Apoptosis after traumatic human spinal cord injury

OBJECT: Apoptosis is a form of programmed cell death seen in a variety of developmental and disease states, including traumatic injuries. The main objective of this study was to determine whether apoptosis is observed after human spinal cord injury (SCI). The spatial and temporal expression of apoptotic cells as well as the nature of the cells involved in programmed cell death were also investigated. METHODS: The authors examined the spinal cords of 15 patients who died between 3 hours and 2 months after a traumatic SCI. Apoptotic cells were found at the edges of the lesion epicenter and in the adjacent white matter, particularly in the ascending tracts, by using histological (cresyl violet, hematoxylin and eosin) and nuclear staining (Hoechst 33342). The presence of apoptotic cells was supported by staining with the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling technique and confirmed by immunostaining for the processed form of caspase-3 (CPP-32), a member of the interleukin-1beta-converting enzyme/Caenorhabditis elegans D 3 (ICE/CED-3) family of proteases that plays an essential role in programmed cell death. Apoptosis in this series of human SCIs was a prominent pathological finding in 14 of the 15 spinal cords examined when compared with five uninjured control spinal cords. To determine the type of cells undergoing apoptosis, the authors immunostained specimens with a variety of antibodies, including glial fibrillary acidic protein, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), and CD45/68. Oligodendrocytes stained with CNPase and a number of apoptotic nuclei colocalized with positive staining for this antibody. CONCLUSIONS: These results support the hypothesis that apoptosis occurs in human SCIs and is accompanied by the activation of caspase-3 of the cysteine protease family. This mechanism of cell death contributes to the secondary injury processes seen after human SCI and may have important clinical implications for the further development of protease inhibitors to prevent programmed cell death.     

Topographic assessment of irregular astigmatism after photorefractive keratectomy

OBJECTIVE: To correlate new quantitative topographic indexes of corneal irregular astigmatism to best spectacle-corrected visual acuity (BSCVA) following excimer laser photorefractive keratectomy (PRK). SETTING: Department of Ophthalmology, LSU Eye Center, and Refractive Surgery Center of the South, Ear, Nose & Throat Hospital, New Orleans, Louisiana; Manhattan Eye, Ear and Throat Hospital, New York, New York, USA. METHODS: Videokeratography data (TMS-1) were obtained preoperatively and 1, 3, 6, 12, 18, and 24 months postoperatively from 100 eyes having PRK for low to mild myopia. Algorithms measured fine local irregularity with the surface regularity index (SRIp), varifocality with the coefficient of variation of corneal power (CVPp), and central islands with the elevation/depression magnitude (EDM). RESULTS: The SRIp and CVPp increased after surgery and remained significantly higher than the preoperative levels throughout the 24 month follow-up (P < .05). The increase in EDM was significant from 1 to 6 months (P < .05) but not thereafter. Multiple regression analysis revealed that variables having a statistically significant relationship with postoperative BSCVA were CVPp and EDM at 1 month, CVPp at 3 months, and CVPp, haze, and age at 6 months. No statistically significant correlation between any measures of irregular astigmatism and BSCVA was found after 1 year of follow-up. CONCLUSION: The quantitative measures used in this study are sensitive methods by which irregular astigmatism after keratorefractive procedures can be classified, evaluated, and compared.     

Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor

Angiotensin II is the effector molecule of the renin-angiotensin system. Virtually all of its biochemical actions are mediated through a single class of cell-surface receptors called AT1. These receptors contain the structural features of the seven-transmembrane, G-protein-coupled receptor superfamily. Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and activation. Here, we show that a glutathione S-transferase fusion protein containing the carboxyl-terminal 54 amino acids of the rat AT1A receptor physically binds to Jak2 in an angiotensin II-dependent manner. Deletional analysis, using both in vitro protocols and cell transfection analysis, showed that this association is dependent on the AT1A receptor motif YIPP (amino acids 319-322). The wild-type AT1A receptor can induce Jak2 tyrosine phosphorylation. In contrast, an AT1A receptor lacking the YIPP motif is unable to induce ligand-dependent phosphorylation of Jak2. Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT1A receptor. The binding of the AT1A receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intracellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors.     

The evaluation of argon laser photocoagulation in a series of animal models of upper gastrointestinal bleeding

During the past five years we have evaluated argon laser photocoagulation in various canine models of upper gastrointestinal hemorrhage. In gastric erosions, the eight-watt argon laser was uniformly effective in stopping bleeding. In our standard acute ulcer model the seven-watt argon laser was effective in stopping bleeding from most ulcers and only occasionally produced deep injury. With the addition of a jet of CO2 exiting the laser catheter coaxial to the laser beam, the argon laser was 100% effective and no deep injury resulted. The application of the argon laser in a more physiologic canine bleeding model using a single bleeding vessel in an ulcer base is currently under study. The development of improved animal models of gastrointestinal bleeding should contribute to the identification of effective and safe endoscopic hemostatic methods.     

An unusual case of large right atrial myxoma

A case of right atrial myxoma is described. The patient had vague and variable symptoms and it was not until five years after first presentation that she had developed clinical and electrocardiographic evidence of right atrial hypertrophy, and angiocardiographic evidence of a fist-sized myxoma which was subsequently removed surgically.     

The prevalence of diabetes mellitus in three population groups in the Republic of Mali

A new method of estimating intracranial decompensation in man is described. An on-line computer system is connected to an intracranial pressure (ICP) monitoring system to compute regression plots of mean ICP vs standard deviation; standard deviation is used as a measure of ICP instability. Two zones with distinctly different slopes are a characteristic feature of these plots. It is thought that the changes of slope signify intracranial decompensation.     

Acute choroidal ischemia as a complication of photocoagulation

Acute choroidal vascular insufficiency as a complication of photocoagulation has been little noticed. In 17 eyes of 16 patients photocoagulated with either xenon or argon sources for proliferative sickle cell retinopathy, gray lesions of the fundus developed peripheral to the photocoagulation sites. Histologic examination of similar gray lesions produced in monkeys showed necrosis and atrophy of the outer half of the retina. Intense photocoagulation of the human fundus, even with smaller spot sizes, may occlude a choroidal artery, producing separate gray lesions of distinctive shape. The lesions in both the patients and the monkeys progressed to granular hyperpigmentation by two to three weeks after photocoagulation.