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R Smith

Publications and source records attributed to R Smith.

At least 415 records · Page 23Linked to original sources
PubMed1998

hnRNP A2 selectively binds the cytoplasmic transport sequence of myelin basic protein mRNA.

Segregation of mRNAs in the cytoplasm of polar cells has been demonstrated for proteins involved in Xenopus and Drosophila oogenesis, and for some proteins in somatic cells. It is assumed that vectorial transport of the messages is generally responsible for this localization. The mRNA encoding the basic protein of central nervous system myelin is selectively transported to the distal ends of the processes of oligodendrocytes, where it is anchored to the myelin membrane and translated. This transport is dependent on a 21-nucleotide cis-acting segment of the 3'-untranslated region (RTS). Proteins that bind to this cis-acting segment have now been isolated from extracts of rat brain. A group of six 35-42-kDa proteins bind to a 35-base oligoribonucleotide incorporating the RTS, but not to several oligoribonucleotides with the same composition but randomized sequences, thus establishing specificity for the base sequence in the RTS. The most abundant of these proteins has been identified, by Edman sequencing of tryptic peptides and mass spectroscopy, as heterogeneous nuclear ribonucleoprotein (hnRNP) A2, a 36-kDa member of a family of proteins that are primarily, but not solely, intranuclear. This protein was most abundant in samples from rat brain and testis, with lower amounts in other tissues. It was separated from the other polypeptides by using reverse-phase HPLC and shown to retain preferential association with the RTS. In cultured oligodendrocytes, hnRNP A2 was demonstrated by confocal microscopy to be distributed throughout the nucleus, cell soma, and processes.

Amino Acid Sequence↗
PubMed1998

Calcium is essential for the structural integrity of the cysteine-rich, ligand-binding repeat of the low-density lipoprotein receptor.

Seven cysteine-rich repeats form the ligand-binding region of the low-density lipoprotein (LDL) receptor. Each of these repeats is assumed to bind a calcium ion, which is needed for association of the receptor with its ligands, LDL and beta-VLDL. The effects of metal ions on the folding of the reduced N-terminal cysteine-rich repeat have been examined by using reverse-phase high-performance liquid chromatography to follow the formation of fully oxidized isomers with different disulfide connectivities. In the absence of calcium many of the 15 possible isomers formed on oxidation, whereas in its presence the predominant product at equilibrium had the native disulfide bond connectivities. Other metals were far less effective at directing disulfide bond formation: Mn2+ partly mimicked the action of Ca2+, but Ba2+, Sr2+, and Mg2+ had little effect. This metal-ion specificity was also observed in two-dimensional 1H NMR spectral studies; only Ca2+ induced the native three-dimensional fold. The two paramagnetic ions, Gd3+ and Mn2+, and Cd2+ did not promote adoption of a well-defined structure, and the two paramagnetic ions did not displace calcium ions. The location of calcium ion binding sites in the repeat was also explored by NMR spectroscopy. The absence of chemical shift changes for the side chain proton resonances of Asp26, Asp36, and Glu37 from pH 3.9 to 6.8 in the presence of calcium ions and their proximal location in the NMR structures implicated these side chains as calcium ligands. Deuterium exchange NMR experiments also revealed a network of hydrogen bonds that stabilizes the putative calcium-binding loop.

Amino Acid Sequence↗
PubMed1998

Economic costs of expanded criteria donors in renal transplantation.

BACKGROUND: The organ shortage has increased interest in the use of "expanded criteria" donors (ECDs). Although much has been written concerning the clinical outcomes associated with the use of such donors, little has been published concerning the financial results associated with their use. METHODS: A retrospective cost identification study of recipients of kidneys from expanded criteria cadaveric donors was used. RESULTS: Of a total of 78 cadaveric renal transplants in fiscal year 1995, there were 38 kidneys (49%) transplanted from ECDs. Graft survival at 1 year was not statistically different between patients who received kidneys from ECDs and those who received non-ECD kidneys (84% vs. 85%, respectively). Length of stay (P < 0.05), serum creatinine at 1 year after transplantation (P < 0.01), and the percentage of patients requiring hemodialysis (P < 0.05) were all higher among patients who received kidneys from ECDs. Cold ischemic time was significantly longer in patients who received kidneys from ECDs (31.4+/-12 hr vs. 24.0+/-9 hr; P < 0.05). The total average and median costs were $12,190 and $10,911 higher in recipients of kidneys from ECDs as compared with non-ECD controls (P < 0.01). Stepwise linear regression demonstrated that length of stay was the major clinical determinant of total costs; only the use of antilymphocyte induction was otherwise significantly associated. When kidneys from ECDs were transplanted into "high-risk" recipients (age > 60 or retransplant patient), the average total costs were $15,311 more than when kidneys from ECDs were transplanted into non-high-risk patients (n=16 and 21, respectively; P < 0.05) and $20,680 more than when a non-ECD, non-high-risk pairing was undertaken (n=26; P < 0.05). CONCLUSIONS: Kidney transplantation with organs from ECDs is significantly more expensive than with organs from non-ECDs, even in the face of similar graft survival rates. Further study is needed to determine the cost-effectiveness of renal transplantation utilizing kidneys from ECDs vis-a-vis hemodialysis.

Adult↗
PubMed1998

Maternal viral load, CD4 cell count and vertical transmission of HIV-1.

HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10-fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy.

CD4 Lymphocyte Count↗
PubMed1998

Predicted lung cancer risk among miners exposed to diesel exhaust particles.

Several quantitative risk assessment models have been published for occupational and environmental exposures to diesel exhaust particles (DEP). These risk assessment models are reviewed and applied to predict lung cancer for miners exposed to DEP. The toxicologically based unit risk estimates varied widely (from 2 to 220 x 10(-6) per micrograms/m3). The epidemiologically based unit risk estimates were less variable and suggest higher risks (from 100 to 920 x 10(-6) per micrograms/m3). The wide range of risk estimates derived from these analyses reflects the strong assumptions and large uncertainties underlying these models. All of the models suggest relatively high risks (i.e., > 1/1,000) for miners with long-term exposures greater than 1,000 micrograms/m3. This is not surprising, given the fact that miners may be exposed to DEP concentrations similar to those that induced lung cancer in rats and mice, and substantially higher that the exposure concentrations in the positive epidemiologic studies.

Humans↗
PubMed1998

N-acetylcysteine prevents development of the hyperdynamic circulation in the portal hypertensive rat.

Partial portal vein ligation (PPVL) leads to the development of a hyperdynamic circulation. It is associated with elevated levels of tumor necrosis factor (TNF-alpha) and nitric oxide (NO) production, both of which can result in oxidant injury. In this study, we have investigated whether PPVL is associated with the development of oxidative stress, by measuring urinary F2-isoprostanes. In addition, we have examined whether N-acetylcysteine (NAC) can ameliorate oxidant injury and prevent the development of the hyperdynamic circulation. Urinary excretion of F2-isoprostanes increased sixfold following PPVL together with a significant increase in plasma nitrite and nitrate. Treatment with NAC inhibited the formation of F2-isoprostanes as well as the increase in plasma nitrite and nitrate. Hemodynamic studies in anesthetized rats showed that following PPVL, cardiac output and portal pressure increased, and systemic vascular resistance decreased, consistent with the development of a hyperdynamic circulation. These changes were prevented by chronic administration of NAC. We conclude that NAC prevents the development of the hyperdynamic circulation and that the formation of reactive oxygen species may be important in the pathogenesis of these hemodynamic changes.

Acetylcysteine↗
PubMed1998

The value of head ultrasound in infants with macrocephaly.

OBJECTIVE: To assess the value of head ultrasound (HUS) in neurologically normal infants with macrocephaly and to develop a rational approach to radiological investigation of macrocephalic infants. MATERIALS AND METHODS: A retrospective analysis of infants with macrocephaly (seen by one pediatric neurologist at this institution) was conducted. Infants with normal neurological examinations, no evidence of raised intracranial pressure and who had undergone a HUS were included. RESULTS: Twenty-seven infants were included in the analysis. Mean age at first assessment was 4.8 months. In 12 of 27 (44%), HUS was reported as normal. The remaining 15 had clinically insignificant abnormalities on HUS; 7 had prominent ventricles and 7 had increased subarachnoid fluid, with 1 infant having both. Seven infants had CT or MRI in addition to HUS. No clinically significant abnormalities were seen on CT or MRI scans that were not evident on HUS. Four infants had mild developmental abnormalities on initial evaluation. Mean duration of follow-up was 13.1 months. No infant developed neurological abnormalities during the follow-up period. CONCLUSION: In infants with macrocephaly with a normal neurological examination and no signs of raised intracranial pressure, HUS in conjunction with close neurological follow-up is reliable for the detection or exclusion of relevant intracranial pathology.

Abnormalities, Multiple↗
PubMed1998

Corticotropin-releasing hormone: a biochemical predictor of preterm delivery in a pilot randomized trial of the treatment of preterm labor.

OBJECTIVE: We assessed the ability of maternal plasma corticotropin-releasing hormone measurements to predict preterm delivery in the setting of a pilot study comparing transdermal glyceryl trinitrate with standard beta-mimetic therapy for preterm labor and to determine the effect of these tocolytics on maternal plasma corticotropin-releasing hormone concentrations. STUDY DESIGN: Twenty-six consecutive patients with preterm labor were randomized to tocolytic treatment with transdermal glyceryl trinitrate (n=13) or intravenous albuterol (n=13). RESULTS: Plasma corticotropin-releasing hormone immunoreactivity levels were higher in women who were delivered within 7 days (41.4+/-13.5 pmol/L) than in those continuing to term (14.2+/-2.4 pmol/L, p=0.011) and were not altered by treatment. Two women in each of the treatment groups delivered within 7 days of the initiation of treatment, two women in the glyceryl trinitrate group were changed to albuterol because of persistence of contractions. Glyceryl trinitrate treatment was associated with significantly fewer maternal side effects. Neither treatment altered umbilical artery Doppler ultrasonographic findings. CONCLUSION: Transdermal glyceryl trinitrate is better tolerated than intravenous albuterol but may be no more efficacious than albuterol for the treatment of preterm labor. Biologic markers such as plasma corticotropin-releasing hormone levels may be an important method of identifying women at high risk of preterm delivery.

Administration, Cutaneous↗
PubMed1998

Imaging the problem scaphoid.

Scaphoid fractures can be difficult to diagnose on X-ray, even at 2 weeks. We have compared prospectively bone scanning versus MRI scanning in 22 patients with persistent signs and symptoms suggestive of a scaphoid fracture at 2 weeks and found both methods to be sensitive, but MRI to be more specific, particularly in diagnosing soft tissue injuries like scapho-lunate ligament ruptures and triangular fibrocartilage tears. An early MRI scan at 2 weeks allows the clinician to make the appropriate decision in this group of patients whose diagnoses include; occult scaphoid fractures, other occult carpal and radial fractures, ligamentous injuries and those without apparent injuries. MRI has also been useful in defining the group of injuries which may imitate a clinically occult scaphoid fracture.

Adolescent↗