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Biomedical subjects

B Davis

Publications and source records attributed to B Davis.

At least 127 records · Page 7Linked to original sources
PubMed1996

Effects of azathioprine withdrawal in kidney recipients with stable function two years after transplant.

To assess the effects of azathioprine withdrawal, renal recipients with grafts > 2 yr function (103 study patients) were tapered off azathioprine over a 1-yr period and compared to 69 patients 2 yr after transplant who were not tapered (controls). Of the 103 study patients, 16 (15%) were living-donor transplants and 87 were cadaveric. Of the 69 control patients, 9 (13%) were living related transplants and 60 were cadaveric. The mean HLA match for those tapered was 3.3 Ag and 3.1 Ag for those remaining on azathioprine. Two study patients restarted azathioprine on their own. Age, sex, and cause of renal failure in both groups was similar. Of the 101 study patients remaining, 9 (8.8%) returned to dialysis due to biopsy proven chronic rejection. There were no acute rejection episodes. Six of the 69 control patients (8.7%) also returned to dialysis for the same reason. Of the 92 patients who have completed the taper, 85 have been off azathioprine for six or more months. There was not a significant difference between the mean 12- and 24-month creatinine levels of the study patients (1.6 mg%, 1.7 mg%) and those of the controls (1.5 mg%, 1.8 mg%). The mean 12- and 24-month hematocritis of patients tapered (41.3%, 40.8%) were comparable with patients not tapered (42.3%, 42.8%). Of interest, the mean hematocritis of both study and control patients rose from 28.9% and 33.5%, respectively, to 41.3% and 42.3% 1 yr following entry into the study. The mean 12- and 24-month white blood counts of those tapered (8.9, 8.7) did not differ significantly from those continued on azathioprine (8.8, 8.8). In stable renal transplant patients on triple drug immunosuppression for at least 2 yr, azathioprine can be discontinued, in a tapered protocol, without an increased risk of graft loss or compromise of renal function.

Azathioprine↗
PubMed1995

Perturbed pKA-values in the denatured states of proteins.

We show in this study that the ionisation equilibria of denatured proteins in pure water are inconsistent with the "fully-unfolded" conformation being an extended coil where the residues are isolated from one another by the intervening solvent. The effects of acid and salt on the stability of the barley chymotrypsin inhibitor 2 (CI2) were investigated and the pKA-values of all carboxylate residues in the native protein were determined by NMR. A comparison of the experimentally determined pH-dependence of the protein stability and that calculated using observed pKA-values in the native state, reveals that the pKA-values in the denatured state are, on average, 0.3 pH units lower than those of model compounds. An increase in ionic strength eliminates these pKA shifts in the denatured state. This shows that there are electrostatic interactions in the denatured state of CI2. Since previous studies on barnase and the Ovomucoid Third Domain also report anomalous titration behaviours of the denatured states, it appears that perturbed pKA-values in the denatured state is a general phenomenon, indicating that the unfolded conformation in pure water is a fairly compact species. In addition, we used a mutational approach to determine the pKA-values of a carboxylate group in both the native and denatured states. The pKA-value in the native state obtained by this method is in precise agreement with that obtained by NMR.

Hydrogen-Ion Concentration↗
PubMed1995

The myeloid zinc finger gene, MZF-1, regulates the CD34 promoter in vitro.

MZF-1 is a C2H2 zinc finger gene encoding a putative transcriptional regulator of myeloid differentiation. The MZF-1 protein contains 13 C2H2 zinc fingers arranged in bipartite DNA binding domains containing zinc fingers through 4 and, in the carboxy-terminus, 5 through 13. We previously identified the DNA consensus binding site recognized by the two DNA binding domains. To assess the transcription regulatory function of MZF-1, the full-length MZF-1 coding region was fused to the DNA binding domain of the yeast transactivator GAL4. The expression vector was cotransfected with the chloramphenicol acetyl transferase (CAT) reporter gene regulated by the thymidine kinase promoter containing GAL4 DNA binding sites into NIH 3T3, 293, K562, and Jurkat cell lines. MZF-1 represses CAT reporter gene expression via GAL4 binding sites in the nonhematopoietic cell lines NIH 3T3 and 293. In contrast, MZF-1 activates CAT reporter gene expression in the hematopoietic cell lines K562 and Jurkat. The MZF-1 binding sites are present in the promoters of several genes expressed during myeloid differentiation, including the CD34 promoter. MZF-1 transcriptional regulation of this physiologically relevant promoter was assessed in both hematopoietic and nonhematopoietic cell lines. Recombinant MZF-1 protein specifically binds to the consensus binding sites in the CD34 promoter in mobility shift assays. MZF-1 expression vectors were cotransfected with the luciferase reporter plasmids regulated by the CD34 promoter into both nonhematopoietic and hematopoietic cell lines. As with the heterologous DNA binding domain, MZF-1 represses reporter gene expression in nonhematopoietic cell lines and activates expression in hematopoietic cell lines. Activation of CD34 expression in hematopoietic cell lines is dependent on the presence of intact MZF-1 binding sites. The cell type-specific regulation of the CD34 promoter by MZF-1 suggests the presence of tissue-specific regulators/adapters or differential MZF-1 modifications that determine MZF-1 transcriptional regulatory function.

3T3 Cells↗
PubMed1995

Physical working capacity after acute myocardial infarction in patients with low ejection fraction and effect of captopril.

Previous studies after acute myocardial infarction (AMI) have reported conflicting results on the effects of angiotensin-converting enzyme inhibition on physical working capacity. In an effort to provide more insight into this subject, we examined the effects of captopril on working capacity of patients who had low ejection fractions but no congestive heart failure after AMI. One hundred sixty-six participants were recruited from 5 centers after randomization to either captopril or placebo for the Survival and Ventricular Enlargement study. Upright cycle ergometer tests were performed with continuous measurements of respiratory gases at 4, 12, and 24 months after AMI. Our study concurs with 2 of 3 previous post-AMI studies and supports the conclusion that working capacity is not affected by angiotensin-converting enzyme inhibition at 4 or 12 months after AMI in patients without congestive heart failure. In addition, no significant effect of captopril was noted at 24 months after AMI. Peak oxygen uptake tended to decrease between 12 and 24 months in the placebo group by an average (+/- SD) of -22 +/- 322 ml/min (n = 66), but to increase in the captopril group (+62 +/- 289, n = 57), a difference that was significant (Mann-Whitney chi-square, p = 0.02). This post-hoc observation suggests that a late beneficial effect may have been masked by inadequate study duration. Known benefits of captopril appear not to include an increase in working capacity within the first 24 months after AMI.

Aged↗
PubMed1995

Backbone dynamics of chymotrypsin inhibitor 2: effect of breaking the active site bond and its implications for the mechanism of inhibition of serine proteases.

The backbone dynamics of uniformly 15N-labeled chymotrypsin inhibitor 2 (CI2) and of the complex formed by the association of two fragments consisting of residues 20-59 and 60-83 have been studied. A data set consisting of 15N longitudinal (T1) and transverse (T1 rho) relaxation times and (1H)-15N NOE enhancements has been measured for all backbone NH groups in both proteins. Information on internal motions has been extracted from these data using the model-free approach to determine order parameters (S2) and effective internal correlation times (tau e). The data indicate that most of the backbone of CI2 is highly constrained (S2 approximately 0.9) with the exception of residues in the binding loop (residues 54-64), which have slightly lower order parameters. Most of the residues in the CI2(20-59).(60-83) complex are also highly constrained (S2 approximately 0.9). However, the loss of the covalent bond between Met59 and Glu60 leads to a large increase in the mobility of residues in the loop region. The residues in the first half of the loop region have significantly lower order parameters than those in the second half of the loop. This observation suggests that the NH2 group that is released on cleavage of the scissile bond remains anchored in its original position, inhibiting the attack of water on the acyl-enzyme that is formed between the protease and the cleaved inhibitor. More importantly, the NH2 group is optimally placed for reversing the formation of the acyl-enzyme so that the equilibrium between the cleaved and uncleaved inhibitor, bound to the protease, greatly favors the uncleaved complex.

Amino Acid Sequence↗
PubMed1995

Outbreak of HIV infection in a Scottish prison.

OBJECTIVE--To investigate the possible spread of HIV infection and its route of transmission among prison inmates. DESIGN--In response to an outbreak of acute clinical hepatitis B and two seroconversions to HIV infection, counselling and testing for HIV were offered to all inmates over a two week period in July 1993. Information was sought about drug injecting, sexual behaviour, and previous HIV testing. SETTING--HM Prison Glenochil in Scotland. SUBJECTS--Adult male prisoners. MAIN OUTCOME MEASURES--Uptake of HIV counselling and testing; occurrence and mode of HIV transmission within the prison. RESULTS--Of a total 378 inmates, 227 (60%) were counselled and 162 (43%) tested for HIV. Twelve (7%) of those tested were positive for antibody to HIV. One third (76) of those counselled had injected drugs at some time, of whom 33 (43%) had injected in Glenochil; all 12 seropositive men belonged to this latter group. Thirty two of these 33 had shared needles and syringes in the prison. A further two inmates who injected in the prison were diagnosed as positive for HIV two months previously. Evidence based on sequential results and time of entry into prison indicated that eight transmissions definitely occurred within prison in the first half of 1993. CONCLUSION--This is the first report of an outbreak of HIV infection occurring within a prison. Restricted access to injecting equipment resulted in random sharing and placed injectors at high risk of becoming infected with HIV. Measures to prevent further spread of infection among prison injectors are urgently required.

Adult↗
PubMed1995

Factors that influence the provision of sexual health care by Dutch cancer nurses.

A descriptive-correlational design was used with a sample of Dutch cancer nurses (n = 104) to describe provision of sexual health care (SHC) and to explore influential factors. This report is limited to the second goal. The Theory of Reasoned Action provided the conceptual framework for investigation of five previously identified factors and one unexplored factor. Knowledge, comfort, attitude (towards sexuality) and subjective norm were significantly related with provision of SHC. Multiple regression analysis demonstrated that knowledge and comfort were significant explanatory variables, accounting for 37% of the variance.

Adult↗
PubMed1995

Factors affecting ED length-of-stay in surgical critical care patients.

To determine what patient characteristics are associated with prolonged emergency department (ED) length-of-stay (LOS) for surgical critical care patients, the charts of 169 patients admitted from the ED directly to the operating room (OR) or intensive care unit (ICU) during a 6-week period in 1993 were reviewed. The ED record was reviewed for documentation of factors that might be associated with prolonged ED LOS, such as use of computed tomographic (CT), radiology special procedures, and the number of plain radiographs and consultants. ED LOS was considered to be the time from triage until a decision was made to admit the patient. Using a Cox proportional hazards model, use of CT and special procedures were the strongest independent predictors of prolonged ED length-of-stay. The number of plain radiographs and consultants had only a minimal effect. Use of a protocol-driven trauma evaluation system was associated with a shorter ED LOS. In addition to external factors that affect ED overcrowding, ED patient management decisions may also be associated with prolonged ED length-of-stay. Such ED-based factors may be more important in surgical critical care patients, whose overall ED LOS is affected more by the length of the ED work-up rather than the time spent waiting for a ICU bed or operating suite.

Adolescent↗
PubMed1995

Risk assessment of environmental chemicals.

Risk assessment is an evolving process, based not only upon toxicology but also upon a broad background of knowledge in fields ranging from chemistry to physiology and molecular biology and from environmental transport processes to applied statistics. Risk assessment procedures must be continually updated to reflect advances in these basic sciences. This review addresses several areas of risk assessment that are receiving heightened attention, including neurotoxicity, immunotoxicity, reproductive and developmental toxicity, genotoxicity, carcinogenicity, and toxicokinetics and modeling. Risk assessors must work with the scientific community at large to incorporate advances in the basic sciences into their extrapolations. A concerted attempt to better define the variability and decrease the uncertainty of hazard estimates will result in more efficient protection of the public and the environment against toxic hazards.

Animals↗
PubMed1995

Microfluctuations of steady-state accommodation and the cardiopulmonary system.

The relationship between variations in steady-state accommodation (microfluctuations) and rhythmic cycles in cardiopulmonary system was investigated. As previously reported, vascular pulse frequency was consistently correlated with the high frequency component of steady-state accommodation microfluctuations. In a new finding, respiration rate and an associated cycle in the instantaneous pulse rate also showed a correlation with a low frequency component of the accommodation power spectra. This apparent coherence between respiration frequency and an accommodation low frequency component was maintained during rapid breathing and was evident at the expected frequency during regulated breathing patterns. This association may reflect the direct influence of the autonomic nervous system upon the ciliary muscle or may be caused by the modulation of intraocular pulse by the autonomic nervous system.

Accommodation, Ocular↗
PubMed1994

The structure of the transition state for the association of two fragments of the barley chymotrypsin inhibitor 2 to generate native-like protein: implications for mechanisms of protein folding.

Possible early events in protein folding may be studied by dissecting proteins into complementary fragments. Two fragments of chymotrypsin inhibitor 2 [CI2-(20-59) and CI2-(60-83)] associate to form a native-like structure in a second-order reaction that combines collision and rearrangement. The transition state of the reaction, analyzed by the protein engineering method on 17 mutants, is remarkably similar to that for the folding of the intact protein--a structure that resembles an expanded version of the folded structure with most interactions significantly weakened. The exception is that the N-terminal region of the single alpha-helix (the N-capping box) is completely formed in the transition state for association of the fragments, whereas it is reasonably well formed for the intact protein. Preliminary evidence on the structures of the individual fragments indicates that both are mainly nonnative, lacking native secondary structure and having regions of nonnative buried hydrophobic clusters. The association reaction does not result from the collision of a subpopulation of two fully native-like fragments but involves a considerable rearrangement of structure.

Amino Acid Sequence↗
PubMed1994

Detection of an intermediate in the folding of the (beta alpha)8-barrel N-(5'-phosphoribosyl)anthranilate isomerase from Escherichia coli.

We have used thermodynamic and kinetic techniques to monitor the guanidinium chloride induced (GdmCl-induced) denaturation of N-(5'-phosphoribosyl)anthranilate isomerase from Escherichia coli (ePRAI). Although CD-monitored equilibrium denaturation curves are consistent with cooperative unfolding of the protein centered at 1.45 M GdmCl, fluorescence readings drop by over 25% in the region preceding the CD-monitored transition, suggesting non-two-state behavior. Kinetics experiments measure a slow relaxation rate with negative fluorescence amplitude when protein is diluted from 0 to 0.5 M GdmCl, corroborating results from equilibrium conditions. Detection of several unfolding and refolding rates in final GdmCl concentrations from 0 to 5.0 M indicates the presence of at least one intermediate along unfolding and refolding pathways. GdmCl dependence of the relaxation rates can be explained most easily by a nonsequential mechanism for ePRAI unfolding, though a sequential mechanism cannot be ruled out. The data corroborate the fragment complementation studies of Eder and Kirschner [Eder, J., & Kischner, K. (1992) Biochemistry 31, 3617-3625], which are consistent with unfolding of the C-terminal portion of a yeast-derived PRAI in its folding intermediate. In ePRAI, such partial unfolding would expose W391 to quenching by solvent molecules; W356, ePRAI's other tryptophan, is buried in the hydrophobic core and is unlikely to be affected by local changes in structure. A C-terminally unfolded folding intermediate has been demonstrated in the folding of tryptophan synthase (alpha-subunit), a related beta alpha-barrel enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldose-Ketose Isomerases↗
PubMed1994

Steady-state accommodation response and VDT screen conditions.

Steady-state accommodation response was measured for seven different visual display terminal (VDT) screen conditions and a hard-copy control condition. The screen conditions included variations in screen polarity, contrast and chromatic characteristics of the text and background. Accommodation response was measured for seven young subjects using a free-space infrared optometer, the Canon Autoref R-1. The accommodation response was measured every 1.3 s over a period of 60 s for each test condition, and both the mean and standard deviation of the responses were derived. A small but significantly higher accommodation response was found for hard copy, blue-on-red and red-on-blue screen conditions compared with white-on-black, green-on-black and black-on-white screen conditions. Screen polarity and contrast had little effect on accommodation response for the black-and-white screen conditions. The variability of accommodation response showed little difference between test conditions. For short-term VDT screen viewing, the accommodation response appears to be relatively accurate and stable across a wide range of screen conditions.

Journal Article↗