysfunction in the pathogenesis of hypertension in the SHR was investigated. Neonatal SHR received thymic implants from donor Wistar rats. When these thymus-implanted SHR were 6 weeks old they underwent bilateral renal denervation. The renal denervation procedure was repeated when the SHR were 9, 12, 15 and 18 weeks old. When the implanted, denervated SHR were 20 weeks old their average systolic pressure (SP) was 146 +/- 4.0 mmHg (mean +/- s.e.m.). The SP of age-matched, sham-operated Wistar-Kyoto (WKY) rats was 127 +/- 2.2 mmHg, while it averaged 196 +/- 4.4 mmHg in 20-week-old sham-operated SHR. Therefore, neonatal thymic implants in combination with chronic renal denervation abolish three-quarters of the hypertension in the SHR. These results support the hypothesis that immunological dysfunction and enhanced sympathetic activity cause spontaneous hypertension.

Animals↗
PubMed1986

Current concepts and perspectives of renal volume regulation in relationship to hypertension.

The renal-body fluid mechanism for arterial pressure control is almost certainly the most primitive of all the pressure-regulating mechanisms in animals. Through the stages of evolution, the system has been greatly improved. Nervous controls provide rapid pressure-control mechanisms that function almost instantaneously, many hours or days before the renal-body fluid mechanism can act fully. The renin-angiotensin-aldosterone system plays another important role: this system ensures that very large changes in salt intake, from as little as one-tenth normal up to as high as 10 times normal, have very little effect on the regulated level of the arterial pressure. Finally, the long-term autoregulatory mechanism helps to dissociate the long-term control of cardiac output from long-term control of arterial pressure; it also makes it possible for extremely slight increases in body fluid volume to cause chronic volume-loading hypertension.

Aldosterone↗
PubMed1985

Genetic variability of flight metabolism in Drosophila melanogaster. II. Relationship between power output and enzyme activity levels.

The major goal of the studies reported here was to determine the extent to which genetic variation in the activities of the enzymes participating in flight metabolism contributes to variation in the mechanical power output of the flight muscles in Drosophila melanogaster. Isogenic chromosome substitution lines were used to partition the variance of both types of quantitative trait into genetic and environmental components. The mechanical power output was estimated from the wingbeat frequency, wing amplitude and wing morphology of tethered flies by applying the aerodynamic models of Weis-Fogh and Ellington. There were three major results. (1) Chromosomes sampled from natural populations provide a large and repeatable genetic component to the variation in the activities of most of the 15 flight metabolism enzymes investigated and to the variation in the mechanical power output of the flight muscles. (2) The mechanical power output is a sensitive indicator of the rate of flight metabolism (i.e., rate of oxygen consumption during tethered flight). (3) In spite of (1) and (2), no convincing cases of individual enzyme effects on power output were detected, although the number and sign of the significant enzyme-power correlations suggests that such effects are not totally lacking.

Animals↗
PubMed1985

Immune system dysfunction contributes to the aetiology of spontaneous hypertension.

Spontaneously hypertensive rats (SHRs) have a depressed T lymphocyte system, especially a reduced activity of the suppressor T cells, and it has been postulated that an auto-immune defect may be important in the aetiology of hypertension in these rats. In an earlier study we demonstrated that chronic immunosuppressive therapy prevents approximately 50% of the hypertension in the SHR. In the present study, an attempt was made to correct the immune imbalance by implanting thymic tissue from normotensive rats into SHRs. Weekly thymic implants from Wistar donor rats into 16-week-old SHRs produced a maximal reduction (P less than 0.05) in the tail-cuff pressure, after 4 weeks, to a level of 156 +/- 2.3 mmHg (n = 8) in thymus-implanted SHRs versus 189 +/- 2.5 mmHg (n = 6) in sham-implanted SHRs. Also, neonatal thymic implants delayed development of spontaneous hypertension and attenuated the final hypertensive state. Mean arterial pressure averaged 186 +/- 2.8 mmHg in 22-week-old, neonatally sham-implanted SHRs, while it was reduced (P less than 0.05) to 164 +/- 4.2 mmHg in the neonatally thymus-implanted SHRs at this time. The thymic implants had little effect on total T cell, helper T cell or suppressor T cell counts. However, the antihypertensive effect of the thymic implants was associated with a substantial increase in the blastogenic responsiveness of suppressor T cells from the SHRs. These results support the hypothesis that immunological dysfunction plays an important role in the aetiology of spontaneous hypertension.

Animals↗
PubMed1985

Renal nerves are not necessary for onset or maintenance of DOC-salt hypertension in rats.

The effect of renal denervation on the onset and maintenance of mineralocorticoid-salt [deoxycorticosterone (DOC)-salt] hypertension was determined. A unilateral right nephrectomy was performed on all rats. Rats were divided into renal-denervated and sham-operated groups. All rats received 10 mg/wk of DOC pivalate and 0.9% saline to drink ad libitum. Renal denervation was repeated at 3-wk intervals to prevent renal nerve regeneration. Renal denervation had no effect on the onset or maintenance of DOC-salt hypertension. Hypertension developed over the same time course in both the renal-denervated and sham-operated rats regardless of the time frame of unilateral nephrectomy and renal denervation. Tail-cuff pressure measurements reached plateau levels of 187 +/- 5.7 mmHg in sham-operated and 183 +/- 4.6 mmHg in renal-denervated rats after 4 wk of DOC-salt administration. Mean arterial pressure averaged 197 +/- 10.3 mmHg in sham-operated and 200 +/- 7.9 mmHg in renal-denervated rats after 8 wk of treatment. Intact renal nerves are not necessary for the development or maintenance of DOC-salt hypertension in rats.

Animals↗