Robotic surgery does not affect upstaging of T1 renal masses

Partial nephrectomy is the mainstay of treatment for localized kidney cancer. A proportion of patients are upstaged post-operatively to locally advanced di     

Beyond C4d: Other Complement-Related Diagnostic Approaches to Antibody-Mediated Rejection

Complement is a multifunctional system of receptors and regulators as well as effector molecules. Both the pathogenic and diagnostic power of complement is based on the capacity of the complement system to amplify innate and adaptive immunity. This amplification is accomplished through two strategies: (1) enzymatic reactions in the complement cascade, and (2) stimulation of leukocytes, platelets and parenchymal cells through specific receptors or receptor-independent pore formation. The mechanisms by which complement mediates and modifies nonspecific inflammation, antibody-mediated injury and T-cell responses are of particular significance to the pathogenesis of transplant rejection. Understanding the mechanisms by which complement integrates the interactions of leukocytes, platelets and parenchymal cells offers opportunities to further refine the diagnosis of rejection.     

Intracellular trafficking of fluorescently tagged proteins associated with pathogenesis in Candida albicans.

Proteins that enter the secretory pathway play important roles in virulence and pathogenesis in Candida albicans, but our understanding of the trafficking of these proteins is in its early stages. In Saccharomyces cerevisiae, dominant negative alleles of YPT1 and SEC4 interrupt secretory traffic at pre- and post-Golgi steps, respectively. We therefore used a dominant negative genetic approach to examine the intracellular trafficking of several proteins associated with virulence or azole resistance. When the dominant negative ypt1(N121I) allele of C. albicans was overexpressed, yellow-fluorescent protein (YFP) tagged forms of two plasma membrane transporters (Cdrlp and Ftrlp) and the vacuolar membrane ABC transporter Mltlp accumulated in intracellular structures that appeared related to the ER, but localization of Cdc10p and Int1p was unaffected. When the dominant negative sec4(S28N) allele of C. albicans was overexpressed, Cdrlp and Ftrlp accumulated intracellularly, and localization of Mltlp, Cdc10p and Int1p was unaffected. These results imply that (i) Cdrlp and Ftrlp are transported to the plasma membrane by the general secretory pathway, (ii) Mlt1p enters the secretory pathway but is diverted to the vacuole at an early post-Golgi step, and (iii) like Cdc10p, Int1p does not enter the general secretory pathway.     

Combined prostacyclin and thromboxane synthetase inhibitor UK 38485 in flap survival

Thromboxane, a prostanoid derivative, is a central mediator of the progressive dermal ischemia seen in the distal dying flap. Prostacyclin; a vasoactive prostanoid derivative, has been found to enhance ischemic flap survival. This study examines the effects of prostacyclin and UK 38485 (specific thromboxane synthetase inhibitor), separately and combined, in axial flap survival in the pig. Each increased flap survival over control flaps; their combined use demonstrated an even greater flap survival (p less than 0.005).     

Alcohol stimulates the release of dopamine in the ventral pallidum but not in the globus pallidus: a dual-probe microdialysis study.

The mesoaccumbens dopamine system has been hypothesized to be a common neural substrate mediating the actions of various drugs of abuse, including ethanol. However, the involvement of the mesopallidal dopamine system has received very little attention. The present study examined the effects of intraperitoneal (IP) ethanol administration on the extracellular levels of dopamine in the ventral pallidum (VP) and globus pallidus (GP) of Wistar rats. Rats were bilaterally implanted with microdialysis probes aimed at the VP and GP or nucleus accumbens (NAc) and dorsal striatum (dSTR). During microdialysis testing, rats with probes located in the VP and GP were injected IP with sterile saline or 15% (v/v) ethanol in saline at doses of 0.75, 1.5, or 2.25 g/kg. Rats with NAc and dSTR probes were injected with saline or 2.25 g/kg ethanol. The IP administration of 1.5 and 2.25 g/kg ethanol significantly (p <0.05) elevated the extracellular levels of dopamine in the VP (maximal increase: 136 and 182% of baseline, respectively) but not in the GP. No effects on extracellular dopamine levels were observed following the IP injections of 0.75 g/kg ethanol or saline. The IP administration of 2.25 g/kg ethanol significantly (p <0.05) elevated the extracellular levels of dopamine in the NAc (maximal increase: 198% of baseline) and dSTR (maximal increase: 155% of baseline). Analysis of the effects of 2.25 g/kg ethanol on dopamine release revealed greater increases in the VP, NAc, and dSTR compared to the GP. The data suggest that the mesopallidal, mesoaccumbens, and nigrostriatal dopamine systems are more sensitive to the effects of ethanol than the nigropallidal dopamine system.     

HLA alleles and haplotypes among the Lakota Sioux: report of the ASHI minority workshops, part III

Human leukocyte antigen (HLA) class I and II alleles were defined for 302 Lakota Sioux American Indians as part of the American Society for Histocompatibility and Immunogenetics coordinated studies on minority populations. The study group was comprised of adult volunteers from the Cheyenne River and Ogala Sioux tribes residing, respectively, on the Cheyenne River and Pine Ridge Reservations in South Dakota. Of the participants, 263 (87%) claimed full American Indian ancestry through both maternal and paternal grandparents. The study group included 25 nuclear families that were informative for genotyping. HLA phenotypes from 202 adults with no other known first-degree relative included in the study were used for calculation of allele and haplotype frequencies by maximum likelihood estimation. HLA-A, -B, and -Cw alleles were found to be in Hardy Weinberg equilibrium. Deviation from equilibrium was observed for DRB1 alleles (p=0.01), but could be attributed to the sample size and the occurrence of some genotypes with low expected frequencies. Polymorphism among the Sioux was limited with four to seven alleles comprising >80% of those observed at each locus. Several alleles were found at high frequency (0.05-0.30) among the Sioux that are also prevalent in other Native Americans and Alaska Natives, including: A*2402, *3101, and *0206; B*3501,*3901, *5101, and *2705; Cw*0702, *0404, and *03041; DRB1*0407, *0404, *1402, and *16021; and DQB1*0301, *0302, and *0402. DRB1*0811, which has been only previously described in Navajo and Tlingit Indians, was found to occur at a frequency of 0.119 among the Sioux. Two new alleles were defined among the Sioux: Cw*0204 and DRB1*040703, which were found in two and four individuals, respectively. In the haplotype analyses, significant linkage disequilibrium (p<0.00001) was seen in all pairwise comparisons of loci and numerous two and three locus haplotypes were found to have strong, positive linkage disequilibrium values. The two most common extended haplotypes among the Sioux, determined by maximum likelihood estimation and genotyping were: A*31012, B*3501, Cw*0404, DRB1*0407; and A*24021, B*3501, Cw*0404, DRB1*0404.     

Projections from primary somatosensory cortex to the neostriatum: the role of somatotopic continuity in corticostriatal convergence

We characterized the organization of corticostriatal projections from rodent primary somatosensory cortex (SI), testing the hypothesis that projections from SI areas representing subcomponents of the forelimb exhibit greater neostriatal overlap than projections from areas representing separate body parts. The anterograde tracers Fluoro-Ruby (FR), Alexa Fluor (AF), and biotinylated dextran amine (BDA) were injected into physiologically identified regions of rat SI. Injection locations were confirmed by examining the SI barrel fields and limb representations in tangential sections processed for cytochrome oxidase (CO). Experimental animals were divided into two groups: one group received multiple tracer injections in neighboring SI regions that represent separate body parts (whiskers, forepaw, and hindpaw); the other group received injections in SI areas that represent different components of the forelimb (forepaw, antebrachium, and brachium). The distribution of labeled terminals and their varicosities in the neostriatum and in the thalamus were plotted and quantitatively analyzed. For most animals, tracer overlap in the thalamus was either minimal or completely absent. In the neostriatum, projections from the whisker, forelimb, and hindlimb representations terminated in regions that rarely overlap with each other, while those originating from different parts of the forelimb representation were more likely to terminate in overlapping parts of the neostriatum. To the extent that neostriatal activation depends on corticostriatal convergence, the corticostriatal projections in the sensorimotor channel appeared to be organized so that neostriatal neurons may signal when multiple components of the same body part are activated simultaneously.