Glyceraldehyde-3-phosphate dehydrogenase: Nuclear translocation participates in neuronal and nonneuronal cell death

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein levels increase in particulate fractions in association with cell death in HEK293 cells, S49 cells, primary thymocytes, PC12 cells, and primary cerebral cortical neuronal cultures. Subcellular fractionation and immunocytochemistry reveal that this increase primarily reflects nuclear translocation. Nuclear GAPDH is tightly bound, resisting extraction by DNase or salt treatment. Treating primary thymocytes, PC12 cells, and primary cortical neurons with antisense but not sense oligonucleotides to GAPDH prevents cell death. Because cell-death-associated nuclear translocation of GAPDH and antisense protection occur in multiple neuronal and nonneuronal systems, we propose that GAPDH is a general mediator of cell death and uses nuclear translocation as a signaling mechanism.     

Acute Renal Allograft Rejection Following Pegylated IFN-α Treatment for Chronic HCV in a Repeat Allograft Recipient on Hemodialysis: A Case Report

Interferon alpha (IFN-alpha) can be effective therapy for patients with chronic kidney disease who have chronic hepatitis C (HCV). However, acute allograft rejection has been reported in association with IFN-alpha following kidney transplantation, and therefore IFN therapy is recommended prior to, rather than after, kidney transplantation whenever feasible. The special case of repeat allograft recipients who contract HCV after the first transplantation presents special difficulties. This report features the case of a repeat allograft recipient who presented with neutropenic fevers after 5 months of pegylated IFN-alpha therapy, initiated 6 months following the functional loss of his third graft and the reinitiation of hemodialysis (HD). Physical exam, radiographic and laboratory findings led to allograft nephrectomy. The pathologic findings supported a diagnosis of acute-on-chronic rejection. This represents a rare case of IFN-alpha induced rejection following allograft failure and return to HD in a repeat allograft recipient. It also calls attention to the need for a high index of suspicion for the development of allograft rejection, which may require allograft nephrectomy even after allograft 'failure'.     

Detection of Human T-Lymphotropic Virus (HTLV) tax Sequences in New York City Blood Donors Seronegative for HTLV Types 1 and 2

A potential public health concern is the reported detection of the human T-lymphotropic virus (HTLV) tax gene in the lymphocytes of up to 11% of a low-risk group of New York City blood donors (NYBD). This study aimed to independently confirm the prevalence of HTLV tax sequences in 293 NYBD. All NYBD tested negative for antibodies to HTLV types 1 and 2 and HTLV Tax. HTLV tax sequences were not detected in the NYBD lymphocytes. These data demonstrate the lack of HTLV-1 tax in this group of NYBD at low risk for HTLV infection.     

Biological correlates of deliberate self-harm behaviour: a study of electroencephalographic,biochemical and psychological variables in parasuicide

Clinical, electroencephalographic and biochemical variables were measured in 40 patients who attempted suicide and 27 age-matched controls. Patients had significantly higher scores for depression, hopelessness, neuroticism and psychoticism and lower scores for extraversion than controls. They also had significantly lower contingent negative variation (CNV), higher postimperative negative variation and lower whole blood serotonin values than controls. Within the patient group, vulnerability to parasuicide, as determined by previous or repeated acts of deliberate self-harm, was associated with higher scores for hopelessness and suicide intent, lower scores for extraversion and decreased CNV. Factor analysis revealed significant correlations between psychological variables and auditory evoked potential amplitudes for the vulnerable group. A profile of variables associated with increased risk of self-harm in patients presenting with attempted suicide is proposed from our data.     

Views of problem drinking among Native American,Hispanic, and Anglo children

Native American, Hispanic, and Anglo sixth graders reacting to an example of teenage problem drinking expressed similar beliefs and attitudes in many respects. However, Native American children viewed the problem as less serious, subscribed more to a disease theory of alcoholism, attributed less causal responsibility to the individual, and adopted a less aggressive approach toward treatment than did Hispanic, and especially Anglo, children. Their less conventional value orientations accounted for all these differences except their stronger endorsement of a disease theory of problem drinking.     

Irradiation of rabbit retina with diode and Nd:YAG lasers.

AIMS--This study was carried out to compare the effects of continuous wave infrared laser radiation on pigmented and albino rabbit retinas at two wavelengths: 810 nm (diode) and 1064 nm (Nd:YAG). METHODS--Transpupillary laser pulses were applied with a spot size of 200 microns and durations of 200 ms (pigmented rabbits) and 0.5-1 s (albino rabbits). Light and electron microscopic analyses were performed immediately after exposure. RESULTS--In pigmented rabbits, threshold lesions were induced using a power of 100 mW with the diode and 200 mW with the Nd:YAG lasers. Damage was incurred by the retinal pigment epithelium with extension into the superficial and mid choroid posteriorly and into the outer retina anteriorly. In albino rabbits, lesions of comparable anteroposterior extension were identified using a power of 10 W with the Nd:YAG laser. Using diode laser irradiation, a maximum power output of 1.2 W failed to produce discernible lesions. CONCLUSIONS--The observed patterns of morphological damage are produced by complex tissue radiation interactions. In pigmented animals, this was primarily related to absorption of radiant energy by melanin within the retinal pigment epithelium and the choroidal melanocytes. In albino rabbits, laser induced effects occurred as a consequence of multiple scattering, together with absorption within haemoglobin and possibly also within tissue water. The data obtained provide further insight into the biological mechanisms arising from retinal photocoagulation with near infrared lasers.     

A REPRODUCIBLE MODEL OF CHRONIC REJECTION IN RAT RENAL ALLOGRAFTS

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 668 after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.