Overnight increases in haematocrit: additional evidence for a nocturnal fall in plasma volume.

Our previously published studies with monkeys describe a characteristic nocturnal haemodynamic pattern consisting of a monotonic decline in cardiac output and central venous pressure, and a concomitant rise in total peripheral resistance. These findings led us to hypothesize that there is a reduction in total plasma volume during the night. Since a fall in plasma volume should cause an increase in haemoglobin and plasma protein concentration, we designed this experiment to test the hypothesis that haematocrit levels would be significantly greater in the morning than in the evening. In a study of five monkeys, the levels of haematocrit were measured at 1700 h and at 0900 h the next morning for 14 days. The average morning haematocrit levels were 6.5% higher than the average evening values. Lower plasma volume and possibly greater blood viscosity could contribute to the pathophysiology of the morning increase in the incidence of 'silent' ischaemia and catastrophic vascular events such as sudden cardiac death, myocardial infarctions and strokes in man.     

Pseudo dicentric chromosome (5;21): a rare example of maternal germline mosaicism

Karyotyping of a malformed male newborn revealed the unbalanced karyotype of 46,XY, psudic(5;21)(q12;p13), +5 resulting in trisomy for the short arm of chromosome 5 and partial trisomy for 5q. Both parents had normal karyotypes in their peripheral blood lymphocytes. A second pregnancy ended in a miscarriage at 16 weeks gestation, sonographically 12 weeks. Karyotyping of chorionic villi from the abortus revealed the same unbalanced karyotype that had been identified in the first child. Fluorescence in-situ hybridization analysis confirmed a trisomy 5p. Microsatellite marker analysis ruled out illegitimacy and proved the maternal origin of the trisomic section of chromosome 5. Extended chromosome analysis of 60 metaphase cells from maternal skin fibroblasts and 40 metaphase cells from lymphocytes did not reveal mosaicism for psudic(5;21). These findings suggest the presence of a maternal germline mosaicism.     

Synthesis and properties of photocross-linked poly(propylene fumarate) scaffolds

The photocross-linking of poly(propylene fumarate) (PPF) to form porous scaffolds for bone tissue engineering applications was investigated. PPF was cross-linked using the photoinitiator bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide (BAPO) and exposure to 30 min of long wavelength ultraviolet (UV) light. The porous photocross-linked PPF scaffolds (6.5 mm diameter cylinders) were synthesized by including a NaCl porogen (70, 80, and 90 wt% at cross-linking) prior to photocross-linking. After UV exposure, the samples were placed in water to remove the soluble porogen, revealing the porous PPF scaffold. As porogen leaching has not been used often with cross-linked polymers, and even more rarely with photoinitiated cross-linking, a study of the efficacy of this strategy and the properties of the resulting material was required. Results show that the inclusion of a porogen does not significantly alter the photoinitiation process and the resulting scaffolds are homogeneously cross-linked throughout their diameter. It was also shown that porosity can be generally controlled by porogen content and that scaffolds synthesized with at least 80 wt% porogen possess an interconnected pore structure. Compressive mechanical testing showed scaffold strength to decrease with increasing porogen content. The strongest scaffolds with interconnected pores had an elastic modulus of 2.3+/-0.5 MPa and compressive strength at 1% yield of 0.11+/-0.02 MPa. This work has shown that a photocross-linking/porogen leaching technique is a viable method to form porous scaffolds from photoinitiated materials.     

RNA primer removal and gap filling on a model minicircle replication intermediate

Replication of kinetoplast DNA minicircles in Crithidia fasciculata occurs by a unidirectional mechanism involving continuous synthesis of one strand (L strand) and discontinuous synthesis of the complementary strand (H strand). L-strands are initiated by RNA priming at alternate origins (A and B) resulting in daughter molecules with a single nick or gap in the L strand at either ori A or ori B. Some of the gapped molecules contain ribonucleotides at the 5' side of the gap. We have investigated the ability of recombinant forms of kinetoplast replication proteins, DNA polymerase beta and structure specific endonuclease 1, to repair gaps in a model minicircle substrate. Structure specific endonuclease 1 was shown to efficiently remove all ribonucleotides from the 5' side of the model substrate by stepwise cleavage of the RNA primer. Polymerase beta was then able to extend the 3' terminus of the gap to yield a nicked molecule capable of covalent joining by a DNA ligase. These results demonstrate that the nuclease and polymerase enzymes present at antipodal protein complexes flanking the kinetoplast disk are capable of complete RNA primer removal and subsequent gap filling of newly synthesized minicircle L strands.     

A complex translocation in a 5-year-old boy with acute myeloblastic leukemia

A complex translocation [t(2;10;11)(q34;q11;q13)], an extra chromosome #8, and a duplication of 17q were the major findings in blast cells found in the bone marrow of a 5-yr-old boy with AML-M2 both before treatment and during relapse. The child died 8.5 mo after diagnosis, despite intensive combination chemotherapy.     

Thermal pleasantness sensation: an indicator of thermal stress

Summary The degree of pleasantness or unpleasantness of thermal sensation aroused by a particular peripheral thermal stimulus has been shown to be an indicator of thermal state of the body in relation to the thermoregulatory set point. This phenomenon is known as thermal alliesthesia. The quantification of thermal alliesthesia was possible using two methods: (1) A set of temperature stimuli (15, 20, 25, 30, 35, and 38 C) was applied, by means of a Peltier thermode 5.5×2.7 cm², on the back of the hand, the forehead, and the back of the neck. When each stimulus had been applied for 5 s the subjects voted their degree of thermal pleasantness/unpleasantness on a psychophysical scale ranging from +2.0 for very pleasant to –2.0 for very unpleasant. (2) The subjects were also asked to adjust the Peltier thermode temperature, without looking at the temperature scale, such that the temperature (on the back of the neck) was maintained at the level the subjects considered most pleasant. The subjects also rated their general thermal comfort sensation on a five point scale ranging from +2.0 for very comfortable to –2.0 for very uncomfortable. Rectal temperature and skin temperature at eight locations were continuously recorded. Passive thermal exposures (54) were made with nine passive subjects and 42 exposures were done with working (50 watt) subjects. All exposures were carried out in a climatic chamber at a constant temperature, relative humidity (45%), and air speed (0.3 m/s). Each subject underwent 6 exposures at six room temperatures of 15, 20, 25, 30, 35, and 40 C. The results of work exposures confirmed the findings of previous studies; namely, the effect of core temperature change overrides any effect due to mean skin temperature on alliesthesial response. A mathematical function to predict the mean slope of the thermal pleasantness rating/stimulus line (a measure of the alliesthesial response) was derived using the data obtained from the passive thermal exposures. The results indicate that alliesthesial response can be used as a quantitative indicator of thermal stress.Supported by the European Coal and Steel Community, Luxembourg     

Endoplasmic reticulum stress and unfolded protein response in inclusion body myositis muscle

Proteins in the endoplasmic reticulum (ER) require an efficient system of molecular chaperones whose role is to assure their proper folding and to prevent accumulation of unfolded proteins. The response of cells to accumulation of unfolded proteins in the ER is termed "unfolded protein response" (UPR). UPR is a functional mechanism by which cells attempt to protect themselves against ER stress, resulting from the accumulation of the unfolded/misfolded proteins. Because intracellular inclusions, containing either amyloid-beta (Abeta) or phosphorylated tau, are the characteristic feature of sporadic inclusion body myositis (s-IBM) muscle biopsies, we studied expression and immunolocalization of five ER chaperones, calnexin, calreticulin, GRP94, BiP/GRP78, and ERp72, in s-IBM and control muscle biopsies. Physical interaction of the ER chaperones with amyloid-beta precursor protein (AbetaPP) was studied by a combined immunoprecipitation/immunoblotting technique in s-IBM and control muscle biopsies, and in AbetaPP-overexpressing cultured human muscle fibers. In all s-IBM muscle biopsies, all five of the ER chaperones were immunodetected in the form of inclusions that co-localized with amyloid-beta. By immunoblotting, expression of ER chaperones was greatly increased as compared to the controls. By immunoprecipitation/immunoblotting experiments, ER chaperones co-immunoprecipitated with AbetaPP. Our studies provide evidence of the UPR in s-IBM muscle and demonstrate for the first time that the ER chaperones calnexin, calreticulin, GRP94, BiP/GRP78, and ERp72 physically associate with AbetaPP in s-IBM muscle, suggesting their playing a role in AbetaPP folding and processing.     

Job Accommodations,Return to Work and Job Retention of People with Physical Disabilities: A Systematic Review

Journal of Occupational Rehabilitation - Purpose We aimed to identify job accommodations that help persons with physical disabilities maintain or return to work and explore the barriers and...