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T cells that are gene-modified with tumor-specific T cell receptors are a promising treatment for metastatic melanoma patients. In a clinical trial, we treated seven metastatic melanoma patients with autologous T cells transduced to express a tyrosinase-reactive T cell receptor (TCR) (TIL 1383I) and a truncated CD34 molecule as a selection marker. We followed transgene expression in the TCR-transduced T cells after infusion and observed that both lentiviral- and retroviral-transduced T cells lost transgene expression over time, so that by 4 weeks post-transfer, few T cells expressed either lentiviral or retroviral transgenes. Transgene expression was reactivated by stimulation with anti-CD3/anti-CD28 beads and cytokines. TCR-transduced T cell lentiviral and retroviral transgene expression was also downregulated in vitro when T cells were cultured without cytokines. Transduced T cells cultured with interleukin (IL)-15 maintained transgene expression. Culturing gene-modified T cells in the presence of histone deacetylase (HDAC) inhibitors maintained transgene expression and functional TCR-transduced T cell responses to tumor. These results implicate epigenetic processes in the loss of transgene expression in lentiviral- and retroviral-transduced T cells., Graphical Abstract, Nishimura and colleagues demonstrate that transgene expression in gene-modified anti-tumor T cells is reversibly downregulated over time in vivo and in vitro. Treatment with IL-15 or with HDAC inhibitors (sodium butyrate or vorinostat) reduced this downregulation and maintained T cell functional responses to tumor cells.

Prior to this study, the Access Services Librarian systematically improved interlibrary loan (ILL) and related services offered by the R. Barbara Gitenstein Library of The College of New Jersey (TC...

Subject specialists seek to understand humanists' perceptions of e-books. The investigator conducted an online survey of humanities faculty at The College of New Jersey (TCNJ) to find out. ...

CATACOMB is a catalytic antagonist PRC2 subunit whose expression is induced upon DNA demethylation., Using biochemical characterization of fusion proteins associated with endometrial stromal sarcoma, we identified JAZF1 as a new subunit of the NuA4 acetyltransferase complex and CXORF67 as a subunit of the Polycomb Repressive Complex 2 (PRC2). Since CXORF67’s interaction with PRC2 leads to decreased PRC2-dependent H3K27me2/3 deposition, we propose a new name for this gene: CATACOMB (catalytic antagonist of Polycomb; official gene name: EZHIP). We map CATACOMB’s inhibitory function to a short highly conserved region and identify a single methionine residue essential for diminution of H3K27me2/3 levels. Remarkably, the amino acid sequence surrounding this critical methionine resembles the oncogenic histone H3 Lys27-to-methionine (H3K27M) mutation found in high-grade pediatric gliomas. As CATACOMB expression is regulated through DNA methylation/demethylation, we propose CATACOMB as the potential interlocutor between DNA methylation and PRC2 activity. We raise the possibility that similar regulatory mechanisms could exist for other methyltransferase complexes such as Trithorax/COMPASS.

A major obstacle hindering the development of effective immunity against viral infections, their associated disease, and certain cancers is their inherent genomic instability. Accumulation of mutations can alter processing and presentation of antigens recognized by antibodies and T cells that can lead to immune escape variants. Use of an agent that can intrinsically combat rapidly mutating viral or cancer-associated antigens would be quite advantageous in developing effective immunity against such disease. We propose that T cells harboring cross-reactive TCRs could serve as a therapeutic agent in these instances. With the use of hepatitis C virus, known for its genomic instability as a model for mutated antigen recognition, we demonstrate cross-reactivity against immunogenic and mutagenic nonstructural protein 3:1406-1415 and nonstructural protein 3:1073-1081 epitopes in PBL-derived, TCR-gene-modified T cells. These single TCR-engineered T cells can CD8-independently recognize naturally occurring and epidemiologically relevant mutant variants. TCR-peptide MHC modeling data allow us to rationalize how TCR structural properties accommodate recognition of certain mutated epitopes and how these substitutions impact the requirement of CD8 affinity enhancement for recognition. A better understanding of such TCRs’ promiscuous behavior may allow for exploitation of these properties to develop novel, adoptive T cell-based therapies for viral infections and cancers exhibiting similar genomic instability.

The success in recent clinical trials using T cell receptor (TCR)-genetically engineered T cells to treat melanoma has encouraged the use of this approach toward other malignancies and viral infections. Although hepatitis C virus (HCV) infection is being treated with a new set of successful direct anti-viral agents, potential for virologic breakthrough or relapse by immune escape variants remains. Additionally, many HCV+ patients have HCV-associated disease, including hepatocellular carcinoma (HCC), which does not respond to these novel drugs. Further exploration of other approaches to address HCV infection and its associated disease are highly warranted. Here, we demonstrate the therapeutic potential of PBL-derived T cells genetically engineered with a high-affinity, HLA-A2-restricted, HCV NS3:1406-1415-reactive TCR. HCV1406 TCR-transduced T cells can recognize naturally processed antigen and elicit CD8-independent recognition of both peptide-loaded targets and HCV+ human HCC cell lines. Furthermore, these cells can mediate regression of established HCV+ HCC in vivo. Our results suggest that HCV TCR-engineered antigen-reactive T cells may be a plausible immunotherapy option to treat HCV-associated malignancies, such as HCC.

ACRL recommends that librarians with faculty status have the same privileges and responsibilities as other faculty on campus. A recent study revealed librarians feel that being on an equal footing with other faculty improves the relationship. It is not clear whether disciplinary faculty feel the same way. This paper presents a study investigating faculty perceptions of librarians in two types of institutions: those granting and not granting librarians faculty status. The study found no noticeable differences in perceptions of librarians and library services. However, the authors identified variables other than librarian-faculty-status as important in affecting the relationship between librarians and teaching faculty. These factors can help better understand faculty needs. Effective strategies can be established to meet those needs.

Dysregulation of Polycomb Repressive Complex 2 (PRC2) function is a common feature of many cancer types, including both solid and hematologic malignancies. A number of chromosomal translocations involving Polycomb group proteins have been identified; however, the molecular function of these fusion proteins remains largely unexplored. Here we characterize two endometrial stromal sarcoma (ESS) associated fusion proteins: JAZF1-SUZ12 and MBTD1-CXORF67. We identify JAZF1 as a previously unreported subunit of the NuA4 complex, which when fused to SUZ12 creates a bridge between the NuA4 and PRC2 complexes. Intriguingly, the MBTD1-CXORF67 fusion binds to PRC2 and leads to strongly reduced levels of the PRC2 catalytic products H3K27me2/3. We demonstrate that this inhibitory function is mediated by the CXORF67 half of the fusion protein. Because of this striking property, we propose a new gene name: CATACOMB (CATalytic Antagosnist of polyCOMB; official gene name: EZHIP). We map CATACOMB’s inhibitory function to a short, highly conserved region and identify a single methionine residue essential for diminution of H3K27me2/3 levels. Remarkably, the amino acid sequence surrounding this critical methionine resembles that of the oncogenic histone H3 lysine-27-to-methionine (H3K27M) mutation found in high-grade pediatric gliomas. Finally, we show CATACOMB expression is silenced through DNA methylation and upon treatment with DNA demethylating agents, CATACOMB is expressed, binds to PRC2, and antagonizes its catalytic activity. In conclusion, we have identified an endogenous inducible gene, CATACOMB, which can regulate the catalytic activity of PRC2 and propose that such mechanism of regulation of histone modifications through the expression of antagonistic subunits may also exist for other histone-modifying enzyme complexes. Citation Format: Andrea Piunti, Edwin Smith, Marc Morgan, Michal Ugarenko, Natalia Khaltyan, Kathryn Helmin, Caila Ryan, David Murray, Ryan Rickels, Bahar Yilmaz, Emily Rendleman, Jeffrey Savas, Benjamin Singer, Serdar Bulun, Ali Shilatifard. CATACOMB: An endogenous inducible gene that antagonizes H3K27 methylation activity of Polycomb Repressive complex 2 via a H3K27M-like mechanism [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B46.

The super elongation complex (SEC) is required for robust and productive transcription through release of RNA polymerase II (Pol II) with its P-TEFb module and promoting transcriptional processivity with its ELL2 subunit. Malfunction of SEC contributes to multiple human diseases including cancer. Here, we identify peptidomimetic lead compounds, KL-1 and its structural homolog KL-2, which disrupt the interaction between the SEC scaffolding protein AFF4 and P-TEFb, resulting in impaired release of Pol II from promoter-proximal pause sites and a reduced average rate of processive transcription elongation. SEC is required for induction of heat-shock genes and treating cells with KL-1 and KL-2 attenuates the heat-shock response from Drosophila to human. SEC inhibition downregulates MYC and MYC-dependent transcriptional programs in mammalian cells and delays tumor progression in a mouse xenograft model of MYC-driven cancer, indicating that small-molecule disruptors of SEC could be used for targeted therapy of MYC-induced cancer.

T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity. It is critical to re-evaluate the importance of other biophysical, structural, or cellular factors that drive the reactivity of TCR gene-modified T-cells. Using a model for altered antigen recognition, we determined how TCR-pMHC affinity influenced the reactivity of hepatitis C virus (HCV) TCR gene-modified T-cells against a panel of naturally occurring HCV peptides and HCV-expressing tumor targets. The impact of other factors, such as TCR-pMHC stabilization and signaling contributions by the CD8 co-receptor, as well as antigen and TCR density were also evaluated. We found that changes in TCR-pMHC affinity did not always predict or dictate IFNγ release or degranulation by TCR gene-modified T-cells, suggesting that less emphasis might need to be placed on TCR-pMHC affinity as a means of predicting or augmenting the therapeutic potential of TCR gene-modified T-cells used in ACT. A more complete understanding of antigen recognition by gene-modified T-cells and a more rational approach to improve the design and implementation of novel TCR-based immunotherapies is necessary to enhance efficacy and maximize safety in patients.

The identification of native sources and vectors of introduced species informs their ecological and evolutionary history and may guide policies that seek to prevent future introductions. Population genetics provides a powerful set of tools to identify origins and vectors. However, these tools can mislead when the native range is poorly sampled or few molecular markers are used. Here, we traced the introduction of the Asian seaweed Gracilaria vermiculophylla (Rhodophyta) into estuaries in coastal western North America, the eastern United States, Europe, and northwestern Africa by genotyping more than 2,500 thalli from 37 native and 53 non‐native sites at mitochondrial cox1 and 10 nuclear microsatellite loci. Overall, greater than 90% of introduced thalli had a genetic signature similar to thalli sampled from the coastline of northeastern Japan, strongly indicating this region served as the principal source of the invasion. Notably, northeastern Japan exported the vast majority of the oyster Crassostrea gigas during the 20th century. The preponderance of evidence suggests G. vermiculophylla may have been inadvertently introduced with C. gigas shipments and that northeastern Japan is a common source region for estuarine invaders. Each invaded coastline reflected a complex mix of direct introductions from Japan and secondary introductions from other invaded coastlines. The spread of G. vermiculophylla along each coastline was likely facilitated by aquaculture, fishing, and boating activities. Our ability to document a source region was enabled by a robust sampling of locations and loci that previous studies lacked and strong phylogeographic structure along native coastlines.

The source and vector of an introduced species inform its ecological and evolutionary history and may guide management that seeks to prevent future introductions. Surprisingly, few studies have successfully used genetic tools to independently inform the specific source and pathway of biological invasions. The ecological history of many introduced species, including their origins and vectors, is often based on suppositions or educated guesses. Here, we used mitochondrial and microsatellite genotyping to trace the invasion of the Asian seaweed Gracilaria vermiculophylla (Rhodophyta) along the three coastlines of the Northern Hemisphere to which it has been introduced: the western coast of North America, eastern coast of the United States and the coasts of Europe and northwest Africa. Analyzing 37 native and 53 introduced sites, we identified the Pacific coastline of northeastern Japan as the ultimate source of the Northern Hemisphere invasion. Coincidentally, most exports of the oyster Crassostrea gigas historically originated from this region and both species often grow in close proximity. Based on genetic signatures, each of the three coastlines likely received thalli directly from Japan, as well as material from another introduced coastline (i.e., a secondary invasion). Our ability to document a source region, which was enabled by a robust sampling of locations and loci that previous studies lacked, reflected strong phylogeographic structure along native coastlines. We suggest Gracilaria vermiculophylla is an important representative example of many species likely exported out of Japan by the oyster trade and its genetic signatures that may be a hallmark of oyster introduction legacies.

Author(s): Fechner, Uli; de Graaf, Chris; Torda, Andrew E; Gussregen, Stefan; Evers, Andreas; Matter, Hans; Hessler, Gerhard; Richmond, Nicola J; Schmidtke, Peter; Segler, Marwin HS; Waller, Mark P; Pleik, Stefanie; Shea, Joan-Emma; Levine, Zachary; Mullen, Ryan; van den Broek, Karina; Epple, Matthias; Kuhn, Hubert; Truszkowski, Andreas; Zielesny, Achim; Fraaije, Johannes Hans; Gracia, Ruben Serral; Kast, Stefan M; Bulusu, Krishna C; Bender, Andreas; Yosipof, Abraham; Nahum, Oren; Senderowitz, Hanoch; Krotzky, Timo; Schulz, Robert; Wolber, Gerhard; Bietz, Stefan; Rarey, Matthias; Zimmermann, Markus O; Lange, Andreas; Ruff, Manuel; Heidrich, Johannes; Onlia, Ionut; Exner, Thomas E; Boeckler, Frank M; Bermudez, Marcel; Firaha, Dzmitry S; Holloczki, Oldamur; Kirchner, Barbara; Tautermann, Christofer S; Volkamer, Andrea; Eid, Sameh; Turk, Samo; Rippmann, Friedrich; Fulle, Simone; Saleh, Noureldin; Saladino, Giorgio; Gervasio, Francesco L; Haensele, Elke; Banting, Lee; Whitley, David C; Oliveira Santos, Jana Sopkova-de; Bureau, Ronan; Clark, Timothy; Sandmann, Achim; Lanig, Harald; Kibies, Patrick; Heil, Jochen; Hoffgaard, Franziska; Frach, Roland; Engel, Julian; Smith, Steven; Basu, Debjit; Rauh, Daniel; Kohlbacher, Oliver; Boeckler, Frank M; Essex, Jonathan W; Bodnarchuk, Michael S; Ross, Gregory A; Finkelmann, Arndt R; Goller, Andreas H; Schneider, Gisbert; Husch, Tamara; Schutter, Christoph; Balducci, Andrea; Korth, Martin; Ntie-Kang, Fidele; Gunther, Stefan; Sippl, Wolfgang; Mbaze, Luc Meva'a

Baker's Law predicts uniparental reproduction will facilitate colonization success in novel habitats. While evidence supports this prediction among colonizing plants and animals, few studies have investigated shifts in reproductive mode in haplo-diplontic species in which both prolonged haploid and diploid stages separate meiosis and fertilization in time and space. Due to this separation, asexual reproduction can yield the dominance of one of the ploidy stages in colonizing populations. We tested for shifts in ploidy and reproductive mode across native and introduced populations of the red seaweed Gracilaria vermiculophylla. Native populations in the northwest Pacific Ocean were nearly always attached by holdfasts to hard substrata and, as is characteristic of the genus, haploid–diploid ratios were slightly diploid-biased. In contrast, along North American and European coastlines, introduced populations nearly always floated atop soft-sediment mudflats and were overwhelmingly dominated by diploid thalli without holdfasts. Introduced populations exhibited population genetic signals consistent with extensive vegetative fragmentation, while native populations did not. Thus, the ecological shift from attached to unattached thalli, ostensibly necessitated by the invasion of soft-sediment habitats, correlated with shifts from sexual to asexual reproduction and slight to strong diploid bias. We extend Baker's Law by predicting other colonizing haplo-diplontic species will show similar increases in asexuality that correlate with the dominance of one ploidy stage. Labile mating systems likely facilitate colonization success and subsequent range expansion, but for haplo-diplontic species, the long-term eco-evolutionary impacts will depend on which ploidy stage is lost and the degree to which asexual reproduction is canalized.

The synthesis and spectroscopic characterisation of [ScCl(15-crown-5)(MeCN)][SbCl6]2, [ScCl2(18-crown-6)][FeCl4] and [ScCl2([15]aneS2O3)][FeCl4] ([15]aneS2O3 = 1,4-dithia-7,10,13-trioxacyclopentadecane) are reported, the last containing the first example of thioether-scandium(III) coordination. The structure of [ScCl(15-crown-5)(MeCN)][SbCl6]2 reveals a pentagonal bipyramidal cation with axial Cl and MeCN, whilst [ScCl2(18-crown-6)][FeCl4] is also pentagonal bipyramidal with axial Cl ligands. 1H and 45Sc NMR spectroscopies have been used to study the speciation in the ScCl3/18-crown-6 system in the presence of the Lewis acids SbCl5 and FeCl3 in anhydrous MeCN. Hydrolysis of any of the above complexes and of [Sc(12-crown-4)2]3+ (formed from ScCl3(thf)3, crown and SbCl5), results in the formation of [ScCl3(H2O)3]·crown, the solution NMR spectra of which show a common scandium species and uncomplexed crown ether. The structure of [ScCl3(H2O)3]·18-crown-6 reveals a mer octahedral scandium species which is hydrogen bonded via the scandium-coordinated water to the 18-crown-6 (secondary coordination) leading to infinite chains. Similar complexes have been isolated directly from reaction of ScCl3·6H2O and the crown ethers in absolute ethanol, including [ScCl3(H2O)3]n·(crown) (n = 1 or 2, crown = 18-crown-6; n = 2, crown = 15-crown-5 or 12-crown-4). Hydrated scandium nitrate and the crown ethers react in ethanol solution to form a surprisingly diverse range of structural types containing the crown ethers hydrogen bonded to the scandium-aquo-nitrato or scandium-aquo-hydroxo-nitrato complexes. X-Ray crystal structures are reported for [Sc(H2O)2(NO3)3]·(12-crown-4)2, [Sc(H2O)4(NO3)2]NO3·15-crown-5 and [Sc2(NO3)2(H2O)6(OH)2](NO3)2·12-crown-4. However, in the related [Sc2(NO3)4(H2O)4(OH)2][Na(12-crown-4)2](NO3)·(H2O)3 the hydrogen bonding occurs between the lattice water and the scandium dimer unit.

Long-term evolution of cardiomyopathy in dialysis patients Background. Left ventricular enlargement is very common at the inception of dialysis therapy, and highly predictive of future cardiac morbidity and mortality. It is not known whether cardiac size increases further while on dialysis therapy and whether potentially reversible risk factors for later progression can be identified. Methods. Baseline and yearly echocardiograms were performed in a prospective inception cohort of 433 dialysis patients. The mean patient follow-up was 41 months; 29 patients had four consecutive echocardiograms at yearly intervals. Results. The patient subset with four echocardiograms was older (58 vs. 51 years, P 5 0.02) and had a lower mass ventricular mass index (128 vs. 149 g/m 2 , P 5 0.02) than the parent group. Using repeated measures analysis of variance, applied to those with four echocardiograms, there were progressive increases over time in posterior wall thickness (P 5 0.015), left ventricular end-diastolic diameter, left ventricular mass index (P 5 0.001), and cavity volume index (P 5 0.001). Mass-to-volume ratios did not change. The biggest changes in mass (18 g/m 2 2 14%)and volume index (13 ml/m 2 2 18%) occurred between baseline and year 1, although increases in both were seen after year 1. Hemodialysis versus peritoneal dialysis (41 g/m 2 , P 5 0.008) and anemia (10 g/m 2 per 1 g/dl drop in hemoglobin, P 5 0.02) were associated with progressive left ventricular enlargement, but only within the first year of dialysis therapy. The left ventricular enlargement seen after year 1 was independent of anemia, blood pressure, serum albumin and mode of dialysis. Conclusions. Progressive cardiac enlargement, particularly left ventricular dilation with compensatory hypertrophy, continues after starting dialysis therapy. Most of the additional cardiac enlargement seems to occur in the first year of dialysis therapy, suggesting that intervention beyond one year may be relatively ineffective.

Background. Left ventricular disease occurs frequently in dialysis patients. It may be manifest as concentric LV hypertrophy, LV dilatation with or without LV hypertrophy, or systolic dysfunction. Little is known concerning the clinical outcome and risk factors for these disorders. Methods. A cohort of 432 end-stage renal disease patients who survived at least 6 months had an echocardiogram on initiation of dialysis therapy. Clinical, laboratory and echocardiographic data was obtained annually during follow-up. Results. On initiation of ESRD therapy 16% of patients had systolic dysfunction, 41% concentric LV hypertrophy, 28% LV dilatation, and only 16% had normal echocardiograms. Median time to development of heart failure was 19 months in patients with systolic dysfunction, 38 months in concentric LV hypertrophy and 38 months in LV dilatation. The relative risks of heart failure in the three groups were significantly worse than in the normal group, after adjusting for age, diabetes and ischaemic heart disease. Median survival was 38 months in systolic dysfunction, 48 months in concentric hypertrophy, 56 months in LV dilatation, and >66 months in the normal group. Two hundred and seventy-five patients had a follow-up echocardiogram 17 months after starting dialysis therapy together with serial measurement of potential risk factors prior to the echocardiogram. On follow-up echocardiogram the degree of concentric LV hypertrophy was independently related to hypertension while on dialysis, older age, and anaemia while on dialysis ; the degree of LV dilatation was related to ischaemic heart disease, anaemia, hypertension and hypoalbuminemia while on dialysis ; the degree of systolic dysfunction was associated with ischaemic heart disease and anaemia during follow-up. Conclusions. Manifestations of left ventricular disease are frequent and persistent in chronic uraemia, and are associated with high risks of heart failure and death. Potentially reversible risk factors include anaemia, hypertension, hypoalbuminaemia and ischaemic heart disease.

Outcome and risk factors of ischemic heart disease in chronic uremia. To determine the prognosis and risk factors for ischemic heart disease in chronic uremia, a cohort of 432 dialysis patients were followed prospectively from start of dialysis therapy until death or renal transplantation. Baseline demographic, clinical and echocardiographic data were obtained. After the initiation of dialysis laboratory data were collected at monthly intervals, and clinical and echocardiographic data at yearly intervals. Twenty-two percent of patients (N = 95) had either a history of angina pectoris or myocardial infarction on starting dialysis therapy. Median time to onset of heart failure was 24 months in those with ischemic heart disease on initiation of dialysis, compared to 55 months in those without (P < 0.0001). This effect was independent of age, diabetes and underlying cardiomyopathy. Median survival was 44 months in those with ischemic disease compared to 56 months in those without (P = 0.0001). This adverse impact was independent of age and diabetes mellitus but, when cardiac failure was added to the Cox's model, ischemic heart disease was no longer an independent predictor of survival. De novo ischemic heart disease, not evident on starting dialysis therapy, occurred in 41 (9%) patients. When compared to patients who never developed ischemic disease (N = 296; 69%), significant and independent predictors of de novo disease were older age (P = 0.0007), diabetes mellitus (P = 0.0001), high blood pressure during follow up on dialysis (P = 0.02) and hypoalbuminemia (P = 0.03), whereas anemia was not an independent predictor. LV mass index was 174 ± 7 g/m2 in those who developed de novo ischemic disease compared to 155 ± 3 g/m2 (P < 0.001) in those who did not. Concentric LV hypertrophy, LV dilation and systolic dysfunction were independent risk factors for de novo ischemic heart disease. We conclude that ischemic heart disease occurs frequently in dialysis patients, that its adverse impact is mediated through the development of heart failure, and that the most important, potentially reversible risk factors are hypertension, hypoalbuminemia, and underlying cardiomyopathy.

In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular (LV) hypertrophy, or LV dilatation. To determine the impact of renal transplantation on uremic cardiomyopathy, all dialysis patients participating in a long-term cohort study who received a successful renal transplant were followed with echocardiography. The transplanted group comprised 102 of 433 (24%) endstage renal disease (ESRD) patients. They were significantly younger and, on starting ESRD therapy, had significantly less ischemic heart disease and cardiac failure than the overall ESRD cohort. During followup, ischemic heart disease developed in only 1 patient and none experienced cardiac failure. In the 12% (n = 12) of patients with systolic dysfunction before renal transplant, fractional shortening normalized in all patients, increasing from 21.5 +/- 4.6% to 33.5 +/- 5.6% after transplantation. In the 41% (n = 41) with concentric LV hypertrophy before transplantation, the LV mass index improved from 158 +/- 39 g/m2 to 132 +/- 39 g/m2. LV dilatation was present in 32% (n = 32) of patients before transplantation. After transplantation, LV volume fell from 116 +/- 3.1 ml/m2 to 89 +/- 21 ml/m2, and LV mass index in this group fell from 166 +/- 55 g/m2 to 135 +/- 37 g/m2. It was not possible to associate risk factors characteristic of the uremic state with the improvement in cardiac structure and function, although the fall in LV mass was significantly associated with fall in blood pressure. We conclude that correction of the uremic state by renal transplantation leads to normalization of LV contractility in systolic dysfunction, regression of hypertrophy in concentric LV hypertrophy, and improvement of cavity volume in LV dilatation. The degree of improvement suggests that dialysis patients with uremic cardiomyopathy would benefit from renal transplantation.

As RUSA is exploring how, if at all, the word “reference” succeeds in describing what its members do in the twenty-first-century library, it seemed an opportune moment to publish David Murray’s column reflecting on reference services. I hope that this column will help us to continue the discussion of how best to describe, in a usable fashion, the complex work that public service librarians are engaged in. I would be eager to feature the work of other writers who would like to contribute to this discussion, and encourage anyone interested in writing on this topic to contact me at btrott@wrl.org. We all agree, I believe, that our work is important to our users, and the challenge is in finding a way to recognize the changes that have happened in that work without abandoning the strengths that brought us to this point. I believe that David’s column is a good start to that discussion.—Editor

The objective of this study was to determine the effect of left ventricular (LV) mass, volume, and mass-to-volume ratio on mortality in chronic dialysis patients. The Design was a multicenter, prospective inception cohort study with a median follow-up of 41 months. The Setting was three university-affiliated nephrology units. A total of 433 patients who (1) survived6 months from the start of ESRD therapy and (2) had a technically satisfactory baseline echocardiogram were studied. Measurements included a baseline clinical, laboratory and echocardiographic assessment. LV hypertrophy was present in 74% and LV dilation was present in 36% of patients. In patients with normal cavity volume (or = 90 mL/m2) and normal systolic function, high LV mass index (120 g/m2) and mass-to-volume ratios (2.2 g/mL) were independently associated with late mortality (2 yr after starting dialysis therapy). After adjusting for baseline age, diabetes, and ischemic heart disease, the relative risk for the former was 3.29 and for the latter was 2.24. Cavity volume was of no prognostic significance in this group. In patients with LV dilation and normal systolic function, high cavity volume (120 mL/m2) and low mass-to-volume ratio (1.8 mL/m2) were independently associated with late mortality, the relative risk in the former being 17.14 and the latter being 4.27. LV mass index was of no prognostic significance in this group. The baseline echocardiographic classification, based on LV mass and cavity volume, was the strongest predictor of late mortality, after adjusting for age, gender, diabetes mellitus, coronary artery disease, angina pectoris, chronic hypertension, and hemoglobin and serum albumin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

A major obstacle hindering the development of effective immunity against viral infections, their associated disease, and certain cancers is their genomic instability. Accumulation of mutations can alter processing/presentation of antigens recognized by antibodies and T cells leading to immune escape variants. A therapeutic agent that can combat rapidly mutating viral or cancer-associated antigens would be advantageous in providing effective immunity. We propose T cells harboring cross-reactive TCRs may offer a solution in these instances. Using hepatitis C virus (HCV), known for its genomic instability, as a model for mutant antigen recognition, we demonstrate cross-reactivity of TCRs against immunogenic and mutagenic NS3:1406-1415 and NS3:1073-1081 epitopes in TCR-gene-modified T cells. Our approach includes (1) functional studies demonstrating crossreactive profiles; (2) epidemiological data supporting the relevance of mutant epitope prevalence in infected individuals; (3) TCR-pMHC structural modeling to rationalize how TCR structural properties accommodate recognition of certain mutated epitopes and how they impact the requirement of CD8; lastly, we (4) provide preliminary clinical evidence of cross-reactive TCR benefit in that T cell clones isolated from HCV-infected patients who spontaneously resolved infection exhibited broader cross-reactivity compared to those of individuals with chronic infection. Together this approach serves as a model to address diseases with genomic instability and highlights potential benefit of cross-reactive TCRs. A better understanding of such TCRs’ promiscuous behavior may allow for exploitation of these properties to develop novel adoptive T cell-based therapies.

Superposition (convolution using a noninvariant kernel) has been shown to be a highly promising technique for use in calculating dose distributions in radiotherapytreatment planning. However, one major difficulty that currently prevents use in routine planning is the computational effort required to perform the calculation in three dimensions. To help solve this problem the superposition technique has been implemented on a parallel processor multicomputer in order to examine the performance characteristics of such a system. Up to eight elements have been connected in a pipeline (linear array), and tree networks of three and seven processors have also been constructed (using INMOS T800 transputers). The significant results obtained with these networks are: (1) Both topologies provide near‐linear speedup with increasing processor number (8 processors provide 7.81 times the computing power of a single processor when using an optimal communication packet size); (2) increasing communication packet size from 1 voxel to an optimum of approximately 40 voxels significantly reduces communication overhead per processor. Overhead per processor for a 7‐element linear array is 6.9% when using 1‐voxel packets, but only 1.8% when using 40‐voxel packets; (3) the topology of the network has some effect on communication overhead: Arranging 7 processors in a 1–2–4 binary tree reduces overhead to 80.1% of that encountered using a 7‐element linear array (with packet size of 1 voxel).

Purpose: The majority of cases of Cushing’s disease are due to the presence of a corticotroph microadenoma. Less frequently no adenoma is found and histology shows either corticotroph hyperplasia, or apparently normal pituitary. In this study we have used molecular pathology to determine whether the tissue labeled histologically as “normal” is indeed abnormal. Experimental Design: Tissue from 31 corticotroph adenomas and 16 nonadenomatous pituitaries were subject to methylation-sensitive PCR to determine the methylation status of the p16 gene CpG island. The proportion of methylated versus unmethylated CpG island was determined using combined bisulphite restriction analysis. Methylation status was correlated with immunohistochemical detection of p16. Results: Seventeen of 31 adenomas (54.8%), 4 of 6 cases of corticotroph hyperplasia, and 7 of 10 apparently normal pituitaries showed p16 methylation. Ten of 14 (71%; P = 0.01) adenomas and 2 of 3 cases of corticotroph hyperplasia, which were methylated, failed to express p16 protein. However, only 2 of 7 apparently normal pituitaries that were methylated failed to express p16 protein. Quantitative analysis of methylation using combined bisulphite restriction analysis showed only unmethylated CpG islands in postmortem normal pituitaries; however, in adenomas 80–90% of the cells within a specimen were methylated. The reverse was true for corticotroph hyperplasia and apparently normal pituitaries where only 10–20% of the cells were methylated. Thus, the decreased proportion of cells that were methylated, particularly in those cases of apparently normal pituitary, is the most likely explanation for the lack of association between this change and loss of cognate protein in these cases. Conclusions: To our knowledge this is the first report that describes an intrinsic molecular change, namely methylation of the p16 gene CpG island, common to all three histological patterns associated with Cushing’s disease. Thus, the use of molecular pathology reveals abnormalities undetected by routine pathological investigation. In cases of “apparently” normal pituitaries it is not possible to determine whether the change is associated with adenoma cells “scattered” throughout the gland, albeit few in number, or with the ancestor-clonal origin of these tumor cells.

Echocardiographic abnormalities are the rule in patients starting dialysis therapy and are associated with the development of cardiac failure and death. It is unknown, however, whether regression of these abnormalities is associated with an improvement in prognosis. As part of a prospective cohort study with mean follow-up of 41 mo, 227 patients had echocardiography at inception and after 1 yr of dialysis therapy. Improvements in left ventricular (LV) mass index, volume index, and fractional shortening were seen in 48, 48, and 46%, respectively. Ninety patients had developed cardiac failure by 1 yr of dialysis therapy. Twenty-six percent of the remaining 137 patients subsequently developed new-onset cardiac failure. The mean changes in LV mass index were 17 g/m(2) in those who subsequently developed cardiac failure compared with 0 g/m(2) among those who did not (P = 0.05). The corresponding values were -8 versus 0% for fractional shortening (P < 0.0001). The associations between serial change in both LV mass index and fractional shortening and subsequent cardiac failure persisted after adjusting for baseline age, diabetes, ischemic heart disease, and the corresponding baseline echocardiographic parameter. Regression of LV abnormalities is associated with an improved cardiac outcome in dialysis patients. Serial echocardiography adds prognostic information to one performed at baseline.

Despite considerable differences in technique and blood purification characteristics, hemodialysis and peritoneal dialysis have been thought to have similar patient outcomes. An inception cohort of433 end-stage renal disease patients was followed prospectively for a mean of 4 1 mo. The outcomes of hemodialysis (HD) and peritoneal dialysis (PD) patients were compared using intention to treat analysis based on the mode of therapy at 3 mo. After adjustment for PD patients less likely to have chronic hypertension and more likely to have diabetes, ischemic heart disease, and cardiac failure at baseline (P < 0.05), a biphasic mortality pattern was observed. For the first 2 yr, there was no statistically significant difference in mortality. After 2 yr, mortality was greater among PD patients with an adjusted PD/HD hazard ratio of 1.57 (95% confidence interval (CI), 0.97 to 2.53). Both the occurrence (adjusted hazards ratio 6.87 (95% CI, 2.01 to 23.5)) and the direction (toward PD, adjusted hazards ratio 6.25 (95% CI, 1.54 to 25)) of a therapy switch were subsequently associated with mortality after 2 yr. Progressive clinical and echocardiographic cardiac disease were not responsible for this late mortality. Lower mean serum albumin levels in PD patients in the first 2 yr of therapy (3.5 ± 0.5 versus 3.9 ± 0.5 g/dl, P < 0.0001) accounted for a large proportion of the increase in subsequent mortality. Hemodial- ysis has a late survival advantage over peritoneal dialysis; antecedent hypoalbuminemia is a major marker of the in- creased late mortality in PD patients. (J Am Soc Nephrol 9

Little is known about the epidemiology of cardiac disease in diabetic end-stage renal disease. We therefore prospectively followed a cohort of 433 patients who survived 6 months after the inception of dialysis therapy for an average of 41 months. Clinical and echocardiographic data were collected yearly. At baseline, diabetic patients (n = 116) had more echocardiographic concentric left ventricular hypertrophy (50 vs 38 %, p = 0.04), clinically diagnosed ischaemic heart disease (32 vs 18%, p = 0.003) and cardiac failure (48 vs 24%, p < 0.00001) than non-diabetic patients (n = 317). After adjusting for age and sex, diabetic patients had similar rates of progression of echocardiographic disorders, and de novo cardiac failure, but higher rates of de novo clinically diagnosed ischaemic heart disease (RR 3.2, p = 0.0002), overall mortality (RR 2.3, p < 0.0001) and cardiovascular mortality (RR 2.6, p < 0.0001) than non-diabetic patients. Mortality was higher in diabetic patients following admission for clinically diagnosed ischaemic heart disease (RR 1.7, p = 0.05) and cardiac failure (RR 2.2, p = 0.0003). Among diabetic patients older age, left ventricular hypertrophy, smoking, clinically diagnosed ischaemic heart disease, cardiac failure and hypoalbuminaemia were independently associated with mortality. The excessive cardiac morbidity and mortality of diabetic patients seem to be mediated via ischaemic disease, rather than progression of cardiomyopathy while on dialysis therapy. Potentially remediable risk factors include smoking, left ventricular hypertrophy, and hypoalbuminaemia.

To determine the possible association between anemia and clinical and echocardiographic cardiac disease, a cohort of 432 end-stage renal disease patients (261 on hemodialysis and 171 on peritoneal dialysis) who started dialysis therapy between 1982 and 1991 were followed prospectively for an average of 41 months. Baseline demographic, clinical, and echocardiographic assessments were performed, as well as monthly serial clinical and laboratory tests while the patients were on dialysis therapy. The mean (+/-SD) hemoglobin level during dialysis therapy was 8.8 +/- 1.5 g/dL. After adjusting for age, diabetes, and ischemic heart disease, as well as for blood pressure and serum albumin levels measured serially, each 1 g/dL decrease in mean hemoglobin was independently associated with the presence of left ventricular dilatation on repeat echocardiogram (odds ratio, 1.46; P = 0.018) and the development of de novo (relative risk [RR] = 1.28; P = 0.018) and recurrent (RR = 1.20; P = 0.046) cardiac failure. In addition, each 1 g/dL decrease in the mean hemoglobin level was independently associated with mortality while the patients were on dialysis therapy (RR = 1.14; P = 0.024). Anemia had no independent association with the development of ischemic heart disease while the patients were on dialysis therapy. Anemia, an easily reversible feature of end-stage renal disease, is an independent risk factor for clinical and echocardiographic cardiac disease, as well as mortality in end-stage renal disease patients.

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed up prospectively for an average of 41 months. Baseline and annual demographic, clinical, and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while patients were on dialysis therapy. Among hemodialysis patients, after adjustment was made for age, diabetes, and ischemic heart disease, as well as hemoglobin and blood pressure levels measured serially, a 10-g/L fall in mean serum albumin level was independently associated with the the development of de novo (relative risk [RR], 2.22; P = 0.001) and recurrent cardiac failure (RR, 3.84; P = 0.003), de novo (RR, 5.29; P = 0.001) and recurrent ischemic heart disease (RR, 4.24; P = 0.005), cardiac mortality (RR, 5.60; P = 0.001), and overall mortality (RR, 4.33; P < 0.001). Among peritoneal dialysis patients, a 10-g/L fall in mean serum albumin level was independently associated with the progression of left ventricular dilation as seen on follow-up echocardiography (beta, 13.4 mL/m2; P = 0.014), the development of de novo cardiac failure (RR, 4.16; P = 0.003), and overall mortality (RR, 2.06; P < 0.001). Hypoalbuminemia, a major adverse prognostic factor in dialysis patients, is strongly associated with cardiac disease.

Hypocalcemia and hyperphosphatemia with secondary hyper-parathyroidism are characteristic of end-stage renal disease (ESRD). Although calcium levels critically affect almost all cellular processes, the impact of chronic hypocalcemia and other abnormalities of calcium-phosphate homeostasis on the prognosis of ESRD patients is unknown.An inception cohort of 433 patients starting ESRD therapy was followed prospectively for an average of 41 months. Serum calcium and other parameters were measured monthly. The mean calcium levels were 9.4 +/- 0.7 mg/dl. 23% of the patients had mean calcium levels8.8 mg/dl. After adjusting for baseline age, diabetes mellitus, ischemic heart disease, smoking and cholesterol levels, as well as serial albumin, hemoglobin, mean arterial blood pressure, phosphate and alkaline phosphatase levels, chronic hypocalcemia was strongly associated with mortality (RR 2.10, p = 0.006 for a mean calcium level8.8 mg/dl). The association with mortality was similar in hemodialysis (RR 2.10, p = 0.006) and peritoneal dialysis patients (2.67, p = 0.034). Using similar covariate adjustment, chronic hypocalcemia was associated with de novo ischemic heart disease (RR 5.23, p0.001), recurrent ischemic heart disease (RR 2.46, p = 0.006), de novo cardiac failure (RR 2.64, p0.001), and recurrent cardiac failure (RR 3.30, p0.001). Hypocalcemia retained its independent impact on morbidity and mortality when analyzed as a time-dependent covariate.Chronic hypocalcemia, a very common, reversible feature of chronic uremia, is independently associated with morbidity and mortality in ESRD patients.

Congestive heart failure in dialysis patients: Prevalence, incidence, prognosis and risk factors. Cardiovascular disease is the most common cause of death in dialysis subjects. Congestive heart failure (CHF) is a common presenting symptom of cardiovascular disease in the dialysis population. Information regarding prevalence, incidence, risk factors and prognosis is crucial for planning rational interventional studies. A prospective multicenter cohort study of 432 dialysis patients followed for a mean of 41 months was carried out. Prospective information on a variety of risk factors was collected. Annual echocardiography and clinical assessment was performed. Major endpoints included death and the development of morbid cardiovascular events. One hundred and thirty-three (31%) subjects had CHF at the time of initiation of dialysis therapy. Multivariate analysis showed that the following risk factors were significantly and independently associated with CHF at baseline: systolic dysfunction, older age, diabetes mellitus and ischemic heart disease. Seventy-six of 299 subjects (25%) who did not have baseline CHF subsequently developed CHF during their course on dialysis. Compared to those subjects who never developed CHF (N = 218) multivariate analysis identified the following risk factors for the development of CHF: older age, anemia during dialysis therapy, hypoalbuminemia, hypertension during dialysis therapy, and systolic dysfunction. Seventy-five of the 133 (56%) subjects with CHF at baseline had recurrent CHF during follow-up. Independent and significant risk factors for CHF recurrence were ischemic heart disease and systolic dysfunction, anemia during dialysis therapy and hypoalbuminemia. The median survival of subjects with CHF at baseline was 36 months compared to 62 months in subjects without CHF. In this study the prevalence of CHF on starting ESRD therapy and the subsequent annual incidence was high. CHF was a strong, independent, adverse prognostic indicator. Risk factors for CHF include older age, pre-existing cardiac diseases (systolic dysfunction and ischemic heart disease), and potentially reversible abnormalities related to chronic uremia (anemia, hypertension and hypoalbuminemia).

Clinical and echocardiographic disease in patients starting end-stage renal disease therapy. End-stage renal disease (ESRD) patients have a high cardiovascular mortality rate. Precise estimates of the prevalence, risk factors and prognosis of different manifestations of cardiac disease are unavailable. In this study a prospective cohort of 433 ESRD patients was followed from the start of ESRD therapy for a mean of 41 months. Baseline clinical assessment and echocardiography were performed on all patients. The major outcome measure was death while on dialysis therapy. Clinical manifestations of cardiovascular disease were highly prevalent at the start of ESRD therapy: 14% had coronary artery disease, 19% angina pectoris, 31% cardiac failure, 7% dysrhythmia and 8% peripheral vascular disease. On echocardiography 15% had systolic dysfunction, 32% left ventricular dilatation and 74% left ventricular hypertrophy. The overall median survival time was 50 months. Age, diabetes mellitus, cardiac failure, peripheral vascular disease and systolic dysfunction independently predicted death in all time frames. Coronary artery disease was associated with a worse prognosis in patients with cardiac failure at baseline. High left ventricular cavity volume and mass index were independently associated with death after two years. The independent associations of the different echocardiographic abnormalities were: systolic dysfunction–older age and coronary artery disease; left ventricular dilatation–male gender, anemia, hypocalcemia and hyperphosphatemia; left ventricular hypertrophy–older age, female gender, wide arterial pulse pressure, low blood urea and hypoalbuminemia. We conclude that clinical and echocardiographic cardiovascular disease are already present in a very high proportion of patients starting ESRD therapy and are independent mortality factors.

The distribution of sodium- and potassium-stimulated ATPase (Na, K-ATPase) along the crypt-villus axis and crypt cytokinetics were examined in an infective model of celiac disease produced by infection of the rat with the nematodeNippostrongylus brasiliensis. In controls, levels of enzyme activity remained stable during enterocyte migration to the villous apex. In the jejunum of infected rats, the structural lesion of villous atrophy and crypt hyperplasia, observed at day 10 of infection, was associated with a three-dimensional expansion of the crypts. Cell cycle time was shortened and this resulted in a markedly increased crypt cell production rate. Enterocytes emerged from the crypts at a faster rate, and this functional immaturity was paralleled by decreased Na, K-ATPase activity. Further decreases in enzym levels were observed during enterocyte migration along the villi. This may reflect enterocyte damage or increased enzyme turnover. In the ileum of these animals, enterocyte maturation was prolonged and enzyme activity was increased at the level of the crypt villus junction with further increases noted during enterocyte transit. These changes in ileal Na, K-ATPase appear to be adaptive.

Thirteen cases of inflammatory bowel disease suspected to be intestinal tuberculosis are analyzed. In nine, the diagnosis was established from such criteria as caseation necrosis, positive acid-fast stains or cultures of the diseased tissue. In four others, enteric tuberculosis remained a diagnostic possibility as judged by the following criteria: coexistence of the bowel lesion with established tuberculosis elsewhere, a clear response to antituberculous chemotherapy, or typical features on roentgenographic, surgical or histologie examination. The patients with intestinal tuberculosis were not necessarily recent immigrants or poor, nor did they have coexistent active pulmonary disease. Although most exhibited classic features of intestinal tuberculosis, the diagnosis was rarely considered at first. A greater awareness of the entity is needed to avoid confusion between intestinal tuberculosis and Crohn's disease.

Nippostrongylus brasiliensis infection of the rat resulted, at day 10 of infection, in decreased levels of jejunal enterocyte sodium-potassium-activated adenosine triphosphatase (Na,K-ATPase) and potassium-activated p-nitrophenyl phosphatase (K-pNPPase) activities. Parallel decreases occurred in active sodium efflux from jejunal enterocytes in the presence and absence of actively transported monosaccharides. Ileal enterocyte Na,K-ATPase and K-pNPPase activities were significantly increased, as was active sodium efflux. In contrast to controls, the presence of monosaccharides produced a stimulation of active sodium efflux from ileal enterocytes derived from infected rats. Enzyme and sodium transport changes in the jejunal enterocytes probably reflect cellular immaturity. Functional changes in ileal enterocytes probably represent a compensatory phenomenon.

(1957). White Space on the Rorschach: Interpretation and Validity. Journal of Projective Techniques: Vol. 21, No. 1, pp. 47-53.

In the early part of 1949 the Junior Chamber of Commerce of Sterling, Illinois contacted the Psychology Department of Northwestern University, inquiring about the probable cost of a short clinic on child guidance to be held in Sterling under the direction of one of the University professors. Upon arrangement of mutually satisfactor) terms Dr. T. W. Richards, of the Northwestern Psychology Department, went to Sterling and held the proposed clinic from Tuesday, February 14, to Friday, February 17, 1949. As held, this clinic consisted of twelve individual clinical interviews with twelve children, arranged through the school systems, spaced at one-hour intervals over the four mornings. During the afternoons and evenings, Dr. Richards addressed a large joint Parent-Teachers Association meeting, held four seminars for varied groups, and served as a moderator of a parentteen-aged panel. At Dr. Richards' suggestion, the author travelled to Sterling on March 23, 1949 and talked with various members of the Junior Chamber of Commerce and with the superintendent of the Sterling school system in an effort to gain some idea of the effect of the guidance clinic. Everyone contacted had high regard for the work of Dr. Richards. Dissatisfaction with the general effect of the speeches and seminars was, however, evident. This is not surprising since such a clinic had, so far as is known, never previously been held in as small a town as Sterling. Essential information had been unavailable. The town's knowledge of child psychology was unknowh. Unknown, too, was the readiness of the population to accept and act upon current theories and information. No basis had existed upon which to determine the type of presentation best calculated to arouse interest and motivate personal utilization of approved principles of child rearing.

Impact of hypertension on cardiomyopathy, morbidity and mortality in end-stage renal disease. A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed prospectively for an average of 41 months. Baseline and annual demographic, clinical and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while on dialysis therapy. The average mean arterial blood pressure level during dialysis therapy was 101 ± 11mm Hg. After adjusting for age, diabetes and ischemic heart disease, as well as hemoglobin and serum albumin levels measured serially, each 10mm Hg rise in mean arterial blood pressure was independently associated with: the presence of concentric LV hypertrophy (OR 1.48, P = 0.02), the change in LV mass index ( β = 5.4 g/m 2 , P = 0.027) and cavity volume ( β = 4.3 ml/m 2 , P = 0.048) on follow-up echocardiography, the development of de novo cardiac failure (RR 1.44, P = 0.007), and the development of de novo ischemic heart disease (RR 1.39, P = 0.05). The association with LV dilation was of borderline statistical significance (OR 1.48, P = 0.06). Mean arterial blood pressures greater than 106mm Hg were associated with both echocardiographic and clinical endpoints. Paradoxically, low mean arterial blood pressure (RR 1.36 per 10mm Hg fall, P = 0.009) was independently associated with mortality. The association of low blood pressure with mortality was a marker for having had cardiac failure prior to death. We conclude that even moderate hypertension worsens the echocardiographic and clinical outcome in ESRD patients, especially in those without previous clinical cardiac disease.

A 67-year-old white man presented with bloody diarrhea and passed a 22-cm long segment of full-thickness sigmoid colon following a barium enema. He had advanced peripheral and cerebral vascular disease and had undergone pelvic irradiation for a bladder cancer five years previously. He recovered uneventfully from the bowel sloughage. This was apparently due to an intussusception of the sigmoid colon followed by the formation of adhesions between the edges of the adjacent viable bowel.

Data from studies of the use of behavior therapy in the treatment of overweight are used to compute correlations between initial weight and weight change. There is a tendency for those with the highest initial weight to lose the most weight. The relationship appears higher when both men and women are included than if data are only from women and when treatment is longer. It is suggested that these results may tentatively be seen as implying a similar relationship between initial disturbance and outcome of treatment in psychotherapy generally.

2 groups of 9 overweight women received 12 sessions of self-control training in the presence of fattening foods. In one group self-control was followed by eating a low-calorie food. Results were compared with 2 control groups. Weights for 12 wk. pretreatment and 12 and 24 wk. posttreatment were collected. Only the group receiving self-control training and a substitute low-calorie food lost significant average weight (—8.89 lb.) during treatment. Subject differences between groups preclude firm identification of the reason for this. By 24 wk. posttreatment an average 7.33 lb. had been regained. Comparable studies indicating success with group behavior therapy have either no or inadequate follow-up, or other shortcomings. There is no reliable evidence to date that group behavior therapy will result in permanent weight loss.