Cryptic introgressions contribute to transgressive segregation for early blight resistance in tomato.

KEY MESSAGE: We identified cryptic early blight resistance introgressions in tomato breeding lines and demonstrated efficient genotypic selection for resistance in the context of a tomato breeding program. Early blight is a widespread and problematic disease affecting tomatoes (Solanum lycopersicum). Caused by the fungal pathogen Alternaria linariae (syn. A. tomatophila), symptoms include lesions on tomato stems, fruit, and foliage, often resulting in yield losses. Breeding tomatoes with genetic resistance would enhance production sustainability. Using cross-market breeding populations, we identified several quantitative trait loci (QTL) associated with early blight resistance. Early blight resistance putatively derived from 'Campbell 1943' was confirmed in modern fresh market tomato breeding lines. This resistance offered substantial protection against early blight stem lesions (collar rot) and moderate protection from defoliation. A distinctive and potentially novel form of early blight foliar resistance was discovered in a processing tomato breeding line and is probably derived from S. pimpinellifolium via 'Hawaii 7998'. Additional field trials validated the three most promising large-effect QTL, EB-1.2, EB-5, and EB-9. Resistance effects for EB-5 and EB-9 were consistent across breeding populations and environments, while EB-1.2's effect was population specific. Using genome-wide marker-assisted backcrossing, we developed fresh market tomato lines that were near-isogenic for early blight QTL. Resistance in these lines was largely mediated by just two QTL, EB-5 and EB-9, that together captured 49.0 and 68.7% of the defoliation and stem lesion variance, respectively. Our work showcases the value of mining cryptic introgressions in tomato lines, and across market classes, for use as additional sources of disease resistance.

Resistance to Crown and Root Rot Caused by Phytophthora capsici in a Tomato Advanced Backcross of Solanum habrochaites and Solanum lycopersicum.

Phytophthora capsici causes devastating disease on many vegetable crops, including tomato and other solanaceous species. Solanum habrochaites accession LA407, a wild relative of cultivated tomato, has shown complete resistance to four P. capsici isolates from Michigan cucurbitaceous and solanaceous crops in a previous study. Greenhouse experiments were conducted to evaluate 62 lines of a tomato inbred backcross population between LA407 and the cultivated tomato 'Hunt 100' and 'Peto 95-43' for resistance to two highly virulent P. capsici isolates. Roots of 6-week-old seedlings were inoculated with each of two P. capsici isolates and maintained in the greenhouse. Plants were evaluated for wilting and plant death three times per week for 5 weeks. Significant differences were observed in disease response among the inbred tomato lines. Most lines evaluated were susceptible to P. capsici isolate 12889 but resistant to isolate OP97; 24 tomato lines were resistant to both isolates. Heritability of Phytophthora root rot resistance was high in this population. Polymorphic molecular markers located in genes related to resistance and defense responses were identified and added to a genetic map previously generated for the population. Resistant lines and polymorphic markers identified in this study are a valuable resource for development of tomato varieties resistant to P. capsici.

Successful ABO-incompatible kidney transplantation with antibody removal and standard immunosuppression.

ABO-incompatible (ABOi) kidney transplantation is an established therapy, though its implementation to date has been in part limited by the requirement for additional immunosuppression. Here, we describe the outcomes of 37 patients undergoing ABOi kidney transplantation utilizing perioperative antibody depletion and receiving an identical tacrolimus-based immunosuppressive regimen to contemporaneous ABO-compatible (ABOc) recipients, with the exception that mycophenolate was commenced earlier (7-14 days pretransplant). Antibody depletion was scheduled according to baseline anti-ABO antibody titer (tube IAT method: median 1:128, range 1:8 to 1:4096). Patient and graft survival for the 37 ABOi recipients was 100% after a median 26 months (interquartile range [IQR] 18-32). Eight rejection episodes (two antibody-mediated and six cellular) in ABOi recipients were successfully treated with biopsy-proven resolution. Latest median eGFR is 50 mL/min × 1.73 m² (IQR 40-64) for ABOi patients and 54 mL/min × 1.73 m² (IQR 44-66) in the ABOc patients (p = 0.25). We conclude that ABOi transplantation can be performed successfully with perioperative antibody removal and conventional immunosuppression. This suggests that access to ABOi transplantation can include a broader range of end-stage kidney disease patients.

Population structure and genetic differentiation associated with breeding history and selection in tomato (Solanum lycopersicum L.).

Tomato (Solanum lycopersicum L.) has undergone intensive selection during and following domestication. We investigated population structure and genetic differentiation within a collection of 70 tomato lines representing contemporary (processing and fresh-market) varieties, vintage varieties and landraces. The model-based Bayesian clustering software, STRUCTURE, was used to detect subpopulations. Six independent analyses were conducted using all marker data (173 markers) and five subsets of markers based on marker type (single-nucleotide polymorphisms, simple sequence repeats and insertion/deletions) and location (exon and intron sequences) within genes. All of these analyses consistently separated four groups predefined by market niche and age into distinct subpopulations. Furthermore, we detected at least two subpopulations within the processing varieties. These subpopulations correspond to historical patterns of breeding conducted for specific production environments. We found no subpopulation within fresh-market varieties, vintage varieties and landraces when using all marker data. High levels of admixture were shown in several varieties representing a transition in the demarcation between processing and fresh-market breeding. The genetic clustering detected by using the STRUCTURE software was confirmed by two statistics, pairwise F(st) (θ) and Nei's standard genetic distance. We also identified a total of 19 loci under positive selection between processing, fresh-market and vintage germplasm by using an F(st)-outlier method based on the deviation from the expected distribution of F(st) and heterozygosity. The markers and genome locations we identified are consistent with known patterns of selection and linkage to traits that differentiate the market classes. These results demonstrate how human selection through breeding has shaped genetic variation within cultivated tomato.

Quality of CD8+ T cell immunity evoked in lymph nodes is compartmentalized by route of antigen transport and functional in tumor context.

Revealing the mechanisms that underlie the expansion of antitumor CD8+ T cells that are associated with improved clinical outcomes is critical to improving immunotherapeutic management of melanoma. How the lymphatic system, which orchestrates the complex sensing of antigen by lymphocytes to mount an adaptive immune response, facilitates this response in the context of malignancy is incompletely understood. To delineate the effects of lymphatic transport and tumor-induced lymphatic and lymph node (LN) remodeling on the elicitation of CD8+ T cell immunity within LNs, we designed a suite of nanoscale biomaterial tools enabling the quantification of antigen access and presentation within the LN and resulting influence on T cell functions. The expansion of antigen-specific stem-like and cytotoxic CD8+ T cell pools was revealed to be sensitive to the mechanism of lymphatic transport to LNs, demonstrating the potential for nanoengineering strategies targeting LNs to optimize cancer immunotherapy in eliciting antitumor CD8+ T cell immunity.

A dispersed family of repetitive DNA sequences exhibits characteristics of a transposable element in the genus Lycopersicon.

A segment of DNA 5' to the transcribed region of an auxin-regulated gene, ARPI, from Lycopersicon esculentum Mill. cv. VFN8 contains a sequence with the structural characteristics of a transposable element. The putative element (Lyt1) is 1340 bp long, has terminal inverted repeats of approximately 235 bp and is flanked by 9-bp direct repeats. Lyt1 has a structure similar to the Robertson's Mutator (Mu) family from maize. The terminal inverted repeats are 80% AT-rich, are 96.6% identical, and define a larger family of repetitive elements. Southern analysis and genomic dot-blot reconstructions detected at least 41 copies of Lyt1-hybridizing sequences in red-fruited Lycopersicon spp. (L. esculentum, L. pimpinellifolium and L. cheesmanii), and 2-8 copies in the green-fruited species (L. hirsutum, L. pennellii, L. peruvianum, L. chilense and L. chmielewskii). There were two to four copies in the Solanum spp. closely allied with the genus Lycopersicon (S. lycopersicoides, S. ochranthum and S. juglandifolium), while the more distantly related Solanum spp. showed little (one to two copies in S. tuberosum) to no (S. quitoense) detectable hybridization under stringent conditions. Linkage analysis in the F2 progeny of a cross between L. esculentum and L. cheesmanii indicated that at least six loci that hybridize to the Lyt1 sequence are dispersed in the genome. Polymerase chain reaction and Southern analyses revealed that some red-fruited accessions and L. chmielewskii lacked Lyt1 5' to the transcribed region of ARPI. Subsequent sequence analysis indicated that only one copy of the 9-bp direct repeat (target site) was present, suggesting that transposition of the element into the ARPI gene occurred after the divergence of the red-fruited and green-fruited Lycopersicon species.

Genetic variation in homothallic and hyphal swelling isolates of Pythium ultimum var. ultimum and P. utlimum var. sporangiferum.

Genetic variation in a collection of 22 Pythium ultimum isolates was analyzed using restriction fragment length polymorphisms (RFLPs), random amplified polymorphic DNA (RAPD), and sequence characterized amplified regions (SCARs) as genetic markers. Qualitative evidence for the occurrence of sexual outcrossing in the field, asexual mechanisms affecting variation, and differences in aggressiveness between isolates was found. Codominant SCAR and RFLP markers detected multiple alleles in several isolates. Genetic analysis of F1 progeny from a cross indicates that heterozygosity is one cause of multiple alleles and contributes to genetic variation. Segregation analysis of F2 progeny fit diploid expectations and supported the use of the molecular markers for phenetic analysis. One isolate contained three alleles at one locus suggesting that polyploidy, aneuploidy or heterokaryosis may also contribute to genetic variation. Phenetic analysis using UPGMA clustering of Nei's distance calculated from RFLP data, UPGMA clustering of similarity matrixes calculated from RAPD data, and principle component analysis of RAPD data revealed no clustering of the three morphological types of Pythium ultimum (var. ultimum, var. sporangiferum, and group HS). Our results suggest that the three morphological variants of this homothallic oomycete are not genetically distinct.

Prostaglandin D2 release by guinea pig skin during in vitro anaphylaxis induced by antigen and compound 48/80.

The release of prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and histamine induced by antigen and compound 48/80 was studied using an in vitro model of anaphylaxis in guinea pig skin. Abdominal skin from ovalbumin-sensitized guinea pigs was cut into 0.5-1.0 mm-thick slices which were incubated in Tyrode solution at 37 degrees C with or without either ovalbumin or 48/80. Released PGD2 and PGE2 were measured by radioimmunoassay and gas chromatography-mass spectrometry, respectively. Release of PGD2 was detectable at 2 min after challenge (50 micrograms/ml ovalbumin), reaching a maximum at about 15 min. Histamine release was more rapid, achieving 50% of maximum at about 4 min compared to about 7 min for PGD2. In 11 experiments incubation with ovalbumin (50 micrograms/ml for 10 min) induced a significant 6-fold increase in PGD2 compared to unchallenged controls (399 +/- 53 and 67 +/- 19 ng/g dry weight skin, respectively; mean +/- SEM) and a net 47.2% histamine release. In contrast, a smaller (27%) rise in PGE2 was found. Indomethacin (14 microns) completely suppressed evoked PGD2 and PGE2 synthesis without evident effect on histamine release, suggesting that the release of histamine in this model is not dependent on prostaglandin production. The mast cell degranulating agent compound 48/80 (50 micrograms/ml) released significant amounts of PGD2 (340 +/- 86 ng/g skin compared to 89 +/- 30 ng/g for control skin, n = 5) but had no appreciable effect on PGE2. These results show that guinea pig skin can synthesize significant quantities of PGD2 in anaphylactic reactions. Prostaglandin D2 produced in acute allergic reactions in skin in vivo may contribute to the inflammatory reaction, either directly or in synergism with other mediators.

Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria.

Previous studies identified autoantibodies against the IgE high affinity receptor alpha-chain, Fc epsilon RI alpha, in sera of selected patients with severe chronic idiopathic urticaria. We have now determined the incidence of anti-Fc epsilon RI alpha autoantibodies in a group of 163 patients. Intradermal injection of autologous serum caused skin reactions indicative of mast cell degranulation in 98 (60%) patients. Based on histamine release from IgE-sensitized and nonsensitized basophil leukocytes of healthy donors, we detected anti-Fc epsilon RI alpha autoantibodies in sera from 38 (23%) urticaria patients and evidence for anti-IgE antibodies in a further nine patients. The sera that released histamine from basophils induced histamine release (4-34%, n = 12) from mast cells in incubated skin slices. Protein-G affinity chromatography of sera demonstrated that mast cell histamine release was IgG-mediated. Preincubation of sera or the IgG fraction with a recombinant alpha-chain of Fc epsilon RI inhibited histamine release from mast cells and basophils. Further studies with the mouse anti-human Fc epsilon RI alpha antibody 29C6 showed that mast cells and basophils were similarly sensitive to IgG-mediated direct cross-linking of Fc epsilon RI, with 0.01-1.0 micrograms/ml 29C6 evoking histamine release in each case. These studies demonstrate that circulating levels of anti-Fc epsilon RI alpha autoantibodies mediate histamine release from skin mast cells in vitro and, taken together with in vivo evidence of mast cell degranulation following intradermal injection of autologous serum, support the concept that anti-Fc epsilon RI alpha autoantibodies are relevant to the pathogenesis of severe chronic urticaria in about 25% of patients.

Adverse influence of recipient lymphoid resistance to in vitro immunosuppression on the outcome of kidney transplants.

The study investigated whether preoperative in vitro sensitivity of lymphocytes from potential renal transplant recipients could identify patients at increased risk of acute rejection following transplantation and immunosuppression with cyclosporine, azathioprine, and prednisolone. Mixed lymphocyte culture responses were measured preoperatively in the presence of methylprednisolone, CsA, and antithymocyte globulin, and without immunosuppressive agents in 50 transfused recipients of primary cadaver renal transplants. Patients were classified as sensitive if all three immunosuppressive agents produced more than 50% inhibition of their MLC responses, and as resistant if one or more agents failed to produce 50% inhibition. All patients received postoperatively a standardized triple immunosuppressive regimen. Acute rejection was confirmed histologically and treated with Pred with or without ATG or monoclonal antibody OKT3. A total of 29 patients (58%) were sensitive and 21 (42%) were resistant; 4 patients were resistant to 3 agents, 5 were resistant to MP and ATG, 6 were resistant to MP and CsA, and 6 were resistant to MP alone. Sensitive and resistant groups did not differ in age, sex, transfusion history, HLA A, B and DR mismatches or duration of follow-up. The resistant group had a higher rate of graft loss from acute rejection (chi 2 = 6.0, d.f. = 1, P less than 0.02), more episodes of acute rejection (chi 2 = 8.7, d.f. = 3, P less than 0.05), and a higher proportion of patients in whom reflux nephropathy was the cause of renal failure (chi 2 = 18.3, d.f. = 1, P less than 0.001). The resistant group also had a higher proportion of highly sensitized patients and higher serum creatinine concentrations than the sensitive group, although the differences did not reach statistical significance. The study indicates that patients at high risk of acute rejection of renal allografts can be identified by a pretransplant in vitro assay, a finding that could influence recipient selection and immunosuppression.

The safety and efficacy of laparoscopic live donor nephrectomy: a systematic review.

BACKGROUND: The aim of this systematic review was to compare the safety and efficacy of laparoscopic live donor nephrectomy with the "gold" standard of open live donor nephrectomy. SEARCH STRATEGY: Three search strategies were devised to enable literature retrieval from the Medline, Current Contents, Embase, and Cochrane Library databases up until, and including, February 2000. STUDY SELECTION: Inclusion of a report was determined on the basis of a predetermined protocol, independent assessment by two reviewers, and a final consensus decision. English language reports were selected and acceptable study designs included randomized-controlled trials, controlled clinical trials, case series, or case reports. Each report was required to provide information on at least one of several safety and efficacy outcomes as detailed in the protocol. DATA COLLECTION AND ANALYSIS: Twenty-five reports met the inclusion criteria. They were tabulated and critically appraised in terms of the methodology and design, sample size, outcomes, and the possible influence of bias, confounding, and chance. RESULTS: High level evidence comparing the safety and efficacy of laparoscopic live donor nephrectomy with open donor nephrectomy was not available at the time of this review. Limited low level evidence suggested that the laparoscopic approach might be advantageous regarding the donor's hospital stay, convalescence, pain, and resumption of employment. CONCLUSIONS: The ASERNIP-S Review Group concluded that the evidence-base for laparoscopic live donor nephrectomy was inadequate to make a safety and efficacy recommendation. Clinical and research recommendations were developed regarding the introduction and current practice of this procedure in Australia.

Renal xenografts from triple-transgenic pigs are not hyperacutely rejected but cause coagulopathy in non-immunosuppressed baboons.

BACKGROUND: The genetic modification of pigs is a powerful strategy that may ultimately enable successful xenotransplantation of porcine organs into humans. METHODS: Transgenic pigs were produced by microinjection of gene constructs for human complement regulatory proteins CD55 and CD59 and the enzyme alpha1,2-fucosyltransferase (H-transferase, HT), which reduces expression of the major xenoepitope galactose-alpha1,3-galactose (alphaGal). Kidneys from CD55/HT and CD55/CD59/HT transgenic pigs were transplanted into nephrectomised, nonimmunosuppressed adult baboons. RESULTS: In several lines of transgenic pigs, CD55 and CD59 were expressed strongly in all tissues examined, whereas HT expression was relatively weak and did not significantly reduce alphaGal. Control nontransgenic kidneys (n=4) grafted into baboons were hyperacutely rejected within 1 hr. In contrast, kidneys from CD55/HT pigs (n=2) were rejected after 30 hr, although kidneys from CD55/CD59/HT pigs (n=6) maintained function for up to 5 days. In the latter grafts, infiltration by macrophages, T cells, and B cells was observed at days 3 and 5 posttransplantation. The recipients developed thrombocytopenia and abnormalities in coagulation, manifested in increased clotting times and an elevation in the plasma level of the fibrin degradation product D-dimer, within 2 days of transplantation. Treatment with low molecular weight heparin prevented profound thrombocytopenia but not the other aspects of coagulopathy. CONCLUSIONS: Strong expression of CD55 and CD59 completely protected porcine kidneys from hyperacute rejection and allowed a detailed analysis of xenograft rejection in the absence of immunosuppression. Coagulopathy appears to be a common feature of pig-to-baboon renal transplantation and represents yet another major barrier to its clinical application.

The release of prostaglandin D2 from human skin in vivo and in vitro during immediate allergic reactions.

1. The release of prostaglandin D2 (PGD2) during immediate allergic reactions in human skin was investigated in vivo and in vitro. 2. Skin exudates were collected from abraded sites on the thigh of atopic subjects sensitive to D. pteronyssinus antigen and from non-atopic control subjects. Challenge with antigen caused the release of PGD2 and histamine, but not PGE2, from the skin of the atopic subjects. The molar ratio of histamine to PGD2 was about 140:1. Control subjects were unresponsive. 3. PGD2 was released from passively sensitized human skin challenged with antigen in vitro. The time course was similar in vitro and in vivo. The ratio of histamine to PGD2 in vitro was 78:1. 4. The identities of the prostaglandins were confirmed by high performance liquid chromatography and radioimmunoassay to PGD2 and PGE2. 5. PGD2 is the major arachidonic acid cyclo-oxygenase product synthesized by human mast cells. It is pro-inflammatory in human skin but its functions as a mediator in immediate hypersensitivity reactions in human skin are not clear. The results of this study suggest that, relative to histamine, PGD2 contributes little to the oedema and erythema of immediate reactions in human skin.

Phenotypic identity of gastric mucous neck cells and mucous cells of cardiac, pyloric, and Brunner's glands.

AIM: To investigate the tissue specificity of a novel monoclonal antibody raised to a tissue fraction of normal human liver and which identified certain cells of gastric and duodenal mucosa. METHODS: A total of 155 samples of various tissues obtained from 100 surgical specimens were fixed in cold ethanol-paraformaldehyde, embedded in paraffin wax, and 3 microns sections were studied by immunohistochemical and lectin staining procedures. RESULTS: Immunohistochemical staining showed a major tissue specific component which was strongly expressed by mucous neck cells of the body of the stomach, glands of the cardia and pyloric antrum, and by Brunner's glands. Staining for antigen in the periductal glands of normal major biliary and pancreatic ducts was variable and relatively weaker. It was not detected elsewhere in normal intestine or in the other normal tissues tested. Barrett's mucosa of gastric cardia type, and pyloric gland metaplasia in the gall bladder and small bowel affected with Crohn's disease stained for the antigen. The tissue distribution of the antigen was identical with that of a glycoprotein, demonstrated by an induced affinity for concanavalin A following treatment of tissue sections with periodic acid. The antigen was not sensitive to sialidase. CONCLUSIONS: The tissue component identified (designated here as antigen D10) seems to be characteristic of certain differentiated epithelial cells derived from that part of foregut giving rise to stomach, duodenum, and biliary and pancreatic ducts. The antibody will be of use in investigating pathological processes involving tissue differentiation at these sites, and in the oesophagus and intestines.

A possible mechanism of immunoregulation produced by alpha 2-macroglobulin.

Most of the plasma suppressive activity was associated with alpha 2M in both normal subjects and cancer patients. alpha 2M binding to physiological levels of proteases was associated with an increase in the ability to suppress lymphocyte reactivity in the TEEM test. alpha 2M binding to proteases released a peptide that was a component of the alpha 2M; this peptide suppressed lymphocyte reactivity to mitogenic, antigenic, and allogenic stimuli in the TEEM test and in the lymphocyte transformation assay. Physically and biologically similar peptides have been found in the plasma of cancer patients and patients with thermal burns, uremia, and acute pancreatitis.

Acceleration of B16 melanoma growth in mice after blood transfusion.

Evidence suggests that blood transfusions depress immunologic reactivity; as some tumors are influenced by the immune status of their host, it is possible that transfusions could promote tumor growth by impairing host immunity. The influence of blood transfusion on the growth of a transplantable B16 melanoma was examined in nude (athymic) CBA mice and immunocompetent C57 BL/6J mice. Recipients were given infusions of saline solution or syngeneic or H-2-incompatible allogeneic blood transfusions on two occasions 3 days apart. Infusions were begun 10 days before inoculation of a single cell suspension of B16 melanoma. Growth was determined by measurements of primary tumor volume and tumor weight after excision. There was no statistically significant difference in tumor size or weight between the three recipient groups of athymic mice. However, immunocompetent mice given H-2-incompatible allogeneic blood had higher rates of tumor engraftment--saline solution recipients versus allogeneic recipients: chi 2 = 13.2, df = 1, p less than 0.001; syngeneic recipients versus allogeneic recipients: chi 2 = 2.97, df = 1, p greater than 0.05. In the allogeneic group significantly larger and heavier tumors developed than in mice given syngeneic blood or saline solution. The study indicates that H-2-incompatible allogeneic blood transfusions can influence the growth of a transplantable murine tumor by a mechanism that involves a cell-mediated immune response.

Two Loci from Lycopersicon hirsutum LA407 Confer Resistance to Strains of Clavibacter michiganensis subsp. michiganensis.

ABSTRACT We used molecular markers to identify quantitative trait loci (QTL) that contribute to resistance to bacterial canker of tomato caused by Clavibacter michiganensis subsp. michiganensis. Resistance was first identified as a marker-trait association in an inbred backcross (IBC) population derived from crossing Lycopersicon hirsutum accession (LA407) with L. esculentum. Single-marker QTL analysis suggested that at least two loci originating from L. hirsutum LA407, Rcm 2.0 on chromosome 2 and Rcm 5.1 on chromosome 5, contribute to resistance in replicated trials. Two segregating F(2) populations were developed by crossing resistant inbred backcross lines (IBLs) to elite L. esculentum lines and used to confirm QTL associations detected in the IBC population. In these populations, realized heritability estimates were higher for selection based on maximal disease than for selection based on disease progression. Realized heritability in the population carrying Rcm 2.0 was 0.63 and 0.14, respectively, for each selection criteria. Realized heritability estimates were 0.85 for selection based on maximal disease and 0.37 for selection based on disease progression in a population carrying Rcm 5.1. The disease response of F(3) families selected for resistance suggested that both Rcm 2.0 and Rcm 5.1 confer resistance to bacterial strains in the repetitive sequence-based polymerase chain reaction DNA fingerprint classes A and C. Markers linked to Rcm 2.0 explained up to 56% of the total phenotypic variation for resistance in one population, and markers linked to Rcm 5.1 explained up to 73% of the total phenotypic variation for resistance in a separate population.

Peritoneal calcification in a peritoneal dialysis patient: a case report.

A case of peritoneal calcification in a 44-year-old female treated with peritoneal dialysis for 13 years is reported. The patient, who had secondary hyperparathyroidism and had suffered repeated episodes of catheter-related peritonitis, presented with intraperitoneal bleeding and underwent laparotomy and excision of some of the calcified peritoneal plaques. She remains well on peritoneal dialysis 1 year later with occasional mild intraperitoneal bleeding and reduced peritoneal filtration.

Blood transfusion and tumor growth.

The definitive study of the relationship between blood transfusion and cancer recurrence has not been published. The existing studies fail to adequately control for anemia, duration of surgery, magnitude of the procedure, blood loss, and stage of disease, variables that are related to the administration of blood and are also associated with cancer recurrence. None of the negative studies has the number of patients necessary to achieve statistical validity. Experimental studies indicate that tumor growth may be inhibited or promoted by allogeneic blood transfusion depending on the route and timing of the transfusion relative to tumor inoculation, the route of tumor inoculation and the specific tumor used, and the strain and species of the animal and blood donor. The available evidence suggesting a relationship between blood transfusion and cancer recurrence does not support any changes in the use of blood for patients with malignancies.

Arachidonic acid metabolites and the skin.

The relevance of arachidonic acid metabolites in inflammatory skin diseases has been expanded by recent developments in analytical chemistry. The metabolites include prostaglandins, leukotrienes and monohydroxy fatty acids. In ultraviolet light-induced inflammation the concentrations of arachidonic acid, prostaglandin E2, prostaglandin F2 alpha and 6-oxo-prostaglandin F1 alpha are elevated. Indomethacin totally suppresses the evoked prostaglandin increase, but erythema is only partially suppressed. This indicates that prostaglandins are partially involved in erythema production. In psoriasis the first histological change is an infiltration into the epidermis by neutrophilic leucocytes. It has been suggested that chemotactic factors, such as complement derived factors or leukotriene B4 play a role in the pathogenesis of psoriasis.