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Biomedical subjects

H Robinson

Publications and source records attributed to H Robinson.

At least 37 records · Page 2Linked to original sources
PubMed2000

The efficacy of acarbose in type 2 diabetes mellitus in Jamaica.

The efficacy and tolerability of acarbose was studied in type 2 diabetic patients eating a typical Jamaican diet. The study was an open label parallel group study without placebo control. Of the 51 subjects recruited, five (9.8%) did not complete the study and were excluded from further analysis. Six (13%) of the remaining 46 had adverse side effects and did not complete the protocol. Of the remaining 40 (Gp A), acarbose was added to their previous regime of diet alone (n = 15), [Gp B], oral hypoglycaemic agents, OHAs (n = 17), [Gp C], or insulin (n = 8), Gp D]. In addition, during the run-in period all subjects had one session each with a dietitian and a diabetes educator. Over a 3-month period, significant reductions in average glucose (mmol) were observed in Gp B 10.5 +/- 1.1 to 8.4 +/- 0.9 (p < 0.027) and, from 11.0 +/- 1.0 to 8.7 +/- 0.7 (p < 0.01) in Gp C. Similarly, total glycosylated haemoglobin fell from 14.8 +/- 1.1% to 12.2 +/- 1.0% (p < 0.016) in Gp B, from 14.9 +/- 1.1 to 11.9 +/- 1.1% (p < 0.002) in Gp C, and from 14.1 +/- 1.4 to 11.8 +/- 1.4 (p < 0.02) in Gp D. Twenty-three per cent (23%) of the patients experienced flatulence; 7.5%, changes in bowel habits and 5%, abdominal cramps and discomfort. Acarbose is effective as monotherapy and as combination therapy with oral hypoglycaemic agents or insulin. Side effects were common, but tolerable.

Acarbose↗
PubMed1999

Structure and recognition of sheared tandem G x A base pairs associated with human centromere DNA sequence at atomic resolution.

G x A mismatched base pairs are frequently found in nucleic acids. Human centromere DNA sequences contain unusual repeating motifs, e.g. , (GAATG)n x (CATTC)n found in the human chromosome. The purine-rich strand of this repeating pentamer sequence forms duplex and hairpin structures with unusual stability. The high stability of these structures is contributed by the "sheared" G x A base pairs which present a novel recognition surface for ligands and proteins. We have solved the crystal structure, by the multiple-wavelength anomalous diffraction (MAD) method of d(CCGAATGAGG) in which the centromere core sequence motif GAATG is embedded. Three crystal forms were refined to near-atomic resolution. The structures reveal the detailed conformation of tandem G x A base pairs whose unique hydrogen-bonding surface has interesting interactions with bases, hydrated magnesium ions, cobalt(III)hexaammine, spermine, and water molecules. The results are relevant in understanding the structure associated with human centromere sequence in particular and G x A base pairs in nucleic acids (including RNA, like ribozyme) in general.

Adenine↗
PubMed1999

Structural basis of electron transfer modulation in the purple CuA center.

The X-ray structure of an engineered purple CuA center in azurin from Pseudomonas aeruginosa has been determined and refined at 1.65 A resolution. Two independent purple CuA azurin molecules are in the asymmetric unit of a new P21 crystal, and they have nearly identical conformations (rmsd of 0.27 A for backbone atoms). The purple CuA azurin was produced by the loop-engineering strategy, and the resulting overall structure is unperturbed. The insertion of a slightly larger Cu-binding loop into azurin causes the two structural domains of azurin to move away from each other. The high-resolution structure reveals the detailed environment of the delocalized mixed-valence [Cu(1.5).Cu(1.5)] binuclear purple CuA center, which serves as a useful reference model for other native proteins, and provides a firm basis for understanding results from spectroscopic and functional studies of this class of copper center in biology. The two independent Cu-Cu distances of 2.42 and 2.35 A (with respective concomitant adjustments of ligand-Cu distances) are consistent with that (2.39 A) obtained from X-ray absorption spectroscopy with the same molecule, and are among the shortest Cu-Cu bonds observed to date in proteins or inorganic complexes. A comparison of the purple CuA azurin structure with those of other CuA centers reveals an important relationship between the angular position of the two His imidazole rings with respect to the Cu2S2(Cys) core plane and the distance between the Cu and the axial ligand. This relationship strongly suggests that the fine structural variation of different CuA centers can be correlated with the angular positions of the two histidine rings because, from these positions, one can predict the relative axial ligand interactions, which are responsible for modulating the Cu-Cu distance and the electron transfer properties of the CuA centers.

Azurin↗
PubMed1999

Ultra-high resolution DNA structures.

This paper describes the progress in our efforts at producing ultra-high resolution (< 0.8 A) DNA structures using advanced cryo-crystallography and synchrotron. Our work is aimed at providing reliable geometric (bond length and bond angle), electronic and motional information of DNA molecules in different conformational contexts. These highly-reliable, new structures will be the basis for constructing better DNA force-field parameters, which will benefit the structural refinement of DNA, protein-DNA complexes, and ligand-DNA complexes.

Antibiotics, Antineoplastic↗
PubMed1999

High-resolution A-DNA crystal structures of d(AGGGGCCCCT). An A-DNA model of poly(dG) x poly(dC).

A-DNA conformation is favored by guanine-rich sequences, such as (dG)n x (dC)n, or under low-humidity conditions. Earlier A-DNA crystal structures revealed some conformational variations which may be the result of sequence-dependent effects and/or crystal packing forces. Here we report the high-resolution crystal structure of d(AGGGGCCCCT) in two crystal forms (either in the P212121 or the P6122 space group) to gain insights into the conformation and dynamics of the (dG)n x (dC)n sequence. The P212121 form has been analyzed using data to 1.1 A resolution by the anisotropic temperature factor refinement procedure of the SHELX97 program. Such analysis affords us with the detailed geometric, conformational and motional property of an A-DNA structure. The backbone torsional angles fall in a narrow range, except for the alpha/gamma angles which have two distinct combinations (gauche-/gauche+ or trans/trans). An A-DNA model of poly(dG) x poly(dC) has been constructed using the conformational parameters derived from the crystal structure of the P212121 form. In the crystal structure of the P6122 space group, the central eight base pairs of the decamer adopt A-DNA conformation with the two terminal nucleotides flipped out to form base pairs with the neighboring nucleotides. Comparison of the A-DNA structure of the same sequence from two different crystal forms, reinforced the conclusion that molecules crystallized in the same space group have a more similar conformation, whereas the same molecule crystallized in different space groups has different (local) conformations.

DNA↗
PubMed1999

Chromosome numbers in Compositae. XVIII.

Chromosome numbers and other cytogenetic data were determined from microsporocytes in 316 collections including 13 tribes of Compositae, mostly from Africa, Australia, Mexico, Central America, and South America. First reports are provided for 66 species and the genera Cassinia (2n ≈ 14(II)), Feldstonia (2n = 11(II)), Gochnatia (2n ≈ 23(II)), and Pseudoconyza (n = 10). In addition, new chromosome numbers are established at the generic level in Acourtia, Calea, Craspedia, Gnaphalium, Helipterum, Liabum, Leucheria, Smallanthus, Trixis, and Viguiera and at the specific level in 13 additional species.

Journal Article↗
PubMed1999

Management of mental disorders in rural primary care: a proposal for integrated psychosocial services.

Mental health facilities and specialized providers are particularly lacking in rural areas. Even when these are available, poverty, negative attitudes toward mental health treatments, and traditional rural values of privacy and autonomy often result in low utilization rates. Consequently, most mental health care in rural America is provided by primary care physicians who are also faced with competing demands, including tensions among limited time and resources, the multiple and complex needs of patients, and economic forces determining reimbursements. We propose that in the best interest of physicians and their patients, fully integrated psychosocial services in rural primary care settings would reduce the burden of time-consuming mental health care, conform to patient preference for immediate on-site care, reduce nonproductive medical care use, and eliminate duplication of effort by physicians and mental health professionals. The treatment model we propose would provide multiple arenas for psychosocial intervention - with the individual, the family, and the community - based on the patient's self-identified needs. The integration of psychosocial services within primary rural care is readily available, economically feasible, and urgently needed, but physicians must take the lead to implement this collaborative treatment partnership.

Case Management↗
PubMed1998

Effects of alpha-pompilidotoxin on synchronized firing in networks of rat cortical neurons.

We studied the effect of a novel neurotoxin, alpha-pompilidotoxin (alpha-PMTX) on the spontaneously synchronized network firing of cultured rat cortical neurons. Alpha-PMTX acted immediately and irreversibly to disrupt synchronous activity, leaving only residual sparse, uncorrelated firing and was effective at concentrations of 10 nM. In the presence of bicuculline to block inhibitory synaptic transmission, the shutdown in synchronized activity occurred with a significant delay, required a higher concentration of alpha-PMTX (> 100 nM), and was preceded by a transiently increased level of firing. It appears that both inhibitory and excitatory neuronal activity or synaptic transmission are amplified by alpha-PMTX, but that intense activity eventually leads to inactivation or transmitter depletion.

Action Potentials↗
PubMed1998

2'-Deoxyisoguanosine adopts more than one tautomer to form base pairs with thymidine observed by high-resolution crystal structure analysis.

The questions of whether different tautomeric forms of nucleic acid bases exist to any significant extent in DNA, or what their possible roles in mutation may be, are under intense scrutiny. 2'-Deoxyisoguanosine (iG) has been suggested to have a propensity to adopt the enol form. Isoguanine (also called 2-hydroxyadenine) can be found in oxidatively damaged DNA generated from treating DNA with a Fenton-type reactive oxygen-generating system and is known to cause mutation. We have analyzed the three-dimensional structure of the DNA dodecamer d(CGC[iG]AATTTGCG) (denoted iG-DODE) by X-ray crystallography and NMR. The crystal structure of the iG-DODE complexed with the minor groove binder Hoechst 33342, refined to 1.4 A resolution, showed that the two independent iG.T base pairs in the dodecamer duplex adopt different (one in Watson-Crick and the other in wobble) conformations. The high-resolution nature of the structure also affords unprecedented clear information about the conformation and interactions of the Hoechst drug. The Hoechst 33342 binds in the narrow minor groove at the iGAATT site, with the N-methylpiperazine ring near the iG4.T21 base pair. Three hydrogen bonds are found between the NH of the Hoechst ligand and T-O2 DNA atoms. In solution, the two iG.T base pairs in iG-DODE predominantly are in the wobble form at 2 degreesC. At higher temperatures, another duplex form (likely involving the enol form of iG) is in slow exchange with the keto form and becomes significantly populated, reaching approximately 40% at 40 degreesC. Our data support the conclusion that iG pairs with T in a Watson-Crick configuration to a significant extent at physiological temperature (37 degreesC), which may explain the facile incorporation rate of T across from an iG during in vitro DNA replication.

Adenosine↗
PubMed1998

The hyperthermophile chromosomal protein Sac7d sharply kinks DNA.

The proteins Sac7d and Sso7d belong to a class of small chromosomal proteins from the hyperthermophilic archaeon Sulfolobus acidocaldarius and S. solfactaricus, respectively. These proteins are extremely stable to heat, acid and chemical agents. Sac7d binds to DNA without any particular sequence preference and thereby increases its melting temperature by approximately 40 degrees C. We have now solved and refined the crystal structure of Sac7d in complex with two DNA sequences to high resolution. The structures are examples of a nonspecific DNA-binding protein bound to DNA, and reveal that Sac7d binds in the minor groove, causing a sharp kinking of the DNA helix that is more marked than that induced by any sequence-specific DNA-binding proteins. The kink results from the intercalation of specific hydrophobic side chains of Sac7d into the DNA structure, but without causing any significant distortion of the protein structure relative to the uncomplexed protein in solution.

Amino Acid Sequence↗
PubMed1998

The PPVT-R: validity as a quick screen of intelligence in a postacute rehabilitation setting for brain-injured adults.

The utility of the Peabody Picture Vocabulary Test-Revised (PPVT-R) as a surrogate for the Wechsler Adult Intelligence Test-Revised (WAIS-R) was investigated in 61 brain-injured adult participants in a postacute rehabilitation setting. Idiographic comparison revealed substantial disagreement in clinical classification between the two instruments, and it is concluded that the PPVT-R is not a good surrogate for the WAIS-R for this purpose. In contrast, the PPVT-R was judged an adequate surrogate for the WAIS-R for the purpose of group comparison, as is common in biomedical research. Finally, contrary to prior report, the PPVT-R was demonstrated to measure more than simply Vocabulary. As such, in the absence of independent validation research, perhaps the most parsimonious conclusion regarding what the PPVT-R is measuring is that like each of the various subtests of the WAIS-R, the PPVT-R shares some of the variance of the construct termed intelligence, as well as demonstrates some unique variance that is likely comprised of error and, perhaps, a unique or different facet of intelligence.

Acute Disease↗
PubMed1998

The crystal structure of the hyperthermophile chromosomal protein Sso7d bound to DNA.

Sso7d and Sac7d are two small (approximately 7,000 Mr), but abundant, chromosomal proteins from the hyperthermophilic archaeabacteria Sulfolobus solfataricus and S. acidocaldarius respectively. These proteins have high thermal, acid and chemical stability. They bind DNA without marked sequence preference and increase the Tm of DNA by approximately 40 degrees C. Sso7d in complex with GTAATTAC and GCGT(iU)CGC + GCGAACGC was crystallized in different crystal lattices and the crystal structures were solved at high resolution. Sso7d binds in the minor groove of DNA and causes a single-step sharp kink in DNA (approximately 60 degrees) by the intercalation of the hydrophobic side chains of Val 26 and Met 29. The intercalation sites are different in the two complexes. Observations of this novel DNA binding mode in three independent crystal lattices indicate that it is not a function of crystal packing.

Amino Acid Sequence↗
PubMed1998

Molecular structure of two crystal forms of cyclic triadenylic acid at 1A resolution.

The three dimensional structures of cyclic deoxytriadenylic acid, c-d(ApApAp), from two different trigonal crystal forms (space groups P3 and R32) have been determined by x-ray diffraction analysis at 1A resolution. Both structures were solved by direct methods and refined by anisotropic least squares refinement to R-factors of 0.109 and 0.137 for the P3 and R32 forms, respectively. In both crystal forms, each of the two independent c-d(ApApAp) molecules sits on the crystallographic 3-fold axis. All four independent c-d(ApApAp) molecules have similar backbone conformations. The deoxyriboses are in the S-type pucker with pseudorotation angles ranging from 156.7 degrees to 168.6 degrees and the bases have anti glycosyl torsion angles (chi falling in two ranges, one at -104.3 degrees and the other ranging from -141.0 degrees to -143.8 degrees). In the R32 form, a hexahydrated cobalt(II) ion is found to coordinate through bridging water molecules to N1, N3, and N7 atoms of three adjacent adenines and oxygen atoms of phosphates. Comparison with other structures of cyclic oligonucleotides indicates that the sugar adopts N-type pucker in cyclic dinucleotides and S-type pucker in cyclic trinucleotides, regardless whether the sugar is a ribose or a deoxyribose.

Adenine Nucleotides↗
PubMed1998

Examination of factors associated with instability of the FMR1 CGG repeat.

We examined premutation-female transmissions and premutation-male transmissions of the FMR1 CGG repeat to carrier offspring, to identify factors associated with instability of the repeat. First we investigated associations between parental and offspring repeat size. Premutation-female repeat size was positively correlated with the risk of having full-mutation offspring, confirming previous reports. Similarly, premutation-male repeat size was positively correlated with the daughter's repeat size. However, increasing paternal repeat size was associated also with both increased risk of contraction and decreased magnitude of the repeat-size change passed to the daughter. We hypothesized that the difference between the female and male transmissions was due simply to selection against full-mutation sperm. To test this hypothesis, we simulated selection against full-mutation eggs, by only examining premutation-female transmissions to their premutation offspring. Among this subset of premutation-female transmissions, associations between maternal and offspring repeat size were similar to those observed in premutation-male transmissions. This suggests that the difference between female and male transmissions may be due to selection against full-mutation sperm. Increasing maternal age was associated with increasing risk of expansion to the full mutation, possibly because of selection for smaller alleles within the offspring's soma over time; a similar effect of increasing paternal age may be due to the same selection process. Last, we have evidence that the reported association between offspring sex and risk of expansion may be due to ascertainment bias. Thus, female and male offspring are equally likely to inherit the full mutation.

Adult↗
PubMed1998

Mid-trimester ultrasound diagnosis of isolated talipes equinovarus: accuracy and outcome for infants.

Seventeen fetuses were diagnosed with isolated congenital talipes equinovarus (CTEV) on mid-trimester ultrasound at the Royal Women's Hospital, Melbourne, between January, 1992 and December 1995. Sixteen of the 17 cases had an amniocentesis performed and all karyotypes were normal. The remaining case was phenotypically normal, except for a clubfoot. None of the pregnancies was complicated by any of the recognized intrauterine environmental causes of CTEV. Four of the babies were delivered prematurely and all survived the neonatal period. Six (35%) infants did not have CTEV at birth, although 2 had postural varus feet. Nine of the 11 infants who did have CTEV at birth were treated within days of birth with plaster of Paris for periods of 6 to 12 weeks. Two infants required no further treatment, 5 required orthotics and 2 required surgery. The other 2 infants with CTEV at birth were treated with orthotics at 8 weeks of age. All infants were considered to have an excellent result at the 2 year follow-up. Seven (41%) of the prospective parents received antenatal counselling by an orthopaedic surgeon and the lack of study on outcome following an ultrasound diagnosis of CTEV was the impetus for our work.

Clubfoot↗