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D Hare

Publications and source records attributed to D Hare.

At least 55 records · Page 3Linked to original sources
PubMed1988

Determining stereo-specific 1H nuclear magnetic resonance assignments from distance geometry calculations.

Stereo-specific 1H nuclear magnetic resonance assignments can be obtained following distance geometry structure calculations. The key to this method is to allow stereo-related atoms or methyls to float between pro-R and pro-S configurations, the final configuration being determined by the experimental constraints. Resonances from stereo-related pairs are given initial random assignments (either pro-R or pro-S) for identifying nuclear Overhauser effects (NOEs). A list of distance constraints using these assignments is compiled and a series of structures calculated where the chirality of non-C alpha chiral centers is not constrained; no pseudoatom corrections are required. Calculated structures are both locally and globally well-determined since the assignments rely upon the structure determination rather than the structure quality relying upon stereo-specific assignments. The method represents a global approach to determining stereo-specific assignments versus previously reported methods where only intraresidue NOEs and J-coupling information are used.

Magnetic Resonance Spectroscopy↗
PubMed1986

Wobble dG X dT pairing in right-handed DNA: solution conformation of the d(C-G-T-G-A-A-T-T-C-G-C-G) duplex deduced from distance geometry analysis of nuclear Overhauser effect spectra.

We report below on features of the three-dimensional structure of the d(C-G-T-G-A-A-T-T-C-G-C-G) self-complementary duplex (designated 12-mer GT) containing symmetrical G X T mismatches in the interior of the helix. The majority of the base and sugar protons in the 12-mer GT duplex were assigned by two-dimensional nuclear Overhauser effect (NOESY) spectra in H2O and D2O solution. A set of 92 short (less than 4.5-A) proton-proton distances defined by lower and upper bounds for one symmetrical half of the 12-mer GT duplex were estimated from NOESY data sets recorded as a function of mixing time. These experimental distances combined with nucleotide bond length parameters were embedded into Cartesian space; several trial structures were refined to minimize bond geometry and van der Waals and chirality error. Confidence in this approach is based on the similarity of the refined structures for the solution conformation of the 12-mer GT duplex. The G and T bases pair through two imino-carbonyl hydrogen bonds, and stacking is maintained between the G X T wobble pair and adjacent Watson-Crick G X C pairs. The experimental distance information is restricted to base and sugar protons, and hence structural features such as base pair overlap, glycosidic torsion angles, and sugar pucker are well-defined by this combination of NMR and distance geometry methods. By contrast, we are unable to define the torsion angles about the bonds C3'-O3'-P-O5'-C5'-C4' in the backbone of the nucleic acid.

Base Sequence↗
PubMed1986

Extrahelical adenosine stacks into right-handed DNA: solution conformation of the d(C-G-C-A-G-A-G-C-T-C-G-C-G) duplex deduced from distance geometry analysis of nuclear Overhauser effect spectra.

This paper reports on features of the three-dimensional structure of the d(C-G-C-A-G-A-G-C-T-C-G-C-G) self-complementary duplex (designated adenosine 13-mer), which contains symmetrical extrahelical adenosines in the interior of the helix. The majority of the protons have been assigned from two-dimensional nuclear Overhauser effect (NOESY) spectra of the adenosine 13-mer in H2O and D2O solution. The measurement of NOESY cross-peak volume integrals as a function of mixing time has yielded a set of 96 short (less than 4.5-A) proton-proton distances defined by lower and upper bounds, which have served as input parameters for a distance geometry analysis of one symmetric half of the adenosine 13-mer duplex. We demonstrate that the extrahelical adenosine stacks into the duplex for all refined structures without disruption of base pairing on either side of the modification site. The distance geometry refinement yields two classes of conformations consistent with distance measurements but which differ in orientation of the stacked extrahelical adenosine at the modification site.

Adenosine↗
PubMed1986

Sequence-dependent conformation of DNA duplexes. The AATT segment of the d(G-G-A-A-T-T-C-C) duplex in aqueous solution.

The nonexchangeable base and sugar protons of the octanucleotide d(G-G-A-A-T-T-C-C) have been assigned by two-dimensional correlated (COSY) and nuclear Overhauser effect (NOESY) methods in aqueous solution. The assignments are based on distance connectivities of less than 4.5 A established from NOE effects between base and sugar protons on the same strand and occasionally between strands, as well as, coupling connectivities within the protons on each sugar ring. We observe the NOEs to exhibit directionality and are consistent with the d(G-G-A-A-T-T-C-C) duplex adopting a right-handed helix in solution. The relative magnitude of the NOEs between base and sugar H2' protons of the same and 5'-adjacent sugars characterizes the AATT segment to the B-helix type in solution.

Base Sequence↗
PubMed1985

Variability in limb malformations and possible significance in the pathogenesis of an inherited congenital neuromuscular disease of Charolais cattle (syndrome of arthrogryposis and palatoschisis).

Limb abnormalities in 30 calves with an inherited congenital neuromuscular disorder known as syndrome of arthrogryposis and palatoschisis were classified according to the range of severity of joint deformity in either flexion or extension, and restricted joint movement. Joint movement was variably affected; it was either normal, lax, restricted in the range of mobility, or occasionally, fixed. The characteristic findings were: bilateral hyperextension of the hind fetlock, flexion deformity of the forelimb that particularly involved the fetlock and the carpus, with restricted articular movement and complete rigidity in some cases. One-third of calves also had medial deviation of the forelimb due to angular deformity of articular surfaces in the carpus. All nine live calves were floppy due to marked generalized muscular hypotonia. Birth weight of deformed calves was reduced. In some calves muscle development was impaired as judged by muscle weight, and histological examination. In some calves the gross appearance, muscle weight and histological examination revealed no abnormal development and indicated that the effects on skeletal muscle were secondary. No lesions were found in the spinal cord of 23 of 24 calves examined histologically. The remaining calf had a localized cavitation in the dorsal white matter at T2-3. Based on the observations in calves in this study it is proposed that both primary and secondary factors contribute to the phenotypic expression of this congenital deformity. The primary lesion is considered to be a neurogenic abnormality of differentiation in the central nervous system. Cytogenetic analysis of 16 carrier cows and two deformed calves showed normal karyotypes. Serology for Akabane virus in 16 carrier cows was negative.

Abnormalities, Multiple↗
PubMed1979

Benign prostatic hyperplasia in an XX man.

A sixty-nine-year-old white phenotypic male who was being investigated for a myeloproliferative disorder, was found to have an XX karyotype in all cells examined in bone marrow, lymphocytes, and skin fibroblast cultures. Despite essentially no testosterone in the plasma, he also suffered from severe prostatic hyperplasia, a finding not reported previously in patients with this genotype. While endocrine studies showed normal follicle-stimulating hormone, the luteinizing hormone level was twice the upper limit of normal and estrogens were in the normal female range. Except for complete absence of Leydig cells, testicular histology resembled that usually found in Klinefelter syndrome. The patient died of the combined effects of the myeloproliferative disease and urinary tract obstruction. The mechanism of occurrence of the sex chromosome anomaly as well as the cause and implication of the unusual finding of prostatic hyperplasia are discussed.

Aged↗
PubMed1976

The victim is guilty.

Our society in many situations tends to blame the victim. Questions are raised whether this occurs more commonly with women and what its effects are. An examination of the treatment of women as patients may help answer these questions. In 1971 twice as many men as women were on chronic hemodialysis, raising the possibility of different allotment of medical resources and different admission criterion for this very expensive therapy. This example only indicates that women may be treated differently. The following commentary indicates women may be blamed for their illness. A prestigious medical journal has published articles claiming the clinical syndrome, Iceland disease, is really epidemic hysteria. One of the three main reasons given for such a claim is that it occurs primarily in women. Aside from the fact that many physiologic diseases do have skewed sex ratios, one wonders why it is considered inappropriate for a physiologic disease to have a male/femal ratio different from 1.0 yet not so for a psychological disease. Once women are put into this category, in essence blamed for their illness, there will be no more search for pathology that might be corrected. they may undergo detrimental therapy, in this case removal of their uteri-a hysterectomy, probably in the true sense of the word.

Encephalomyelitis↗