PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

BUILDING THE FOUNDATION OF EXCELLENCE IN HEART FAILURE NURSING

This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing."     

The relationship between reproductive state and "sexually" dimorphic brain areas in sexually reproducing and parthenogenetic whiptail lizards

The anterior hypothalamus-preoptic area and ventromedial hypothalamus are sexually dimorphic in the reproductively active whiptail lizard Cnemidophorus inornatus. The anterior hypothalamus-preoptic area, which is involved in the control of male-typical copulatory behaviors, is larger in males, whereas the ventromedial hypothalamus, which is involved in the control of female-typical receptivity, is larger in females. In the parthenogenetic whiptail lizard C. uniparens, which is a direct descendant of C. inornatus and exhibits both male-like and female-like pseudosexual behaviors, both brain areas are comparable in size to those of female C. inornatus. This study was conducted to determine whether these brain areas change in size in either species or sex during a time of year when these animals are reproductively inactive, or after removal of the gonads. In male C. inornatus both brain areas changed during reproductive inactivity (either seasonally or surgically induced) and became equivalent to the size characteristic of reproductively active female C. inornatus. When corrected for brain size, the anterior hypothalamus-preoptic area was significantly smaller in intact hibernating and castrated males than in intact males from the summer breeding season. Conversely, the ventromedial hypothalamus was significantly larger in intact hibernating and castrated males than in intact males from the summer breeding season. The two brain areas were not significantly different among the groups of female C. inornatus or parthenogenetic C. uniparens. These results suggest that 1) the brain of whiptail lizards may differentiate seasonally and 2) the female state may be a neutral one to which the male brain reverts during reproductive inactivity.     

Adenosine and its analogs stimulate phosphoinositide hydrolysis in the kidney

Renal blood flow, glomerular filtration rate and sodium excretion are known to be affected by adenosine. The present studies were undertaken to investigate the actions of adenosine and its analogs (both agonists and antagonists) on phosphoinositide (PI) hydrolysis in the outer medullary slices. Adenosine was found to cause a dose-dependent stimulation of PI hydrolysis (ED50, 2.8 microM) in renal slices from outer medulla. The adenosine analogs 5'-(N-cyclopropyl)-carboxamidoadenosine (NCCA) and 5'-N-ethylcarboxamidoadenosine (NECA) also stimulated PI hydrolysis in renal medulla. Stimulation of PI hydrolysis was blocked by the adenosine antagonists: aminophylline, 1,3-dipropyl-7-methylxanthine (DMX) and 8-(p-sulfophenyl)-theophylline (8-SPT). Caffeine not only antagonized adenosine-stimulated PI hydrolysis but also increased PI hydrolysis independently. These results indicate that adenosine stimulates PI hydrolysis in renal medulla through a receptor-mediated mechanism.     

Sexual behavior and 2-deoxyglucose uptake in male red-sided garter snakes (Thamnophis sirtalis parietalis).

The [14C]2-deoxyglucose (2-DG) technique was used to study patterns of neural activity associated with the species-typical courtship behavior of male red-sided garter snakes (Thamnophis sirtalis parietalis). Males in this species court females intensely during the first month following spring emergence from their prolonged winter hibernation. Autoradiographic methods were used to measure the accumulation of radioactive label in various regions through the brains of male garter snakes that courted females, males that failed to court females, and males not exposed to females. Male garter snakes that actively courted females showed a pronounced increase in 2-DG accumulation, and therefore presumably neural activity, in the region of the anterior hypothalamus/preoptic area, relative to males that did not actively court females. Males exposed to females (regardless of whether they courted or not) showed widespread, non-specific increases in 2-DG uptake relative to males not exposed to females. The results indicate the utility of the 2-DG technique for studying complex, species-typical behaviors in vertebrates.     

Up-regulation of guinea pig myometrial beta-adrenoreceptors by systemic estradiol and progesterone

The effects of systemic administration of 17 beta-estradiol (E2) and progesterone (P) on the concentration and affinity of myometrial beta-adrenoreceptors were studied in non-pregnant, previously oophorectomized guinea pigs receiving a continuous infusion of E2, P, a combination of the two hormones, or placebo for 7 days. Myometrial beta-adrenoreceptors were characterized by using (-)-[125I-cyanopindolol as the specific beta-adrenoreceptor ligand. Compared to that in the control group, E2 administration resulted in a 7-fold increase in the density of myometrial beta-adrenoreceptors. Administration of P alone resulted in a significant increase in both beta-adrenergic receptor concentration and the receptor dissociation constant (Kd). Finally, a combination of E2 and P treatment did not result in any synergistic or additive effect for the beta-adrenergic receptors, while the Kd was twice that of the control or E2-treated animals. We conclude that systemic administration of these sex steroid hormones, directly or indirectly, modulates myometrial beta-adrenergic receptor concentrations and their ligand affinity.     

Blood pressure and retinopathy in type I diabetes

The relationship between blood pressure and diabetic retinopathy was evaluated in 249 young subjects with type I diabetes. Although hypertension is known to be associated with an increased risk for retinopathy, the effects of high-normal blood pressure are unknown. Retinopathy (158 of 249 subjects, 63%) is considerably more common in a young diabetic population than is hypertension (7 of 249 subjects, 2%). Thus, if blood pressure is important in the etiology or progression of diabetic retinopathy, levels below the hypertensive range (less than 141/90 mmHg) must be considered. The combined effect of hypertension and high-normal blood pressure (greater than 90th percentile but less than 141/90 mmHg) was studied. Elevation in diastolic blood pressure, alone, and in combination with elevated systolic blood pressure, correlated significantly (P less than 0.03) with retinopathy. The presence of high-normal blood pressure resulted in a prospectively higher occurrence of retinopathy and of progression of preexisting retinopathy. Glycohemoglobin (HbA1) and duration of diabetes also correlated with retinopathy. Both good glycemic control and maintenance of diastolic blood pressure below the 90th percentile for age may be important in relation to diabetic retinopathy.     

Prevalence of Vision Loss and Associations With Age-Related Eye Diseases Among Nursing Home Residents Aged ≥65 Years

ObjectivesTo examine data from Delaware nursing homes to determine prevalence of age-related eye diseases (AREDs), vision impairment, and blindness and to compare the findings with the results of 11 US investigations of vision and eye health in nursing homes.DesignThis is a cross-sectional, retrospective study of nursing home patients.Setting and ParticipantsTwenty nursing homes in Delaware participated in the study, yielding comprehensive eye examination records for 2019 study participants.MethodsSummary statistics and regression analyses.ResultsThe overall prevalence of vision impairment or blindness was 63.8% and was above 60% for each age, sex, and race category. Prevalence of vision impairment or blindness was 68.4% among patients with cataracts, 69.4% among patients with macular degeneration, 70.5% among patients with glaucoma, and 68.4% among patients with diabetic retinopathy. Prevalence of blindness was 14.1%. Among patients with AREDs, prevalence of blindness ranged from 15.0% for patients with cataracts to 22.6% for patients with diabetic retinopathy. When compared with other investigations, we found wide variation in vision and eye factors reported and wide variation in the prevalence of those factors. Only 4 studies diagnosed both AREDs and visual function. Seven studies reported AREDs, and 7 reported vision impairment and/or blindness. Vision impairment or blindness ranged from 29% to 67%; cataract ranged from 32% to 83%; macular degeneration ranged from 4.6% to 70.7%. Glaucoma ranged from 5.3% to 41.4%; diabetic retinopathy ranged from 1.7% to 3.1%.Conclusions and ImplicationsComprehensive eye examinations showed that vision impairment and blindness affected 63.8% of nursing home residents. Compared with other studies, there was a wide range of vision factors reported and wide variation in the prevalence of vision impairment or blindness and AREDs. This investigation suggests the importance of eye care in nursing homes and the importance of reporting standard vision and eye health factors to inform policy and practice.