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Biomedical subjects

B Cohen

Publications and source records attributed to B Cohen.

At least 181 records · Page 10Linked to original sources

Human metallothionein gene expression determined by quantitative reverse transcription-polymerase chain reaction as a biomarker of cadmium exposure.

Expression of the metallothionein (MT) gene in frozen human lymphocytes has been developed as a new molecular biomarker of heavy metal exposure. Workers at a Polish battery factory with high exposure to cadmium were monitored for airborne exposure and blood cadmium levels. A novel quantitative reverse transcription-PCR (RT-PCR) technique, making use of a homologous internal standard, was used to assess the level of MT-specific mRNA in frozen stored aliquots of blood samples taken from exposed and control workers. Results from this assay showed a statistically significant 2.5-fold increase in MT mRNA in exposed compared to control workers. The RT-PCR results also showed significant correlation with airborne cadmium, as registered on personal monitors and with blood cadmium levels. The results suggest that gene induction measured by quantitative RT-PCR is a promising approach for application as a biomarker of biologically effective dose in small samples of frozen tissues or cells.

Base Sequence↗

Soluble and membrane-anchored forms of the human IFN-alpha/beta receptor.

The recently cloned ligand binding component of the type I human interferon-alpha/beta receptor (IFN-alpha/beta R) and its soluble analogue (p40) were characterized. p40 is a potent inhibitor of type I IFNs and antibodies directed against p40 completely block the activity of type I IFNs in human cells. These antibodies immunoprecipitate cellular 102-kDa (major) and 51-kDa (minor) forms of IFN-alpha/beta R. We find that the 51-kDa IFN-alpha/beta R. Two types of cDNA clones were isolated and sequenced, a 1.5-kb cDNA coding for the transmembrane 51-kDa IFN-alpha/beta R and a 4.5-kb cDNA coding for p40. In addition to ligand binding, IFN-alpha/beta R is directly involved in signaling, because it becomes phosphorylated at Tyr residues on ligand binding and it is physically associated with the cytoplasmic tyrosine kinase JAK1.

Amino Acid Sequence↗

Some contemporary ethical considerations related to organ transplantation.

With the increasing number of transplantable organs and tissues, as well as improvements in transplantation results, has come a severe shortage of organ donors. Consequently, new ethical dilemmas, related to the fair allocation of available organs and the use of alternative sources of donor organs, are of growing concern. Establishing fair allocation priorities is a serious problem in organ transplantation. Ethically, they should be defined by society as a whole rather than exclusively by the medical profession. Proposed solutions for the organ donor shortage, each with their unique ethical constraints, include the use of related donors, partial organ transplantation, cell transplantation using fetal tissue, and the use of animal organs "xenotransplantation ". Commercial trading in donor organs must be regarded as an unethical activity rather than an ethical dilemma since the donors are motivated by monetary rather than by humanitarian reasons. These ethical dilemmas could be largely avoided by an effective reduction in the severe shortage of postmortal organ donations.

Ethics, Medical↗

Ligand-induced association of the type I interferon receptor components.

Two transmembrane polypeptides, IFNAR and IFN-alpha/Beta R, were previously identified as essential components of the type I interferon (IFN) receptor, but their interrelationship and role in ligand binding were not clear. To study these issues, we stably expressed and characterized the two polypeptides in host murine cells. In human cells, native IFN-alpha/beta R is a 102-kDa protein but upon reduction only a 51-kDa protein is detected. In host murine cells human IFN-alpha/beta R was expressed as a 51-kDa protein. Host cells expressing IFN-alpha/beta R bound IFN-alpha 2 with a high affinity (Kd of 3.6 nM), whereas cells expressing IFNAR exhibited no ligand binding. Upon coexpression of IFNAR and the 51-kDa IFN-alpha/beta R, the affinity for IFN-alpha 2 was increased 10-fold, approaching that of the native receptor. We show by cross-linking that both the cloned (51-kDa) and native (102-kDa) IFN-alpha/beta R bind IFN-alpha 2 to form an intermediate product, while IFNAR associates with this product to form a ternary complex. Hence, IFNAR and IFN-alpha/beta R are components of a common type I IFN receptor, cooperating in ligand binding. Ligand-induced association of IFNAR and IFN-alpha/beta R probably triggers transmembrane signaling.

3T3 Cells↗

Effect of exercise training programme on bone mineral density in novice college rowers.

Exercise has important effects on skeletal mineralization. Changes in bone mineral density (BMD) and bone mineral content (BMC) as measured by dual energy X-ray absorptiometry were investigated in a group of 17 male novice college oarsmen over a 7-month period and were compared with eight age-matched controls. The rowing training programme consisted of approximately 8 h rowing, 1 h weight training, and 1 h running per week. After 7 months training the mean BMD of the lumbar spine (L1-L4) had increased significantly by 2.9% (P < 0.001) and the mean BMC had increased by 4.2% (P < 0.001). There was no significant change in the control group. Neither group showed a significant change in BMD or BMC in the femoral neck, greater trochanter or Ward's triangle. This study provides further evidence that exercise plays an important role in bone mineral formation.

Absorptiometry, Photon↗

Semicircular canal contributions to the three-dimensional vestibuloocular reflex: a model-based approach.

1. We studied the contribution of the individual semicircular canals to the generation of horizontal and torsional eye movements in cynomolgus monkeys. Eye movements were elicited by sinusoidal rotation about a vertical (gravitational) axis at 0.2 Hz with the animals tilted in various attitudes of static forward or backward pitch. The gains of the horizontal and torsional components of the vestibuloocular reflex (VOR) were measured for each tilt position. The gains as a function of tilt position were fit with sinusoidal functions, and spatial gains and phases were determined. After control responses were recorded, the semicircular canals were plugged, animals were allowed to adapt, and the test procedure was repeated. Animals were prepared with only the anterior and posterior canals intact [vertical canal (VC) animals], with only the lateral canals intact [lateral canal (LC) animal], and with only one anterior and the contralateral posterior canals intact [right anterior and left posterior canal (RALP) animals; left anterior and right posterior canal (LARP) animals]. 2. In normal animals, the gain of the horizontal (yaw axis) velocity of the compensatory eye movements decreased as they were pitched forward or backward, and a torsional velocity appeared, reversing phase at the peak of the horizontal gain. After the anterior and posterior canals were plugged (LC animal), the horizontal component was reduced when the animal was tilted backward; the gain was zero with about -60 degrees of backward tilt. The spatial phase of the torsional component had the same characteristics. This is consistent with the fact that both responses were produced by the lateral canals, which from our results are tilted between 28 and 39 degrees above the horizontal stereotaxic plane. 3. After both lateral canals were plugged (VC animals), horizontal velocity was reduced in the upright position but increased as the animals were pitched backward relative to the axis of rotation. Torsional velocities, which were zero in the upright position in the normal animal, were now 180 degrees out of phase with the horizontal velocity. The peak values of the horizontal and torsional components were significantly shifted from the normal data and were closely aligned with each other, reaching peak values at approximately -56 degrees pitched back (-53 degrees horizontal, -58 degrees torsional). The same was true for the LARP and RALP animals; the peak values were at -59 degrees pitched back (-55 degrees horizontal, -62 degrees torsional). Likewise, in the LC animal the peak yaw and roll gains occurred at about the same angle of forward tilt, 35 degrees (30 degrees horizontal, 39 degrees torsional). Thus, in each case, the canal plugging had transformed the VOR from a compensatory to a direction-fixed response with regard to the head. Therefore there was no adaptation of the response planes of the individual canals after plugging. 4. The data were compared with eye velocity predictions of a model based on the geometric organization of the canals and their relation to a head coordinate frame. The model used the normal to the canal planes to form a nonorthogonal coordinate basis for representing eye velocity. An analysis of variance was used to define the goodness of fit of model predictions to the data. Model predictions and experimental data agreed closely for both normal animals and for the animals with canal lesions. Moreover, if horizontal and roll components from the LC and VC animals were combined, the summation overlay the response of the normal monkeys and the predictions of the model. In addition, a combination of the RALP and LARP animals predicted the response of the lateral-canal-plugged (VC) animals. 5. When operated animals were tested in light, the gains, peak values, and spatial phases of horizontal and roll eye velocity returned to the preoperative values, regardless of the type of surgery performed. This indicates that vision compensated for the lack o

Animals↗

Symptomatic spinal epidural lipomatosis in a patient with Cushing's disease.

Spinal epidural lipomatosis (SEL) is a rare complication of iatrogenic Cushing's syndrome (CS). There is only one case reported of symptomatic SEL in association with endogenous CS. We present a patient with compressive myeloradiculopathy due to SEL and Cushing's disease and suggest that in SEL of hypercortisolism, the excess of corticosteroids is the stimulus for the growth of adipose tissue in the spinal canal and that treatment should be aimed at correcting the endocrine abnormality.

Adult↗

Bone remodelling in the proximal femur after Charnley total hip arthroplasty.

We measured bone mineral density (BMD) in the proximal femur by dual-energy X-ray absorptiometry (DEXA) in 20 patients after cemented total hip arthroplasty over a period of one year. We found a statistically significant reduction in periprosthetic BMD after six months on the medial side and on the lateral side adjacent to the mid and distal thirds of the prosthesis. At one year after operation there was a mean 6.7% reduction in BMD in the region of the calcar and a mean 5.3% increase in BMD in the femoral shaft distal to the tip of the implant. These changes reflect a pattern of reduced stress in the proximal femur and increased stress around the tip of the prosthesis. They support current concepts of bone remodelling in the proximal femur in response to prosthetic implantation.

Absorptiometry, Photon↗