Increased leaf area index and efficiency drive enhanced production under elevated atmospheric [CO2 ] in a pine-dominated stand showing no progressive nitrogen limitation.

Enhancement of net primary production (NPP) in forests as atmospheric [CO2 ] increases is likely limited by the availability of other growth resources. The Duke Free Air CO2 Enrichment (FACE) experiment was located on a moderate-fertility site in the southeastern US, in a loblolly pine (Pinus taeda L.) plantation with broadleaved species growing mostly in mid-canopy and understory. Duke FACE ran from 1994 to 2010 and combined elevated [CO2 ] (eCO2 ) with nitrogen (N) additions. We assessed the spatial and temporal variation of NPP response using a dataset that includes previously unpublished data from 6 years of the replicated CO2 × N experiment and extends to 2 years beyond the termination of enrichment. Averaged over time (1997-2010), NPP of pine and broadleaved species were 38% and 52% higher under eCO2 compared to ambient conditions. Furthermore, there was no evidence of a decline in enhancement over time in any plot regardless of its native site quality. The relation between spatial variation in the response and native site quality was suggested but inconclusive. Nitrogen amendments under eCO2 , in turn, resulted in an additional 11% increase in pine NPP. For pine, the eCO2 -induced increase in NPP was similar above- and belowground and was driven by both increased leaf area index (L) and production efficiency (PE = NPP/L). For broadleaved species, coarse-root biomass production was more than 200% higher under eCO2 and accounted for the entire production response, driven by increased PE. Notably, the fraction of annual NPP retained in total living biomass was higher under eCO2 , reflecting a slight shift in allocation fraction to woody mass and a lower mortality rate. Our findings also imply that tree growth may not have been only N-limited, but perhaps constrained by the availability of other nutrients. The observed sustained NPP enhancement, even without N-additions, demonstrates no progressive N limitation.

Serum bile acid levels as a predictor for the severity of liver fibrosis in patients with chronic hepatitis C.

Serum bile acids (SBAs) are commonly elevated in cholestatic liver diseases, but it is unclear if SBA levels are also elevated in noncholestatic chronic liver diseases and whether those levels correlate with disease severity. We analysed SBA levels of 135 consecutive patients with chronic hepatitis C virus infection and correlated these levels with the degree of liver fibrosis as determined by liver biopsy. In addition, we assessed the accuracy of SBA levels as a noninvasive predictor for liver fibrosis by its comparison to the patients' FibroTest scores. Two-thirds (90/135 patients, 67%) of the study patients had nonsevere liver fibrosis (Metavir F0-F2), and the others (45/135, 33%) had severe fibrosis or cirrhosis (Metavir F3-F4). The SBA levels were significantly higher in patients with severe fibrosis as compared to nonsevere fibrosis (11.46 ± 10.01 vs 6.37 ± 4.69, P < 0.0001). Furthermore, a receiver operator characteristics curve based on a model that included serum bile acids, age, body mass index, serum AST, glucose and cholesterol levels suggested that this combination reliably predicts the degree of liver fibrosis and is not inferior to the current noninvasive FibroTest score (areas under the curve of 0.837 vs 0.83, respectively, P = 0.87). We conclude that measurement of SBA levels may have a clinical role as a simple noninvasive tool to assess the severity of HCV-induced liver disease. Combined with widely available laboratory parameters, SBA levels can predict disease severity with a high degree of accuracy.

Increased incidence and mortality associated with skin cancers after cardiac transplant.

Skin cancer incidence has been shown to be increased in the context of transplant-associated immunosuppression. There is, however, limited information specifically about the incidence of skin cancer after cardiac transplantation in the United States. A 10-year retrospective cohort study of 6271 heart transplants at 32 US transplant centers revealed increased postprocedure incidence of nonmelanoma and melanoma skin cancers, especially cutaneous squamous cell carcinoma, for which the incidence increased from 4- to 30-fold compared to the age and gender equivalent general population. Incidence of skin cancer in this study was consistent with prior single-center data regarding cardiac transplant patients. Comparison of all-cause mortality statistics for patients with basal cell carcinoma, squamous cell carcinoma and melanoma, respectively, demonstrated increased mortality associated with melanoma. Skin cancer screening and prophylaxis may be of some utility in reducing morbidity and mortality in cardiac transplant patients.

Canopy nitrogen, carbon assimilation, and albedo in temperate and boreal forests: Functional relations and potential climate feedbacks.

The availability of nitrogen represents a key constraint on carbon cycling in terrestrial ecosystems, and it is largely in this capacity that the role of N in the Earth's climate system has been considered. Despite this, few studies have included continuous variation in plant N status as a driver of broad-scale carbon cycle analyses. This is partly because of uncertainties in how leaf-level physiological relationships scale to whole ecosystems and because methods for regional to continental detection of plant N concentrations have yet to be developed. Here, we show that ecosystem CO(2) uptake capacity in temperate and boreal forests scales directly with whole-canopy N concentrations, mirroring a leaf-level trend that has been observed for woody plants worldwide. We further show that both CO(2) uptake capacity and canopy N concentration are strongly and positively correlated with shortwave surface albedo. These results suggest that N plays an additional, and overlooked, role in the climate system via its influence on vegetation reflectivity and shortwave surface energy exchange. We also demonstrate that much of the spatial variation in canopy N can be detected by using broad-band satellite sensors, offering a means through which these findings can be applied toward improved application of coupled carbon cycle-climate models.

Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial.

Nonalcoholic steatohepatitis (NASH), a chronic liver disease without an approved therapy, is associated with lipotoxicity and insulin resistance and is a major cause of cirrhosis and hepatocellular carcinoma. Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial. ARREST, a 52-week, double-blind, placebo-controlled, phase 2b trial randomized 247 patients with NASH (n = 101, n = 98 and n = 48 in the Aramchol 400 mg, 600 mg and placebo arms, respectively; NCT02279524 ). The primary end point was a decrease in hepatic triglycerides by magnetic resonance spectroscopy at 52 weeks with a dose of 600 mg of Aramchol. Key secondary end points included liver histology and alanine aminotransferase (ALT). Aramchol 600 mg produced a placebo-corrected decrease in liver triglycerides without meeting the prespecified significance (-3.1, 95% confidence interval (CI) -6.4 to 0.2, P = 0.066), precluding further formal statistical analysis. NASH resolution without worsening fibrosis was achieved in 16.7% (13 out of 78) of Aramchol 600 mg versus 5% (2 out of 40) of the placebo arm (odds ratio (OR) = 4.74, 95% CI = 0.99 to 22.7) and fibrosis improvement by ≥1 stage without worsening NASH in 29.5% versus 17.5% (OR = 1.88, 95% CI = 0.7 to 5.0), respectively. The placebo-corrected decrease in ALT for 600 mg was -29.1 IU l-1 (95% CI = -41.6 to -16.5). Early termination due to adverse events (AEs) was <5%, and Aramchol 600 and 400 mg were safe, well tolerated and without imbalance in serious or severe AEs between arms. Although the primary end point of a reduction in liver fat did not meet the prespecified significance level with Aramchol 600 mg, the observed safety and changes in liver histology and enzymes provide a rationale for SCD1 modulation as a promising therapy for NASH and fibrosis and are being evaluated in an ongoing phase 3 program.

Fibrotest or Fibroscan for evaluation of liver fibrosis in haemophilia patients infected with hepatitis C.

Non-invasive modalities to estimate fibrosis stage are desirable in hepatitis C-infected haemophilia patients. Previous studies found a high rate of significant fibrosis both by Fibrotest (FT) and Fibroscan (FS) in these patients. To estimate liver fibrosis and to assess the concordance between FT and FS in hepatitis C-infected haemophilia patients. FT and FS were performed at different laboratories and were unaware of the results of the alternative test. Three successive liver stiffness measurements (LSM) were performed at different sites on the liver. Two-validated algorithms were used to improve evaluation of fibrosis by non-invasive methods. Fifty-seven hepatitis C-infected haemophilia patients were evaluated by FT and FS. Acquisition of LSMs was not feasible in two patients: obesity--one, surgical scars--one. Fibrosis stage > or=F2, > or =F3 or =F4 were estimated in about a half, about a third and in 15-20% of the evaluated patients by FS and FT respectively. The corresponding concordance rates and kappa score for fibrosis stage > or =F2, > or =F3 or =F4 between FT and FS were 62%, 69%, 85% and 0.24, 0.32, 0.44 respectively. Using the two aforementioned algorithms, additional 14 patients could be reliably estimated for fibrosis stage > or =F2. High proportion hepatitis C-infected haemophilia patients were estimated with significant or advanced stages of liver fibrosis using both tests. Nevertheless, the agreement between modalities was only fair and improved with more advanced stages of fibrosis. Practical algorithms for the accuracy of FT and FS may improve reliable evaluation of fibrosis in this population.

Stereotype threat effects in settings with features likely versus unlikely in operational test settings: A meta-analysis.

The stereotype threat literature primarily comprises lab studies, many of which involve features that would not be present in high-stakes testing settings. We meta-analyze the effect of stereotype threat on cognitive ability tests, focusing on both laboratory and operational studies with features likely to be present in high stakes settings. First, we examine the features of cognitive ability test metric, stereotype threat cue activation strength, and type of nonthreat control group, and conduct a focal analysis removing conditions that would not be present in high stakes settings. We also take into account a previously unrecognized methodological error in how data are analyzed in studies that control for scores on a prior cognitive ability test, which resulted in a biased estimate of stereotype threat. The focal sample, restricting the database to samples utilizing operational testing-relevant conditions, displayed a threat effect of d = -.14 (k = 45, N = 3,532, SDδ = .31). Second, we present a comprehensive meta-analysis of stereotype threat. Third, we examine a small subset of studies in operational test settings and studies utilizing motivational incentives, which yielded d-values ranging from .00 to -.14. Fourth, the meta-analytic database is subjected to tests of publication bias, finding nontrivial evidence for publication bias. Overall, results indicate that the size of the stereotype threat effect that can be experienced on tests of cognitive ability in operational scenarios such as college admissions tests and employment testing may range from negligible to small. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins.

A murine monoclonal antibody was identified by its ability to induce a reversible antiproliferative effect on a human lymphoma cell line. Immunoprecipitation studies revealed that the antibody reacted with a 26-kilodalton cell surface protein (TAPA-1). A diverse group of human cell lines, including hematolymphoid, neuroectodermal, and mesenchymal cells, expressed the TAPA-1 protein. Many of the lymphoid cell lines, in particular those derived from large cell lymphomas, were susceptible to the antiproliferative effects of the antibody. TAPA-1 may therefore play an important role in the regulation of lymphoma cell growth. A cDNA clone coding for TAPA-1 was isolated by using the monoclonal antibody to screen an expression library in COS cells. Analysis of the deduced amino acid sequence indicated that the protein is highly hydrophobic and that it contains four putative transmembrane domains and a potential N-myristoylation site. TAPA-1 showed strong homology with the CD37 leukocyte antigen and with the ME491 melanoma-associated antigen, both of which have been implicated in the regulation of cell growth.

Assessment centers versus cognitive ability tests: Challenging the conventional wisdom on criterion-related validity.

Separate meta-analyses of the cognitive ability and assessment center (AC) literatures report higher criterion-related validity for cognitive ability tests in predicting job performance. We instead focus on 17 samples in which both AC and ability scores are obtained for the same examinees and used to predict the same criterion. Thus, we control for differences in job type and in criteria that may have affected prior conclusions. In contrast to Schmidt and Hunter's (1998) meta-analysis, reporting mean validity of .51 for ability and .37 for ACs, we found using random-effects models mean validity of .22 for ability and .44 for ACs using comparable corrections for range restriction and measurement error in the criterion. We posit that 2 factors contribute to the differences in findings: (a) ACs being used on populations already restricted on cognitive ability and (b) the use of less cognitively loaded criteria in AC validation research. (PsycINFO Database Record

Effects of predictor weighting methods on incremental validity.

It is common to add an additional predictor to a selection system with the goal of increasing criterion-related validity. Research on the incremental validity of a second predictor is generally based on forming a regression-weighted composite of the predictors. However, in practice predictors are commonly used in ways other than regression-weighted composites, and we examine the robustness of incremental validity findings to other ways of using predictors, namely, unit weighting and multiple hurdles. We show that there are settings in which the incremental value of a second predictor disappears, and can even produce lower validity than the first predictor alone, when these alternatives to regression weighting are used. First, we examine conditions under which unit weighting will negate gain in predictive power attainable via regression weights. Second, we revisit Schmidt and Hunter's (1998) summary of incremental validity of predictors over cognitive ability, evaluating whether the reported incremental value of a second predictor is different when predictors are unit weighted rather than regression weighted. Third, we analyze data reported in the published literature to discern the frequency with which unit weighting might affect conclusions about whether there is value in adding a second predictor to a first. Finally, we shift from unit weighting to multiple hurdle selection, examining conditions under which conclusions about incremental validity differ when regression weighting is replaced by multiple-hurdle selection. (PsycINFO Database Record

Acute hepatitis B in the era of immunisation: pitfalls in the identification of high risk patients.

BACKGROUND: Since the adoption of a universal hepatitis B immunisation strategy, the reported incidence of acute hepatitis B has declined dramatically worldwide including in Israel. However, new cases of acute hepatitis B still occur. The aim of this study was to describe the incidence of acute hepatitis B in a referral area, routes of transmission, and outcome. METHODS: The charts of all new hepatitis B patients, who visited the clinic in the years 2002 and 2003 (January 2002 to December 2003), were reviewed. The main criteria for a diagnosis of acute hepatitis B were transient increase of alanine transaminase activity, and hepatitis B surface antigen seroconversion. RESULTS: Twenty nine men and seven women were diagnosed with acute hepatitis B infection during the study period. Two patients were previously vaccinated with hepatitis B vaccine. One case of hepatitis D coinfection was reported. The incidence of acute hepatitis B in the referral area was estimated as 2.25 per 100,000 adult population. Mean age was 36 years (17-75). Twenty one patients (18 men and 3 women) acquired the virus through unprotected sexual contact, and seven patients through iatrogenic exposure. Thirty three patients underwent spontaneous seroconversion while three patients became chronic carriers. CONCLUSIONS: Despite a universal immunisation policy, frequent cases of acute hepatitis B in Israel are still seen. High risk heterosexual activity and iatrogenic exposure seem to be the commonest routes of transmission. Further recommendations regarding vaccination policy are discussed.

Liver regeneration and alpha-fetoprotein messenger RNA expression in the retrorsine model for hepatocyte transplantation.

Recently, we described a new model for hepatocyte transplantation with nearly total replacement of the liver by exogenous hepatocytes (E. Laconi et al., Am. J. Pathol., 153: 319-329, 1998). The model is based on the mitoinhibitory effect of the pyrrolizidine alkaloid retrorsine on hepatocytes in the resident liver while transplanted hepatocytes proliferate. In this study, we exploit this novel approach to address the important and controversial issue of whether hepatocytes, when proliferating extensively, undergo dedifferentiation and give rise to foci of undifferentiated hepatocytes. Genetically marked hepatocytes (isolated from normal Dipeptidyl peptidase IV+ Fischer 344 rats) were delivered intraportally (2 x 10(6) cells) into the liver of retrorsine-treated Dipeptidyl peptidase IV- mutant Fischer 344 rats in conjunction with partial hepatectomy. Transplanted hepatocytes were detected histochemically or immunohistochemically, and cell proliferation was studied by in situ hybridization for histone-3 mRNA. Expression of alpha-fetoprotein (AFP) mRNA, a marker of hepatocyte dedifferentiation, was also revealed by in situ hybridization. One day after partial hepatectomy and hepatocyte transplantation, endogenous hepatocytes and oval cells expanding in the liver expressed histone-3 mRNA (cells had entered S phase); 2 days later, transplanted hepatocytes and nonparenchymal cells also expressed histone-3 mRNA. Although the majority of endogenous hepatocytes did not divide and became arrested as quiescent megalocytes, the exogenous hepatocytes, as well as newly formed small hepatocytes, most probably derived from liver progenitor cells, underwent extensive proliferation. After 7-14 days, the nonparenchymal cells stopped proliferating, but transplanted hepatocytes and small endogenous hepatocytes continued to proliferate for 1 month, forming foci of dividing parenchymal cells. Although many of the hepatocytes in clusters were in S phase (histone-3 mRNA positive), none expressed AFP mRNA. In contrast, high expression of AFP mRNA was observed in proliferating oval and transitional cells, forming duct-like structures of cytokeratin-19-positive cells. From these studies, we conclude that hepatocyte proliferation in the adult liver is not associated with dedifferentiation.

Coupling factor ATPase complex of Rhodospirillum rubrum. Purification and characterization of an oligomycin and N,N'-dicyclohexylcarbodiimide-sensitive (Ca+ + Mg2+)-ATPase.

An ATPase complex sensitive to the energy transfer inhibitors oligomycin, dicyclohexylcarbodiimide and venturicidin has been solubilized from Rhodospirillum rubrum chromatophores with Triton X-100 and further purified by centrifugation on a glycerol gradient. The partially purified RrFo . F1 contains 13 distinct polypeptide subunits, as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, including the subunits of the oligomycin-sensitive, water-soluble RrF1 ATPase. The ATPase activity of RrF0 . F1 as that of the membrane-bound enzyme complex depends on Ca2+ or Mg2+ and from detailed kinetic studies it is concluded that the divalent cation-ATP complex is the substrate for both ATPase complexes. Free ATP and free Mg2+ act as competitive inhibitors, with Ki values of 1 mM and 7 muM, respectively. The subunit composition of the purified RrFo . F1 and its similarity to the membrane-bound ATPase with respect to cation dependence and sensitivity to energy transfer inhibitors suggests that it contains all the subunits of the R. rubrum coupling factor-ATPase complex.

Accurate preoperative diagnosis of pericardial constriction using cine computed tomography.

OBJECTIVES: The purpose of this study was to determine the accuracy of cine computed tomography in the diagnosis of constrictive pericarditis. BACKGROUND: Constrictive pericarditis is characterized by abnormalities of both cardiac structure and function. Accurate diagnosis requires detection of both a thickened pericardium and abnormal ventricular diastolic filling. At present, no one diagnostic technique has demonstrated sufficient accuracy in this setting. Cine computed tomography is a relatively new cardiac imaging mode with very high time and spatial resolution that has the potential to accurately diagnose constrictive pericarditis. METHODS: Twelve consecutive patients were retrospectively identified who had catheterization findings suggestive of constrictive physiology, had undergone a cine computed tomographic examination and had pathologic data that delineated the status of the pericardium. Group 1 (with constrictive pericarditis; n = 5) had surgical confirmation of thickened pericardium and improved clinically after pericardiectomy. Group 2 (no constrictive pericarditis; n = 7) had cardiomyopathy with normal pericardium. Seven normal volunteers (Group 3) were also studied. Cine computed tomograms were obtained for the entire heart (8-mm slices, 17 frames/s, nonionic contrast medium). Pericardial thickness was measured at 10 degrees intervals at three ventricular levels in each subject. The rapidity of diastolic filling was assessed by calculating the percent filling fraction in early diastole. RESULTS: Pericardial thickness was 10 +/- 2 mm (mean +/- SD) in Group 1, 2 +/- 1 mm in Group 2 and 1 +/- 1 mm in Group 3 (p < 0.05, constrictive pericarditis vs. no constrictive pericarditis). Left ventricular filling fraction was 83 +/- 6% in Group 1, 62 +/- 9% in Group 2 and 44 +/- 5% in Group 3. Right ventricular filling fraction was 93 +/- 5% in Group 1, 62 +/- 14% in Group 2 and 35 +/- 6% in Group 3 (p < 0.05, Group 1 vs. Groups 2 and 3). Both indexes provided a clear-cut distinction between patients with and without constriction. CONCLUSIONS: Cine computed tomography simultaneously provides both anatomic and physiologic data that allow accurate preoperative diagnosis of pericardial constriction.

To induce or not to induce: do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy?

BACKGROUND: Induction immunosuppression utilizing lymphocytolytic agents in the early peri-operative period has a number of theoretical and practical advantages and disadvantages. However, the efficacy of cytolytic agents as induction therapy remains unproven. METHODS: To assess the current impact of induction therapy in heart transplantation, we queried a multi-institutional database regarding the frequency of use, type of agent, duration of therapy and outcomes of 6,553 patients transplanted from 1990 to 2001. A study group of 5,897 patients were identified who survived the first 48 hours post-transplant and received either no induction therapy (n = 4,161) or induction with OKT3 or anti-thymocyte preparations (n = 1,736). RESULTS: By multivariate analysis, risk factors for rejection death were identified and then applied to a model of overall mortality. Among patients with a 1-year risk of rejection death at >5%, induction therapy provided a survival advantage, but survival with induction was decreased when the risk of rejection death was <2%. Specific patient sub-sets that received a survival benefit in the current era with induction included younger patients of black race with >/=4 HLA mismatches and long-term (>6 months) support on a ventricular assist device (VAD). CONCLUSIONS: Use and application of induction therapy continues to be controversial in heart transplantation. At present, this approach appears to be beneficial in selected patients who are at high risk for rejection death, but likely detrimental in patients who are at low risk for rejection death. Those with a combination of longer term VAD support, of black ethnicity, and having extensive HLA mismatching are most likely to benefit from cytolytic induction therapy.

Effect of theophylline on erythrocytosis in chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) tend to develop secondary erythrocytosis to compensate for their chronic hypoxia. Theophylline has recently been shown to reduce hematocrit and erythropoietin blood levels in normal subjects and in patients with erythrocytosis after renal transplantation. OBJECTIVE: To determine whether theophylline may be used to lower the hematocrit in patients with COPD. METHODS: Two hundred four patients with COPD were studied retrospectively and 10 patients prospectively (8 starting treatment with the drug [group 1] and 2 who suspended its long-term use [group 2]) for the correlation between theophylline therapy and hematocrit and erythropoietin level. RESULTS: In the patients studied retrospectively, lower hematocrits were found in the theophylline-treated than in the untreated patients (0.43 +/- 0.006 vs 0.46 +/- 0.007, respectively; P < .002). Twelve untreated patients and 2 of those treated with theophylline had hematocrits above 52%. Oxygen saturation levels were similar in both groups, and exclusion of patients with oxygen saturation lower than 88% did not change the pattern, suggesting that the effect of theophylline could not be entirely explained by improved oxygen availability. Seven of the 8 patients studied prospectively in group 1 (P < .02) and the 2 patients in group 2 showed inverse correlations between hematocrits and theophylline administration. A similar pattern was observed with serum erythropoietin levels in 5 of 7 patients studied. The effects were reproducible on rechallenge in 3 of the 4 patients in group 1 and the 2 patients in group 2. CONCLUSIONS: Theophylline may have a beneficial effect in treatment and prevention of erythrocytosis in patients with COPD.

Relapsing hepatitis A. Review of 14 cases and literature survey.

We have reviewed our experience with 14 cases of relapsing hepatitis A (RH-A), as well as 68 cases reported in the literature. Relapse occurs in 3 to 20% of patients with acute hepatitis A, and rarely takes the form of a polyphasic disease (multiple relapses). After a stage of typical hepatitis A, remission phase ensues, with partial or complete resolution of clinical and biochemical manifestations. Relapse usually occurs after a short period (usually less than 3 weeks). Relapse is usually clinically milder than the first phase, with variable liver function abnormalities and a tendency toward more marked cholestatic features. Not uncommonly, immune manifestations occur during this phase, including purpura, nephritis, and arthralgia, with common laboratory findings of rheumatoid factor as well as false-positive reaction to HCV-EIA tests. The clinical course in relapsing hepatitis A is almost always benign, and uneventful recovery is the rule with few exceptions. Steroid treatment, first reported in the present series, resulted in marked clinical improvement. Preliminary results suggest that R-HA is associated with a continuing viremia as well as shedding of virus in stools during the relapse phase. The pathogenesis of R-HA probably involves an interaction between persistent viral infection and immune mechanisms responding to the continuing antigenic stimulation.

Engraftment of human kidney tissue in rat radiation chimera: II. Human fetal kidneys display reduced immunogenicity to adoptively transferred human peripheral blood mononuclear cells and exhibit rapid growth and development.

BACKGROUND: Transplantation of human kidney tissue under the kidney capsule of immunodeficient animals (severe combined immunodeficiency [SCID]/Lewis and SCID/nude chimeric rats), and the subsequent intraperitoneal infusion of allogeneic human peripheral blood mononuclear cells (PBMC), results in a rapid and consistent human renal allograft rejection. We investigated the consequences of grafting human fetal kidney fragments instead of the adult tissue. METHODS: The development of human fetal kidney tissue and its interaction with allogeneic human PBMC in chimeric rats were analyzed by histology, immunohistochemistry, and in situ hybridization. RESULTS: We report successful establishment of human fetal kidney to SCID/Lewis and SCID/nude chimeric rats. The intrarenal human fetal renal implants displayed rapid growth and maintained numerous developing glomeruli and tubular structures up to 4 months after transplantation. In contrast to the adult human kidney, infusion of allogeneic human PBMC resulted in either minimal human T-cell infiltration or abundant nonrejecting T-cell infiltrates, characterized by a reduced number of T cells of the CD45RO+ or HLA-DR+ subsets, both leading to less tissue destruction as well as to continued growth of the human fetal renal tissue. This observation was found to be related to the reduced protein expression of tissue HLA class I and II, intercellular adhesion molecule 1, and vascular adhesion molecule 1 in the fetal grafts compared with the adult grafts. Lack of tissue expression of Fas ligand in the fetal grafts suggests that the latter does not contribute to the delayed rejection of human fetal kidneys. CONCLUSIONS: Our model should be useful for the study of human fetal renal development and the human alloresponse against fetal tissue.

Effects of heart failure on baroreflex control of sympathetic neural activity.

Baroreflex control of heart rate, vascular resistance and norepinephrine is impaired in patients with heart failure, but recent animal studies demonstrate preserved baroreflex control of sympathetic nerve activity in this disorder. Studies were therefore performed to compare baroreflex control of efferent sympathetic nerve activity to muscle in 10 normal subjects (age mean +/- SEM 21 +/- 1 years) and in 11 patients with moderate to severe heart failure (age 48 +/- 5 years, New York Heart Association class II to IV, left ventricular ejection fraction 19 +/- 2%, pulmonary capillary wedge pressure 27 +/- 2 mm Hg, cardiac index 2.04 +/- 0.22 liters/min/m2). Baroreflex activation was produced by intravenous infusion of phenylephrine (0.5 to 2.0 micrograms/kg/min) and deactivation by infusion of nitroprusside (0.4 to 2.5 micrograms/kg/min). During phenylephrine infusion, comparable increases in mean arterial pressure were produced in normal subjects (89 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01) and in patients with heart failure (90 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01). The patients with heart failure exhibited significantly attenuated (p less than 0.01 for normal vs heart failure) decreases in heart rate (93 +/- 5 to 90 +/- 6 beats/min, p = not significant [NS]) compared with normal subjects (67 +/- 3 to 58 +/- 4 beats/min, p less than 0.01) and tended to demonstrate attenuated sympathoinhibitory responses to this pressor stimulus. More strikingly, patients with heart failure demonstrated significant impairment of baroreflex responses during nitroprusside-induced baroreceptor deactivation. In normal subjects, nitroprusside produced a decrease in mean arterial (90 +/- 2 to 80 +/- 3 mm Hg, p less than 0.001) and right atrial (4 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01) pressures with a resultant reflex increase in heart rate (68 +/- 3 to 81 +/- 4 beats/min, p less than 0.001) and muscle sympathetic nerve activity (326 +/- 74 to 746 +/- 147 U/min, p less than 0.01). In patients with heart failure (n = 10), nitroprusside produced comparable (p = NS for normal vs heart failure) decreases in mean arterial (89 +/- 2 to 77 +/- 2 mm Hg, p less than 0.001) and right atrial (6 +/- 1 to 1 +/- 1 mm Hg, p less than 0.001) pressures, but did not significantly alter heart rate (91 +/- 6 to 97 +/- 4 beats/min, p = NS) or sympathetic nerve activity (936 +/- 155 to 1179 +/- 275 U/min, p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)