Experiments with rectangular supersonic jets with potential noise reduction technology.

This paper describes the aeroacoustics experiments conducted with supersonic jets, exhausting from rectangular nozzles with an aspect ratio of 2, to examine the jet noise reduction by two different methods. The first method involves the use of fluid inserts, which are produced by distributed air blowing into the diverging section of a convergent-divergent exhaust nozzle. The second method involves the integration of fluid shields in dual flow rectangular jets. In the dual flow nozzle, a single shield below the exit is augmented with fluid shields extending on both sides of the rectangular jet. The purpose of the extended bypass flow is to reduce the noise radiated to the sides of a jet aircraft. In addition to the nozzles with the two noise reduction configurations, acoustic measurements are performed with a single flow rectangular jet, referred to as the baseline. In all cases, the jets are operated as overexpanded, shock-containing jets. In some cases, the jets are operated with the core flow mixtures of helium and air to simulate high temperature jets. The far-field noise measurements are performed on an arc with the microphones approximately 70 equivalent nozzle diameters from the nozzle exit. For the purposes of assessing the noise reduction capability of the dual stream jet, comparisons are made with a baseline rectangular jet on an equal thrust per unit exit area basis. The nondimensional acoustic spectra and overall sound pressure level directivities are shown and compared.

Faecal calcium excretion does not decrease during long-term feeding of a low-calcium diet in adult dogs.

According to a previous meta-analysis, adult dogs do not notably increase calcium absorption from the gastrointestinal tract when calcium intake is decreased. This results in a negative calcium balance even with a moderate calcium reduction. In this study we wanted to verify (i) whether a negative calcium balance occurs at a calcium intake equivalent to NRC (2006) (Nutrient requirements of dogs and cats, 2006, The National Academies Press, Washington, DC) minimal requirements, and if so (ii) whether the negative calcium balance will persist for up to 6 months on a low-calcium diet. After a pre-feeding period of at least 18 weeks with calcium intake slightly exceeding maintenance requirements (200 mg/kg body weight0.75 ), 12 dogs (6 Beagles, 6 Foxhound crossbreds) were fed a low-calcium diet for 28 weeks. One dog was removed from the trial for reasons unrelated to the study at week 23. Calcium intake amounted to 60 mg/kg body weight0.75 corresponding to the minimal requirement for maintenance in dogs (NRC, 2006 (Nutrient requirements of dogs and cats, 2006, The National Academies Press, Washington, DC)). Digestion trials were carried out at week 7, 14, 21 and 28 of the low calcium feeding period. At these time points, and at week 18 of the pre-trial, blood samples were taken and analysed for calcium, ionised calcium, phosphorus, parathyroid hormone, vitamin D, serum crosslaps and bone alkaline phosphatase. Apparent calcium digestibility was negative throughout the study, suggesting a negative calcium balance. There was no systematic decrease in faecal calcium excretion. Serum calcium, ionised calcium and phosphorus remained within the reference range. Serum crosslaps increased continuously from baseline to week 28 of trial, with averages increasing from 0.102 ng/ml to 0.279 ng/ml, suggesting osteoclastic activity, indicative of calcium mobilisation from the skeleton. The study supports the theory of a lack of adaptation of intestinal calcium absorption from diets with relatively low calcium content in dogs. This agrees with clinical findings in dogs eating low-calcium diet.

Demonstration of uniformity of calcium absorption in adult dogs and cats.

A meta-analysis was conducted to understand quantitative aspects of calcium (Ca) and phosphorus (P) absorption in adult dogs and cats. 34 studies in dogs and 14 studies in cats met the criteria for inclusion in the meta-analysis. Intake and faecal excretion values of Ca and P were subjected to a modified Lucas test and subsequent regression analyses. According to the current scientific consensus, Ca true digestibility (absorption) should increase at low Ca intake and decrease at high Ca intake. If true, this should result in a nonlinear relationship between the percentage of Ca excreted and dietary Ca intake. The present meta-analysis showed a highly significant linear relationship (p < 0.0001) between Ca intake and Ca excretion suggesting a lack of systematic quantitative adaptation in true Ca digestibility. This finding suggests either that the time period covered by standard digestion trials is too short to induce adaptation mechanisms or that dogs and cats at maintenance will not efficiently alter quantitative Ca absorption percentage according to the amount ingested. If the latter is true, a dietary Ca supply differing greatly from the recommended dietary intake might impair the health of cats and dogs when fed long term. The data plots for P intake and faecal excretion were less uniform suggesting other factors not just dietary intake influence faecal P excretion. In adult cats, the dietary Ca:P ratio strongly influenced the true digestibility of P, whereas this effect was less marked in adult dogs. Faecal P excretion was significantly correlated to faecal Ca excretion in both species (p < 0.0001), and surprisingly, the level of P intake did not appear to be an important determinant of true digestibility of P.

Antifungal prophylaxis in liver transplantation: a systematic review and network meta-analysis.

Invasive fungal infections (IFIs) cause significant morbidity and mortality in liver transplant recipients, but the need and best agent for prophylaxis is uncertain. A comprehensive literature search was performed to identify randomized controlled trials comparing regimens for antifungal prophylaxis in liver transplant recipients. Direct comparisons were made between treatments using random-effects meta-analysis and a Bayesian network meta-analysis was performed for the primary end point of proven IFI. Fourteen studies met inclusion criteria, reporting comparisons of fluconazole, liposomal amphotericin B (L-AmB), itraconazole, micafungin and placebo. Overall, antifungal prophylaxis reduced the rate of proven IFI (odds ratio [OR] 0.37, confidence interval [CI] 0.19-0.72, p = 0.003), suspected or proven IFI (OR 0.40, CI 0.25-0.66, p = 0.0003) and mortality due to IFI (OR 0.32, CI 0.10-0.83, p = 0.02) when compared to placebo. All-cause mortality was not significantly affected. There was no difference in risk of adverse events requiring cessation of prophylaxis (OR 1.11, 95% CI 0.48-2.55, p = 0.81). In the network meta-analysis an equivalent reduction in the rate of IFI was seen with fluconazole (OR 0.21, CI 0.06-0.57) and L-AmB (OR 0.21, CI 0.05-0.71) compared with placebo. Routine prophylaxis with fluconazole or L-AmB reduces the incidence of IFI following liver transplantation, and the available evidence suggests that the two are equivalent in efficacy.

Systematic review and meta-analysis of hypothermic machine perfusion versus static cold storage of kidney allografts on transplant outcomes.

BACKGROUND: Adequate preservation of renal allografts for transplantation is important for maintaining and improving transplant outcomes. There are two prevalent methods: hypothermic machine perfusion and static cold storage. The preferred method of storage, however, remains controversial. The objective was to review systematically the evidence comparing outcomes from these two modalities. METHODS: A literature search was performed using MEDLINE, Embase, the Cochrane Library, the Transplant Library and the International Clinical Trials Registry Platform. The final date for searches was 30 November 2012. Studies were assessed for methodological quality. Summary effects were calculated as relative risk (RR) with 95 per cent confidence interval (c.i.). Randomized clinical trials (RCTs) and non-RCTs were included, but evaluated separately. Results from RCTs alone were used for meta-analysis. RESULTS: Eighteen studies met the inclusion criteria, including seven RCTs (1475 kidneys) and 11 non-RCTs (728 kidneys). The overall risk of delayed graft function was lower with hypothermic machine perfusion than static cold storage (RR 0·81, 95 per cent c.i. 0·71 to 0·92; P = 0·002). There was no difference in the rate of primary non-function (RR 1·15, 0·46 to 2·90; P = 0·767). There was a faster initial fall in the level of serum creatinine with hypothermic machine perfusion in two RCTs, but not in another. There was no relationship between rates of acute rejection or patient survival and the method of preservation. CONCLUSION: Data from the included studies suggest that hypothermic machine perfusion reduces delayed graft function compared with static cold storage. There was no difference in primary non-function, acute rejection, long-term renal function or patient survival. A difference in renal graft survival is uncertain.

Preservation solutions for static cold storage of kidney allografts: a systematic review and meta-analysis.

Static cold storage is the most prevalent method for renal allograft preservation. Several solutions have been designed to counteract the detrimental effects of cold ischemia and reperfusion. The aim of this study was to appraise the evidence for the currently available preservation solutions. We performed a systematic literature search using MEDLINE, EMBASE, the Cochrane Library, the Transplant Library and trial registries. Inclusion criteria specified any comparative, prospective study for deceased donor renal allografts. Studies were assessed for methodological quality. The primary outcome was delayed graft function (DGF). Fifteen trials with a total of 3584 kidneys were included. Eurocollins was associated with a higher risk of DGF than University of Wisconsin solution (UW) in two randomized controlled trials (RCTs) and histidine-tryptophan-ketoglutarate (HTK) in two RCTs. UW was associated with an equal risk of DGF compared with Celsior in three RCTs and HTK in two RCTs. There was limited data regarding other comparisons and outcomes. The choice of preservation solution has an effect on the incidence of DGF, which might, in turn, affect long-term outcomes. Both UW and HTK have lower rates of DGF than Eurocollins. There is no difference in the incidence of DGF with the use of Celsior, HTK and UW. These findings are supported by registry data.

Reprinted article "Exercise training versus angioplasty for stable claudication. Long and medium term results of a prospective, randomised trial".

OBJECTIVES: To compare percutaneous transluminal angioplsty (PTA) against exercise training in the treatment of stable claudication. DESIGN: Prospective, randomised trial. MATERIALS: Fifty-six patients with unilateral, stable, lower limb claudication assessed prior to randomisation, at 3 monthly intervals for 15 months, and at approximately 6 years follow-up. Thirty-seven patients were available for long term review. OUTCOME MEASURES: Ankle/brachial pressure index (ABPI), treadmill claudication and maximum walking distances, percentage fall in ankle systolic pressure after exercise. RESULTS: Significant increases were seen in ABPI in the patients treated with PTA at all assessment to 15 months. However in terms of improved walking performance, the most significant changes in claudication and maximum walking distance were seen in the exercise training group. At long term follow-up, there was no significant difference between the groups. Subgroup analysis by angiographic site of disease showed greater functional improvement in those patients with disease confined to the superficial femoral artery treated by exercise training. The overall prognosis for the whole group of patients was benign, with only two (4%) undergoing amputation. CONCLUSIONS: Exercise training confers a greater improvement in claudication and maximum walking distance than PTA, especially in patients with disease confined to the superficial femoral artery.

The effects of increasing water content to reduce the energy density of the diet on body mass changes following caloric restriction in domestic cats.

Caloric restriction induces body mass loss that is often regained when restriction ends. This study aimed to determine if dietary energy density modulates the extent of post-restriction body mass regain. Water (20% wt:wt) was added to a standard dry commercially available feline diet. Twenty-seven domestic short-haired cats underwent a 20% caloric restriction on this diet. Following restriction, cats were offered the same dry diet ad libitum either without additional water or with 40% added water, therefore maintaining macronutrient composition whilst manipulating energy density. Despite no significant difference in energy intake during ad libitum consumption, post-restriction body mass regain was greater on the high energy dense (0% hydrated), compared to the low energy dense (40% hydrated) diet. The same protocol was repeated with a separate cohort of 19 cats with additional measures of physical activity, gut transit time and energy digestibility. Activity levels on the low energy dense diet were significantly higher than in cats on the high energy dense diet (p=0.030) and were similar to those recorded during caloric restriction. These results suggest that body mass gain following caloric restriction is ameliorated, and physical activity enhanced, by feeding a diet which is low in energy density due to the addition of 40% water.

Imprecision when using measuring cups to weigh out extruded dry kibbled food.

Many pet cats and dogs are fed dry extruded kibbled food by measuring cup, yet the precision and accuracy of this feeding strategy is not known. Over 12 studies, we assessed precision and accuracy of weighing out food portions, of various dry kibbled foods, by measuring cup. Poor precision was noted in all studies, with intra- and inter-subject coefficients of variation ranging from 2 to 13% and 2 to 28% respectively. Variable accuracy was also noted, which ranged from an 18% under-estimate to an 80% over-estimate in portion size. No specific factors were associated with imprecision, but the degree of inaccuracy was negatively associated with portion size (R = -0.67, p = 0.022), and positively associated with the number of subjects participating in the study (R = 0.60, p = 0.048). This is the first study to document imprecision and inaccuracy of using measuring cups to estimate portions of extruded dry kibbled food. Over time, such errors could contribute to insidious weight gain in companion animals, potentially contributing to the development of obesity. Imprecision in measuring food portions could also contribute to failure of weight management programmes for obese animals.

Specific cytotoxic T cells are found in the nonrejected kidneys of blood-transfused rats.

Preoperative, donor-specific blood transfusion leads to indefinite survival of rat renal allografts in the strain combinations used. 51Cr-release assays have shown that the level of specific cytotoxic effector activity in the grafts of transfused (nonrejected kidney) animals is very high and may equal or exceed that seen in the grafts of untreated (rejected kidney) recipients. Such cytotoxicity demonstrates specificity for the alloantigens of the kidney, is T cell-mediated, and may persist within the transplant.

Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues.

Dendritic cells (DC) are critical accessory cells for primary immune responses and they may be important stimulators of transplantation reactions, but little is known of their traffic into the tissues. We have studied the migration of purified splenic DC and T lymphocytes, labeled with 111Indium-tropolone, in syngeneic and allogeneic mice. First we demonstrate that DC can migrate from the blood into some lymphoid and nonlymphoid tissues. Immediately after intravenous administration, radio-labeled DC were sequestered in the lungs, but they actively migrated into the liver and spleen and reached equilibrium levels between 3 and 24 h after transfer. At least half of the radiolabel accumulated in the liver, but the spleen was the principal site of DC localization in terms of specific activity (radiolabel per weight of tissue). DC were unable to enter Peyer's patches, or mesenteric and other peripheral lymph nodes from the bloodstream. This was also true in splenectomized recipients, where the otherwise spleen-seeking DC were quantitatively diverted to the liver. In contrast, T cells homed readily to the spleen and lymph nodes of normal mice and increased numbers were present in these tissues in splenectomized mice. Thus, unlike T cells, DC cannot recirculate from blood to lymph via the nodes. We then show that migration of DC from the blood into the spleen is dependent on the presence of T cells: DC did not enter the spleens of nude mice, but when they were reconstituted with T cells the numbers entering the spleen resembled those in euthymic mice. In nude mice, as in splenectomized recipients, the DC that would normally enter the spleen were quantitatively diverted to the liver. These findings suggest that there is a spleen-liver equilibrium for DC, that may be akin to that existing between spleen and lymph node for T cells. Finally, we followed the traffic of radiolabeled DC via the afferent lymphatics after subcutaneous footpad inoculation. DC accumulated in the popliteal nodes but did not migrate further to the inguinal nodes. There was no difference between euthymic and nude mice, showing that unlike traffic to the spleen, this route probably does not require T cells. These migration patterns were not affected by major histocompatibility barriers, and were only seen with viable, but not glutaraldehyde-fixed, DC.(ABSTRACT TRUNCATED AT 400 WORDS)

Specific suppression of allograft rejection by trinitrophenyl (TNP)-induced suppressor cells in recipients treated with TNP-haptenated donor alloantigens.

Suppressor T cells, activated by injection of trinitrobenzene sulphonic acid in DA rats, prevented rejection of LEW kidney allografts in a donor-specific manner when adoptively transferred into syngeneic recipients along with trinitrophenyl (TNP)-haptenated LEW alloantigen. TNP-haptenated third-party alloantigen was ineffective in this system. The donor-specific suppression was dependent, too, on the haptenic portion of the chemically modified alloantigen. Hence, fluorescein isothiocyanate-donor antigen did not lead to suppression in the presence of TNP-reactive suppressor cells. There is, however, some crossreaction between DNP- and TNP-haptenated alloantigens so that TNP-reactive cells and DNP-donor antigen suppressed rejection whereas DNP-reactive cells and TNP-donor antigen did not prevent graft rejection. The suppressor cells were sensitive to cyclophosphamide and radiation but were resistant to hydrocortisone. They appear to be T cells of the OX8 (suppressor/cytotoxic) phenotype since they are positive for the pan T cell antigen W3/13, are Ig negative, and do not carry the W3/25 (T helper cell) marker. However, these suppressor cells are adherent to nylon wool. They are found mainly in the spleen, are detected there within 2 d of TNBS injection, and can persist for up to 12 wk. We propose that these cells are first-order T suppressor (Ts1) cells that act in the afferent phase of the response to a renal allograft.

Cytokine gene transcription in vascularised organ grafts: analysis using semiquantitative polymerase chain reaction.

Cytokine gene transcription has been analyzed by direct analysis of RNA obtained from mouse heterotopic cardiac transplants. The level of expression of the cytokine genes was assessed using semiquantitative polymerase chain reaction (PCR). Expression of the cytokines investigated fell into three groups. The first group included interleukin 1 beta (IL-1 beta), IL-5, IL-6, and interferon gamma (IFN gamma). These genes were expressed in normal heart tissue at low level and were upregulated following both syngeneic and allogeneic transplantation. Genes in the second group (IL-1 alpha, IL-3) were not expressed at detectable levels in normal heart but were induced following either syngeneic or allogeneic heart grafting. IL-2, IL-4, and tumor necrosis factor beta (IFN beta) comprised the third group and these cytokines were expressed only in allogeneic grafts after transplantation.

Migration of dendritic leukocytes from cardiac allografts into host spleens. A novel pathway for initiation of rejection.

It has been a long-standing dogma that host sensitization against fully-vascularized organ allografts occurs peripherally within the graft itself. In this report we show that donor-derived MHC class II-positive (Ia+) DL migrate rapidly out of mouse cardiac allografts into the recipients' spleens where they home to the peripheral white pulp and associate predominantly with CD4+ T lymphocytes. This provides a novel route for central sensitization against fully vascularized allografts, and most likely represents a pathway by which immune responses are generated against antigens on blood-borne DL emigrating from peripheral tissues.

Peripheral tolerance to alloantigen results from altered regulation of the interleukin 2 pathway.

Tolerance to alloantigen may be induced in rats by administration of blood followed by transplantation of a renal allograft. The mechanism of this tolerance was investigated by directly analyzing the functional activity of graft-infiltrating cells. We have previously shown cytotoxic T lymphocyte infiltration of, and major histocompatibility complex induction on, grafts of tolerant animals. We now report that cells isolated from the grafts of tolerant rats show a reduced expression of the p55 interleukin 2 receptor (IL-2R) chain on the cell surface compared with that seen on the cells of untreated animals. Scatchard analysis further reveals low expression of high affinity IL-2R. This is due to reduced transcription of both IL-2R alpha and beta chain mRNAs and results in a reduced ability of cells to proliferate in response to IL-2. Cells isolated from tolerant animals are unable to make biologically active IL-2 in culture, whereas cells from untreated animals make high levels. This is not reflected at the mRNA level as the IL-2 gene is induced in both tolerant and untreated animals to similar levels. The induction of tolerance is abrogated by administration of recombinant IL-2 to animals at the time of transplantation. Thus, we conclude that an altered regulation of the IL-2 pathway results in tolerance in these alloantigen-treated and transplanted animals.

Migration patterns of dendritic cells in the mouse. Homing to T cell-dependent areas of spleen, and binding within marginal zone.

Using quantitative techniques we have shown elsewhere that dendritic cells (DC) migrate from blood into the spleen, under the control of T cells. Here we traced the localization of DC within the spleen and sought to explain the means by which they entered. DC were labeled with a fluorochrome, Hoescht 33342, and injected intravenously. Spleens were removed 3 or 24 h later and DC were visualized within particular areas that were defined by mAbs and FITC anti-Igs. At 3 h most DC were in the red pulp, whereas by 24 h the majority had homed to T-dependent areas of the white pulp and may have become interdigitating cells. Lymphoid DC, isolated from spleen and perhaps normally present in blood, may thus be a migratory stage distinct from the relatively fixed interdigitating cells. We also developed a frozen section assay to investigate the interaction of DC with various lymphoid elements. When DC were incubated on sections of spleen, at 37 degrees C but not at 4 degrees C they attached specifically within the marginal zone and did not bind to T areas; in contrast, macrophages attached only to red pulp and T cells did not bind specifically. However, DC did not bind to sections of mesenteric lymph node, whereas T cells localized in particular regions at 4 degrees C but not at 37 degrees C, probably the high endothelial venules. DC may thus express "homing receptors," similar to those of T cells, for certain endothelia. We propose that T cells can modify the vascular endothelium in certain areas to allow egress of DC from the bloodstream.

The specificity of rejection and the absence of susceptibility of pancreatic islet beta cells to nonspecific immune destruction in mixed strain islets grafted beneath the renal capsule in the rat.

The specificity of rejection of isolated pancreatic islets was examined in the rat using a quantitative model in which syngeneic (DA) or a mixture of syngeneic and allogeneic (DA and LEW or PVG) islets were implanted beneath the capsule of the kidney of nondiabetic normal rats (DA). 3 wk after transplantation total insulin extraction assays of the kidney with its islet implant together with immunohistological examination of the site of transplantation for evidence of syngeneic or allogeneic tissue demonstrated the total destruction of allogeneic islets without any evidence of damage to syngeneic islets either distant or in immediate proximity to allogeneic islets. Pancreatic islets, and especially beta cells, appear to be particularly vulnerable to the effector arm of both autoimmune and alloimmune responses, a vulnerability that has been attributed to the cytotoxic effects of lymphokines, notably IL-1, released in both autoimmune and alloimmune responses. The experiments reported here demonstrate not only the exquisite specificity of the allograft reaction but are not compatible with a hypothesis that B cells within an intact islet are nonspecifically susceptible to destruction by lymphokines.

Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1.

Dendritic cells (DC) in nonlymphoid organs can internalize and process foreign antigens before migrating to secondary lymphoid tissues to initiate primary immune responses. However, there is little information on which stimuli promote migration of DC from the tissues. Systemic administration of lipopolysaccharide (LPS), which induces in vivo production of cytokines, led to a reduction in the numbers of major histocompatibility complex class II-positive (Ia+) leukocytes in mouse hearts and kidneys: > 95% of DC were depleted 1-3 d after injection of 50 micrograms LPS. Several lines of evidence indicated that this response was due to migration of DC rather than loss of Ia expression or cytotoxic effects. In skin of treated mice, the number of Ia+ epidermal Langerhans' cells (LC) was reduced, and "cords" of Ia+ leukocytes became evident in the dermis. The latter cells expressed little NLDC145 and may have originated from recruited or resident DC progenitors. Systemic administration of recombinant tumor necrosis factor (rhTNF)-alpha resulted in a decrease in numbers of Ia+ cells in heart and kidney and of epidermal LC, and it also induced dermal cords. Administration of a rh-interleukin (IL)-1 resulted in a decrease in Ia+ cells only in renal medulla, appeared to activate a subset of epidermal LC, and induced dermal cords. Similar microgram doses of rhIL-2 had no obvious effect. Treatment with a neutralizing anti-TNF antiserum before LPS administration inhibited the depletion of LC from skin but not from heart or kidney. Therefore, TNF-alpha and IL-1 alpha may promote DC migration from nonlymphoid tissues and may have differential effects on different DC populations, but it is unclear whether they act on DC directly or indirectly (e.g., via other cytokines).

Migration and maturation of Langerhans cells in skin transplants and explants.

The behavior of Langerhans cells (LC) has been examined after skin transplantation and in an organ culture system. Within 24 h (and even within 4 h of culture), LC in epidermal sheets from allografts, isografts, and explants dramatically increased in size and expression of major histocompatibility complex class II molecules, and their numbers were markedly decreased. Using a new procedure, dermal sheets were then examined. By 24 h, cells resembling LC were found close to the epidermal-dermal junction, and by 3 d, they formed cords in dermal lymphatics before leaving the skin. In organ culture, the cells continued to migrate spontaneously into the medium. These observations establish a direct route for migration of LC from the epidermis into the dermis and then out of the skin. These processes are apparently induced by a local inflammatory response, and are independent of host-derived mediators. The phenotype of migratory cells was then examined by two-color immunocytochemistry and FACS analysis. The majority of migratory leukocytes were Ia+ LC, the remainder comprised Thy-1+, CD3+, CD4-, CD8- presumptive T cell receptor gamma/delta+ dendritic epidermal cells, which clustered with the LC, and a small population of adherent Ia-, FcRII+, CD11a/18+ macrophages. In contrast to the cells remaining within the epidermis of grafted skin at 1 d, the migratory cells were heterogeneous in phenotype, particularly with respect to F4/80, FcRII, and interleukin 2 receptor alpha expression, which are useful markers to follow phenotypic maturation of LC. Moreover, cells isolated from the epidermis of grafts at 1 d were more immunostimulatory in the allogeneic mixed leukocyte reaction and oxidative mitogenesis than LC isolated from normal skin, though less potent than spleen cells. The day 1 migratory cells were considerably more immunostimulatory than spleen cells, and day 3-5 migratory cells even more so, suggesting that functional maturation continues in culture. Thus, maturation of LC commences in the epidermis and continues during migration, but the cells do not need to be fully mature in phenotype or function before they leave the skin. In vivo, the migration of epidermal LC via the dermis into lymphatics and then to the draining nodes, where they have been shown previously to home to T areas, would provide a powerful stimulus for graft rejection.

Analysis of HL-A antigens in patients with Hodgkin's disease and their families.

The HL-A phenotypes of 127 patients with Hodgkin's disease have been determined. A very significant association has been found between Hodgkin's disease and two HL-A antigens, HL-A11 (P < 0.009), and W5 (P < < 0.0005). The families of 40 of these patients were genotyped for HL-A antigens. A normal mendelian segregation of the relevant antigen was found in all 12 families of HL-All positive patients and in 6 of 8 families of W5 positive patients. These findings suggest that certain Hodgkin's patients have a genetically determined susceptibility to their disease. It is postulated that this susceptibility could be due to linkage between HL-A genes and genes controlling immune responsiveness. Analysis of subgroups of Hodgkin's patients based on age, sex, and pathology suggests that these HL-A associations are most marked in certain subgroups.