Genome-wide association mapping for stripe rust (Puccinia striiformis F. sp. tritici) in US Pacific Northwest winter wheat (Triticum aestivum L.).

KEY MESSAGE: Potential novel and known QTL for race-specific all-stage and adult plant resistance to stripe rust were identified by genome-wide association mapping in the US PNW winter wheat accessions. Stripe rust (Puccinia striiformis F. sp. tritici; also known as yellow rust) is a globally devastating disease of wheat (Triticum aestivum L.) and a major threat to wheat production in the US Pacific Northwest (PNW), therefore both adult plant and all-stage resistance have been introduced into the winter wheat breeding programs in the PNW. The goal of this study was to identify quantitative trait loci (QTL) and molecular markers for these resistances through genome-wide association (GWAS) mapping in winter wheat accessions adapted to the PNW. Stripe rust response for adult plants was evaluated in naturally occurring epidemics in a total of nine environments in Washington State, USA. Seedling response was evaluated with three races under artificial inoculation in the greenhouse. The panel was genotyped with the 9K Illumina Wheat single nucleotide polymorphism (SNP) array and additional markers linked to previously reported genes and QTL for stripe rust resistance. The population was grouped into three sub-populations. Markers linked to Yr17 and previously reported QTL for stripe rust resistance were identified on chromosomes 1B, 2A, and 2B. Potentially novel QTL associated with race-specific seedling response were identified on chromosomes 1B and 1D. Potentially novel QTL associated with adult plant response were located on chromosomes 2A, 2B, 3B, 4A, and 4B. Stripe rust was reduced when multiple alleles for resistance were present. The resistant allele frequencies were different among sub-populations in the panel. This information provides breeders with germplasm and closely linked markers for stripe rust resistance to facilitate the transfer of multiple loci for durable stripe rust resistance into wheat breeding lines and cultivars.

The role of ANK interactions with MYBBP1a and SPHK1 in catabolic events of articular chondrocytes.

OBJECTIVE: To determine the role of progressive ankylosis protein (ANK)/Myb-binding protein 1a (MYBBP1a) and sphingosine kinase 1 (SPHK1) interactions in catabolic events of articular chondrocytes. METHOD: ANK/MYBBP1a and SPHK1 interactions were identified using yeast two-hybrid screening and co-immunoprecipitation. To determine the role of these interactions in catabolic events of articular chondrocytes, ank/ank and wild type (WT) mouse chondrocytes transfected with full-length or mutant ank expression vectors (EVs) or femoral heads were treated with interleukin-1beta (IL-1ß) in the absence or presence of SPHK inhibitor. Catabolic marker mRNA levels were analyzed by real time PCR; proteoglycan loss using safranin O staining and MMP-13 immunostaining were determined in femoral head explants; NF-κB activity was determined by transfecting chondrocytes with an NF-κB-specific luciferase reporter and analyzing nuclear translocation of p65 by immunoblotting; MYBBP1a nuclear or cytoplasmic amounts were determined by immunohistochemistry and immunoblotting. RESULTS: The ANK N-terminal region interacted with SPHK1, whereas a cytoplasmic C-terminal loop interacted with MYBBP1a. Lack of ANK/MYBBP1a and SPHK1 interactions in ank/ank chondrocytes resulted in increased MYBBP1a nuclear amounts and decreased SPHK1 activity, and consequently decreased NF-κB activity, catabolic marker mRNA levels, proteoglycan loss, and MMP-13 immunostaining in IL-1ß-treated articular chondrocytes or femoral heads. Transfection with full-length ank EV reduced nuclear MYBBP1a amounts and fully restored SPHK and NF-κB activities in IL-1ß-treated ank/ank chondrocytes, whereas transfection with P5L or F376del mutant ank reduced nuclear MYBBP1a or increased SPHK activity, respectively, and consequently either transfection only partially restored NF-κB activity. CONCLUSION: ANK/MYBBP1a and SPHK1 interactions stimulate catabolic events in IL-1ß-mediated cartilage degradation.

CD40-CD40 ligand interactions are critical in T-B cooperation but not for other anti-viral CD4+ T cell functions.

CD40-CD40 ligand (CD40L) interaction is required for the generation of antibody responses to T-dependent antigens as well as for the development of germinal centers and memory B cells. The role of the CD40-CD40L interaction in the induction of antigen-specific. Th cells and in mediating Th cell effector functions other than cognate help for B cells is less well understood. Using CD40- and CD40L-deficient mice together with lymphocytic choriomeningitis virus and vesicular stomatitis virus as viral model antigens, this study corroborates earlier findings that no lg isotype switching of virus-specific antibodies was measurable upon infection of CD40- or CD40L-deficient mice. In contrast, in vivo induction of virus-specific CD4+ T cells measured by proliferation and cytokine secretion of primed virus-specific Th cells in vitro was not crucially dependent on the CD40-CD40L interaction. In addition, virus-specific Th cells primed in a CD40-deficient environment, adoptively transferred into CD40-competent recipients, were able to mediate lg isotype switch. Th-mediated effector functions distinct from and in addition to T-B collaboration were analyzed in CD40- and CD40L-deficient and normal mice: (a) local inflammatory reactions upon LCMV infection mediated by LCMV-specific Th cells were not dependent on a functional CD40-CD40L interaction, (b) cytokine-mediated protection by CD4+ T cells primed by vesicular stomatitis virus against a challenge infection with recombinant vaccinia virus expressing the glycoprotein of vesicular stomatitis virus was found to be equivalent in CD40L-deficient and normal mice. Thus, CD40-CD40L interaction plays a crucial role in T-B interactions for Th-dependent activation of B cells but not, or to a much lesser extent, in T cell activation, antigen-specific Th cell responses in vitro, and for interleukin-mediated Th cell effector functions in vivo.

Humoral immune responses in CD40 ligand-deficient mice.

Individuals with X-linked hyper-IgM syndrome fail to express functional CD40 ligand (CD40L) and, as a consequence, are incapable of mounting protective antibody responses to opportunistic bacterial infections. To address the role of CD40L in humoral immunity, we created, through homologous recombination, mice deficient in CD40L expression. These mice exhibited no gross developmental deficiencies or health abnormalities and contained normal percentages of B and T cell subpopulations. CD40L-deficient mice did display selective deficiencies in humoral immunity; basal serum isotype levels were significantly lower than observed in normal mice, and IgE was undetectable. Furthermore, the CD40L-deficient mice failed to mount secondary antigen-specific responses to immunization with a thymus-dependent antigen, trinitrophenol-conjugated keyhole limpet hemocyanin (TNP-KLH). By contrast, the CD40L-deficient mice produced antigen-specific antibody of all isotypes except IgE in response to the thymus-independent antigen, DNP-Ficoll. These results underscore the requirement of CD40L for T cell-dependent antibody responses. Moreover, Ig class switching to isotypes other than IgE can occur in vivo in the absence of CD40L, supporting the notion that alternative B cell signaling pathways regulate responses to thymus-independent antigens.

Understanding age effects associated with changes in secondary health conditions in a Canadian spinal cord injury cohort.

STUDY DESIGN: Longitudinal cohort. OBJECTIVES: To determine whether changes in secondary health conditions (SHC) associated with spinal cord injury (SCI) were effectively modeled from a longitudinal or cross-sectional perspective, and whether the changes in SHCs were attributable to age or years post-injury (YPI). SETTING: Toronto Rehabilitation Institute, Lyndhurst Centre. METHODS: Telephone survey methods were used to collect data on (1) demographics, (2) impairment, (3) health status, and (4) self-reported SHCs at two time intervals (1995-1997; 2003-2004) from 344 adults with SCI. Generalized estimating equations were applied to model the longitudinal and cross-sectional effects. RESULTS: Health status decreased over time (P<0.0005), whereas the number of SHCs increased (P<0.0001). Regardless of age or YPI, the longitudinal component of aging better predicted SHC occurrence and was associated with spasticity [odds ratio, OR=1.055 (95% confidence interval, CI, 1.018 to 1.093, P<0.01)], kidney problems [OR=1.154 (95% CI, 1.084 to 1.229, P<0.0001)], cardiac problems [OR=1.168 (95% CI, 1.060 to 1.286, P<0.01)], high blood pressure [OR=1.121 (95% CI, 1.058 to 1.188, P<0.0001)], chronic pain [OR=1.058 (95% CI, 1.021 to 1.096, P<0.01)], and arthritis/joint pain [OR=1.113 (95% CI, 1.075 to 1.152, P<0.0001)]. CONCLUSION: Within a relatively short period of time, persons with SCI experienced substantive declines in health. The findings suggest that a longitudinal perspective is more sensitive for predicting the risk of self-reported SHCs than a cross-sectional one.

A Hydrothermal-Sedimentary Context for the Origin of Life.

Critical to the origin of life are the ingredients of life, of course, but also the physical and chemical conditions in which prebiotic chemical reactions can take place. These factors place constraints on the types of Hadean environment in which life could have emerged. Many locations, ranging from hydrothermal vents and pumice rafts, through volcanic-hosted splash pools to continental springs and rivers, have been proposed for the emergence of life on Earth, each with respective advantages and certain disadvantages. However, there is another, hitherto unrecognized environment that, on the Hadean Earth (4.5-4.0 Ga), would have been more important than any other in terms of spatial and temporal scale: the sedimentary layer between oceanic crust and seawater. Using as an example sediments from the 3.5-3.33 Ga Barberton Greenstone Belt, South Africa, analogous at least on a local scale to those of the Hadean eon, we document constant permeation of the porous, carbonaceous, and reactive sedimentary layer by hydrothermal fluids emanating from the crust. This partially UV-protected, subaqueous sedimentary environment, characterized by physical and chemical gradients, represented a widespread system of miniature chemical reactors in which the production and complexification of prebiotic molecules could have led to the origin of life. Key Words: Origin of life-Hadean environment-Mineral surface reactions-Hydrothermal fluids-Archean volcanic sediments. Astrobiology 18, 259-293.

T-cell activation and receptor downmodulation precede deletion induced by mucosally administered antigen.

The fate of antigen-specific T cells was characterized in myelin basic protein (MBP) T-cell receptor (TCR) transgenic (Tg) mice after oral administration of MBP. Peripheral Th cells are immediately activated in vivo, as indicated by upregulation of CD69 and increased cytokine responses (Th1 and Th2). Concurrently, surface TCR expression diminishes and internal TCR levels increase. When challenged for experimental autoimmune encephalomyelitis during TCR downmodulation, Tg mice are protected from disease. To characterize Th cells at later times after antigen feeding, it was necessary to prevent thymic release of naive Tg cells. Therefore, adult Tg mice were thymectomized before treatment. TCR expression returns in thymectomized Tg mice 3 days after MBP feeding and then ultimately declines in conjunction with MBP-specific proliferation and cytokine responses (Th1-type and Th2-type). The decline correlates with an increase in apoptosis. Collectively, these results demonstrate that a high dose of fed antigen induces early T-cell activation and TCR downmodulation, followed by an intermediate stage of anergy and subsequent deletion.

Long-term consequences of early infant injury and trauma upon somatosensory processing.

Long-term consequences of early infant injury upon somatosensory processing were tested in school aged children. The aim was to test whether the long-term changes in sensitivity reported in animal models, in regions both local to and distant from the injury site, could be observed in humans. To do this we used quantitative sensory testing (QST) in children aged 9-12 years who had undergone cardiac surgery in infancy. Cutaneous mechanical and thermal thresholds were measured at the thoracic scar region and at control contralateral thoracic and reference thenar areas in this early surgery group (n=9), and compared with thresholds at the same regions in age and gender-matched controls (n=9). The results showed that the cardiac surgery group was significantly less sensitive to von Frey hair tactile stimulation in the non-injured thenar area than the control group; mean threshold 5.02, SD+/-1.59 compared to 2.76, SD+/-0.79 (von Frey hair number, p=0.04). In addition, their lateral thoracotomy scar areas were significantly less sensitive to von Frey hair stimulation (mean=9.82, SD+/-1.97, p<0.001) and to cooling and warming than any other site tested. Eight of the nine children in the early surgery group did not perceive warmth on their scars and were only able to detect uncomfortable heat as the temperature was raised. Three of these children felt a paradoxical cold prior to the hot sensation and all reported subtle abnormalities in everyday sensations. Questionnaires revealed perceived differences in pain perception, individual aberrant sensations and pain interfering with daily life that warrant further study. We conclude that tissue injured in early infancy remains measurably altered to mechanical and thermal stimulation in later life. These findings are consistent with the results of animal studies that early infant injury has not only local, but also global long-term consequences upon sensory processing.

Thirty robotic adrenalectomies: a single institution's experience.

BACKGROUND: Robotic adrenalectomy is a minimally invasive alternative to traditional laparoscopic adrenalectomy. To date, only case reports and small series of robotic adrenalectomies have been reported. This study presents a single institution's series of 30 robotic adrenalectomies, and evaluates the procedure's safety, efficacy, and cost. METHODS: Thirty patients underwent robotic adrenalectomy at the Johns Hopkins Hospital between April 2001 and January 2004. Patient morbidity, hospital length of stay, operative time, and conversion rate to traditional laparoscopic or open surgery are presented. Improvement in operative time with surgeon experience is evaluated. Hospital charges are compared to charges for traditional laparoscopic and open adrenalectomies performed during the same time period. RESULTS: Median operative time was 185 min. Patient morbidity was 7%. There were no conversions to traditional laparoscopic or open surgery. The median hospital stay was 2 days. Operative time improved significantly by 3 min with each operation. Hospital charges for robotic adrenalectomy (12,977 dollars) were not significantly different than charges for traditional laparoscopic (11,599 dollars) or open adrenalectomy (14,600 dollars). CONCLUSIONS: Robotic adrenalectomy is a safe and effective alternative to traditional laparoscopic adrenalectomy.

Abdominal wall dysfunction in adult bladder exstrophy: a treatable but under-recognized problem.

PURPOSE: Bladder exstrophy is defined by urogenital and skeletal abnormalities with cosmetic and functional deformity of the lower anterior abdominal wall. The primary management objectives have historically been establishment of urinary continence with renal function preservation, reconstruction of functional and cosmetically acceptable external genitalia, and abdominal wall closure of some variety. The literature has focused on the challenges of neonatal approaches to abdominal wall closure; however, there has been a paucity of long-term followup to identify the presence and severity of abdominal wall defects in adulthood. Our goal was to characterize the adult disease and determine effective therapy. METHODS: A retrospective review of a consecutive series of six patients was performed. RESULTS: We report and characterize the presence of severe abdominal wall dysfunction in these adult exstrophy patients treated as children. We tailored an abdominal wall and pelvic floor reconstruction with long-term success to highlight a need for awareness of the magnitude of the problem and its solvability. CONCLUSIONS: The natural history of abdominal wall laxity and the long-term consequences of cloacal exstrophy closure have gone unexplored and unreported. Evaluation of our series facilitates understanding in this complex area and may be valuable for patients who are living limited lives thinking that no solution is available.

Regional chemotherapy devices: effect of experience and anatomy on complications.

PURPOSE: Regional hepatic arterial infusion (HAI) devices have been used for 17 years, but reports of unacceptably high complication rates have led to controversy about their use. Inadequate or misdirected infusion has been reported to occur in up to 45% of patients. We evaluated whether surgeon experience or presence of variant arterial anatomy related to risk of coagulation. MATERIALS AND METHODS: We reviewed 70 patients undergoing placement of HAI catheters. Surgeons were classed as experienced after 10 procedures and arterial anatomy was evaluated angiographically with confirmation at operation. Complications were categorized as technical (17%) or chemotherapy-related (16%). RESULTS: Inexperienced surgeons had a technical complication rate of 37% (80% of the patients involved had standard anatomy), while experienced surgeons had a technical complication rate of 7% (P < .01). Experienced surgeons had no complications in patients with standard anatomy, while inexperienced surgeons had a 42% (eight of 19) complication rate in similar patients (P < .01). CONCLUSION: We conclude that technical complications are closely associated with surgeon experience and arterial anatomy.

Molecular mechanisms of murine Fc epsilon RII/CD23 regulation.

The low affinity receptor for IgE (Fc epsilon RII or CD23), expressed primarily on mouse B cells, is known to be upregulated by interleukin-4 (IL-4) at both the mRNA and protein levels. Fc epsilon RII expression is superinduced when the IL-4 is combined with cell activation. In order to explore the molecular regulation of Fc epsilon RII expression, mouse B cell lines were screened to develop a cell line model. The B cell lymphoma A20.1, was found to behave in a manner similar to mouse B cells in that Fc epsilon RII levels are very low on cells cultured in media alone (< 10(3)/cell), increased by culture in the presence of IL-4, and superinduced by LPS and IL-4 (> 10(5)/cell). The steady state mRNA levels for Fc epsilon RII corresponded to the level of cell surface expression. Transcription assays indicated that the Fc epsilon RII level increases could be explained entirely by increased transcription rates. The A20.1 cell line was subsequently used to analyse the Fc epsilon RII promoter. Nested deletion analysis of the 1.3 kB 5' of the mouse Fc epsilon RII transcription start site, using CAT reporter plasmids transfected into A20.1 cells, identified major elements activating the Fc epsilon RII promoter within 250 bp of the transcription start site. Constructs containing greater than 250 bp of 5' sequence showed significantly reduced CAT activity suggesting negative regulatory regions. Coincident with the restricted tissue expression of murine Fc epsilon RII, the promoter was B cell specific in that little CAT expression was seen in fibroblast, mast cells or T cell lines. Expression was seen, however, in both mouse and human B cell lines. Finally, the promoter was analysed for response to IL-4. Stimulation with IL-4 plus LPS resulted in only a modest increase in CAT activity (approximately 2-fold), in contrast to transcription assays, where increases approximated that seen at the cell surface. Thus, the IL-4 response must also require sequences distal to the regions examined.

Systemic and portal prostacyclin and thromboxane response to hemorrhage in portal hypertension.

Prostacyclin (PGI2) and thromboxane (Tx-A2) levels increase in hemorrhagic shock. Prostanoids have been implicated as mediators of the systemic and splanchnic hyperemia characteristic of portal hypertension (PHT). We hypothesized that prostanoid pharmacokinetics could be altered during shock in PHT and mediate the poor tolerance of PHT animals to hemorrhage. Hemodynamics and PGI2 and Tx-A2 levels were determined in portal, systemic venous, and arterial vascular beds at baseline and following hemorrhage and resuscitation. Portal and systemic PGI2 levels were elevated at baseline in PHT animals, with no change in resting Tx-A2. Following hemorrhage, PGI2 and Tx-A2 levels increased in normal animals, but were unchanged in PHT. Portal hypertension PGI2 production was elevated at rest, while Tx-A2 levels were diminished. There is a diminished prostanoid response to hemorrhage in PHT animals compared to normal. This abnormality in prostanoid pharmacokinetics may contribute to the abnormal response to hemorrhage in PHT.

A valid experimental brain death organ donor model.

BACKGROUND: This study was designed to establish a validated canine brain death model. Ten consecutive dogs were studied to investigate the effects of brain death on hemodynamic, metabolic, and hormonal function. METHODS: Brain death was induced by inflation of a subdurally placed balloon and was validated neuropathologically. Functional data and blood samples were collected before and 15, 45, 90, 240, 360, and 420 minutes after the induction of brain death. No inotropic or vasoactive support was given. The results are expressed as mean +/- standard error of the mean. RESULTS: The Cushing reflex occurred in all animals and lasted 13.3 +/- 1.5 minutes. Raised catecholamine levels were documented at 15 minutes, whereas the pituitary gland hormones vasopressin and adrenocorticotrophic hormone decreased significantly after 15 and 45 minutes, respectively. Triiodothyronine, thyroxine, and glucagon decreased significantly from 0.58 +/- 0.05 ng/ml, 2.20 +/- 0.15 micrograms/dl, and 49.7 +/- 9.1 pg/ml to 0.34 +/- 0.03 ng/ml (p < 0.05 versus baseline; paired two-tailed t-test), 1.14 +/- 1.14 micrograms/dl (p < 0.05), and 6.9 +/- 1.4 pg/ml (p < 0.05). Insulin and lactate dehydrogenase showed a moderate increase after brain death. Diabetes insipidus occurred after 45 minutes in nine animals (urine output 13.5 +/- 1.8 ml/kg/hour). Left and right ventricular end-diastolic pressure increased significantly toward the end of all experiments. Cardiac output increased and systemic and pulmonary vascular resistance decreased, but heart rate remained unchanged. CONCLUSION: This simple, reproducible, moderately invasive, and reliable model of brain death in animals assesses donor organ function and preservation. Cushing reflex, hyperdynamic state, catecholamine storm, vasopressin and adrenocorticotropic hormone cessation, total cerebral necrosis, and diabetes insipidus were consistent findings.

Improved tolerance of the pediatric myocardium to brain death.

The occurrence of brain death has been shown to significantly diminish left ventricular function in the adult porcine model. This study examined whether the pediatric myocardium is as sensitive as the adult myocardium to the detrimental effects of brain death in the porcine model. Left ventricular intracavitary pressure and major and minor axis epicardial dimensions were measured in eleven 1-month old pigs (7.5 to 10 kg) during a vena caval occlusion. Brain death was induced in six pigs by acutely ligating the brachiocephalic and left subclavian arteries. The remaining five pigs served as controls. Data were then collected every hour for 6 hours. The plot of the stroke work versus the end diastolic volume, called the preload recruitable stroke work relationship, was determined from the measured pressure and calculated intracavitary volume data. The slope of this linear relationship is an index of contractility, and the x intercept (Vo) is an index of diastolic mechanics. At each hour after instrumentation two vena caval occlusions were performed, and the mean slope of the preload recruitable stroke work line was calculated as a percentage of the baseline slope in both the brain-dead and control group. The mean values from the brain-dead pigs were 118%, 138%, 126%, 154%, 123%, and 87% of the baseline value for the 6 hours after brain death. The mean control values were 128%, 117%, 133%, 123%, 114%, and 111% of baseline for the 6 hours after instrumentation alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Load-independent analysis of a pulsatile right ventricular assist device.

BACKGROUND: Right ventricular assist devices are becoming increasingly used as both a bridge to heart transplantation and as a means of temporary support after cardiopulmonary bypass. There has also been a resurgence of interest in pulsatile devices fueled by anecdotal, clinical reports. However, a load-independent analysis of biventricular function after right ventricular assistance comparing a pulsatile versus a continuous-flow right ventricular assist device has not been performed, and we hypothesize that a pulsatile device is less detrimental to cardiac function than a conventional, nonpulsatile pump. METHODS: Sixteen dogs (20 to 25 kg) were instrumented through a median sternotomy for placement of left ventricular and right ventricular epicardial dimension transducers in the major, minor, and septal-free wall axes. Intracavitary micromanometers were placed in both ventricles as well. Baseline pressure-dimension data were collected, and the right atrium and pulmonary artery were cannulated. Right ventricular bypass with the use of a pneumatically driven pulsatile right ventricular assist device (SV = 60 ml; n = 7) or a conventional continuous-flow centrifugal right ventricular assist device (n = 9) was instituted for a 4-hour duration. Animals were then weaned from right ventricular support and decannulated. After bypass, biventricular function data were then collected. The load-insensitive stroke work-end diastolic volume relationship known as preload recruitable stroke work was derived and expressed as a fraction of baseline function along with conventional hemodynamic indexes, cardiac output, and pulmonary vascular resistance. RESULTS: Results of this analysis show no significant benefit to either right ventricular or left ventricular function (right ventricular preload recruitable stroke work index: 0.863 +/- 0.3 [pulsatile] versus 0.849 +/- 0.2 [continuous], left ventricular preload recruitable stroke work index: 0.880 +/- 0.4 [pulsatile] versus 0.821 +/- 0.3 [continuous] after pulsatile right ventricular support. Likewise, cardiac output (1.4 +/- 0.1 [pulsatile] versus 1.5 +/- 0.2 [continuous] L/min) and pulmonary vascular resistance (4.8 +/- 1.0 [pulsatile] versus 3.2 +/- 1.1 [continuous] Wood Units) were not significantly different in either study group. CONCLUSIONS: We conclude from these data that pneumatically driven pulsatile right ventricular assist devices provide no additional benefit to myocardial performance beyond that of conventional, nonpulsatile pumps. Further studies investigating a speculative benefit from pulsatile circulatory support are necessary to further define a potential role for these novel devices.

Mechanisms underlying the plasticity of hippocampal stimulation-induced reward.

It has been reported that the very slow acquisition of hippocampal self-stimulation can be markedly facilitated by pretreatment with a program of repeated daily hippocampal stimulation (kindling). Three experiments were performed to investigate the neurophysiological basis of this effect. Experiment 1 demonstrated that unilateral stimulation pretreatment produced a facilitation of learning to lever press for stimulation delivered to the contralateral hippocampal electrode. Thus, there is a transfer of facilitation. In Experiment 2 it was shown that this transfer effect was not affected by lesion of the originally kindled focus, a result suggesting that the facilitated acquisition was not due to feedback to the kindled site. In Experiment 3 electrical activity during hippocampal self-stimulation was examined in order to explore the possible correlation between hippocampal reward and epileptiform activity. No relation was apparent: Lever pressing persisted even when no afterdischarge was elicited. The findings of these experiments are consistent with the hypothesis that the facilitatory effect of stimulation reflects the development of transsynaptic potentiation.

Rotational stimulation disrupts spatial learning in fornix-lesioned rats.

Normal and fornix-lesioned rats were trained to find water in a version of a spatial discrimination task involving the use of a cross maze modified for interspersing rotational stimulation before the start of each trial. The central (cross) portion of the maze rested on a turntable and consisted of a covered start box opening into the intersection of the cross, allowing choice among three covered alleys, each of which led through a black curtain onto a stationary goal arm. The animal could be started in one of three positions (0 degree, 90 degrees, 270 degrees) in relation to the rewarded goal arm. Room cues were not available until after the animal made the choice in the covered tunnel area. A 20-day testing period in which one to ten full revolutions were interspersed before the start of each trial revealed marked differences between normal and fornix-lesioned animals. The overall performance of normal animals improved from 40% correct choices to 85% correct during the testing period. Fornix-lesioned rats showed no significant improvement during the same period. Performance on probe trials in which room cues were made available to the animals during interspersed rotations improved rapidly and was not significantly different between the two groups. The results suggest that adaptation to vestibular system stimulation was required to solve the covered tunnel task in normal rats and that such processes were disrupted in fornix-lesioned rats.

Biliary tract anomalies associated with intestinal malrotation in the adult.

Intestinal malrotation is a rare disorder typically beginning in childhood. In the adult it is an uncommon diagnosis, and it usually begins with bowel obstruction. It is a congenital anomaly only once reported to be associated with other gastrointestinal abnormalities in an adult. We reviewed all patients with intestinal malrotation at the Johns Hopkins Hospital during the past 7 years to determine the incidence of associated biliary tract anomalies. Eight adult patients were found to have complete malrotation of the gut. Four patients (50%) had an associated abnormality of the biliary tree. Two of four patients had a clinical presentation consistent with biliary tract disease rather than intestinal malrotation. Two patients underwent exploration; the gallbladder was found to arise from the left lobe of the liver. Two patients underwent exploration; in these patients the porta hepatic structures were anterior to the duodenum (complete anteroposterior portal hepatic malrotation). None of the biliary abnormalities were suspected before surgery. Malrotation was diagnosed before operation in only two of the eight patients. We conclude that intestinal malrotation is rare in the adult, and it can be associated with biliary tract anomalies or disease. In an adult with suspected intestinal malrotation and biliary tract disease, the surgeon should be aware of possible variable or abnormal extrahepatic choledochal anatomy.

Modulation of splanchnic vascular sensitivity to angiotensin II.

We studied whether the diminished splanchnic vascular response to angiotensin II infusion in portal hypertension could be related to elevated levels of prostacyclin (PGI2). The changes in superior mesenteric artery resistance (RSMA) and systemic vascular resistance (RSYS) during angiotensin II infusion were measured by Doppler flow probe in normal rabbits (NL) and portal hypertensive rabbits (PHT), and in NL and PHT after cyclooxygenase blockade (CO) and after CO and during continuous PGI2 infusion at 300 ng/kg/min. Angiotensin II infusion in NL caused a disproportionately greater increase in RSMA than in RSYS (p less than 0.01). In PHT, angiotensin II response of RSMA was reduced from NL (p less than 0.05). CO dramatically improved the splanchnic response to angiotensin II in PHT animals, but did not significantly alter the RSMA response in NL. PGI2 in NL, NL + CO, and PHT + CO quantitatively established the splanchnic vascular hyporesponsiveness to angiotensin II seen in PHT. We conclude that PGI2 will directly diminish splanchnic response to angiotensin II in NL, and CO will ablate differences in splanchnic response between NL and PHT to angiotensin II. This strongly implies that much of the observed decrease in angiotensin II response in PHT is mediated by PGI2 and that the differences between NL and PHT vascular response is in part the result of circulating vasodilatory substances.