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Biomedical subjects

T George

Publications and source records attributed to T George.

At least 19 recordsLinked to original sources

Nerve growth factor inhibits HCO3- absorption in renal thick ascending limb through inhibition of basolateral membrane Na+/H+ exchange.

Nerve growth factor (NGF) inhibits transepithelial HCO3- absorption in the rat medullary thick ascending limb (MTAL). To investigate the mechanism of this inhibition, MTALs were perfused in vitro in Na+-free solutions, and apical and basolateral membrane Na+/H+ exchange activities were determined from rates of pHi recovery after lumen or bath Na+ addition. NGF (0.7 nM in the bath) had no effect on apical Na+/H+ exchange activity, but inhibited basolateral Na+/H+ exchange activity by 50%. Inhibition of basolateral Na+/H+ exchange activity with ethylisopropyl amiloride (EIPA) secondarily reduces apical Na+/H+ exchange activity and HCO3- absorption in the MTAL (Good, D. W., George, T., and Watts, B. A., III (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 12525-12529). To determine whether a similar mechanism could explain inhibition of HCO3- absorption by NGF, apical Na+/H+ exchange activity was assessed in physiological solutions (146 mM Na+) by measurement of the initial rate of cell acidification after lumen EIPA addition. Under these conditions, in which basolateral Na+/H+ exchange activity is present, NGF inhibited apical Na+/H+ exchange activity. Inhibition of HCO3- absorption by NGF was eliminated in the presence of bath EIPA or in the absence of bath Na+. Also, NGF blocked inhibition of HCO3- absorption by bath EIPA. We conclude that NGF inhibits basolateral Na+/H+ exchange activity in the MTAL, an effect opposite from the stimulation of Na+/H+ exchange by growth factors in other systems. NGF inhibits transepithelial HCO3- absorption through inhibition of basolateral Na+/H+ exchange, most likely as the result of functional coupling in which primary inhibition of basolateral Na+/H+ exchange activity results secondarily in inhibition of apical Na+/H+ exchange activity. These findings establish a role for basolateral Na+/H+ exchange in the regulation of renal tubule HCO3- absorption.

Absorption

Are MAO-A deficiency states in the general population and in putative high-risk populations highly uncommon?

Lack of monoamine oxidase A (MAO-A) due to either Xp chromosomal deletions or alterations in the coding sequence of the gene for this enzyme are associated with marked changes in monoamine metabolism and appear to be associated with variable cognitive deficits and behavioral changes in humans and in transgenic mice. In mice, some of the most marked behavioral changes are ameliorated by pharmacologically-induced reductions in serotonin synthesis during early development, raising the question of possible therapeutic interventions in humans with MAO deficiency states. At the present time, only one multi-generational family and a few other individuals with marked MAO-A deficiency states have been identified and studied in detail. Although MAO deficiency states associated with Xp chromosomal deletions were identified by distinct symptoms (including blindness in infancy) produced by the contiguous Norrie disease gene, the primarily behavioral phenotype of individuals with the MAO mutation is less obvious. This paper reports a sequential research design and preliminary results from screening several hundred volunteers in the general population and from putative high-risk groups for possible MAO deficiency states. These preliminary results suggest that marked MAO deficiency states are very rare.

Adolescent

Management of phacolytic glaucoma: experience of 135 cases.

We retrospectively analyzed 135 eyes with phacolytic glaucoma. A trabeculectomy was added to standard cataract surgery if symptoms endured for more than seven days, or if preoperative control of intraocular pressure (IOP) with maximal medical treatment was inadequate. In the early postoperative period, IOP was significantly lower in the combined surgery group (89 eyes) compared to the cataract surgery group (46 eyes) (p < 0.001). At 6 months there was no difference in IOP or visual acuity between the two groups. There were no serious complications related to trabeculectomy. It is reasonable to conclude that in eyes with a long duration of phacolytic glaucoma, addition of a trabeculectomy to cataract surgery is safe, prevents postoperative rise in intraocular pressure and decreases the need for systemic hypotensive medications. A randomized trial is on to further address this question.

Adult

Saphenous vein covered stenting for right coronary artery lesion containing thrombus.

Vein covered stenting to close coronary pseudoaneurysm and perforation and in the setting of acute myocardial infarction have been described. This case report describes saphenous vein covered stenting to exclude a large thrombus in a right coronary artery lesion. Vein covered stenting may be considered as an option when dealing with a thrombus containing lesion.

Aneurysm, False

Role of murine NK cells and their receptors in hybrid resistance.

Hybrid resistance refers to the rejection of parental strain bone marrow cells by natural killer cells of mice that are F1 hybrids derived from two inbred parental strains. This pattern of rejection is not seen in solid organ transplants. Progress in understanding this exception to the laws of transplantation genetics has occurred with the recent discovery of negative signaling receptors for MHC class I molecules. In the last year the discovery of natural killer cell subsets with non-overlapping inhibitory receptors for parental class I molecules has provided an explanation for hybrid resistance. In some instances, however, positive rather than negative signaling seems to be the basis for rejection of allogeneic as well as parental marrow cell grafts.

Animals

Allorecognition by murine natural killer cells: lysis of T-lymphoblasts and rejection of bone-marrow grafts.

Natural killer (NK) cells of inbred mice reject allogeneic bone-marrow cells, and NK cells of F1 hybrid mice can reject parental bone-marrow cells (hybrid resistance). In some cases these patterns of rejection can be mimicked in vitro by utilizing IL-2 cultured NK effector cells and allogeneic or parental T-lymphoblasts as target cells. Lysis of allogeneic and parental targets in vitro can be explained on the basis of the missing self hypothesis. Subsets of NK cells that bear non-overlapping MHC class I inhibitory receptors belonging to the Ly49 family lyse allogeneic targets because they do not express self class I molecules of the NK cell donor. Parental strain targets are lysed because they do not express all of the self class I antigens of the F1 hybrid, and hence fail to deliver inhibitory signals to all subsets of F1 NK cells. The expression of Ly49 receptors on NK cells is regulated by host MHC to ensure maximal sensitivity to alterations in self class I molecules and to prevent autoreactivity. In many instances, however, the rejection of allogeneic bone marrow cells in vivo cannot be readily explained by the missing self hypothesis. In these instances, it appears that rejection is initiated by class I MHC receptors on NK cells that recognize allogeneic class I molecules as non-self, and activate rather than inhibit NK cell function.

Animals

Interspecific hybridization in poeciliids.

Seventy per cent attempts to ensure interspecific hybridization between Poecilia velifera and P. sphenops were successful and led to the production of true hybrids, but not gynogens or triploids, as evidenced by the mottled or striped colour, chromosome number (2n = 46) and response from scale transplantation. Most hyrbids were infertile as they failed to cross among themselves or with their respective parents; however they were more closely related to P. sphenops as indicated by mating responses and scale transplantation studies. Heterospecific impregnation resulted in 40% reduction in fecundity but retention of interparturition period characteristic of the female species. A skewed ratio of 3 Female Female:2 Male Male, observed in the laboratory populations of both P. velifera and P. sphenops, was also sustained among the progenies sired from heterospecifically inseminated females. The colour patterns of hybrids were of two types: mottled and striped, the latter one being reported for the first time.

Animals

VISTECH contrast sensitivity testing in primary open angle glaucoma.

Contrast sensitivity has been recommended as a screening and diagnostic test in primary open angle glaucoma (POAG). We tested contrast sensitivity (CS) using Vistech charts in 184 eyes of 95 patients. Three groups were examined--established primary open angle glaucoma, glaucoma suspects and age matched controls. The distribution of contrast sensitivities amongst the three groups were similar. The median contrast sensitivity of glaucoma suspects and controls were well within normal limits while that of the POAG group fell along the lower limit of normal. In all three groups the younger subjects scored better than the older, indicating a depression of contrast sensitivity with increasing age. Even if depression of any one spatial frequency was considered abnormal, the test yielded a sensitivity of 55.4% and specificity of 69.5%. Similarly contrast sensitivity testing was found to be of little use in detecting field defects a maximum sensitivity of 47.3% and specificity of 73.3%. Vistech contrast sensitivity testing is not a useful test in POAG screening or diagnosis.

Adult

Facilitation of parental-strain marrow engraftment by T cells of neonatally-tolerant mice.

T cells present in bone marrow cell (BMC) grafts promote engraftment in histoincompatible hosts, but they or other T cells may also initiate lethal graft-vs.-host disease (GVHD). The purpose of this study was to determine whether T cells from donors tolerant of host alloantigens were able to prevent natural killer (NK) cell-mediated rejection of BMC grafts without causing GVHD. Previous studies have shown that H2d C.B-17 SCID BMC grafts were rejected by (BALB/c x B6)F1 (CB6F1,H2d/b) host NK cells, and that this rejection was reversed by adding H2d T cells to the donor inoculum. T cells tolerant of H2d/b alloantigens were produced by irradiating (3 Gy) BALB/c newborn mice, and infusing CB6F1 BMCs. Tolerance was assessed by donor (H2b+) cell chimerism, acceptance of CB6F1 skin grafts, the inability of adoptively transferred lymphocytes to initiate GVHD in irradiated CB6F1 mice, and the inability of spleen or thymus cells to generate cytolytic T lymphocytes against H2b target cells in vitro. Whole or H2-Kb-depleted BMCs isolated from tolerant donors were able to proliferate in both BALB/c and H2b/d (C57BL/6 x DBA/2)F1 hosts as determined by incorporation of a radiolabelled DNA precursor in the spleen. Furthermore, thymocytes from tolerant donors were able to prevent rejection of H2d SCID BMCs. Because the percentage of donor F1 cells was so high in these chimeras, we generated BALB/c to CB6F1 SCID BMC chimeras; the percentage of BALB/c cells was approximately 100%, the BMCs grew well in irradiated CB6F1 hosts, and their lymph node cells failed to cause a graft-vs.-host (GVH) reaction in CB6F1 hosts. Thus, GVHD may be prevented without inhibiting the ability of donor T cells to promote engraftment. Perhaps separate T cells, or separate functions of a common T cell subset, induce GVHD and enhance engraftment of stem cells.

Animals

Eosinophilic vasculitis in connective tissue disease.

BACKGROUND: Neutrophilic and lymphocytic vascular inflammation is common in vasculitis associated with connective tissue disease (CTD). We recently identified eight patients with CTD and eosinophilic vasculitis. OBJECTIVE: The purpose of this study was to characterize a variant form of vasculitis in CTD with eosinophilic infiltration. METHODS: Of 98 CTD patients with cutaneous necrotizing vasculitis, eight were found with predominantly eosinophilic vascular infiltration. Nine CTD patients with cutaneous neutrophilic vasculitis were identified for comparison. Clinical and laboratory findings were reviewed and compared. Indirect immunofluorescence for eosinophil granule major basic protein (MBP), neutrophil elastase, and mast cell tryptase was performed on lesional tissue. MBP levels and eosinophil survival enhancing activity were assayed in sera from three patients. RESULTS: The patients with eosinophilic vasculitis had depressed serum complement levels and peripheral blood eosinophilia; MBP levels were elevated in serum and eosinophil survival was prolonged. Immunofluorescence of tissue showed marked angiocentric eosinophil MBP staining with peripheral neutrophil elastase staining; mast cell tryptase staining was notably absent. The patients with neutrophilic vasculitis were variably hypocomplementemic and did not have peripheral blood eosinophilia. Immunofluorescence showed marked angiocentric neutrophil elastase staining with scattered eosinophil MBP staining; mast cell tryptase staining showed normal mast cell numbers. CONCLUSION: Patients with eosinophilic vasculitis, CTD, and hypocomplementemia show vessel wall destruction in association with vessel wall deposition of cytotoxic eosinophil granule MBP, which suggests that eosinophils mediate vascular damage in this disease process. In addition, perivascular mast cells appear diminished, thereby suggesting that mast cell degranulation occurs.

Adult

The role of Ly49A and 5E6(Ly49C) molecules in hybrid resistance mediated by murine natural killer cells against normal T cell blasts.

We address the mechanism of hybrid resistance (HR) in vitro using NK effector cells and target lymphoblasts from H-2b, H-2d, and H-2b/d mice. The 5E6 (Ly49C)+ subset of F1 NK cells lyse BALB/c (H-2d) but not B6 (H-2b) targets unless either anti-5E6 or anti-H-2Kb MAbs are present. H-2Dd transgenic B6 (D8) targets are not susceptible to F1 Ly49A+ effectors. Furthermore, 5E6+ Ly49A+ F1 effectors lyse B6 and BALB/c targets only in the presence of anti-5E6 and anti-Ly49A MAbs, respectively. Thus, recognition of H-2Kb by 5E6 and H-2Dd by Ly49A transduce independent inhibitory signals. Moreover, anti-5E6 MAbs enable 5E6+ BALB/c NK cells to lyse (BALB/c x B6)F1 targets. These data support the "missing self" and not the "hemopoietic histocompatibility antigen" hypothesis for HR. In addition, 5E6+ NK cells from BALB/c and BALB.B, but not B6 or (BALB/c x B6)F1, mice receive negative signals from both H-2d and Kb class I antigens. Thus, allelic differences in 5E6 (C57BL versus BALB) may regulate recognition events by NK cells.

Alleles

The flashlight test and van Herick's test are poor predictors for occludable angles.

OBJECTIVE: To determine the reliability and validity of the flashlight test and van Herick's test in detecting occludable anterior chamber angles. METHODS: The flashlight test, van Herick's test and gonioscopy were performed independently by two observers on 96 consecutive new patients in our outpatient clinic. Interobserver agreement was determined using the weighted Kappa statistic. Using the glaucoma specialist's assessment of occludability of the angle (assessed by gonioscopy) as a gold standard, the sensitivities and specificities of the two tests were calculated. RESULTS: All three tests showed good agreement (Kappa more than 0.75). The sensitivity and specificity on the flashlight test were 45.5% and 82.7% respectively. For the van Herick's test they were 61.9% and 89.3%. CONCLUSION: The flashlight test and van Herick's test are of limited use as screening tests for occludable angles.

Adolescent

Regulation of HCO3- absorption by prostaglandin E2 and G proteins in rat medullary thick ascending limb.

Arginine vasopressin (AVP) inhibits HCO3- absorption (JHCO3) in the medullary thick ascending limb (MTAL) of the rat by increasing adenosine 3', 5'-cyclic monophosphate. Hyperosmolality also inhibits JHCO3 via a pathway additive to inhibition by AVP. To determine whether these regulatory effects are modulated by prostaglandin E2 (PGE2), MTAL were isolated and perfused in vitro with 25 mM HCO3- solutions (pH 7.4; 290 mosmol/kgH2O). PGE2 (10(-6) M in the bath) had no effect on JHCO3 in the absence of AVP. In contrast, with 10(-10) MAVP in the bath solution, addition of 10(-8) or 10(-6) M PGE2 to the bath increased JHCO3 from 9.7 +/- 0.8 to 14.3 +/- 1.1 pmol.min-1.mm-1 (P < 0.001). In the presence of AVP and hyperosmolality (75 mM NaCl added to perfusate and bath), PGE2 increased JHCO3 from 1.4 +/- 0.1 to 7.5 +/- 0.5 pmol.min-1.mm-1 (P < 0.005). PGE2 also stimulated JHCO3 in the presence of AVP and hypertonic urea. Cholera toxin (CTX, 10(-12)-10(-9) M in the bath) inhibited JHCO3 by 40%, and this inhibition was reversed by PGE2. PGE2 did not reverse inhibition of JHCO3 by forskolin. The stimulation of JHCO3 by PGE2 in the presence of AVP was blocked by pretreatment with pertusis toxin (PTX, 2 x 10(-11) or 10(-8) M). Neither CTX nor PTX affected inhibition of JHCO3 by hyperosmolality. These results demonstrate that PGE2 reverses inhibition of JHCO3 by AVP by acting via a PTX-sensitive G protein (presumably Gi) to inhibit AVP-stimulated adenosine 3', 5'-cyclic monophosphate production. PGE2 may act as a counterregulatory factor to maintain a stable rate of HCO3- absorption in the MTAL during antidiuresis when circulating AVP levels and medullary osmolality are elevated.

Absorption

A comparison of reinforcer assessment methods: the utility of verbal and pictorial choice procedures.

We compared three methods of stimulus preference assessment for verbal children and specifically evaluated the utility of a verbal choice procedure for assessing relative reinforcer value. Using a token system, relative preference for five categories of reinforcers, representing 15 different stimuli, was assessed by three methods: a reinforcer survey, a verbal stimulus-choice questionnaire, and a pictorial stimulus-choice procedure. Results showed that the verbal and pictorial stimulus-choice assessments accurately identified high- and low-preference categories for 3 of 4 participants. Survey results alone often rated multiple categories as high preference, were less likely to identify low-preference categories, and were less likely to correspond with the results of a reinforcer assessment.

Attention Deficit Disorder with Hyperactivity

Deposition of eosinophil granule proteins precedes blister formation in bullous pemphigoid. Comparison with neutrophil and mast cell granule proteins.

Eosinophils, neutrophils, and mast cells have all been implicated in the pathogenesis of bullous pemphigoid (BP). To comparatively characterize the involvement of these cells in BP, 10 lesional skin biopsy specimens were identified retrospectively and studied for tissue localization of eosinophil, neutrophil, and mast cell granule proteins. Subsequently, multiple skin biopsies of lesions in various developmental stages were obtained from 3 patients with untreated BP. Involved and uninvolved skin specimens were also obtained from 2 patients. Using indirect immunofluorescence, retrospectively identified lesions showed eosinophils and extracellular granule protein deposition prominently in areas of blistering. Evolving lesions showed eosinophil granule protein deposition in all stages but was most marked in early erythematous and prebullous (urticarial) lesions and was minimal in uninvolved skin. Vascular cell adhesion molecule-1, E-selectin, and P-selectin were detected on vessels and very late activation antigen-4 was detected on mononuclear cells and eosinophils by immunoperoxidase staining of lesions. Eosinophil granule proteins were increased in the peripheral blood, urine, and blister fluid. Blister fluids caused increased eosinophil survival that was inhibited by antibodies to interleukin-5 and interleukin-3. Although neutrophil and mast cell infiltration was observed, extracellular granule protein deposition from these cells was minimal except in two specimens. These results demonstrate that eosinophils infiltrate and deposit granule proteins early in the development of BP lesions, that eosinophil-activating cytokines are present in blister fluid, and that eosinophil-selective adhesion molecules are present. These studies strongly support a role for eosinophils in blister formation in BP.

Aged

Vitreous opacities in phacolytic glaucoma.

BACKGROUND AND OBJECTIVE: To report five cases of vitreous opacification in phacolytic glaucoma (PG). PATIENTS AND METHODS: The records of patients with PG were retrospectively reviewed. A total of 135 eyes with PG were studied to determine the presence of vitreous opacification. RESULTS: Five eyes with PG demonstrated opacification of the vitreous, which was first noted at surgery and confirmed postoperatively. All patients had had symptoms of PG for 7 days or more (mean +/- SD, 10.6 +/- 2.4 days) before they sought medical attention. Three eyes had a hypopyon on preoperative examination; two of these eyes showed refractile crystals in the anterior chamber. The opacities resolved spontaneously in all five eyes over a period of 12 weeks and interfered with visual activity only in the immediate postoperative period. CONCLUSION: Vitreous opacification in PG is a self-limited process that may not require surgical intervention unless more rapid visual rehabilitation is desired. The vitreous opacification probably results from an exaggeration of the process causing the anterior chamber reaction.

Aged