Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease.

In this study, we demonstrate that two important regulators of the cell cycle, cyclin-dependent kinase-4 and its inhibitor p16, are increased in the brains of cases of Alzheimer's disease patients compared with age-matched controls. Both proteins are increased in the pyramidal neurons of the hippocampus, including those neurons containing neurofibrillary tangles and granulovacuolar degeneration. As p16 is not normally found in terminally differentiated neurons, it seems paradoxical that it is increased in Alzheimer's disease unless it is responding to increases in cyclin-dependent kinase-4 or other cell cycle regulators. Induction of the latter, a protein that signals re-entry and progression through the cell cycle, may itself be the consequence of alpha response to a growth stimulus. Re-entry into the cell cycle is likely deleterious in terminally differentiated neurons and may contribute to the biochemical abnormalities, such as oxidative stress and hyperphosphorylated tau protein, as well as the neuronal degeneration characteristic of the pathology of Alzheimer's disease.     

Signaling mechanisms regulating self-renewal and differentiation of pluripotent embryonic stem cells

An ability to propagate pluripotent embryonic cells in culture is the foundation both for defined germline modification in experimental rodents and for future possibilities for broad-based cellular transplantation therapies in humans. Yet, the molecular basis of the self-renewing pluripotent phenotype remains ill-defined. The relationship between factors that influence embryonic stem cell propagation in vitro and mechanisms of stem cell regulation operative in the embryo is also uncertain. In this article we discuss the role of intracellular signalling pathways in the maintenance of pluripotency and induction of differentiation in embryonic stem cell cultures and the mammalian embryo.     

Congenital cytomegalovirus infection.

The overall prevalence of congenital cytomegalovirus infection among the offspring of a highly immune young female population was 2.4 per cent (23 of 939). To ascertain whether the presence of anticytomegalovirus antibodies protects the developing fetus, we examined the offspring of 239 prospectively studied women. Despite substantial levels of preconceptional antibodies, intrauterine cytomegalovirus infection occured in seven of 208 (3.4 per cent) seroimmune women. Three neonates with congenital infection were born to 31 initially seronegative women. All the congenitally infected infants had subclinical involvement. Maternal humoral immunity may not protect the fetus against congenital cytomegalovirus infection. Neutralization kinetics and restriction enzyme analysis with endonucleases (EcoR-1 and HinD 111) demonstrated antigenic and genetic homology between viral strains isolated from two siblings consecutively infected in utero, indicating that repeat maternal infection with the same virus is transmissible to sequential products of conception.     

Replacing the academic medical center's teaching hospital.

Addressing the need for updated teaching hospital facilities is one of the most significant issues that an academic medical center faces. The authors describe the process they underwent in deciding to build a new facility at the Medical University of South Carolina (MUSC). Initial issues included whether or not the teaching hospital would continue to play a role in clinical education and whether to replace or renovate the existing facility. Once the decision to build was reached, MUSC had to choose between an on-campus or distant site for the new hospital and determine what the function of the old hospital would be. The authors examine these questions and discuss the factors involved in different stages of decision making, in order to provide the academic medicine community guidance in negotiating similar situations. Open communication within MUSC and with the greater community was a key component of the success of the enterprise to date. The authors argue that decisions concerning site, size, and focus of the hospital must be made by developing university-wide and community consensus among many different constituencies. The most important elements in the success at MUSC were having unified leadership, incorporating constituent input, engaging an external consultant, remaining unfazed by unanticipated challenges, and adhering to a realistic, aggressive timetable. The authors share their strategies for identifying and successfully managing these complex and potentially divisive aspects of building a new teaching hospital.     

Abundance of Ixodes scapularis (Acari: Ixodidae) after the complete removal of deer from an isolated offshore island, endemic for Lyme Disease

Monhegan is an isolated 237-ha island lying 16 km off the coast of Maine. Introduced to the island in 1955, white-tailed deer, Odocoileus virginianus Zimmerman, reached a density of approximately 37/km2 by the mid-1990s. Black-legged ticks, Ixodes scapularis Say, first noticed in the late 1980s, flourished thereafter. Norway rats (Rattus norvegicus Berkenhout) on Monhegan are highly infected with Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt, and Brenner, the agent of Lyme disease. By 1996, 13% of year-round residents had contracted the disease. The community's subsequent decision to eliminate deer from the island provided a unique opportunity to monitor the abundance of vector ticks in response to the complete and permanent removal of the primary hosts of their reproductive stage. With the exception of humans and their dogs and cats, there are no other potential hosts for adult I. scapularis on Monhegan. From November 1996 to March 1999, all deer were removed from the island. Previous annual fall flagging of vegetation from 1990 to 1998 produced 6-17 adult ticks/h, of which 24-41% were infected with the Lyme disease spirochete. During this same period, up to 18 larvae and 4 nymphs were removed per Norway rat live-trapped on the island each July. With the absence of deer in the fall of 1999, both the density of host-seeking adult ticks and infection prevalence rose substantially to 28/h and 75.0%, respectively. By the summer of 2003, however, no sub-adult ticks were found on rats, and that fall, only 0.67 adult ticks/h were flagged. Of the 68 adults collected from 2002 to 2003, 20 (29.4%) were infected. Over this same period, adult tick abundance on a deer-populated, reference island continued to gradually increase.     

Identification of a new HLA-B*15 allele,HLA-B*1569

We have identified a new HLA-B*15 allele (B*1569) by polymerase chain reaction (PCR) using sequence-specific primers (SSP) and sequence-based typing (SBT). This novel allele was found in a 67-year-old white Caucasian male and differs from HLA-B*1503 at 3 positions. The nucleotide substitutions at positions 544, 559 and 560 result in amino acid changes at codon 158 from GCC (alanine) to ACC (threonine), and at codon 163 from CTG (leucine) to ACG (threonine).     

Failure of prediction of liver function test abnormalities with the urine urobilinogen and urine bilirubin assays

A prospective observational study of 229 cases was conducted in a busy ambulatory care setting to evaluate the sensitivity, specificity, predictive values, and accuracy of spot urine urobilinogen and urine bilirubin assays as screening tests for serum liver function test (LFT) abnormalities. Both urine tests exhibited remarkably similar characteristics overall once they were adjusted to maximize accuracy and predictive values (occurring at a normal or abnormal "threshold," respectively, of 3.4 or 5.07 mumol/d for urobilinogen and 0 or 1+ for urine bilirubin). The percentage of cases correctly identified were 81% to 83% for serum bilirubin assays, 68% to 72% for other LFTs, but only 62% to 63% for screens for cases with at least one abnormal LFT finding. Poor sensitivities (47% to 49%) limited the detection of abnormal findings by the screen; both screens were reasonably specific (79% to 89%), but negative predictive values were suitable (89%) for serum bilirubin results only and were prohibitively lower (49% to 50%) in predicting all patients without LFT abnormalities. We conclude that spot urine urobilinogen and urine bilirubin determinations, although good screens for isolated serum bilirubin elevations, have unacceptable statistical properties as predictors of other LFT results due to a high proportion of false-negative results.     

Application of an aldrin and dieldrin ELISA to the detection of pesticides in eggs

This paper details the results obtained when a number of egg samples, collected in Egypt from different races of chicken were analyzed for the presence of the organochlorine insecticides aldrin and dieldrin. A simple ELISA was used for the detection and quantification of aldrin and dieldrin. The test was modified for application in this high protein system. Pesticide was detected in 83–352% (14/17) of the samples at levels ranging from 0.006 to 0.7 ppm (0.006 to 0.7 μg ml^‐1). People eating eggs containing these amounts of pesticides which are above the World Health Organisation average daily intake levels would be at increased risk.