New amino acid polymorphism, Ala/Val4058, in exon 45 of the polycystic kidney disease 1 gene: evolution of alleles

The PKD1 gene, which is responsible for the most common form of autosomal dominant polycystic kidney disease, has recently been cloned and sequenced. Many disease-causing mutations have been characterized in this gene, most of them resulting in premature protein termination. However, mutation analysis not routinely implemented for family investigations in a clinical setting, because of the large size and complexity of the gene. Instead, genetic linkage analysis using highly polymorphic CA dinucleotide repeats that map around the gene is still the method of choice. Recently, a few intragenic polymorphisms have been described that are also useful for linkage studies. Here, a new diallelic polymorphism is described for amino acid residue 4058, Ala/Val4058, with allelic frequencies of 0.88 and 0.12, respectively, and a heterozygosity of 0.23, in the Greek and Greek-Cypriot populations. Interestingly, this polymorphism and Ala4091-A/G, which has previously been described in Caucasians, were not detected in DNA from 44 Japanese samples tested. This is particularly important when allelic frequencies in a particular population are used for linkage analysis of families of different ethnic origin. Also, observation of the two polymorphisms together as haplotypes suggests that the Ala/Val4058 polymorphism occurred more recently than the establishment of the Ala4091-A/G polymorphism, and specifically on the G allele.     

Salmonella meningitis: clinical experience of third-generation cephalosporins

Fifteen paediatric patients with Salmonella meningitis were retrospectively reviewed. Presenting symptoms and signs included fever, vomiting, seizures, poor activity, diarrhoea and bulging anterior fontanelle in most patients. Seven out of eight patients with prolonged fever for > 10 days had neurologic sequelae; therefore, prolonged fever is a significant prognostic factor of a poor outcome (p < 0.005). All 15 patients had a brain ultrasound or computed tomography in the acute stage and 11 patients had abnormal findings. The 14 surviving patients were treated with a third-generation cephalosporin for at least 3 weeks. Seven patients (47%) made complete recoveries; two of them were treated solely with a third-generation cephalosporin. Only one mortality (6%) occurred and there were no relapses. In conclusion, high frequencies of prolonged fever, neuroimaging abnormalities and neurologic sequelae were seen in patients with Salmonella meningitis treated with third-generation cephalosporins.     

Comparison of calcium phosphate cement mixture and pure calcium hydroxide as direct pulp-capping agents

This review reports the different genetic factors that have been identified either as risk factor for Alzheimer's disease (AD) or directly causing the disease. First are reviewed epidemiological data and biological mechanisms about the apoplipoprotein E gene allele epsilon 4 that is a major risk factor for Alzheimer's disease. The second part describes the mutations responsible for early-onset autosomal dominant AD found in three different genes. The gene located on chromosome 21 encodes the amyloid precusor protein (APP). The presenilin 1 and presenilin 2 genes, located on chromosome 14 and 1 respectively, encode not yet known membrane proteins.     

Multiclass Multiserver Threshold-Based Systems: A Study of Noninstantaneous Server Activation

In this paper, we consider performance evaluation of a system which shares K servers (or resources) among N heterogeneous classes of workloads, where server allocation and deallocation for class i is dictated by a class specific threshold-based policy with hysteresis control. In particular, the server activation time for class i is noninstantaneous. There are many systems and applications where a multiclass threshold-based queueing system can be of great use. One important utility of using threshold-based approaches is in situations where applications may incur server usage costs. In these cases, one needs to consider not only the performance aspects but also the resulting cost/performance ratio. The motivation for using hysteresis control is to reduce the unnecessary cost of server setup (or activation) and server removal (or deactivation) whenever there are momentary fluctuations in workload. Moreover, servers in such systems and applications are often needed by multiple classes of workloads and, hence, it is desirable to find good approaches to sharing server resources among the different classes of workloads, preferably without statically partitioning the server pool among these classes. An important and distinguishing characteristic of our work is that we consider the modeling and analysis of a multiclass system with noninstantaneous server activation. The main contributions of this work are: 1) in developing an efficient approximation method for solving such models; 2) in verifying the convergence of our iterative method, and 3) in evaluating the resulting accuracy of the technique for computing performance measures of interest, which can subsequently be used in making system design choices     

Carbon monoxide and water vapor contamination of compressed breathing air for firefighters and divers

Compressed breathing air, used in self-contained breathing apparatus (SCBA) by firefighters and other categories of workers as well as by recreational and commercial divers, is prepared with the aid of high-pressure compressors operating in the range of 5000 psig. There have been reports of unexplained deaths of SCUBA divers and anecdotal accounts of decreased time to exhaustion in firefighters using SCBAs. Compressed breathing air has been found to contain elevated levels of carbon monoxide (CO) and water vapor that are consistent with carboxyhemoglobin (COHb) poisoning and freezing of the user's regulator on the breathing apparatus. The Coburn-Forster-Kane equation (CFK equation) was used to estimate COHb levels at rest and at maximum exercise when exposed to different levels of CO in contaminated breathing air. The results demonstrated that, at maximum exercise, the COHb ranged from 6.0 to 17% with the use of 1 to 4 SCBA cylinders contaminated by 250 ppm CO. Standard operating procedures have been developed at the Montreal Fire Department to minimize the risk of compressed breathing air contamination. Results of the quality analysis/quality control program indicate that implementation of these procedures has improved the quality of the compressed breathing air. Recommendations are made for improvement of the air testing procedures mandated by the Canadian CAN3 180.1-M85 Standard on Compressed Breathing Air and Systems.     

The branch site adenosine is recognized differently for the two steps of pre-mRNA splicing

The functional groups responsible for branch site identity in the two steps of pre-mRNA splicing as well as for spliceosome assembly were tested by incorporation of site-specific modifications at the branch site of a pre-mRNA. These results show that recognition of the adenosine occurs early in complex formation and that the branch site adenosine is recognized differently before the first step and for the second step. Further, direct UV cross-linking with these modified RNAs was used to identify a factor whose interaction was dependent upon the identity of the branch site nucleotide.     

The block to HIV-1 envelope glycoprotein-mediated membrane fusion in animal cells expressing human CD4 can be overcome by a human cell component(s)

Membrane fusion mediated by interaction of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein with the human CD4 molecule generally requires that the CD4 be expressed on a human cell. The failure of murine or simian cells expressing human CD4 to form syncytia upon mixing with cells expressing envelope glycoprotein could not be corrected by expression of both molecules at extremely high surface levels using vaccinia virus expression vectors. Video fluorescence microscopic analysis of fluorescent dye transfer between fusing cells indicated that the block occurred at the level of membrane fusion between individual pairs of cells. To gain insight into the basis for this fusion block, we tested the ability of fluorescent probe cells expressing envelope glycoprotein to fuse with transient animal x human hybrid giant cells expressing human CD4. The hybrid giant cells were generated either by low-pH-induced fusion of vaccinia-infected cells or by CD4/HIV-1 envelope glycoprotein-mediated cell fusion. We observed that envelope glycoprotein-expressing probe cells efficiently fused with CD4-expressing animal x human hybrid giant cells, independent of whether the CD4 was originally expressed on the animal or on the human cell. Fusion did not occur with CD4-expressing giant cells derived from animal cells alone. These results indicate that the fusion block is not due to dominant inhibitory components in the animal cell. Rather, they suggest that human cells contain an additional component(s) which, when transferred to the CD4-bearing animal cell, confers the ability to undergo membrane fusion mediated by the HIV-1 envelope glycoprotein.     

Hypertrophic olivary degeneration: case report in a child

We report a case of hypertrophic olivary degeneration (HOD) detected by MRI, in a 14-year-old girl, 13 months after surgical excision of a brainstem cavernous malformation. As in vivo diagnosis of this condition has only become possible with the advent of MRI, the number of reported cases remains relatively small and they are almost exclusively in adults. Many radiologists and particularly paediatric radiologists, may therefore be unfamiliar with this entity. To our knowledge, this is the first specific report of HOD diagnosed by MRI in a child.