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[Elevation of soluble transferrin receptor substance in serum of cancer patients with suppressed natural killer activity].

Soluble transferrin receptor (sTfR) in serum of cancer patients was measured by a sandwich enzyme-linked immunosorbent assay, and the effect of sTfR for natural killer cytotoxicity was also studied. The statistical values of sTfR levels in sera were found to be 250 +/- 77 U (Mean +/- SD) in healthy individuals, while 288 +/- 162 U in chronic liver disease, 402 +/- 290 U in hepatocellular carcinoma, 429 +/- 261 U in gastric cancer, 347 +/- 207 U in acute leukemia and malignant lymphoma, and 251 +/- 100 U in other cancer. No significant difference in the sTfR levels among the patients was observed, although the difference between the healthy individuals and the patient groups was shown to be statistically significant at p less than 0.01 level. The effect of sTfR isolated from serum of a patient with iron-deficiency anemia by means of Sephadex G-200 column for natural killer activity was carried out. Cytotoxicity of natural killer cell in healthy individuals was inhibited by sTfR as the dose dependent manner, and the inhibitory rate was found to be 23.1 +/- 12.8% (Mean +/- SD) when the concentration of the sTfR was 1,250 U added in the cytotoxicity test. Furthermore, the inhibitory activity of serum in cancer patients was correlated with the sTfR level. These results suggest that sTfR is one of the inhibitory factors for the natural killer cell activity in vivo, and the factor could be facilitated for tumor growth and metastasis. Therefore, the measurement of sTfR in serum may be useful for monitoring immunological competency in cancer patients.

Anemia, Hypochromic↗

Emergency heart retransplantation with a positive donor crossmatch.

We report a case of one patient who underwent emergency retransplantation with a highly positive donor crossmatch. Standard immunosuppression was integrated by the addition of plasma exchange during extracorporeal circulation, polyclonal IgG, and cyclophosphamide for the first 30 days. After transplantation the clinical outcome was normal; immunosuppression induced a complete disappearance of the donor-specific antibody. In spite of the heavy immunosuppression, we did not observe any infectious complications. We suggest that a greater immunosuppression established soon after the transplant and adjusted on the basis of immunological monitoring may allow a heart transplant with a positive crossmatch.

Adult↗

[Lung transplantation as a treatment method in terminal respiratory failure].

Lung transplantation is the last treatment for terminal respiratory failure due to irreversible pulmonary disease such as fibrosis and emphysema. In this paper we reported the results of our studies on three major problems for conducting clinical lung transplantation sefely, including lung preservation, early diagnosis of lung allograft rejection and bronchial anastomotic healing. We have developed a method for 48- and 96-hour lung preservation. Under simple hypothermic preservation using phosphate buffered solution resembling extracellular fluid, 48-hour storage of the lung becomes possible. Immunologic monitoring is feasible for early detection of postoperative rejection of the lung transplant. In this study subset and spontaneous blastogenesis of lymphocyte obtained from bronchoalveolar lavage fluid were measured in orthotopic rat lung allotransplantation. Lung allograft rejection is closely connected with wound healing of the bronchial anastomosis in lung transplantation. It seems that clinical applications of single and double lung transplantation is now possible for patients with terminal respiratory disease in our country.

Bronchoalveolar Lavage Fluid↗

[Treatment and follow-up care after heart transplantation].

Today survival rates after heart transplantation of around 80% at 1 year and around 65% at 5 years are realistic. Most patients attain NYHA functional class I. Due to progress in donor and recipient selection, in immunotherapy, and in a systematic follow-up program post transplant, heart transplantation today has become an accepted treatment in special forms of terminal heart disease. Between September 23, 1985, and May 15, 1987, 19 patients were transplanted in Zurich. After an average of 7 months (1-20), 18 patients are alive with NYHA functional class I. The follow-up program checks systematically for the three main problems post transplant (rejection, infection, and drug-induced side-effects). Regular endomyocardial biopsy is the gold standard for diagnosis of rejection. Non-invasive methods, such as cyto-immunological monitoring, neopterin, or beta 2-microglobulin, are not a substitute but valuable adjunctive diagnostic methods.

Adult↗

[Biochemical and functional characteristics of thymus and spleen lymphocytes in C3HA mice during the growth of hepatoma 22 and after immunization with sheep erythrocytes].

Activities of key enzymes of purine metabolism [adenosine deaminase (AD); purine nucleoside phosphorylase (PNP); 5'-nucleotidase] were studied; changes in DNA content, nucleus ploidity in thymocytes, T- and B-lymphocytes in the C3HA mouse spleen during solid 22 hepatoma growth and after the immunization were monitored. Immunological properties of lymphocytes were also investigated measuring antibody formation and the reaction of blasttransformation in response to phytohemagglutinin, concanavalin A and lipopolysaccharide. Within the first 48 hrs after the tumor implantation and immunization certain nonspecific biochemical mechanisms of lymphocytes activation (elevated AD activity, decreased activity of 5'-nucleotidase, augmented intracellular DNA levels, polyploidity) were revealed. As the solid 22 hepatoma reached the maximum growth rate specific alterations in the activities of the purine metabolism key enzymes were observed reflecting the response of thymus and spleen lymphocytes to the presence of the malignant tumor.

5'-Nucleotidase↗

Characterization of natural killer cells with antileukemia activity following allogeneic bone marrow transplantation.

To identify cells with potential antileukemia activity following bone marrow transplantation, we have monitored immunologic reconstitution in a patient with acute lymphocytic leukemia in second remission who received intensive chemotherapy and total body irradiation followed by infusion of allogeneic histocompatible marrow. Prior to transplantation, donor bone marrow cells were depleted of T lymphocytes by in vitro treatment with anti-T12 monoclonal antibody and rabbit complement. In the first 3 weeks following bone marrow transplantation, the predominant regenerating mononuclear cell population in peripheral blood exhibited a phenotype characteristic of natural killer (NK) cells. After 4 weeks, T lymphocytes became predominant, but NK cells persisted. Cultured peripheral blood lymphocytes obtained 12 weeks posttransplant were able to display significant cytotoxicity against leukemic blasts that had been cryopreserved at the time of relapse 5 months prior to bone marrow transplantation. To further characterize those cells with antileukemia activity, we used in vitro cloning techniques to identify four monoclonal populations, termed TC12, -48, -50, and -59, with strong antitumor activity. Cytogenetic analysis demonstrated that each clone was of donor origin. Phenotypic characterization showed that the four clones expressed NKH1A but did not express T3, T4, or T8 antigens. Three of the four clones expressed T11/E rosette antigen. Each clone exhibited strong cytotoxicity against genetically unrelated hematopoietic tumor cell lines such as K562, Molt-4, JM, and U937. In addition, we found that these patient clones were similar to cloned NK cells previously derived from normal individuals. Taken together, these results suggest that at least some clones with antileukemia activity following bone marrow transplantation are cells with NK-like function and phenotype. Functional analysis of these cytolytic cells in larger numbers of patients will be necessary to determine the clinical significance of this finding.

Adult↗

Current expectations in cardiac transplantation.

Survival after cardiac transplantation has improved significantly over the past 3 1/2 years at our Center as compared to previous experience (Fig. 5). Currently, survival rates for 60 patients who have had heart transplantation since late in 1973 (program year mean survival +/- S.E.) are 66 percent (+/- 6.6 S.E.), 63 percent (+/- 7.0) and 58 percent (+/- 8.2) 1, 2, and 3 years after operation, respectively. In this report the major reasons for this successful trend have been summarized. These consist of transvenous endomyocardial biopsy for diagnosis and management of graft rejection, use of RATG, immunologic monitoring for early detection of impending rejection, and cardiac retransplantation in selected cases. The present expectations for survival and rehabilitation after heart transplantation are fully comparable to the current results of renal transplantation from unrelated donors. These considerations support the inclusion of cardiac transplantation as a realistic therapeutic alternative in the management of patients with advanced heart disease irremediable by standard forms of treatment.

Antilymphocyte Serum↗

Vitamin E supplementation in hemodialysis patients: effects on peripheral blood mononuclear cells lipid peroxidation and immune response.

Lipid peroxidation and vitamin E levels in peripheral blood mononuclear cells (PBMC) were studied in 10 patients on maintenance hemodialysis. Significant increases of PBMC malonyldialdehyde (MDA) were detected, together with low vitamin E levels. After a fifteen-day-course of parenteral vitamin E supplementation, PBMC MDA reverted to normal values, while PBMC vitamin E levels remained lower than controls. In a parallel study an immunological monitoring was performed in the same patients before and after vitamin E supplementation. NK activity and PHA blastogenesis were not influenced by treatment, while a reduction of the number of OKT8+ lymphocytes were observed after vitamin E therapy. It is tempting to speculate that peroxidative damage of PBMC cell membranes in hemodialysis patients could, by impairing their functionality, influence immune responses and expression of functionally relevant membrane determinants.

Adult↗

[Spontaneous rupture of renal allografts (author's transl)].

Spontaneous rupture of an allografted kidney is not such a rare complication of kidney transplantation. In our series 5.2% of the transplanted kidneys ruptured spontaneously. The condition is an acute emergency characterized by the triad, acute abdomen, swelling in the region of the transplant and haemorrhagic shock. The aetiology of transplant rupture seems to be multifactorial, but the superimposition of an acute rejection episode on ischaemic tubular damage with acute renal failure was found to be the most important combination of events leading to transplant rupture in our patients. Exceptionally precise immunological monitoring in the early phases following transplantation and early aggressive therapy of an acute rejection crisis associated with acute renal failure should prevent allograft rupture.

Abdomen, Acute↗

HLA typing and karyotyping of limited numbers of lymphocytes is facilitated by in vitro expansion with TCGF.

It is often difficult to obtain sufficient quantities of leukocytes from bone marrow (BM) transplant recipients for post-transplant immunological monitoring and evaluation of engraftment. We have developed a cell culture expansion technique that allows HLA-A,B, and DR typing as well as karyotyping on limited numbers (less than 10(7)) of lymphocytes. Lymphocytes from healthy control donors were allo-activated in vitro and further expanded by culturing in T-cell growth factor (TCGF). After 14 days of culture, these cells were sent for blind HLA-A,B and DR typing and for karyotyping. Surface marker studies showed that 90% of the T-cells expanded in growth factor are OK-la positive. HLA typing with these DR-bearing in vitro expanded T-cells showed excellent correlation with HLA typing on fresh unexpanded lymphocytes. Karyotyping of expanded T-cells showed normal male or female cells as expected. This technique may be especially valuable when testing pediatric or adult patients with very low lymphocyte counts.

Bone Marrow Transplantation↗

Effects of Corynebacterium parvum and BCG therapy on immune parameters in patients with disseminated melanoma a sequential study over 28 days. I. Changes in blood counts, serum immunoglobulins and lymphoid cell populations.

The effects of a single immunization of melanoma patients with BCG or C. parvum on the blood counts, serum immunoglobulin levels and lymphoid subpopulations were followed by multiple assays over 28 days. C. parvum produced a decrease in the white cell count, lymphocyte count and lymphoid T and sIg+ cell numbers, which recovered within 1 week; BCG did not produce such a marked depression. Both agents were associated with increases in T cell numbers and lymphocyte PHA blastogenesis after the first week; these declined to pre-immunization values by 3-4 weeks. The sIg-bearing cell subpopulation also increased after BCG. Different methods of expression the results were compared and the difficulties of immunological monitoring are discussed.

Adult↗

beta 2-Microglobulin and beta 2-microglobulin-binding proteins in inflammatory diseases.

Beta 2 microglobulin (beta 2m) is a 11,800 daltons polypeptide non covalently associated with the heavy chain of class I histocompatibility antigens (HLA-A, B and C) at the surface of nearly all cells. Serum beta 2m levels are passively controlled by the glomerular filtration rate. Increased beta 2m production resulting in elevated serum levels despite normal renal function have been reported in malignancies of the lymphoreticular system (e.g. multiple myeloma) and in various autoimmune or chronic inflammatory diseases, including rheumatoid arthritis. In some situations beta 2m levels were shown to be positively correlated with absolute lymphocyte counts in the peripheral blood or with the score of mononuclear cell infiltrates in biopsy specimens. Together with the demonstration that activated T lymphocytes release beta 2m in culture, these data support the hypothesis that increased production of beta 2m in vivo could represent a non specific indication of lymphocyte activation. Follow-up studies of individual patients are needed to define the clinical situations in which beta 2m determination may improve the immunological monitoring, with special reference to the early diagnosis of relapses and the assessment of individual response to treatment.

Arthritis, Rheumatoid↗

[Squamous cell carcinoma of the palatine tonsils. Effect on the immune system in man].

Immunological monitoring was applied to 56 patients suffering from squamous cell carcinoma of the tonsils. The Immunofluorescence of oral swabs and measurements of unspecific suppressive activity of peripheral lymphocytes were tested. Autologous IgG antibodies directed against antigens of the tumor cells as well as higher levels of suppressor cells could be found in patients with carcinomas. These antibodies reacted similarly with allogeneic tonsillar carcinomas; cross reaction with other allogeneic tumor cells (bladder-kidney carcinoma) could not be detected. The findings indicate therapeutical consequences for the patients with high suppressor activity and immunofluorescence.

Antibodies, Neoplasm↗

Immunosuppressive effect of surgery evaluated by the multitest cell-mediated immunity system.

The immunosuppressive effect of surgery in a series of 100 elective laparotomies was determined by analysing the delayed skin hypersensitivity, the most sensitive in-vivo reflection of cell-mediated immunity. For this purpose, a new method (Multitest cell-mediated immunity system) for simultaneous, multiple, intradermal skin tests was used. This system uses a plastic disposable device for simultaneous intradermal injection of seven immunologically standardized recall antigens, offering the possibility of assessing a patient's immunologic capability in a manner that is painless, rapid, safe, reproducible and quantifiable. Patients were tested preoperatively and on days 1, 3 and 7 after operation. Twenty healthy volunteers, the control group, were similarly tested. Immunosuppression was observed in all patients, reaching a peak on postoperative day 3. Recovery occurred between 7 and 10 days after operation. Immunosuppression was more severe and prolonged in patients with neoplastic disease. By continued immunologic monitoring using the Multitest system, the authors could confirm the suggested immunosuppressive effect of operation and establish that the phenomenon is temporary.

Adolescent↗

Nitric oxide generation. A predictive parameter of acute allograft rejection.

The L-arginine:nitric oxide (NO) biosynthetic pathway has been proposed as an important mediator in host defense mechanisms and may therefore play a role in the acute allograft response. We have studied NO generation in liver allograft rejection and determined its value in immunological monitoring. Stable end products of this pathway have been determined serially in 50 primary liver recipients and compared with 2 known mediators and markers of acute allograft rejection (IL-2R positive lymphocytes and circulating TNF alpha). Plasma concentrations of acid-labile nitrosocompounds (NOx), which increased during acute allograft rejection (P < 0.0001), correlated with rejection severity and were reduced after administration of supplemental high dose glucocorticoids. Concentrations were significantly lower in nonrejection graft complications but were elevated during episodes of sepsis. Correlations between plasma NOx levels and circulating TNF-alpha (r = 0.451, P < 0.001) and IL-2R-positive lymphocytes in peripheral blood (r = 0.781, P < 0.001) were demonstrated. In a logistic analysis of these variables, plasma NOx was the most predictive parameter of an episode of acute cellular rejection. Nitric oxide generation in FK506-treated patients was lower compared with patients receiving a CsA-based immunosuppression regimen and was associated with a reduced frequency of acute rejection in the FK506 group. These data are consistent with a role for NO in the cellular alloantigen immune response and indicate that monitoring of plasma levels of NOx may be useful in the detection of acute allograft rejection.

Biomarkers↗

1995 revised guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with or perinatally exposed to human immunodeficiency virus. National Pediatric and Family HIV Resource Center and National Center for Infectious Diseases, Centers for Disease Control and Prevention.

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection in children who have acquired immunodeficiency syndrome (AIDS). Despite the publication of guidelines for prophylaxis against PCP for children infected with human immunodeficiency virus (HIV) in 1991 (1), ongoing AIDS surveillance has detected no substantial decrease in PCP incidence among HIV-infected infants. Studies indicate that this continued incidence is associated with failure to identify HIV-infected children before PCP occurs and with limitations in the ability of CD4+ measurements to identify children at risk for PCP. In March 1994, the National Pediatric & Family HIV Resource Center, in collaboration with CDC, convened a working group to review additional data about the occurrence of PCP among HIV-infected children and to reevaluate the 1991 PCP prophylaxis guidelines for children. This report summarizes these new data and presents revised PCP prevention guidelines that recommend a) promptly identifying children born to HIV-infected women and initiating regular diagnostic and immunologic monitoring of such children; b) beginning PCP prophylaxis at 4-6 weeks of age for all children who have been perinatally exposed to HIV; c) continuing prophylaxis through 12 months of age for HIV-infected children; and d) making decisions regarding prophylaxis for HIV-infected children > or = 12 months of age based on CD4+ measurements and whether PCP previously has occurred.

AIDS Serodiagnosis↗

Treatment of HIV infection in infancy.

Treatment for HIV infection and preventive methods for HIV-associated infections are now routinely available and recommended for the management of HIV-infected children. These strategies have been associated with improvement in the quality and duration of life for HIV-infected adults and children. The institution of these interventions is dependent on recognition of infants at risk for infection (born to mothers with HIV infection), early diagnosis of HIV infection in infants and young children, and careful clinical and immunologic monitoring. As with other chronic illnesses, management of HIV-infected children should be comprehensive and should involve the active participation of both the primary pediatrician and the HIV specialist. Optimization of interventional strategies is dependent on ongoing and planned clinical trials.

AIDS Vaccines↗