Photon-Induced Quantum Oscillations of the Terahertz Conductivity in Graphene.

In this work, we present a theory that is able to explain the nonmonotonic decreasing behavior (observed in experimental data1-12) of the graphene terahertz conductivity with the increase of the field frequency. In this connection, the displacement of the structure of topological states inside the energy band gap, which appears in graphene due to the strong photon-electron coupling, and the narrowing of this gap, as result of electron transitions from bound photon-dressed electron states to extended states outside the energy gap driven by the field frequency, lead to a periodic change of singularities near the edge of the band gap, resulting in subtle quantum oscillations of the dynamical terahertz conductivity. This quantum contribution complements the Drude response, which fits the spectral range. On the other hand, the scattering processes by impurities favor interband transitions, suppressing this way intraband terahertz absorptions, which are related to optical transitions from inside to outside the gap.

[Risk factors associated with the conformation of the medial longitudinal arch and the symptomatic flat foot in a metropolitan school population in Mexico]. / Factores de riesgo asociados a la conformación del arco longitudinal medial y del pie plano sintomático en una población escolar metropolitana en México.

INTRODUCTION: The investigation on the medial longitudinal arch is aimed at addressing the diagnostic problems of flat foot. The diagnosis is currently based on clinical tests and the appropriate identification of both postural and gait abnormalities. Risk factors are associated with pre-school ages, but there is no adequate analysis of such factors during school ages, when the longitudinal arch reaches its conformational maturity. MATERIAL AND METHODS: Probabilistic methods were used to obtain a sample of 476 patients from elementary schools in the Federal District and the state of Puebla. Once the approval of the research committee was obtained, an analytical, prospective, cross-sectional study was conducted. Anthropometric measurements were performed, together with anamnesis, physical exam of the students, and conventional wet footprint analysis in a standardized and duplicate way. RESULTS: Of the 476 patients, 101 had flat foot (21.2%) and 49 of them had pain symptoms in the feet, knees or both (48.5%), accounting for 10.2% of the patients examined. Forefoot pronation and valgus hindfoot resulted in an increased risk of symptomatic flat foot in the school population in the study. CONCLUSIONS: In cases of flat or cavus foot, the presence of foot and/or knee pain symptoms in the school population was associated in a statistically significant way with one or more of the factors analyzed (overweight, genu valgus, valgus hindfoot, forefoot pronation and claw toes). Girls with such factors had a 3-7 higher chance of having symptomatic flat foot.

The anti-CD2 monoclonal antibody BTI-322 generates unresponsiveness by activation-associated T cell depletion.

The antihuman CD2 MoAb BTI-322 (Lo-CD2a) effectively inhibits T cell responses in vitro to allogeneic cells, which is followed by unresponsiveness to the original stimulator in secondary stimulation. We studied the xenogeneic human antiporcine mixed lymphocyte reaction (MLR), and utilized anti-T cell receptor (TCR) Vbeta family antibody-induced cell proliferation to determine the specificity and mechanism. BTI-322 and its humanized version, MEDI-507, effectively inhibited the primary xenogeneic MLR. After suboptimal primary stimulation using lower numbers of xenogeneic stimulator cells, the unresponsiveness in secondary culture was apparent only for xenogeneic stimulator cells of the original SLA haplotype, and not for third-party stimulators or allogeneic cells. The inhibition of primary MLR was not observed for nylon-wool-purified T cells, but was seen after reconstitution of purified T cells with monocytes. Similarly, anti-Vbeta family-specific stimulation showed family-specific unresponsiveness in secondary culture. This required the presence of the whole BTI-322 molecule: a F(ab')2 fragment was not effective. T cells of a distinct Vbeta family were depleted after stimulation with an anti-Vbeta family-specific antibody and BTI-322. We conclude that the inhibition by BTI-322 of a primary xenogeneic MLR or the response to an anti-TCR Vbeta antibody is associated with unresponsiveness upon restimulation, due to activation-associated cell depletion. In this process, the interaction between monocytes and the Fc part of the antibody is involved. This unique characteristic of BTI-322 suggests the potential of the antibody for tolerance induction in vivo, besides the potential use as a T cell depleting agent.

Effect of pig-specific cytokines on mobilization of hematopoietic progenitor cells in pigs and on pig bone marrow engraftment in baboons.

Mixed hematopoietic chimerism has been found to be a requirement for achieving specific immunologic hyporesponsiveness. Some of the requirements for in vitro and in vivo coexistence of discordant hematopoietic systems in the pig-to-baboon (or human) model have been investigated. We have tested the efficacy of pig-specific cytokines (PSC) (IL3, SCF, GM-CSF) in the mobilization of porcine bone marrow (BM) progenitors in vivo (i) in the pig and (ii) in baboons that underwent a conditioning regimen and porcine BM transplantation. In a preliminary in vitro study, porcine BM cells were incubated in various media to assess the effect of human plasma on pig progenitors in a colony-forming unit (CFU) assay. In in vivo studies, four pigs received PSC and one control pig did not. Six baboons underwent natural antibody removal, with subsequent pig BM transplantation. Four of these six underwent nonmyeloablative (n=2) or myeloablative (n=2) conditioning and all received PSC treatment. Two baboons did not receive PSC, one of which underwent a nonmyeloablative regimen. Sequential blood samples and BM biopsies in pigs and baboons were analyzed by CFU assay for the detection of porcine cells. Baboon samples were analyzed by polymerase chain reaction (PCR) to detect porcine DNA. In the case of the in vitro tests, colony forming by porcine progenitors was not inhibited by media containing human plasma and for the in vivo tests, PSC increased the number of progenitors in pig BM; mobilization of progenitors into the peripheral blood was observed. PSC-treated baboons which experienced transient depletion of leukocytes < 1,000/ml (as an effect of the conditioning regimen) had porcine BM cells detectable by PCR for as long as day 316 after BM transplantation. In conclusion we found that: (i) under the conditions of these studies, in vitro porcine progenitor cell growth was not inhibited by human plasma containing natural antibody and complement; (ii) PSC treatment led to an increased number of progenitors in pig BM and peripheral blood; (iii) the combination of an effective conditioning regimen and treatment with PSC was capable of inducing long-term survival of pig progenitors in baboons, although only a low level of engraftment was achieved.

Prótesis esofágicas / Esophageal prosthesis

El tratamiento paliativo endoscópico de neoplasias esofágicas avanzadas obstructivas que producen disfagia, episodios de broncoaspiración desnutrición o fístulas, incluye la dilatación endoscópica procedimiento de instalación de endoprótesis. Estos métodos son de bajo costo y pueden estar disponibles con facilidad en las unidades de endoscopía. Existen múltiples diferentes diseños de endoprótesis con ventajas y desventajas. Las de tipo metálico auto expandibles y las plásticas o de Tygon. Se describe la técnica para la instalación endoscópica de endoprótesis paso a paso. Existen complicaciones que pueden evitarse o resolverse tales como dolor torácico, oclusión debida a dieta inadecuada, perforación, fístula, sangramiento y desplazamiento ya sea proximal o distal de la prótesis como también enfermedad por reflujo relacionada con prótesis de esófago distal. La sobrevida y calidad de vida de pacientes con neoplasias avanzadas obstructivas pueden ser mejores con endoprótesis.

Transfer of swine major histocompatibility complex class II genes into autologous bone marrow cells of baboons for the induction of tolerance across xenogeneic barriers.

BACKGROUND: The present study examined the potential role of gene therapy in the induction of tolerance to anti-porcine major histocompatibility complex (SLA) class II-mediated responses after porcine renal or skin xenografts. METHODS: Baboons were treated with a non-myeloablative or a myeloablative preparative regimen before bone marrow transplantation with autologous bone marrow cells retrovirally transduced to express both SLA class II DR and neomycin phosphotransferase (NeoR) genes, or the NeoR gene alone. Four months or more after bone marrow transplantation, the immunological response to a porcine kidney or skin xenograft was examined. Both the renal and skin xenografts were SLA DR-matched to the transgene, and recipients were conditioned by combinations of complement inhibitors, adsorption of natural antibodies, immunosuppressive therapy, and splenectomy. RESULTS: Although the long-term presence of the SLA transgene was detected in the peripheral blood and/or bone marrow cells of all baboons, the transcription of the transgene was transient. Autopsy tissues were available from one animal and demonstrated expression of the SLA DR transgene in lymphohematopoietic tissues. After kidney and skin transplantation, xenografts were rejected after 8-22 days. Long-term follow-up of control animals demonstrated that high levels of induced IgG antibodies to new non-alphaGal epitopes developed after organ rejection. In contrast, induced non-alphaGal IgG antibody responses were minimal in the SLA DR-transduced baboons. CONCLUSIONS: Transfer and expression of xenogeneic class II DR transgenes can be achieved in baboons. This therapy may prevent late T cell-dependent responses to porcine xenografts, which include induced non-alphaGal IgG antibody responses.

Long-term discordant xenogeneic (porcine-to-primate) bone marrow engraftment in a monkey treated with porcine-specific growth factors.

BACKGROUND: Mixed allogeneic hematopoietic chimerism has previously been reliably achieved and shown to induce tolerance to fully MHC-mismatched allografts in mice and monkeys. However, the establishment of hematopoietic chimerism has been difficult to achieve in the discordant pig-to-primate xenogeneic model. METHODS: To address this issue, two cynomolgus monkeys were conditioned by whole body irradiation (total dose 300 cGy) 6 and 5 days before the infusion of pig bone marrow (BM). Monkey anti-pig natural antibodies were immunoadsorbed by extracorporeal perfusion of monkey blood through a pig liver, immediately before the intravenous infusion of porcine BM (day 0). Cyclosporine was administered for 4 weeks and 15-deoxyspergualin for 2 weeks. One monkey received recombinant pig cytokines (stem cell factor and interleukin 3) for 2 weeks, whereas the other received only saline as a control. RESULTS: Both monkeys recovered from pancytopenia within 4 weeks of whole body irradiation. Anti-pig IgM and IgG antibodies were successfully depleted by the liver perfusion but returned to pretreatment levels within 12-14 days. Methylcellulose colony assays at days 180 and 300 revealed that about 2% of the myeloid progenitors in the BM of the cytokine-treated recipient were of pig origin, whereas no chimerism was detected in the BM of the untreated control monkey at similar times. The chimeric animal was less responsive by mixed lymphocyte reaction to pig-specific stimulators than the control monkey and significantly hyporesponsive when compared with a monkey that had rejected a porcine kidney transplant. CONCLUSION: To our knowledge, this is the first report of long-term survival of discordant xenogeneic BM in a primate recipient.

Porcine kidney and heart transplantation in baboons undergoing a tolerance induction regimen and antibody adsorption.

BACKGROUND: Xenotransplantation would provide a solution to the current shortage of organs for transplantation. Our group has been successful in inducing tolerance in mice and monkey models of allogeneic transplantation. The present study attempts to extend the same tolerance-inducing regimen to a pig-to-baboon organ transplantation model. METHODS: Nine baboons underwent a conditioning regimen (consisting of nonmyeloablative or myeloablative whole body and thymic irradiation, splenectomy, antithymocyte globulin, pharmacologic immunosuppression and porcine bone marrow transplantation [BMTx]), which has previously been demonstrated to induce donor-specific allograft tolerance in monkeys. In addition, immunoadsorption of anti-alphaGal antibody (Ab) was performed. Four of the nine baboons received pig kidney transplants (KTx), and one also underwent repeat transplantation with an SLA-matched kidney. Two received heterotopic pig heart transplants (HTx). Three baboons underwent conditioning without organ transplantation for long-term studies of natural Ab kinetics. RESULTS: In the three baboons that received the conditioning regimen without an organ transplant, immunoadsorption reduced Ab by approximately 90%, but recovery of Ab to pretreatment level or higher occurred within 7 days. In contrast, the level of Ab remained low after organ transplant. No Ab to pig antigens other than alphaGal was detected in any baboon before or after BMTx, KTx, or HTx. No graft succumbed to hyperacute rejection. KTx function began to deteriorate within 3-6 days, with oliguria and hematuria progressing to anuria, and the kidneys were excised after 3, 6, 9, 11, and 14 days, respectively. One HTx ceased functioning at 8 days; the second baboon died with a contracting HTx at 15 days. Features of coagulopathy and thrombocytopenia developed in all six transplanted baboons (high D-dimer, prolonged prothrombin time and partial thromboplastin time, and falling fibrinogen) resulting in serious bleeding complications in two baboons, one of which died on day 9. Donor organs showed progressive acute humoral rejection with deposits of IgM, IgG, and complement; a focal mononuclear cellular infiltrate was also observed. The ureter was the earliest structure of the KTx affected by rejection, with progression to necrosis. CONCLUSIONS: This conditioning regimen prevented hyperacute rejection but was ineffective in preventing the return of Ab, which was associated with the development of acute humoral rejection with features of coagulopathy. No baboon developed anti-pig Ab other than alphaGal Ab. Further modifications of the protocol directed toward suppression of production of Ab are required to successfully induce tolerance to pig organs in baboons.

Depletion of anti-Gal(alpha)1-3Gal antibody in baboons by specific alpha-Gal immunoaffinity columns.

Ongoing studies at our center on facilitating transplantation of discordant xenogeneic organs are focused on tolerance induction. To abrogate hyperacute rejection, we have used adsorption methods to eliminate natural anti-Gal(alpha)1-3Gal (alphaGal) antibodies from the circulation of baboons. We have analyzed data concerning antibody removal in baboons that were 1) immunologically naive, 2) receiving conventional pharmacologic immunosuppressive therapy (IS), and 3) treated with a conditioning regimen for tolerance induction. We compared the efficiency of removing alphaGal antibody 1) by perfusion of whole blood through an alphaGal affinity column (CP; n=5) with 2) perfusion of plasma (separated from cellular components by apheresis) through an alphaGal column (CPA; n=39). Our studies demonstrate that 1) CP and CPA are equally effective in removing anti-alphaGal antibody, 2) CPA is the method of choice if multiple adsorptions are required, 3) CPA in naive animals transiently affects levels of total IgG and IgM, 4) four CPAs repeated at 2-4 day intervals in association with heavy IS reduce the pool of anti-alphaGal antibody and total Ig, and 5) splenectomy and/or IS delay the return of anti-alphaGal antibody.

Anti-Gal(alpha)1-3Gal antibody response to porcine bone marrow in unmodified baboons and baboons conditioned for tolerance induction.

BACKGROUND: Mixed lymphohematopoietic chimerism can provide an effective means of inducing longterm immunological tolerance and has been documented in a monkey allograft model. A conditioning regimen including nonmyeloablative or myeloablative irradiation and splenectomy has been used to induce chimerism in a pig-to-primate transplantation model. Since the presence of anti-Gal(alpha)1-3Gal (alphaGal) natural antibodies leads to the hyperacute rejection of pig organs transplanted into primates, extracorporeal immunoaffinity adsorption (EIA) of anti-alphaGal antibodies is also included in the regimen. The effect of the tolerance induction protocol on the anti-alphaGal antibody response has been assessed. METHODS: Anti-alphaGal antibody was measured after the EIA of plasma through an alphaGal immunoaffinity column in baseline studies involving two unmodified baboons, one splenectomized baboon, and one baboon that received a challenge with porcine bone marrow (BM), and in three groups of baboons (n=2 in each group) that received different conditioning regimens for tolerance induction. Group 1 received a nonmyeloablative conditioning regimen without porcine BM transplantation. Group 2 received nonmyeloablative conditioning with pig BM transplantation and pig cytokine therapy. Group 3 received myeloablative conditioning, an autologous BM transplant (with BM depleted of CD2+ or CD2+/CD20+ cells), and pig BM transplantation. RESULTS: In the baseline studies, a single EIA of anti-alphaGal antibodies in an unmodified animal initially depleted anti-alphaGal antibody, followed by a mild rebound. Nonmyeloablative conditioning (group 1) in the absence of pig cell exposure reduced the rate of anti-alphaGal antibody return. Pig BM cells markedly stimulated anti-alphaGal antibody production in an unmodified baboon (alphaGal IgM and IgG levels increased 40- and 220-fold, respectively). This response was significantly reduced (to an only 2- to 5.5-fold increase of IgM and IgG) in baboons undergoing nonmyeloablative conditioning (group 2). A myeloablative conditioning regimen (group 3) prevented the antibody response to pig BM, with the reduction in response being greater in the baboon that received autologous BM depleted of both CD2+ and CD20+ cells. No new antibody directed against pig non-aGal antigens was detected in any baboon during the 1 month follow-up period. CONCLUSIONS: (i) EIA of anti-alphaGal antibody in unmodified baboons results in a transient depletion followed by a mild rebound of antibody; (ii) exposure to pig BM cells results in a substantial increase in anti-alphaGal antibody production; (iii) a nonmyeloablative conditioning regimen reduces the rate of antibody return and (iv) markedly reduces the response to pig BM cells; (v) the anti-alphaGal response is completely suppressed by a myeloablative regimen if CD2+ and CD20+ cells are eliminated from the autologous BM inoculum. Furthermore, (vi) challenge with pig BM cells appears to stimulate only an anti-alphaGal antibody response without the development of other (non-alphaGal) anti-pig antibodies. We conclude that regimens used for T-cell tolerance induction can be beneficial in reducing the anti-alphaGal antibody response to porcine BM.

Removal of anti-porcine natural antibodies from human and nonhuman primate plasma in vitro and in vivo by a Galalpha1-3Galbeta1-4betaGlc-X immunoaffinity column.

BACKGROUND: Natural antibodies (NAbs) against a terminal alpha1-3 galactosyl (alphaGal) epitope have been identified as the major human anti-pig NAbs. METHODS AND RESULTS: We used two synthetic alphaGal trisaccharides--type 6 (alphaGal6) and type 2(alphaGal2)--linked to an inert matrix to remove NAbs from human plasma in vitro. Flow cytometry indicated that an average of 85% of the NAb binding activity was depleted by adsorption with alphaGal6. By measuring the binding of NAbs to pig peripheral blood mononuclear cells and bone marrow cells, we demonstrated that alphaGal6 was more effective than alphaGal2 in removing NAbs, and the combination of alphaGal6 + alphaGal2 did not further increase removal of NAbs. The specificity of the removal of NAbs (IgM and IgG) reactive with the alphaGal epitope by alphaGal6 matrix was shown by enzyme-linked immunosorbent assay. In vivo studies in nonhuman primates compared plasma perfusion through a alphaGal6 immunoaffinity column with hemoperfusion through a pig liver for changes in blood pressure, hematocrit, platelets, and NAb adsorption. CONCLUSIONS: Both methods reduced the level of anti-pig IgM and IgG xenoreactive antibodies to nearly background, but column perfusion caused less hypotension and reduction in platelets than liver perfusion. Four pig kidneys transplanted into monkeys after column perfusion did not undergo hyperacute rejection, remaining functional for 2-10 days, with a mean functional period of 7 days, demonstrating that a pig kidney can support renal function in a primate.

La vitamina C y sus propiedades antimutagénicas / The antimuthagenic properties of vitamin C

Se efectuó el análisis de algunas características de la vitamina C. Para ello se consideraron sus propiedades químicas y biológicas así como su impacto en la salud. Se revisaron las principales evidencias sobre su capacidad antimutagénica (y potencialmente anticarcinogénica) en diversos organismos y sistemas de prueba, y se consideró la posible aplicación en el humano

Pig to monkey bone marrow and kidney xenotransplantation.

BACKGROUND: The intensity of discordant xenograft cellular rejection makes it unlikely that safe doses of immunosuppressive drugs will alone be sufficient to permit long-term survival. We have therefore concentrated our efforts on establishing tolerance to xenogeneic organs through lymphohematopoietic chimerism and the elimination of preformed natural antibodies (nAbs). METHODS: Here we report the most recent series of 11 technically successful porcine to nonhuman primate transplantation procedures. In eight experimental animals induction therapy consisted of (1) 3 x 100 cGy nonlethal whole body irradiation (day -6 and day -5) to all animals, (2) horse anti-human thymocyte globulin (day -2, day -1, and day 0) to seven of the animals, (3) 700 cGy thymic irradiation (day -1) to five of the animals, and (4) pig bone marrow infused on day 0 (2-9 x 10(8)/cells/kg). On day 0, just before the renal xenograft, the recipient was splenectomized, and antipig nAbs were removed by means of perfusion of the monkey's blood through either a pig liver (n = 6) or a Gal-alpha (1,3)-Gal adsorption column (n = 5). There control animals did not receive this pretransplantation induction therapy but did undergo hemoperfusion and posttransplantation immunosuppression identical to the experimental animals. All 11 recipients were treated after transplantation with cyclosporin A and 15-deoxyspergualin. Recombinant pig-specific growth factors (interleukin-3 and stem cell factor) were given to six experimental animals from day 0 until the termination of the experiment. RESULTS: Analysis of recipients' sera by means of flow cytometry indicated the effective removal of immunoglobulin M and immunoglobulin G nAbs by either liver perfusion or column adsorption. In the eight experimental animals, nAb titers remained low until death (up to 15 days), but in the three control animals nAb titers increased substantially with time. The longest surviving recipient maintained excellent kidney function with creatinine levels at 0.8 to 1.3 mg/dl throughout its course. Death occurred at day 15 from complications caused by a urinary leak and pancytopenia. Histologic examination of the xenograft revealed only focal tubular necrosis and cytoplasmic vacuolization, with trace amounts of fibrin and C3 in peritubular capillaries. In this animal a fraction of the peripheral blood cells (3%) at day 7 were of pig origin as detected by pig-specific monoclonal antibodies. In addition, colony-forming assays performed on a bone marrow biopsy specimen taken at day 14 indicated that approximately 30% of the relatively few myeloid progenitors detected were of swine origin. CONCLUSIONS: We have demonstrated that our protocol is effective in the prevention of hyperacute rejection and in the maintenance of excellent function of the renal xenograft for up to 15 days. These results also indicate that at least short-term engraftment of the xenogeneic donor bone marrow cells is possible to achieve in this discordant large animal combination. Longer survivals will be required to assess the possible effect of this engraftment on induction of tolerance.

Niveles de carboxihemoglobina en donadores de sangre y de monóxido de carbono atmosférico en un área de la ciudad de México / Levels of carboxyhemoglobin in blood donors and of atmospheric carbon monoxide in a Mexico City area

La ciudad de México, con una altura sobre el nivel del mar de 2,240 m, ha alcanzado un elevado nivel de contaminación ambiental. El monóxido de carbono (CO) es uno de los principales contaminantes con capacidad de producir enfermedad cardiovascular de tipo isquémico o de agravar las existentes. El objetivo de este estudio fue conocer qué niveles de carboxihemoglobina (COHb), tiene los donadores de sangre que acuden al Instituto Nacional de Cardiología "Ignacio Chávez" de la ciudad de México, y qué niveles de monóxido de carbono se respiran en la atmósfera que hay en dicho Instituto. De mayo a junio de 1994, se analizaron los niveles venosos de COHb en 186 voluntarios donadores de sangre, y se midió el monóxido de carbono atmosférico en forma cotidiana durante el mismo periodo de tiempo, dentro de la Unidad Coronaria (UC) y en la azotea del 5º piso del Instituto a una distancia aproximada de 300 m de una vía con alto flujo vehicular (periférico sur). Los niveles de COHb en los fumadores fueron de 2.4 ñ 1.4 por ciento, y en los no fumadores de 1.5 ñ 0.6 por ciento, p= 0.002, cifra mucho más alta a la que se tiene de la producción endógena de este gas (0.5 por ciento), pero similar a la informada en otras ciudades del planeta. Los niveles de CO atmosférico nunca sobrepasaron las 4 partes por millón (ppm) (máximo pemitido por la Secretaría de Salud: 11 ppm), Los niveles de COHb no correlacionan con los parámetros estudiados: ocupación laboral, zona de la ciudad en que se habita o trabaja, medio de transporte usado para llegar al Instituto y número de kilómetros recorridos el día antes de la toma de la muestra, pero sí con el tabaquismo. Niveles de CO como los que se respiran en el aire de la UC y en la azotea del Instituto Nacional de Cardiología, no constituyen un peligro para la salud.

An anti-CD2 mAb induces immunosuppression and hyporesponsiveness of CD2+ human T cells in vitro.

We describe here the potent specific immunosuppression obtained in vitro by LO-CD2a, a rat mAb directed against the human CD2 molecule. Addition of low dose LO-CD2a (40 ng/ml) at the time of mixed lymphocyte culture (MLC) initiation inhibits 80% of the proliferation and, more impressive, addition of the mAb 4 days after culture initiation at a similar concentration still suppresses 50% of the MLC. When responder T cells previously treated with LO-CD2a are challenged a second time by the same donor or third party allogeneic cells, hyporesponsiveness occurs in both cases, although reactivity to T cell mitogenic stimulation persists. Finally, the low production of cytokines such as tumor necrosis factor-alpha and IFN-gamma after incubation of human T cells with LO-CD2a suggests the absence of T cell activation. These results demonstrate that LO-CD2a mAb has a significant immunosuppressive effect and induces hyporesponsiveness in vitro, thereby suggesting potential efficacy in vivo for the treatment of acute rejection and for the induction of tolerance in allotransplantation.

The incidence of protein C deficiency in thrombosis-related portal hypertension.

OBJECTIVE: To know the incidence of protein C deficiency associated with noncirrhotic, thrombosis-related portal hypertension. METHODS: Thirty-six patients were studied who had thrombosis-related portal hypertension diagnosed by means of hepatic venography or abdominal echocardiography or during abdominal surgery. Liver disease was excluded in 20 patients based on normal liver function tests and normal histology on liver biopsy. At the time of protein C assays, these patients were not receiving oral anticoagulation, and, in those recently diagnosed, the assays were performed more than 14 days after the last thrombotic event. Antigenic and functional assays for protein C were performed by ELISA and chromogenic assay, respectively. RESULTS: We found 11 patients with protein C deficiency who had a median age of 28 yr (range 19-55 yr) at time of diagnosis. Five patients had a history of systemic thromboembolism, and upper GI bleeding was the most frequent symptom related to portal hypertension (six cases). Antigenic protein C levels were measured in nine of the 11 patients (mean 31.88%, range 10-49%). Functional protein C level was assayed for all 11 patients (mean 40.90%, range 15-58%). After diagnosis, all patients received oral anticoagulants (ideally International Normalized Ratio: 2-3). CONCLUSION: We suggest that protein C screening should be performed in patients with thrombosis-related portal hypertension.