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Biomedical subjects

D R Powell

Publications and source records attributed to D R Powell.

At least 109 records · Page 6Linked to original sources
PubMed1989

Structure of the human chromosomal gene for the 25 kilodalton insulin-like growth factor binding protein.

We have characterized the structure of the human chromosomal gene for the 25 kilodalton insulin-like growth factor binding protein (BP-25) as a first step toward understanding both the factors which regulate BP-25 transcription and also the evolution of the insulin-like growth factor binding proteins. The BP-25 gene is present in the human genome as a single copy which spans 5.2 kilobases and contains four exons. Primer extension localizes the mRNA cap site 165 base pairs (bp) upstream of the ATG translational start codon. Preliminary analysis of the putative promoter region for BP-25 demonstrates characteristics consistent with those of many eukaryotic promoters; these include a consensus TATA box beginning 28 bp 5' to the cap site and a consensus CCAAT promoter element beginning 72 bp upstream from the cap site.

Amino Acid Sequence↗
PubMed1988

High molecular weight forms of insulin-like growth factor II and its binding protein identified by protein immunoblotting.

Insulin-like growth factor (IGF)II is a mitogenic polypeptide which circulates in association with a binding protein(s). Immunoblotting studies were performed in human serum and indicate that:(1)a approximately 200 kDa covalently-linked IGF-II/binding protein complex is antigenically related to the 30 kDa binding protein, (2)IGF-II prohormone is associated with this complex, and (3)a major portion of the IGF-II prohormone immunoreactivity in human serum is present in fractions which would not be detected by standard radioimmunoassay methods. Our data provide insight regarding the inter-relationships of IGF-II and its binding protein, and direct evidence for the presence of IGF-II prohormone in human serum.

Humans↗
PubMed1988

Effects of growth hormone therapy and malnutrition on the growth of rats with renal failure.

We examined the effects of methionyl-human growth hormone (met-hGH) and malnutrition on the growth of 5/6 nephrectomized rats and sham-operated controls. One group of sham-operated rats (PFS) was pair-fed with a group of nephrectomized rats in renal failure (RF); another group of sham-operated rats was fed ad libitum (ALS), and a final group of rats with renal failure (RF-GH) was treated with 4 IU/day met-hGH. After 4 weeks, RF-GH rats gained 12.3 +/- 1.7 cm in length; this was more than the 10.2 +/- 1.2 cm gain of RF rats (P less than 0.05). Ingested food was converted into weight gain more efficiently by RF-GH rats than RF rats (267 +/- 26 vs 235 +/- 38 mg weight gain/g food intake, P less than 0.05). RF-GH rats also gained more weight (122 +/- 25 g) than RF rats (98 +/- 27 g), but this difference was not significant (0.05 less than P less than 0.1). Insulin-like growth factor (IGF)-I, glucose and insulin levels were not different between RF and RF-GH rats. Food intake of RF and PFS rats was 64% of ALS intake and was associated with poor gains in weight and length by the PFS and RF groups (relative weight and length gains were ALS greater than PFS greater than RF, P less than 0.05 for all comparisons); this suggests that the poor growth of RF rats when compared with PFS rats was due to factors other than food intake. Serum IGF-I levels of 771 +/- 249 ng/ml in PFS rats were lower than levels of 1109 +/- 253 ng/ml found in the ALS group (P less than 0.05); this is consistent with the malnourished state of PFS rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Insulin-like growth factor (IGF) binding protein complementary deoxyribonucleic acid from human HEP G2 hepatoma cells: predicted protein sequence suggests an IGF binding domain different from those of the IGF-I and IGF-II receptors.

The primary structure of an insulin-like growth factor (IGF) binding protein produced by human HEP G2 hepatoma cells has been deduced from the cDNA sequence. The 234 amino acid protein has a predicted molecular mass of 25,274 and contains a single, distinctive cysteine-rich region. The N-terminal sequence of this protein is quite similar to the limited sequence data available for a rat IGF binding protein produced by BRL-3A cells and suggests a common ancestral origin. In contrast, the HEP G2 IGF binding protein sequence bears no similarity to the N-terminal 15 amino acids of a 53 kilodalton binding protein purified from human plasma. Comparison of full-length protein sequences for the IGF-I and IGF-II receptors with that of the HEP G2 IGF binding protein also fails to demonstrate any significant similarities among these three proteins, and suggests that each contains a unique binding domain for the IGF peptides.

Amino Acid Sequence↗
PubMed1987

Serum concentrations of insulin-like growth factor (IGF)-1, IGF-2 and unsaturated somatomedin carrier proteins in children with chronic renal failure.

Past measurements of somatomedins in chronic renal failure have yielded conflicting results because compounds that accumulate in renal failure and interfere with the somatomedin assays were not removed from assay systems. After serum somatomedins were separated from inhibitory substances by acid chromatography, we measured levels of the major somatomedins, insulin-like growth factor (IGF)-1 and IGF-2, in 16 prepubertal children with chronic renal insufficiency and in 16 age- and sex-matched normal children. Radioimmunoassayable IGF-1 levels were 220 +/- 182 (mean +/- SD) ng/mL in children with renal disease, not significantly different from levels of 248 +/- 155 ng/mL found in normal children. Levels of the less potent mitogen IGF-2, measured by radioreceptor assay, were 661 +/- 213 ng/mL in children with renal disease and were significantly greater than those of 433 +/- 139 ng/mL found in normal children (P less than .05). Since all 16 children with renal disease exhibited significant growth delay, we conclude that low serum IGF levels are unlikely to play a role in this growth failure. Further, since unsaturated somatomedin carrier proteins can interfere with the assay and in vitro biologic actions of the IGFs, and since there was more unsaturated carrier protein binding of IGF-1 by the sera of 15 children with renal disease v 15 normal children (17 +/- 3% v 12 +/- 3% binding of [125I]-IGF-1/50 muL serum, P less than .05), we suggest that somatomedin carrier proteins should be evaluated for their role in the growth failure of children with chronic renal failure.

Carrier Proteins↗
PubMed1987

Antiserum developed for the E peptide region of insulin-like growth factor IA prohormone recognizes a serum protein by both immunoblot and radioimmunoassay.

Nucleotide sequencing of the two known cDNAs encoding human insulin-like growth factor I (IGF-I) predicts two different prohormone forms of IGF-I. The predicted prohormone amino acid sequences (E peptide regions) extend the carboxy-terminus of IGF-I by either an additional 35 (IGF-IA) or 77 (IGF-IB) amino acids. We developed an antiserum directed against a synthetic peptide which is unique to the E peptide region of IGF-IA prohormone. In a RIA using this antiserum, synthetic E peptide immunoreactivity was found in the serum of patients with chronic renal failure. The protein recognized by this antiserum has a mol wt of about 13,000 by neutral gel filtration and about 19,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. These data suggest that the E peptide region of the IGF-IA prohormone is expressed and circulates as part of the prohormone.

Blood Proteins↗
PubMed1986

Purification of the insulin-like growth factor II (IGF-II) receptor from an IGF-II-producing cell line, and generation of an antibody which both immunoprecipitates and blocks the type 2 IGF receptor.

18,54-SF cells, which secrete rat insulin-like growth factor II (rIGF-II), have abundant type 2 IGF receptors. We have purified the type 2 receptor from these cells by solubilization of crude membranes in Triton X-100, followed by chromatography on agarose-immobilized rIGF-II. A partially purified receptor preparation, obtained by chromatography of solubilized membranes over wheat germ agglutinin, was used to immunize a rabbit. The antibody generated both immunoprecipitates the type 2 receptor, and specifically inhibits IGF-II binding to a variety of rat tissues, including 18,54-SF cells, BRL-3A cells and placenta. The presence of abundant type 2 receptors on an rIGF-II-secreting cell line is consistent with an autocrine role for IGF-II in select cells.

Antibodies↗
PubMed1986

Serum somatomedin levels in adults with chronic renal failure: the importance of measuring insulin-like growth factor I (IGF-I) and IGF-II in acid-chromatographed uremic serum.

Somatomedin levels measured by radioreceptor assay (RRA) or RIA on acid-ethanol-extracted or unextracted serum from patients with uremia are quite variable relative to normal values. We have investigated whether compounds accumulating in uremic serum were interfering with these RRA and RIA measurements. Insulin-like growth factor I (IGF-I) and IGF-II were separated from carrier proteins by either Sephadex G-50 acid chromatography or acid-ethanol extraction. IGF-I was measured by RIA, and IGF-II was determined by rat placental membrane RRA. IGF-I levels in the acid-ethanol extracts of serum from eight uremic adults were only 50% of the levels found in seven normal subjects, and IGF-II levels in these uremic patients were 350% of normal values. However, these significant differences were not found when comparable serum samples were acid chromatographed rather than acid-ethanol extracted; instead, IGF-I levels were 343 +/- 168 (mean +/- SD) ng/ml in uremic patients and 325 +/- 54 ng/ml in normal subjects, while IGF-II levels were 780 +/- 215 ng/ml in uremic patients and 588 +/- 46 ng/ml in normal subjects. To determine whether compounds that interfere with somatomedin assays were present in the acid-ethanol extracts of uremic serum, we acid chromatographed these extracts and found that a compound eluting in the carrier protein fraction of the uremic extract artifactually decreased IGF-I levels measured by RIA and increased IGF-II levels measured by RRA. We also found that unsaturated carrier protein binding of IGF-I and IGF-II was significantly increased in the carrier protein fraction of uremic acid-ethanol extracts at the dilutions used for somatomedin assays. We conclude that acid chromatography of unextracted or acid-ethanol-extracted uremic serum is necessary to remove a compound, probably unsaturated carrier protein, which interferes with RIA of IGF-I and RRA of IGF-II. Once this compound is removed, serum IGF-I levels (RIA) in uremic patients are not different from normal, and serum IGF-II levels (RRA) are not lower than normal.

Adult↗
PubMed1984

Phosphorus-nitrogen compounds. 24. Phosphoramide mustard carrier derivatives.

Diethylstilbestrol, psoralen, and propranolol were used as potential carrier molecules for selective concentrations of a nitrogen mustard moiety in breast, skin, and lung tissues, respectively. The propranolol derivative gave two racemic mixtures, which were tested to ascertain any differences in anticancer activity. The insertion of a P = O group between the carrier and oncolytic portions offsets the excess lipophilic contribution of the latter and possibly provides for latentiation of alkylating activity. Murine tumor testing of the phosphoramide mustard derivatives and two intermediates indicated that two compounds possessed marginal activity against mammary carcinoma and lymphocytic leukemia.

Animals↗
PubMed1984

Synthesis, conformational analysis, and antiarrhythmic properties of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one, 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate, and 7-benzyl-9-phenyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ol hydroperchlorate and derivatives: single-crystal X-ray diffraction analysis and evidence for chair-chair and chair-boat conformers in the solid state.

The synthesis of the title ketone has been completed via a type of Mannich reaction starting from 4- thianone . An X-ray diffraction analysis has revealed that the solid system is a chair-boat conformer with the sulfur atom in the boat portion of the bicyclic ring compound. Wolff- Kishner reduction of the ketone group gave 7-benzyl-3-thia-7-azabicyclo [3.3.1]nonane, which was isolated as the hydroperchlorate . However, X-ray diffraction analysis of the salt showed this solid to be a chair-chair conformer. Addition of phenylmagnesium bromide to the ketone gave a tertiary alcohol with the C-C6H5 bond being equatorial with respect to the thiane ring and axial with respect to the piperidine ring. The reaction of the Grignard reagent with the ketone to give this alcohol seems to be very stereospecific. An X-ray analysis of the hydroperchlorate of the alcohol confirmed the system to be a chair-chair form in the solid. The title compounds were screened for antiarrhythmic activity in anesthetized mongrel dogs in which myocardial infarctions had been created when the left anterior descending coronary artery was ligated. Vagal-induced slowing of the sinus mode firing rate was used to determine the underlying ventricular automaticity in the dogs, which averaged 164 +/- 27 beats/min. Ventricular pacing was initiated to rates between 240 and 390/min. This technique resulted in the induction of rapid and sustained ventricular tachycardia. At doses of 3 and 6 mg/kg of body weight, 7-benzyl-3-thia-7-azabicyclo [3.3.1]nonane hydroperchlorate in alcohol (the solution was administered intravenously) was able to suppress markedly the induced ventricular tachycardia in five of six dogs. The compound also caused a 10-15% increase in blood pressure within a few minutes. The antiarrhythmic properties of this compound and others of related structure are discussed, and some comparison is made with the action of lidocaine in similar dog preparations.

Animals↗
PubMed1984

Extracellular siderophores from Aspergillus ochraceous.

A large number of iron-chelating compounds (siderophores) were isolated from supernatants of iron-deficient cultures of a mold isolate, subsequently identified as Aspergillus ochraceous . Siderophores in their iron chelate form were purified to homogeneity by using Bio-Gel P2, silica gel, and C-18 bonded silica gel (reverse-phase) columns. Most of these compounds, as identified by 1H and 13C nuclear magnetic resonance spectroscopy and X-ray crystallography, belong to the ferrichrome family. The organism produces ferrirubin and ferrichrysin as the predominant and the second major compound (62 and 15% of the total siderophores), respectively. Ferrichrysin appears as the first siderophore in the medium on day 2 of growth. Several of the other siderophores are novel and ranged in quantities from 0.2 to 5% of the total. The trivial names asperchrome A, B1, B2, C, D1, D2, and D3 are proposed for these novel compounds, which are all members of the ferrichrome family, and all but the first one contain a common Orn1 - Orn2 - Orn3 - Ser1 -Ser2-Gly cyclic hexapeptide ring with three dissimilar ornithyl delta-N-acyl groups. Another compound which appeared late in the growth period was similar to fusarinine C ( fusigen ). All of these compounds showed growth factor activity to various extents in bioassays with Arthrobacter flavescens Jg-9. None of these compounds showed antibacterial activity against Escherichia coli or Bacillus megaterium.

Aspergillus↗
PubMed1983

Predictors of help-seeking in an urban setting: the search for child care.

The aim of this exploratory study was to identify variables which predict how parents search for child care. Structured interviews were conducted with 50 parents of young children who had searched for full-time nonrelative child care. The respondents represented a 1% sample of Detroit parents. Search behaviors were found to be related to perceived neighborhood age, personal social network ties, and income and family structure. Personal social network ties related to contrasting sets of search behaviors, described as cosmopolitan versus parochial help-seeking patterns. However, perceived neighborhood age modified the relationship between social network ties and search behaviors in that the contrast between cosmopolitan and parochial help-seeking patterns was found only in neighborhoods where most residents had lived more than 10 years (established areas). The findings point to the need for multivariate investigations of the relationship between neighborhood context and patterns of help-seeking, especially in regards to the role of personal social networks. Implications of the findings for the design of a local child care information and referral service are discussed.

Adolescent↗
PubMed1978

The interpersonal relationship between parents and caregivers in day care settings.

A structured interview measuring communicative behaviors and attitudes was used to determine the nature of parent-caregiver relationships. While frequent parent-caregiver communication was found, the data suggest minimal attempts to coordinate day care children's socialization processes. Implications for day care practice, policies, and research are discussed.

Adult↗
PubMed1977

Analysis of various indefinite self-associations.

Two methods have been developed for the analysis of four types of indefinite self-associations. Unlike previous treatments by others, the procedures can be applied to nonideal cases. The two methods were first tested with simulated data, and it was found that one could indeed distinguish between the four types of indefinite self-associations. For a more realistic test, sedimentation equilibrium experiments were performed on solutions of beta-lactoglobulin A at 16 degrees C in 0.15 ionic strength acetate buffer, pH 4.65. The self-association of the beta-lactoglobulin A was best described by either method as a sequential indefinite self-association having two equilibrium constants and one second virial coefficient.

Buffers↗