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Biomedical subjects

D Rhodes

Publications and source records attributed to D Rhodes.

At least 91 records · Page 5Linked to original sources
PubMed1993

Is body fat topography a risk factor for breast cancer?

OBJECTIVE: To determine whether body fat distribution is associated with the onset of breast cancer. DESIGN: Case-control study. SETTING: Memorial Sloan-Kettering Cancer Center, New York, New York. PATIENTS: Three hundred thirteen healthy, white women, born in the United States. MEASUREMENTS: Waist and hip circumferences were measured on the day before diagnostic breast surgery, and an extensive risk assessment of clinical and family history data was done. After the results of diagnostic breast surgery were obtained, study participants were divided into three groups: women with breast cancer (n = 156); controls (n = 126) with benign tissue at biopsy and an average risk for breast cancer; and high-risk women (n = 31), defined as being at a risk for breast cancer development of 1% per year, based on rigorous histologic or clinical criteria. RESULTS: The waist-to-hip ratios (WHR) were identical (mean +/- SD) in case patients (0.80 +/- 0.06), controls (0.80 +/- 0.06), and high-risk women (0.80 +/- 0.08). Further, no trend could be detected between increasing WHR and breast cancer risk; the estimated relative risk for cancer incidence in women with WHR greater than or equal to 0.81 was 0.78 (95% Cl, 0.36 to 1.71), compared with women with WHR of less than 0.73. No difference in WHR was noted between the case patients and controls when analyzed separately according to menopausal status, age, absolute weight, or relative weight. CONCLUSION: In the women studied, body fat topography as defined by WHR was not associated with breast cancer development.

Adipose Tissue↗
PubMed1993

Zinc fingers.

Explore the source record for details and available documents.

Amino Acid Sequence↗
PubMed1992

Adjacent zinc-finger motifs in multiple zinc-finger peptides from SWI5 form structurally independent, flexibly linked domains.

Peptides containing either one, two or three of the three zinc-finger motifs from the yeast transcription factor SWI5 have been prepared by expression in Escherichia coli. The DNA binding characteristics of these peptides were investigated, and a two-dimensional nuclear magnetic resonance (n.m.r.) study undertaken to establish the three-dimensional structures of the two-finger peptide. The peptide containing fingers 1 and 2 binds sequence specifically to two thirds of the DNA binding site recognized either by intact SWI5 or by the isolated three-finger peptide, and hence has the correct tertiary fold for DNA recognition. These results also establish the polarity of DNA binding, since the N-terminal two fingers of SWI5 bind to the 5' end of the DNA binding site. Mild proteolysis of the three-finger peptide using trypsin results in a small number of discrete products, which is consistent with the presence of three structured mini-domains. Nearly complete n.m.r. signal assignments were obtained for two peptides containing finger 2 alone or fingers 1 + 2. Comparison of two-dimensional spectra of these peptides and others clearly shows that the NOE enhancements and chemical shifts characteristic of each finger are quite insensitive to the presence or absence of neighbouring fingers. This clearly indicates that adjacent zinc-finger domains are structurally independent in these peptides from SWI5. However, there must be some steric limitations on the possible relative orientations of the fingers, and to establish limits for these a set of structures for the peptide containing fingers 1 + 2 was calculated using the YASAP simulated annealing protocol in conjunction with n.m.r.-based constraints. A more detailed description of the three-dimensional structures of finger 1 and finger 2, and their relationship to other previously determined structures of single zinc-fingers, is given in the accompanying paper.

Amino Acid Sequence↗
PubMed1992

A new approach to the analysis of DNase I footprinting data and its application to the TFIIIA/5S DNA complex.

We have re-examined DNase I footprinting data for the binding of transcription factor IIIA (TFIIIA) to the 5S RNA gene, taking into account the protein-DNA contacts observed in the crystal structure of the DNase I/DNA complex (1, 2). This structure was not available when many of the original footprinting experiments on the TFIIIA/DNA complex were performed. In this way the pattern of DNase I cleavage can be interpreted to map out with greater precision the regions on the 5S DNA occupied by TFIIIA. Then, assuming the binding site for a zinc-finger may be the same as that found in the structure of the zinc-finger protein Zif268/DNA complex (3), and taking into account footprinting data for truncated forms of TFIIIA, the TFIIIA zinc-fingers were fitted within the permitted regions. On the basis of this, an alignment of the zinc-fingers of TFIIIA with its DNA binding site is proposed, which combines features of earlier models (4).

Animals↗
PubMed1992

Sequence-specific DNA binding by a two zinc-finger peptide from the Drosophila melanogaster Tramtrack protein.

We show that the DNA-binding domain of the Drosophila melanogaster regulatory protein Tramtrack consists of a 66 amino acid sequence containing two zinc-finger motifs and a short sequence N-terminal to the first finger motif. This short N-terminal sequence is essential for DNA binding and we suggest it is involved in maintaining the three-dimensional structure of the first finger domain, as has been seen in the nuclear magnetic resonance structure of one of the zinc-finger domains of the yeast transcription factor SW15. The characterization of the DNA-binding activity of this 66 residue peptide (delta 911zf) shows that it binds in a sequence-specific manner, as a monomer, to a natural target site with an apparent KD approximately 4 x 10(-7) M. The shortest delta 911zf binding site, which retains full affinity, consists of an 11 base-pair sequence with a one nucleotide overhang at each 5' end. DNase I, hydroxyl radical and methylation protection footprinting studies show that, in common with other zinc-finger proteins, delta 911zf binds in the major groove of DNA. The data presented are consistent with the zinc-fingers of Tramtrack contacting both strands of the DNA, and thus the binding differs in detail to that observed in the crystal structure of the three zinc-fingers of Zif268 complexed to their target DNA.

Amino Acid Sequence↗
PubMed1991

Detection of hereditary haemochromatosis in an HLA-identical pedigree showing discordance between HLA class I genes and the disease locus.

Hereditary haemochromatosis is a recessive disease in which primary hepatocellular carcinoma, complicating cirrhosis, is responsible for about one-third of deaths in affected homozygotes. We describe a unique HLA haplo-identical pedigree showing parent-to-offspring transmission of hereditary haemochromatosis in whom HLA typing studies, including class I and class II allogenotype analysis, were of no benefit in identifying affected homozygotes. However, affected siblings in the pre-cirrhotic stage of haemochromatosis, with apparent discordance between the haemochromatosis allele and class I loci on chromosome 6, were detected by undertaking a family study, using analysis of serum parameters of iron status in combination with magnetic resonance imaging (MRI). This pedigree emphasises the critical importance of genetic and non-invasive methods for the identification of asymptomatic homozygotes before cirrhosis develops.

Alleles↗
PubMed1991

Patients with HIV infection have a reduced proportion of lymphocytes expressing the IL2 receptor p55 chain (TAC, CD25).

Using a high-sensitivity immunofluorescence procedure, a proportion of blood lymphocytes can be shown to express the p55 chain of the IL-2 receptor (CD25, TAC) without in vitro stimulation. In this study, we measured the proportion of peripheral blood lymphocytes expressing CD25 in patients with a diagnosis of HIV infection and compared the results with cells from controls. The mean value for HIV-positive samples was 15%, while controls gave a mean value of 31%. The difference between the groups was highly significant (P less than 0.001, Mann-Whitney U test). When expression of CD25 was examined separately in CD4-positive and CD8-positive T cells and in B cells, there was a wider spread of values in the HIV group compared with controls, but no systematic difference. In the patient group studied (110 samples from 53 patients) there was a weak correlation between CD25 and CD4 expression (correlation coefficient r = 0.21, P less than 0.02), but there were patients with low CD25 and high CD4 as well as patients with high CD25 and low CD4, suggesting that CD25 can vary independently of changes in CD4 lymphocytes. Although the majority of very low values of CD25 (less than 10%) were found in patients with stage IV disease, such low values were also common in Stage II disease.

Adult↗
PubMed1991

Beyond zinc fingers: steroid hormone receptors have a novel structural motif for DNA recognition.

The highly conserved DNA-binding domain of the steroid hormone receptors contains two 'zinc finger'-like sequence motifs. The three-dimensional structure in solution has been determined using two-dimensional 1H nuclear magnetic resonance (NMR) spectroscopy and shows that the two 'zinc finger'-like motifs fold to form a single structural domain. The combination of this structural information and mutagenesis data reveals how this family of transcriptional regulators bind to DNA.

Amino Acid Sequence↗
PubMed1991

Betaine deficiency in maize : complementation tests and metabolic basis.

Maize (Zea mays L.) is a betaine-accumulating species, but certain maize genotypes lack betaine almost completely; a single recessive gene has been implicated as the cause of this deficiency (D Rhodes, PJ Rich [1988] Plant Physiol 88: 102-108). This study was undertaken to determine whether betaine deficiency in diverse maize germplasm is conditioned by the same genetic locus, and to define the biochemical lesion(s) involved. Complementation tests indicated that all 13 deficient genotypes tested shared a common locus. One maize population (P77) was found to be segregating for betaine deficiency, and true breeding individuals were used to produce related lines with and without betaine. Leaf tissue of both betaine-positive and betaine-deficient lines readily converted supplied betaine aldehyde to betaine, but only the betaine-containing line was able to oxidize supplied choline to betaine. This locates the lesion in betaine-deficient plants at the choline --> betaine aldehyde step of betaine synthesis. Consistent with this location, betaine-deficient plants were shown to have no detectable endogenous pool of betaine aldehyde.

Journal Article↗
PubMed1991

Elevated Accumulation of Proline in NaCl-Adapted Tobacco Cells Is Not Due to Altered Delta-Pyrroline-5-Carboxylate Reductase.

Tobacco (Nicotiana tabacum L. var Wisconsin 38) cells that are adapted to 428 millimolar NaCl accumulate proline mainly due to increased synthesis from glutamate. These cells were used to evaluate the possible role of Delta(1)-pyrroline-5-carboxylate reductase in the regulation of proline biosynthesis. No increase in the specific activity of Delta(1)-pyrroline-5-carboxylate reductase in crude extracts throughout the growth cycle was observed in NaCl-adapted cells compared to unadapted cells. The enzyme from both cell types was purified extensively. On the basis of affinity for the substrates NADPH, NADH, and Delta(1)-pyrroline-5-carboxylate, pH profiles, chromatographic behavior during purification, and electrophoretic mobility of the native enzyme, the activities of the enzyme from the two sources were similar. These data suggest that the NaCl-dependent regulation of proline synthesis in tobacco cells does not involve induction of pyrroline-5-carboxylate isozymes or changes in its kinetic properties.

Journal Article↗
PubMed1991

Betaines of alfalfa : characterization by fast atom bombardment and desorption chemical ionization mass spectrometry.

Leaf tissue of alfalfa (Medicago sativa L.) was found to contain prolinebetaine, pipecolatebetaine, hydroxyprolinebetaine, and glycinebetaine. As n-butyl esters, these chemical species exhibit molecular cations at mass/charge ratio (m/z) 200, 214, 216, and 174, respectively, when analyzed by fast atom bombardment mass spectrometry. The underivatized betaines exhibit protonated molecular ions at m/z 144, 158, 160, and 118, respectively, when analyzed by desorption chemical ionization mass spectrometry. Extensive (>45-fold) genotypic variation for hydroxyprolinebetaine level was identified in alfalfa. Because a significant inverse correlation between prolinebetaine and hydroxyprolinebetaine levels was observed among 15 alfalfa genotypes evaluated, it is possible that these compounds may be derived from a common intermediate. Birdsfoot trefoil (Lotus corniculatus L.) contained prolinebetaine, but only traces of glycinebetaine, pipecolatebetaine, and hydroxyprolinebetaine. Red clover (Trifolium pratense L.) lacked prolinebetaine, pipecolatebetaine, and hydroxyprolinebetaine, but contained appreciable levels of both glycinebetaine and trigonelline. Trigonelline was not detectable in the leaf tissue of any alfalfa genotype or cultivar evaluated.

Journal Article↗
PubMed1990

Solution structure of the DNA-binding domain of the oestrogen receptor.

Steroid hormone receptors control gene expression through binding, as dimers, to short palindromic response elements located upstream of the genes they regulate. An independent domain of approximately 70 amino acids directs this sequence-specific DNA binding and is highly conserved between different receptor proteins and related transcription factors. This domain contains two zinc-binding Cys2-Cys2 sequence motifs, which loosely resemble the 'zinc-finger' motifs of TFIIIA. Here we describe the structure of the DNA-binding domain from the oestrogen receptor, as determined by two-dimensional 1H NMR techniques. The two 'zinc-finger'-like motifs fold to form a single structural domain and are thus distinct from the independently folded units of the TFIIIA-type zinc fingers. The structure consists of two helices perpendicular to each other. A zinc ion, coordinated by four conserved cysteines, holds the base of a loop at the N terminus of each helix. This novel structural domain seems to be a general structure for protein-DNA recognition.

Amino Acid Sequence↗
PubMed1990

Kinetics of NH(4) Assimilation in Zea mays: Preliminary Studies with a Glutamate Dehydrogenase (GDH1) Null Mutant.

In higher plants it is now generally considered that glutamate dehydrogenase (GDH) plays only a small or negligible role in ammonia assimilation. To test this specific point, comparative studies of (15)NH(4) (+) assimilation were undertaken with a GDH1-null mutant of Zea mays and a related (but not strictly isogenic) GDH1-positive wild type from which this mutant was derived. The kinetics of (15)NH(4) (+) assimilation into free amino acids and total reduced nitrogen were monitored in both roots and shoots of 2-week-old seedlings supplied with 5 millimolar 99% ((15)NH(4))(2)SO(4) via the aerated root medium in hydroponic culture over a 24-h period. The GDH1-null mutant, with a 10- to 15-fold lower total root GDH activity in comparison to the wild type, was found to exhibit a 40 to 50% lower rate of (15)NH(4) (+) assimilation into total reduced nitrogen. Observed rates of root ammonium assimilation were 5.9 and 3.1 micromoles per hour per gram fresh weight for the wild type and mutant, respectively. The lower rate of (15)NH(4) (+) assimilation in the mutant was associated with lower rates of labeling of several free amino acids (including glutamate, glutamine-amino N, aspartate, asparagine-amino N, and alanine) in both roots and shoots of the mutant in comparison to the wild type. Qualitatively, these labeling kinetics appear consistent with a reduced flux of (15)N via glutamate in the GDH1-null mutant. However, the responses of the two genotypes to the potent inhibitor of glutamine synthetase, methionine sulfoximine, and differences in morphology of the two genotypes (particularly a lower shoot:root ratio in the GDH1-null mutant) urge caution in concluding that GDH1 is solely responsible for these differences in ammonia assimilation rate.

Journal Article↗
PubMed1990

Effects of heat shock on amino Acid metabolism of cowpea cells.

When cowpea (Vigna unguiculata) cells maintained at 26 degrees C are transferred to 42 degrees C, rapid accumulation of gamma-aminobutyrate (>10-fold) is induced. Several other amino acids (including beta-alanine, alanine, and proline) are also accumulated, but less extensively than gamma-aminobutyrate. Total free amino acid levels are increased approximately 1.5-fold after 24 hours at 42 degrees C. Heat shock also leads to release of amino acids into the medium, indicating heat shock damage to the integrity of the plasmalemma. Some of the changes in metabolic rates associated with heat shock were estimated by monitoring the (15)N labeling kinetics of free intracellular, extracellular and protein-bound amino acids of cultures supplied with (15)NH(4) (+), and analyzing the labeling data by computer simulation. Preliminary computer simulation models of nitrogen flux suggest that heat shock induces an increase in the gamma-aminobutyrate synthesis rate from 12.5 nanomoles per hour per gram fresh weight in control cells maintained at 26 degrees C, to as high as 800 nanomoles per hour per gram fresh weight within the first 2 hours of heat shock. This 64-fold increase in the gamma-aminobutyrate synthesis rate greatly exceeds the expected (Q(10)) change of metabolic rate of 2.5- to 3-fold due to a 16 degrees C increase in temperature. We suggest that this metabolic response may in part involve an activation of glutamate decarboxylase in vivo, perhaps mediated by a transient cytoplasmic acidification. Proline appears to be synthesized from glutamate and not from ornithine in cowpea cells. Proline became severalfold more heavily labeled than ornithine, citrulline and arginine in both control and heat-shocked cultures. Proline synthesis rate was increased 2.7-fold by heat shock. Alanine, beta-alanine, valine, leucine, and isoleucine synthesis rates were increased 1.6-, 3.5-, 2.0-, 5.0-, and 6.0-fold, respectively, by heat shock. In contrast, the phenylalanine synthesis rate was decreased by 50% in response to heat shock. The differential effects of heat stress on metabolic rates lead to flux and pool size redistributions throughout the entire network of amino acid metabolism.

Journal Article↗
PubMed1990

Effects of ethanol on reinforced variations and repetitions by rats under a multiple schedule.

Response sequences emitted by five Long-Evans rats were reinforced under a two-component multiple schedule. In the REPEAT component, food pellets were contingent upon completion of a left-left-right-right (LLRR) sequence on two levers. In the VARY component, pellets were contingent upon variable sequences (i.e., a sequence was reinforced only if it differed from each of the previous five sequences). The rats learned to emit LLRR sequences in the REPEAT component and variable sequences in VARY. Intraperitoneal injections of ethanol (1.25, 1.75, and 2.25 g/kg) significantly increased sequence variability in REPEAT, thereby lowering reinforcement probability, but had little effect on sequence variability in the VARY component. These results extend previous findings that alcohol impairs the performance of reinforced repetitions but not of reinforced variations in response sequences.

Animals↗