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Biomedical subjects

A Baldwin

Publications and source records attributed to A Baldwin.

At least 19 recordsLinked to original sources
PubMed2005

S100-mediated signal transduction in the nervous system and neurological diseases.

This article presents new information regarding the complement/level of S100 family members expressed in the brain and reviews the contribution of brain S100 family members to nervous system function and disease. A total of ten S100 family members are reported in the literature to be expressed in brain -S100A1, S100A2, S100A4, S100A5, S100A6, S100A10, S100A11, S100A13, S100B, and S100Z. Quantitative Northern blot analysis detected no S100A3, S100A8, S100A9 or S100A14 mRNA in mouse brain suggesting that these family members are not expressed in the brain. In addition, there was a 100-fold range in the mRNA levels for the six family members that were detected in mouse brain: S100A1/S100B levels were 5-fold higher than S100A6/S100A10 levels and 100-fold higher than S100A4/S100A13 levels. Five of these six family members (S1100A1, S100A6, S100A10, S100A13, and S100B) exhibited age-dependent increases in expression in adult mice that ranged from 5- to 20-fold. Although previous studies on S100 function in the nervous system have focused on S100B, other family members (S100A1, S100A3, S100A4, S100A5) have been implicated in neurological diseases. Like S100B, intra- and inter-cellular forms of these family members have been linked to cell growth, cell differentiation, and apoptotic pathways. Studies presented here demonstrate that ablation of S100A1 expression in PC12 cells results in increased resistance to Abeta peptide induced cell death, stabilization of intracellular [Ca2+] homeostasis, and reduced amyloid precursor protein expression. Altogether, these results confirm that S100-mediated signal transduction pathways play an important role in nervous system function/disease and implicate S100A1 in the neuronal cell dysfunction/death that occurs in Alzheimer's disease.

Aging↗
PubMed2001

Elliptic flow in Au+Au collisions at square root(S)NN = 130 GeV.

Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at square root(S)NN = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.

Journal Article↗
PubMed2001

Wagging the dog: an analysis of year 2000 workforce and education outcomes from recommendations of the 1995 Pew Commission report.

Over-production in the number of hospitals and health care workers has led to increased cost of medical care and inequities within the health care delivery system. An increase in managed care penetration within the market-place is believed to mandate dramatic changes in the way that health care is structured and delivered. The 1995 Pew Commission report projected major changes in health care organizations and health manpower through the effects of managed care and public regulation. This paper describes the outcomes to health delivery organizations and the health care workforce five years since the Pew Commission Report and discusses the belief that market forces are more effective mechanisms for addressing health care delivery and workforce requirements than public regulatory initiatives.

Allied Health Personnel↗
PubMed2001

PHP-HT (VitaResc Biotech).

VitaResc (formerly Apex) is developing PHP-HT, pyridoxalated hemoglobin polyoxyethylene conjugate, for the potential treatment of nitric oxide-induced shock (characterized by hypotension), associated with various etiologies, initially in septic shock. A phase I safety study and an initial phase I/II patient trial for NO-induced shock have been completed, and VitaResc has enrolled patients in three of five planned cohorts in a continuation of these trials to include a protocol of continuous infusion and dose escalation [330680,349187,390918]. The results from the dose escalation trials are expected to provide the basis for a randomized, controlled phase II/III pivotal trial of PHP-HT [390918]. VitaResc has licensed PHP-HT exclusively from Ajinomoto for all indications, worldwide, except Japan [275263]. Ajinomoto originally developed the human derived and chemically modified hemoglobin preparation as a blood substitute, but no development has been reported by the company since 1997 [275277,303577]. The other potential indications of PHP-HT include shock associated with burns, pancreatitis, hemodialysis and cytokine therapies [275277]. VitaResc expects the annual market potential of PHP-HT to exceed 1 billion dollars [330680].

Journal Article↗
PubMed2000

Outcome and clinical course of 100 patients with adenovirus infection following bone marrow transplantation.

We conducted a retrospective review of the clinical features and outcome of adenovirus infection in 572 consecutive patients transplanted in a single centre over a 10 year period. One hundred patients (17%) had a total of 105 episodes of adenovirus infection diagnosed at a median of 18 days post transplant (range 2-150 days). The incidence was higher in children than adults (21% vs 9%, P < 0.001) and in unrelated donor vs matched sibling donor transplants (26% vs 9%, P < 0.001). Diarrhoea and fever were the most common presenting features. Reflecting these symptoms, the most common site of isolation was the stool. Serotypes 1, 2 and 7 were the most frequently seen (total of 41/68 or 60% of evaluable cases). In six patients (6%) adenovirus infection was the direct cause of death occurring at a median of 72 days post transplant (range 18-365 days). Five of these six patients had pulmonary involvement and four had associated graft-versus-host disease (GVHD). Three further patients were considered to have severe adenoviral disease (total incidence 9%). Isolation of virus from multiple sites correlated with a poor outcome (P < 0.001). Comorbid viral infection was common in this group with 50% of all patients having other viruses isolated (predominantly polyoma virus and cytomegalovirus). We conclude that adenovirus is commonly isolated after bone marrow transplant and is a cause of significant morbidity but was a rare cause of mortality (6/572 = 1%) in our patient group as a whole. The relative infrequency of severe infection will make it difficult for the transplant physician to decide which patients should receive experimental antiviral drugs such as ribavirin and cidofovir or immunomodulatory therapy with donor white cell infusions.

Adenovirus Infections, Human↗
PubMed2000

Stem-loop binding protein, the protein that binds the 3' end of histone mRNA, is cell cycle regulated by both translational and posttranslational mechanisms.

The expression of the replication-dependent histone mRNAs is tightly regulated during the cell cycle. As cells progress from G(1) to S phase, histone mRNA levels increase 35-fold, and they decrease again during G(2) phase. Replication-dependent histone mRNAs are the only metazoan mRNAs that lack polyadenylated tails, ending instead in a conserved stem-loop. Much of the cell cycle regulation is posttranscriptional and is mediated by the 3' stem-loop. A 31-kDa stem-loop binding protein (SLBP) binds the 3' end of histone mRNA. The SLBP is necessary for pre-mRNA processing and accompanies the histone mRNA to the cytoplasm, where it is a component of the histone messenger RNP. We used synchronous CHO cells selected by mitotic shakeoff and HeLa cells synchronized at the G(1)/S or the M/G(1) boundary to study the regulation of SLBP during the cell cycle. In each system the amount of SLBP is regulated during the cell cycle, increasing 10- to 20-fold in the late G(1) and then decreasing in the S/G(2) border. SLBP mRNA levels are constant during the cell cycle. SLBP is regulated at the level of translation as cells progress from G(1) to S phase, and the protein is rapidly degraded as they progress into G(2). Regulation of SLBP may account for the posttranscriptional component of the cell cycle regulation of histone mRNA.

Animals↗
PubMed2000

The inhibition of fatty acid elongation by pebulate can be effectively counteracted by the safener dichlormid.

The thiocarbamate herbicide pebulate inhibits fatty acid elongation, which is necessary for surface lipid biosynthesis. As both barley and wild oats are susceptible to pebulate, the safener dichlormid was used to study the reversal of its herbicidal effect. Fatty acid elongation was restored by a dichlormid pretreatment in barley, but not in pebulate-expressed oats.

Acetamides↗
PubMed1999

Need for intensive care after operations for head and neck cancer surgery.

We compared the postoperative morbidity of 44 patients who had had major head and neck oncological resections and who were nursed postoperatively on a general ward with that of 33 who were nursed on an intensive care unit at North Manchester General Hospital and Withington Hospital, South Manchester, respectively. There was no difference in the general morbidity (9/44, 20% compared with 9/33, 27%, 95%, CI of difference -0.26 to 0.13). We conclude that it is safe to nurse the patients on a general ward provided that certain conditions are fulfilled.

Adult↗
PubMed1998

Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.

Mutations in the gene for the transcription factor hepatocyte nuclear factor (HNF) 1alpha cause maturity-onset diabetes of the young (MODY) 3, a form of diabetes that results from defects in insulin secretion. Since the nature of these defects has not been defined, we compared insulin secretory function in heterozygous [HNF-1alpha (+/-)] or homozygous [HNF-1alpha (-/-)] mice with null mutations in the HNF-1alpha gene with their wild-type littermates [HNF-1alpha (+/+)]. Blood glucose concentrations were similar in HNF-1alpha (+/+) and (+/-) mice (7.8+/-0.2 and 7.9+/-0.3 mM), but were significantly higher in the HNF-1alpha (-/-) mice (13.1+/-0.7 mM, P < 0.001). Insulin secretory responses to glucose and arginine in the perfused pancreas and perifused islets from HNF-1alpha (-/-) mice were < 15% of the values in the other two groups and were associated with similar reductions in intracellular Ca2+ responses. These defects were not due to a decrease in glucokinase or insulin gene transcription. beta cell mass adjusted for body weight was not reduced in the (-/-) animals, although pancreatic insulin content adjusted for pancreas weight was slightly lower (0.06+/-0.01 vs. 0.10+/-0.01 microg/mg, P < 0.01) than in the (+/+) animals. In summary, a null mutation in the HNF-1alpha gene in homozygous mice leads to diabetes due to alterations in the pathways that regulate beta cell responses to secretagogues including glucose and arginine. These results provide further evidence in support of a key role for HNF-1alpha in the maintenance of normal beta cell function.

Animals↗
PubMed1998

Role for a YY1-binding element in replication-dependent mouse histone gene expression.

Expression of the highly conserved replication-dependent histone gene family increases dramatically as a cell enters the S phase of the eukaryotic cell cycle. Requirements for normal histone gene expression in vivo include an element, designated alpha, located within the protein-encoding sequence of nucleosomal histone genes. Mutation of 5 of 7 nucleotides of the mouse H3.2 alpha element to yield the sequence found in an H3.3 replication-independent variant abolishes the DNA-protein interaction in vitro and reduces expression fourfold in vivo. A yeast one-hybrid screen of a HeLa cell cDNA library identified the protein responsible for recognition of the histone H3.2 alpha sequence as the transcription factor Yin Yang 1 (YY1). YY1 is a ubiquitous and highly conserved transcription factor reported to be involved in both activation and repression of gene expression. Here we report that the in vitro histone alpha DNA-protein interaction depends on YY1 and that mutation of the nucleotides required for the in vitro histone alpha DNA-YY1 interaction alters the cell cycle phase-specific up-regulation of the mouse H3.2 gene in vivo. Because all mutations or deletions of the histone alpha sequence both abolish interactions in vitro and cause an in vivo decrease in histone gene expression, the recognition of the histone alpha element by YY1 is implicated in the correct temporal regulation of replication-dependent histone gene expression in vivo.

Amino Acid Sequence↗
PubMed1997

Evidence for the presence of type I IL-1 receptors on beta-cells of islets of Langerhans.

The cytokine interleukin-1beta (IL-1beta) has been shown to inhibit insulin secretion and destroy pancreatic islets by a mechanism that involves the expression of inducible nitric oxide synthase (iNOS), and the production of nitric oxide (NO). Insulin containing beta-cells, selectively destroyed during the development of autoimmune diabetes, appear to be the islet cellular source of iNOS following treatment with IL-1beta. In this study we have evaluated the presence of type I IL-1 signaling receptors on purified pancreatic beta-cells. We show that the interleukin-1 receptor antagonist protein (IRAP) prevents IL-1beta-induced nitrite formation and IL-1beta-induced inhibition of insulin secretion by isolated islets and primary beta-cells purified by fluorescence-activated cell sorting (FACS). The protective effects of IRAP correlate with an inhibition of IL-1beta-induced iNOS expression by islets and FACS purified beta-cells. To provide direct evidence to support beta-cell expression of IL-1 type I signaling receptors, we show that antiserum specific for the type I IL-1 receptor neutralizes IL-1beta-induced nitrite formation by RINm5F cells, and that RINm5F cells express the type I IL-1 receptor at the protein level. Using reverse transcriptase-polymerase chain reaction (RT-PCR), the expression of type I IL-1 signaling receptors by FACS purified beta-cells and not alpha-cells is demonstrated. These results provide direct support for the expression of type I IL-1 receptors by primary pancreatic beta-cells, the cell type selectively destroyed during the development of autoimmune diabetes.

Animals↗
PubMed1997

Efficacy of naproxen sodium for exercise-induced dysfunction muscle injury and soreness.

OBJECTIVE: To examine the efficacy of naproxen sodium for exercise-induced dysfunction, muscle injury, and soreness. DESIGN: Double-blind crossover. SETTING: Community. PARTICIPANTS: Eight young adult, healthy males. INTERVENTIONS: Ten sets of seven to 10 eccentric actions with each quadriceps femoris with a load equal to 85% of the eccentric one repetition maximum (1RM) followed by 10 days of naproxen sodium or placebo. MAIN OUTCOME MEASURES: Concentric 1RM; cross-sectional area (CSA) and spin-spin relaxation time (T2) of quadriceps femoris, and subjective rating of thigh soreness pre- and 1, 4, and 10 days postexercise; subjective rating of ability to sleep or perform morning activities daily during recovery. RESULTS: Concentric 1RM was reduced by (p = 0.0001) 41% day 1 of recovery; by day 4 of recovery, it had increased (p = 0.0145) to 24% below baseline in the drug trial, but did not change for the placebo trial. By day 10 of recovery, concentric 1RM was 16 and 26% below (p = 0.0001) baseline for the drug and placebo trials, respectively. Quadriceps femoris CSA and T2 were increased (p < or = 0.0250) after exercise, with the greatest (p = 0.0008) responses evident on day 4 of recovery. At this time, each variable showed greater increases (p < or = 0.0129) for the placebo than for the drug trial 8 vs. 5 and 26 vs. 15%, respectively). The CSA of the quadriceps femoris showing an elevated T2 was 27 and 37% greater (p < or = 0.0085) for the placebo than for the drug trial on days 1 and 4 of recovery, respectively. The percentage of quadriceps femoris CSA with an elevated T2 (40%) was 1/3 greater (p < or = 0.0138) for the placebo than for the drug trial on these days. Thigh soreness was lower (day 4, p = 0.0087) and the ability to sleep or perform morning activities was less (p < or = 0.0030) compromised (days 3 and 4) during recovery in the drug trial. CONCLUSIONS: The results suggest that naproxen sodium improved recovery after eccentrically biased exercise, probably by attenuating expression of the inflammatory response to muscle injury.

Adult↗
PubMed1996

A prospective audit of wound infection rates after caesarean section in five West Yorkshire hospitals.

A three month prospective audit of wound infection following emergency and elective caesarean section was carried out in five West Yorkshire hospitals. Among 4076 women undergoing delivery in the five obstetric departments, the caesarean rate was 15.4%. The overall infection rate was 45/628 (7.2%) with a range of 2.5-17.2% between the five centres. The infection rate was 14/226 (6.2%) when antibiotics were used compared with 31/402 (7.7%) without antibiotics. The use of prophylactic antibiotics made no significant difference to the infection rate, which did not correlate with duration of labour or of ruptured membranes. The number of vaginal examinations correlated with the infection rate. In conclusion, the caesarean section rate observed was higher than that estimated for the UK as a whole, but was distorted by one centre with a high rate. For the other four hospitals the caesarean rate was unexceptional. The ratio of emergency to elective operations was comparable with recently reported values in the UK and the wound infection rate was within the widely varying limits found in previous studies. In view of the relatively low infection rate recorded without antibiotics, in the interests of cost effectiveness, prophylaxis may be limited in future to selected women at high risk. Because this was an audit rather than a randomized study we cannot exclude that this is already happening on an empirical basis.

Antibiotic Prophylaxis↗
PubMed1995

The evolving molecular epidemiology of HIV-1 envelope subtypes in injecting drug users in Bangkok, Thailand: implications for HIV vaccine trials.

OBJECTIVE: To genetically characterize HIV-1 strains in injecting drug users (IDU) in Bangkok, Thailand in 1994, and compare these with strains found earlier in Thai IDU; such information is essential for HIV-1 vaccine development and evaluation. METHODS: Peripheral blood mononuclear cells were collected from 84 IDU attending 14 drug treatment clinics in Bangkok in 1994. DNA was amplified using a nested polymerase chain reaction (PCR) procedure and sequenced directly (without cloning) from the PCR products. The V3 and flanking regions (345 nucleotides) of the env gene were analyzed using a neighbor-joining tree. RESULTS: Only one (1%) strain was a typical subtype B virus, 69 (82%) were genetically distinct subtype B' viruses (Thai B), and 14 (17%) were subtype E strains (Thai A). Persons with recently acquired infection were more likely to have subtype E viruses (P < 0.001) than those in our 1991 survey, who were more likely to have subtype B' viruses. Pairwise intra-subtype differences within subtypes E and B' were 5.3 and 4.3%, respectively, compared with 3.4 and 3.5% among strains collected in 1991 in Thailand. CONCLUSION: The genetic diversity within subtypes B' and E in Thailand and the proportion of new infections due to subtype E viruses among Bangkok IDU are increasing significantly. These data highlight the importance of monitoring the molecular epidemiology of HIV-1 in populations being considered for HIV-1 vaccine trials.

AIDS Vaccines↗
PubMed1994

Total knee arthroplasty in patients 80 years of age and older.

Total knee arthroplasty can be performed with acceptably low risk in the elderly patient. The risk for postoperative complications is significantly higher than in younger patients, however. Pain relief is the principle indication for this procedure in elderly patients.

Age Distribution↗
PubMed1993

Stability of intelligence from preschool to adolescence: the influence of social and family risk factors.

Intelligence scores of children in a longitudinal study were assessed at 4 and 13 years and related to social and family risk factors. A multiple environmental risk score was calculated for each child by counting the number of high-risk conditions from 10 risk factors: mother's behavior, mother's developmental beliefs, mother's anxiety, mother's mental health, mother's educational attainment, family social support, family size, major stressful life events, occupation of head of household, and disadvantaged minority status. Multiple risk scores explained one-third to one-half of IQ variance at 4 and 13 years. The stability between 4- and 13-year environmental risk scores (r = .77) was not less than the stability between between 4- and 13-year IQ scores (r = .72). Effects remained after SES and race, or maternal IQ, were partialled; multiple risk was important in longitudinal prediction, even after prior measurement of child IQ was accounted for; the pattern of risk was less important than the total amount of risk present in the child's context.

Adolescent↗