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Biomedical subjects

S Kushner

Publications and source records attributed to S Kushner.

13 recordsLinked to original sources
PubMed1999

Implication of the GABA(B) receptor in gamma vinyl-GABA's inhibition of cocaine-induced increases in nucleus accumbens dopamine.

Previously, we demonstrated that gamma vinyl-GABA (GVG, Vigabatrin) dose-dependently inhibits cocaine-induced increases in dopamine (DA) concentrations in both the rodent and primate brain. Furthermore, it abolishes cocaine self-administration and conditioned place preference, while having no effect on locomotor activity or drug delivery to the brain. In an effort to better understand the mechanisms underlying this inhibition, we examined the effect of the selective GABA(B) receptor antagonist SCH 50911 on the GVG-induced decrease in cocaine's elevation of extracellular DA concentrations in the nucleus accumbens (NACC). Cocaine administration alone (20 mg/kg i.p.) produced a 480% increase in extracellular NACC DA levels. GVG (300 mg/kg i.p.) significantly reduced this increase by 25% (P<0.01). In sharp contrast, extracellular DA levels increased to 550% after the sequential administration of SCH 50911 (3 mg/kg i.p.), GVG, and cocaine. This increase is significantly different than GVG and cocaine (P<0.05) but similar to cocaine alone. These results demonstrate that the GABA(B) antagonist SCH 50911 was able to completely abolish GVG's inhibition of cocaine-induced increases in DA in the NACC and implicates the GABA(B) receptor in the mechanism underlying this inhibition.

Animals↗
PubMed1998

Specificity of diastereomers of [99mTc]TRODAT-1 as dopamine transporter imaging agents.

Recently, we reported the first human study of [99mTc]TRODAT-1, technetium, 2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2- yl]methyl](2-mercaptoethyl)amino]ethyl]amino]-ethanethiolato(3-)-o xo- [1R-(exo-exo)]-, as an imaging agent of central nervous system (CNS) dopamine transporters. Due to the existence of several chiral centers on this molecule, upon the formation of [99mTc]TRODAT-1 complex (2) several diastereomers could be created. Two major diastereomers of [99mTc]TRODAT-1 (2), designated as peak A (2A) and peak B (2B), were separated by HPLC. Biodistribution of the purified diastereomers 2A,B was evaluated in rats. It appears that 2A displayed a higher lipophilicity than 2B (PC = 305 and 229, respectively), and a similar trend was observed for the initial brain uptake at 2 min postinjection (0.50% and 0.28% dose/organ for 2A,B, respectively). At 60 min post-iv-injection, the specific uptakes, as measured by [striatum - cerebellum]/cerebellum ([ST-CB]/CB) ratio, were 1.72 and 2.79 for 2A,B, respectively. The higher [ST-CB]/CB ratio observed for 2B was corroborated by the results of an in vitro binding assay. Higher binding affinity for dopamine transporters was observed for 3B (Ki = 13.87 and 8.42 nM for the analogous rhenium complexes 3A,B, respectively). The structure of the [99mTc]TRODAT-1 complexes was deduced using nonradioactive rhenium as a surrogate for radioactive technetium complex. Reacting free TRODAT-1 ligand with [Bu4N][ReOCl4] yielded two major complexes: Re-TRODAT-1A (3A) and Re-TRODAT-1B (3B) (corresponding with peaks A and B of [99mTc]TRODAT-1, respectively), whose structures were determined by X-ray analysis. The X-ray structures show that both complexes have a pseudo-square-pyramidal structure of [RevO]3+N2S2 core with oxygen occupying the apical position and the N-alkyl substitution in syn-configuration to the oxo-rhenium bond. In conclusion, TRODAT-1 formed at least two diastereomers after complexing with a metal(V)-oxo (M = 99mTc, Re) center core. The two isomers display different binding affinities toward dopamine transporters and distinct properties of localization in the striatum area of the brain where the transporters are located.

Animals↗
PubMed1998

Race and delayed kidney allograft function.

BACKGROUND: Allograft survival among black recipients is poorer than among whites. Delayed allograft function is associated with a significant reduction in renal allograft survival. The relationship between delayed allograft function and black race is incompletely specified and was the focus of this investigation. METHODS: A non-concurrent study of 325 recipients of cadaveric allografts followed for the occurrence of delayed allograft function defined as dialysis during the first week following transplantation for the principal analysis. A secondary definition of delayed allograft function was formulated based on the serum creatinine 2 weeks after transplantation. Unadjusted and adjusted logistic regression analysis were used to examine the unconfounded relationship between race and delayed allograft function. RESULTS: Fifty-seven of 91 (62.6%) black recipients experienced delayed allograft function compared to 113 of 234 (48.3%) whites. The odds ratio for black race as a predictor of delayed allograft function was 1.80, P=0.02, (95% CI, 1.09, 2.95). This finding was stable despite adjustment for other predictors of delayed allograft function in a multivariate model, but the precision of this estimate was less (P=0.10) because of missing data. Additionally, adjusted models with imputed values for missing covariates, models using a secondary definition of delayed allograft function, and models excluding patients whose cyclosporin therapy was delayed, all consistently demonstrated a similar association between black race and delayed allograft function. CONCLUSIONS: This study demonstrated an increased risk of delayed allograft function among black recipients. This relationship may play a role in the poorer allograft outcomes experienced by black recipients. Given the negative effect of delayed allograft function on allograft survival, efforts to identify its modifiable risk factors should be a high priority.

Adult↗
PubMed1996

Delayed function reduces renal allograft survival independent of acute rejection.

BACKGROUND: Mechanisms by which delayed allograft function reduces renal allograft survival are poorly understood. This study evaluated the relationship of delayed allograft function to acute rejection and long-term survival of cadaveric allografts. METHODS: 338 recipients of cadaveric allografts were followed until death, resumption of dialysis, retransplantation, loss to follow-up, or the study's end, which ever came first. Delayed allograft function was defined by dialysis during the first week following transplantation. Multivariate Cox proportional hazards survival analysis was used to assess the relationship of delayed allograft function to rejection and allograft survival. RESULTS: Delayed allograft function, recipient age, preformed reactive antibody levels, prior kidney transplantation, recipient race, rejection during the first 30 days and rejection subsequent to 30 days following transplantation were predictive of allograft survival in multivariate survival models. Delayed allograft function was associated with shorter allograft survival after adjustment for acute rejection and other covariates (relative rate of failure [RR]+1.72 [95% CI, 1.07, 2.76]). The adjusted RR of allograft failure associated with any rejection during the first 30 days was 1.99 (1.23, 3.21), and for rejection subsequent to the first 30 days was 3.53 (2.9 08, 6.00). The impact of delayed allograft function did not change substantially (RR=1.84 [1.15, 2.95]) in models not controlling for acute rejection. These results were stable among several subgroups of patients and using alternative definitions of allograft survival and delayed allograft function. CONCLUSIONS: This study demonstrates that delayed allograft function and acute allograft rejection have important independent and deleterious effects on cadaveric allograft survival. These results suggest that the effect of delayed allograft function is mediated, in part, through mechanisms not involving acute clinical rejection.

Acute Disease↗
PubMed1993

Spatial arrangement and metabolic capacity of fiber types in self-reinnervated cat muscle.

The recovery potential of skeletal muscle was explored by examining cat muscle between 10 and 33 mo after complete transection and immediate surgical reunion of its own nerve. Biochemical analysis of single muscle fibers showed that the activities of key enzymes in energy metabolism (malate and lactate dehydrogenase and adenylokinase) were similar to normal for their respective fiber types, suggesting that incomplete recovery of the ability to sustain submaximal contraction in reinnervated muscles (T.C. Cope, C.B. Webb, and B.R. Botterman. J. Neurophysiol. 65: 648-656, 1991) is explained in some other way. Two independent statistical procedures for assessing the randomness of adjacencies of histochemically identified fiber types showed type grouping in some areas, but there were also many regions with randomly distributed fiber types. These findings demonstrate the potential for substantial recovery of both energy metabolism and dispersion of fiber types after self-reinnervation.

Animals↗
PubMed1988

Axial malalignment in femoral neck fractures. An experimental study.

Varus, valgus, and retroversion-anteversion displacements of femoral neck fractures are easily identified on standard AP and lateral radiographs, but rotational malalignments are frequently overlooked. Alterations of the normal appearance of the trabecular systems will indicate rotatory malalignments. A misleading picture of what seems to be severe osteoporosis may actually be due to malrotation and disappearance of the normal trabecular pattern on radiograph.

Bone Nails↗
PubMed1987

Radiation repair in human endothelial cells.

Damage to blood vessels caused by ionizing radiation is considered to be an important dose limiting factor for late effects in many organs. However, the radiation response of the endothelial cells which line the vasculature has not been well-documented, particularly for human endothelial cells. In the present study, human endothelial cells were obtained from fresh umbilical cords and cultured in monolayer. Immunofluorescent staining of factor VIII antigen was used to verify the endothelial nature of the cultured cells. The cells were irradiated with Cs-137 rays (1.35 Gy/min) in plateau phase to determine radiation sensitivity and ability to repair potentially lethal damage (PLD) and sub-lethal damage (SLD). The endothelial cells demonstrated moderate radiosensitivity that varied slightly between different cords. As demonstrated by delayed plating experiments, PLD repair ability was substantial, with repair factors of 0.70-0.80. SLD repair capability, as demonstrated by split dose experiments, was relatively modest. A survival enhancement of 2.0-2.2, for example, was observed when 8 Gy single dose survival was compared to two 4 Gy doses. In terms of PLD and SLD repair as well as initial slope (alpha) the endothelial cells were similar to normal human lung and skin fibroblasts previously studied. Compared to malignant cell lines, PLD repair was generally larger whereas the initial slope (alpha) was intermediate-steeper than the radioresistant tumor types but shallower than the more sensitive tumor derived cells.

Cell Survival↗
PubMed1980

Anxiety, prospective remembering, and performance of planned actions.

This study contrasted two models of prospective remembering: i.e., remembering in the future to perform an action that has been planned. High anxiety or discomfort is predicted by the first model to be associated with forgetting, and by the second model to be associated with remembering but not performing. Questionnaire data from 73 male and female college students support the second model (p < .01). For planned actions that were forgotten, there was an inverse relationship between importance and comfortableness (p < .01). Prospective remembering may be facilitated by reducing potential conflict between the importance and comfortableness of a planned action, involving other persons, and utilizing external retrieval cues.

Adult↗
PubMedDate not supplied

Genetic linkage between X-chromosome markers and bipolar affective illness.

A pedigree study shows close linkage of bipolar affective illness (manic depression) to the X-chromosome markers colour blindness and glucose-6-phosphate dehydrogenase deficiency. The maximum lod score ranges from 7.52 (assuming homogeneity) to 9.17 (assuming heterogeneity); that is, the odds in favour of linkage range between 3 X 10(7) to 1 and 10(9) to 1. These results provide confirmation that a major psychiatric disorder can be caused by a single genetic defect. As a possible first step in characterizing the primary genetic abnormality, this finding may have important implications for the aetiology, nosology, pathophysiology and, possibly, prevention and treatment of bipolar affective disorder. It also provides a means for identifying and characterizing homogeneous populations of patients and may help in clarifying aetiological heterogeneity.

Bipolar Disorder↗
PubMedDate not supplied

Relationship of turnout to hip abduction in professional ballet dancers.

The ability to externally rotate or turn out the hip is fundamental to ballet. Every classical dancer aims to achieve perfect turnout. The purpose of this study was to determine how much turnout is necessary for maximal abduction. It was hypothesized that moderate turnout is sufficient for this purpose. Twenty-two professional dancers from the Alberta Ballet Company were studied. Measurements of passive hip abduction were taken at 0 degree, 45 degrees, 60 degrees, 70 degrees, 80 degrees, 90 degrees and maximum hip lateral rotation using a goniometer and Leighton flexometer. Statistical analysis was done using Pearson correlation coefficients. A significant positive correlation was found between abduction and lateral rotation (P less than 0.05). The greater the position of external rotation, the more abduction achieved. In conclusion, the traditional emphasis on good turnout has some scientific merit and functional implications.

Adult↗
PubMedDate not supplied

Hyperthermia, chemotherapeutic agents and oncogenic transformation.

The modulating effects of hyperthermia on cytotoxity and oncogenicity of several chemotherapeutic agents were investigated using the C3H 10T1/2 cell system. Logarithmic phase cultures of 10T1/2 cells were treated with various doses of cis-platinum or bleomycin sulphate for 2 h, either alone or with simultaneous hyperthermia (42 degrees C for 2 h). In a second set of experiments, cells were treated for 24 h with either melphalan or cis-platinum followed by a 2 h heat treatment. While hyperthermia alone was found to be ineffective in inducing oncogenic transformation and was only moderately cytotoxic, concurrent hyperthermia with drug treatment enhanced both the toxicity and oncogenic transforming potential of drugs 3-4-fold in C3H 10T1/2 cells. Sequential heat after drug treatment, however, was found to increase toxicity slightly but had no effect on the oncogenicity of the drugs.

Animals↗