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Biomedical subjects

T Brown

Publications and source records attributed to T Brown.

At least 235 records · Page 13Linked to original sources
PubMed1994

Correlation of trauma scoring and outcome in a Canadian trauma centre.

OBJECTIVE: To study the effectiveness of treatment and the outcome in trauma patients, and to correlate these with trauma scoring systems. DESIGN: A prospective study over 1 year of the probability of survival after trauma, based on TRISS methodology. A computerized database provided outcome statistics. SETTING: A regional trauma centre in a Canadian university teaching hospital serving regional and referral patients. PATIENTS: Three hundred consecutive patients treated at a single trauma unit. Two patients were excluded because of lack of physiologic data. Blunt injuries (94%) were most frequently from motor vehicle accidents (46%). INTERVENTIONS: Those appropriate to multidisciplinary trauma management in a level 1 trauma centre. MAIN OUTCOME MEASURES: Survival (Z values) and injury severity (M values) for the total group and subsets were calculated for comparison of outcomes with the Multiple Trauma Outcome Study baseline and other Canadian centres for multisystem and single-system injuries. RESULTS: The mean Injury Severity Score was 21.16 and the mean Revised Trauma Score was 6.75. There were 51 (17%) deaths--a Z value for the study group of 2.26. The M value was 0.78. Forty of the 51 single-system injuries were head injuries and accounted for 15 deaths. The Z value for multisystem injuries only was 0.54, and the M value was 0.77. CONCLUSIONS: The TRISS method for analysing blunt trauma is comparable to other trauma scoring systems. The correlation of outcome analysis with other scoring systems is affected by exclusion rates, pre-referral resuscitation and single- versus multiple-injury mix of cases.

Abdominal Injuries↗
PubMed1993

Anthracycline-DNA interactions at unfavourable base-pair triplet-binding sites: structures of d(CGGCCG)/daunomycin and d(TGGCCA)/adriamycin complexes.

The structures of two hexanucleotide-anthracycline complexes d(CGGCCG)/daunomycin and d(TGGCCA)/adriamycin have been determined using single-crystal X-ray diffraction techniques. In both cases the anthracycline molecule is bound to non-preferred d(YGG) base-pair triplet sites. For both complexes the crystals are tetragonal and belong to the space group P4(1)2(1)2. Unit-cell dimensions are a = 28.07 (2), c = 53.35 (1) and a = 28.01 (1), c = 52.99 (1) A, respectively, and the asymmetric unit of both structures consists of one strand of DNA, one drug molecule and approximately 50 water molecules. For the d(CGGCCG) complex the refinement converged with an R factor of 0.21 for 1108 reflections with F >/= 2sigma(F) in the resolution range 7.0-1.9 A. For the complex involving d(TGGCCA) the final R value was 0.22 for 1475 reflections in the range 7.0-1.7 A with the same criterion for observed data. Both complexes are essentially isomorphous with related structures but differ in terms of the number of favourable van der Waals interactions of the amino sugars of the drug molecules with the DNA duplexes and the formation in the minor groove of heterodromic pentagonal arrangements of hydrogen bonds involving water molecules which link the amino sugars to the DNA. These differences in structure are used to rationalize the lack of affinity of daunomycin-type anthracyclines for d(YGG) and d(YGC) sites.

Journal Article↗
PubMed1993

Polymorphism of the mouse TNF-alpha locus: sequence studies of the 3'-untranslated region and first intron.

We have sequenced the 3'-untranslated region (3'-UTR) and first intron of six strains of Mus musculus, as well as M. spretus, M. castaneus, and M. shanghai. A marked degree of polymorphism was evident in the sequences, and among all of the strains, no two haplotypes were identical. Of particular note, insertional mutations modifying the 5'-TTATTTAT sequence in the 3'-UTR, which in its RNA form acts as a translational repressor, were observed in New Zealand White and M. spretus strains. The mutations that we have identified dictate several restriction-fragment length polymorphisms, which should be useful in following the tumor necrosis factor-encoding gene (TNF) in backcross analysis and in defining the ancestry of TNF in mice of indeterminate parentage. Moreover, the data provide a substrate for the future analysis of differences in the level of TNF expression by genetically distinct mice.

Animals↗
PubMed1993

NMR assignments and solution conformation of the DNA.RNA hybrid duplex d(GTGAACTT).r(AAGUUCAC).

Nearly complete assignments of the 1H-NMR spectrum of the DNA.RNA hybrid d(GTGAACTT).r(AAGUUCAC) have been obtained by two-dimensional methods. Three-bond coupling constants measured from cross-sections of two-dimensional NOE spectra and double quantum-filtered correlation spectra showed that the sugars in the DNA strand are predominantly in the S domain of puckers, whereas the ribofuranoses are mainly C3'-endo. Analysis of time-dependent NOE intensities from one- and two-dimensional experiments showed that the glycosidic torsion angles in the DNA strand are near -120 degrees, whereas those in the RNA strand are in the range- 140 degrees to -160 degrees. These nucleotide conformations correspond to those typically found in B-DNA and A-RNA, respectively. The circular dichroism of the duplex is similar to that of A-form RNA, consistent with a global A-like conformation. A large number of duplex structures was generated in which the nucleotides were fixed in the experimentally determined conformations. A subset of these structures was found that satisfied the internucleotide NOE intensities, backbone constraints and had acceptable Lennard-Jones energies. The base pairs in the duplex were found to have positive inclinations, a translation (Dx) of about 0.4 nm from the helix axis, and more than 10 bp/turn on average. This implies a helical structure in the A family of conformations.

Base Sequence↗
PubMed1993

The structure of an idarubicin-d(TGATCA) complex at high resolution.

The crystal structure of the DNA hexamer d(TGATCA) complexed with the anthracycline antibiotic idarubicin has been determined at 1.6 A resolution. The asymmetric unit consists of a single hexamer oligonucleotide strand, one drug molecule and 35 water molecules. The complex crystallizes in the tetragonal space group P4(1)2(1)2, Z = 8 with lattice dimensions of a = b = 28.19 (3), c = 52.77 (4) A, V = 41 935 A(3). The structure is isomorphous with a series of hexamer-anthracycline complexes and was solved by molecular replacement. Restrained least-squares methods interspersed with computer-graphics map inspection and model manipulation were used to refine the structure. The R factor is 0.22 for 2032 reflections with F >/= 3sigma(F) in the resolution range 8.0-1.6 A. The self-complementary DNA forms a distorted B-DNA double helix with two idarubicin molecules intercalated in the d(TpG) steps of the duplex. The duplex is formed by utilization of a crystallographic twofold axis of symmetry. The idarubicin chromophore is oriented at right angles to the long axis of the DNA base pairs with the anthracycline amino-sugar moiety positioned in the minor groove. Our structure determination allows for comparison with a d(CGATCG)-idarubicin complex recently reported. Despite the sequence alteration at the intercalation step, the structures are very similar. The geometry of the intercalation and the nature of the interactions are conserved irrespective of the DNA sequence involved in the binding.

Journal Article↗
PubMed1993

Synthesis and antibody-mediated detection of oligonucleotides containing multiple 2,4-dinitrophenyl reporter groups.

A series of non-nucleoside-based 2,4-dinitrophenyl (DNP) phosphoramidites have been prepared and used in the multiple labelling of oligonucleotides during solid-phase synthesis. The length of spacer arm between the DNP label and the oligonucleotide phosphate backbone, and the number of attached DNP groups have both been varied in order to determine the optimum conditions for anti-DNP antibody binding. Detection using enzyme-linked colorimetric techniques showed sensitivity equivalent to that obtainable using biotinylated oligonucleotides.

2,4-Dinitrophenol↗
PubMed1993

Thermodynamic stability and drug-binding properties of oligodeoxyribonucleotide duplexes containing 3-deazaadenine:thymine base pairs.

We have used ultraviolet melting techniques to study the effect on stability of incorporating the nucleoside analogue 2'-deoxy-3-deazaadenosine (d3cA) into the duplex 5'-d(CGCAATCG)-3'-d(GCGTTAGC). Our results demonstrate that the successive replacement of dA by d3CA increasingly destabilises the duplex. The destabilising effect of this analogue is considerably enhanced as the pH is lowered and the results are consistent with protonation of 3-deazaadenine (probably at N-1) contributing to duplex destablisation. Surprisingly, the incorporation of d3CA does not significantly affect the binding of distamycin-A.

Adenine↗
PubMed1993

Detection of fructose-3-phosphokinase activity in intact mammalian lenses by 31P NMR spectroscopy.

Recently we have identified two novel phosphorylated metabolites in the lenses of diabetic rats as sorbitol 3-phosphate (Sor-3-P) and fructose 3-phosphate (Fru-3-P). The latter compound is of particular interest since it is a potent glycating agent, which could account, at least in part, for the increased protein cross-linking and cataract formation in the lens of the diabetic rat. In order to gain insight into the mechanism of formation of these compounds, 31P NMR spectra of rat, pig, and rabbit lenses, perfused with media supplemented with glucose, fructose, or sorbitol, were acquired. Perfusion with fructose-supplemented media resulted in the production of Fru-3-P in all three species. This compound was not produced upon perfusion with fructose-deficient media. The identification of the newly synthesized material as Fru-3-P was confirmed by spiking perchloric acid extracts of the perfused lenses with synthetic Fru-3-P. Our results provide strong evidence for the existence of a fructose-3-phosphokinase in mammalian lenses. If this enzyme is present in human lenses as well, it will reinforce the hypothesis that this enzyme and its product, Fru-3-P, may play a role in diabetic cataractogenesis and that lenticular fructose-3-phosphokinase may provide another therapeutic target in the prevention and alleviation of diabetic cataracts.

Animals↗
PubMed1993

Neuroblastoma in a renal transplanted child.

A 3-year-old boy was diagnosed with neuroblastoma 2 years after a renal transplant that was complicated by acute and chronic rejection. Extensive immunosuppressive therapy may have contributed to the development or progression of this tumor which has not been described previously following organ transplantation.

Acute Disease↗
PubMed1993

Assessment of pediatric near-drowning victims: is there a role for cranial CT?

Previous studies have suggested that CT examinations of the brain in children soon after near-drowning incidents are not helpful in predicting clinical outcome and are not necessary. The clinical and CT findings of 19 pediatric near-drowning victims were reviewed for correlation with clinical and neurologic outcome. As expected, a normal initial CT scan was poorly predictive of outcome, whereas an abnormal CT scan in the initial 36 h following an immersion incident was associated with a dismal prognosis. Three children with abnormal initial CT examinations were identified and all died within 3 days of admission. A CT scan performed in the immediate near-drowning period, therefore, may be helpful in identifying some patients who have sustained severe neurologic injury.

Adolescent↗
PubMed1993

Levels of HIV risk behaviour and AIDS knowledge in Thai men having sex with men.

Although many of the earliest cases of AIDS and HIV infection in Thailand were men who had sex with other men (MHSWM), transmission by heterosexual intercourse and needle sharing rapidly became dominant. This resulted in comparatively little attention being given to studies of risk behaviour and seroprevalence in groups of MHSWM with a consequent lack of information about these populations relevant to designing effective interventions. In the Partner Relations Survey, 3.3% of male Thais described their orientation as bisexual or homosexual, most probably an underestimate of the occurrence of same sex behaviour in Thai males. This paper briefly reviews the situation and presents results from a survey in the northeast of Thailand among men who have sex with men. Substantial levels of risk behaviour were found in MHSWM in the Northeast, with high rates of partner exchange and low levels of consistent condom use in insertive and receptive anal intercourse. Significant defects in AIDS knowledge existed implying a strong need for enhanced and expanded interventions in this community. Factors relevant to the design of interventions are highlighted and recommendations for further studies of MHSWM in Thailand are presented.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Craniofacial patterning in Klinefelter (47 XXY) adults.

Radiographic cephalometry incorporating a pattern profile analysis was used to compare 26 adult Klinefelter males from Finland with first degree adult relatives, 15 males and 14 females. Compared with female relatives, the 47 XXY males were larger in almost all craniofacial linear dimensions, but were similar in facial shape apart from greater mandibular prognathism. Mandibular dimensions in particular differed between the Klinefelter and unaffected males, the corpus length being larger, the ramus shorter and the gonial angle more obtuse in the 47 XXY group. The prominent facial profile, most marked in the mandible, was a dominant feature of the Klinefelter subjects who also displayed a more acute median cranial base angle than each control group. Generally, Klinefelter morphology was marked by greater variability or patterning of the craniofacial structures compared with relatives, possibly due to decreased developmental canalization. It is proposed that the 47 XXY complex may affect endochondral growth in the cranial base, as well as having a direct influence on jaw growth.

Adolescent↗
PubMed1993

Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression.

Clinical features and histological findings in two sibs who died from restrictive dermopathy in the neonatal period are described. Fibroblasts cultured from a skin biopsy from the second sib and fibroblasts from normal neonatal skin were studied using monoclonal antibodies to visualise integrin subunits by immunocytochemistry. Restrictive dermopathy fibroblasts displayed increased expression of the alpha-1 and alpha-2 subunits of integrin, those responsible for collagen binding. The increase was not matrix dependent. Integrins may play an important role in tissue differentiation, and our findings support the hypothesis that restrictive dermopathy is a disorder of skin differentiation.

Abnormalities, Multiple↗
PubMed1993

Sequence variation in the androgen receptor gene is not a common determinant of male sexual orientation.

To test the hypothesis that DNA sequence variation in the androgen receptor gene plays a causal role in the development of male sexual orientation, we have (1) measured the degree of concordance of androgen receptor alleles in 36 pairs of homosexual brothers, (2) compared the lengths of polyglutamine and polyglycine tracts in the amino-terminal domain of the androgen receptor in a sample of 197 homosexual males and 213 unselected subjects, and (3) screened the the entire androgen receptor coding region for sequence variation by PCR and denaturing gradient-gel electrophoresis (DGGE) and/or single-strand conformation polymorphism analysis in 20 homosexual males with homosexual or bisexual brothers and one homosexual male with no homosexual brothers, and screened the amino-terminal domain of the receptor for sequence variation in an additional 44 homosexual males, 37 of whom had one or more first- or second-degree male relatives who were either homosexual or bisexual. These analyses show that (1) homosexual brothers are as likely to be discordant as concordant for androgen receptor alleles; (2) there are no large-scale differences between the distributions of polyglycine or polyglutamine tract lengths in the homosexual and control groups; and (3) coding region sequence variation is not commonly found within the androgen receptor gene of homosexual men. The DGGE screen identified two rare amino acid substitutions, ser205-to-arg and glu793-to-asp, the biological significance of which is unknown.

Base Sequence↗