Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bruton's XLA and DiGeorge syndrome patients show that two basic immune systems are distinct from each other in humans - thymus-dependent cell-mediated immunodeficiencies vs. antibody-based immunodeficiencies. The appendix-sacculus lymphoid organ of rabbits, like the bursa of Fabricius, represents a central lymphoid organ. Chronic granulomatous disease of childhood (CGD) revealed that phagocytosis killing of catalase-positive microorganisms employ oxidative burst. Bone marrow transplantation (BMT) proved life saving in severe combined immunodeficiency (SCID). The first BMT cured XSCID and the second BMT cured a complicating aplastic anemia launching BMT as a treatment of many diseases. Now 75 fatal diseases have been cured by myeloablative BMT. BMT also cured experimental autoimmune diseases. BMT alone did not cure lupus with polyarthritis in MRL/lpr mice or polyarthritis in NZB/KN mice, but BMT plus bone (stromal cell) transplants cured these diseases. Autoimmune diseases and lethal glomerulonephritis were prevented or cured in BXSB mice by mixed allogeneic plus syngeneic BMT. X-linked Hyper IgM syndrome (XHIM) was also cured by BMT from a 2-year-old MHC-matched sibling donor. Nonmyeloablative BMT plus mesenchymal stem cells (stromal cells) was effective treatment for a form of collagen-vascular disease and also a lethal form of hypophosphatasia. Mannan-binding lectin, an opsonin that activates the complement system when mutated and at low levels in blood, opens a door to frequent infections throughout childhood and adult life. This new immunodeficiency is based on genetic mutations that involve a native defense system.
 ...
PMID:Cellular immunology in a historical perspective. 1219 Sep 28

Scientific analyses fortified by interpretations of immunodeficiency diseases as 'experiments of nature' have revealed the specific immune systems to be comprised of T cells subserving cell-mediated immunities plus B cells and plasma cells which produce and secrete antibodies. These two separate cellular systems regularly interact with each other to produce a coordinated defense which permits mammals to live within a sea of microorganisms that threaten the integrity and the survival of individuals. We have shown that bone marrow transplantation (BMT) can be used as a form of cellular engineering to construct or reconstruct the immune systems and cure otherwise fatal severe combined immunodeficiency. When severe aplastic anemia complicated the first BMT which was performed to cure a fatal severe combined immunodeficiency, a second BMT cured for the first time a complicating severe aplastic anemia. Subsequently, BMT has been used effectively to treat some 75 otherwise fatal diseases such as resistant leukemias, lymphomas, inborn errors of metabolism, and genetic anomalies of the hematopoietic development such as sickle cell anemia, thalassemia, congenital neutropenias, and many other diseases. More recently, we have employed BMT in mice both to cure and cause autoimmunities, and, together, these experiments showed that autoimmunities actually reside in the hematopoietic stem cells. We have also found that mixed BMT or mixed hematopoietic stem cell transplantation (HSCT) can be used to prevent and cure the most complex autoimmunities such as those occurring in BXSB mice and in (NZW x BXSB)F1 W/BF1 mice. Untreated, the former develop fulminating lethal glomerulonephritis plus numerous humoral autoimmunities. Mice of the (W/B)F1 strain develop autoimmune thrombocytopenic purpura, coronary vascular disease with myocardial infarction, glomerulonephritis, and numerous autoantibodies. All of these abnormalities are prevented or cured by mixed syngeneic (autoimmune) plus allogeneic (normal healthy) BMT or mixed peripheral blood HSCT. Thus, the most complex autoimmune diseases can be prevented or cured in experimental animals by mixed syngeneic plus allogeneic BMT or HSCT which produce stable mixed chimerism as a form of cellular engineering.
 ...
PMID:Mixed bone marrow or mixed stem cell transplantation for prevention or treatment of lupus-like diseases in mice. 1238 26

From March 1994 to January 2001, 15 courses of granulocyte transfusion (GTX) were administered to 13 neutropenic patients (6 male and 7 female patients; median age 7 years, range 3 months to 14 years) affected by: acute lymphoblastic leukemia (ALL) in 6 cases, acute myeloid leukemia (AML) in 5, very severe aplastic anemia in 1, and familial erythrophagocytic lymphohistiocytosis (FEL) in 1. Infections were classified as microbiologically defined and clinically defined infections in 8 and 7 episodes, respectively. Before the GTX transfusions, broad-spectrum antibacterial and antifungal therapy had been administered for a median of 12 (range 5-28) and 8 days (range 2-50), respectively, with no improvement. G-CSF was administered prior to GTX in 9 episodes of infection, with a median of 9 days of treatment (range 4-30). Leukapheresis was obtained from 15 related donors (father, 10; mother, 3; sister, 1; aunt, 1) after s.c. stimulation with G-CSF, 300 micro g daily, starting from day -3 (where day 0 was the day of the first granulocyte collection) and continuing throughout the period of GTX treatment. The donors' median white blood cell (WBC) count at leukapheresis was 31.6 x 10(9)/l (range 12-56), and the median yield was 31.39 x 10(9) WBC (range 2.96-64.73 x 10(9)), with a proportion of PMN of 90-95%. Overall, 70 GTX were administered, with a median of 4 GTX per episode of infection (range 2-11). The combination of GTX with antimicrobial therapy led to complete or partial recovery in 6 and in 3 of 15 episodes (60%), respectively. Priming of the donor with G-CSF was well tolerated, the most common side-effects being bone pain, malaise and paresthesia. All donors are alive and well after a median of 4.5 years (range 0.8-7.7) from donation. We conclude that GTX is potentially useful when the severity of the infection and the host's immunodeficiency make any other antimicrobial treatment ineffectual. Long-term safety data on the stimulation of donors with G-CSF have been reassuring to date. Further controlled studies are needed to assess the exact role of GTX in the outcome of neutropenic patients with severe infection and any criteria for patient selection and the timing of GTX administration.
 ...
PMID:Granulocyte transfusions from G-CSF-stimulated donors for the treatment of severe infections in neutropenic pediatric patients with onco-hematological diseases. 1256 Sep 38

Research was carried out in 335 blood specimens of patients in the age of 3-35 y.o. in order to optimize diagnosis and treatment of such patients with aplastic anemia and hemoblastosis who got hemotransfunction to eliminate cytomegaloviral infection (CMVI). IgM were found out in 37.9% cases (2.8 times higher than in donors), low-avide IgG--in 44.8%. "early" proteins CMV--29.9% and DNA--in 36.8% cases. Concerning the DNA presence, preference was given to research of leucocytic suspension compared with blood serum. Of 28 children of 3-13 y.o. with anemia being seropositive in CMV, IgG antibodies were detected in 13 children while IgM antibodies to Parvovirus B19 were found in 10 children. 7 children with a grave form of disease showed combined infection of Parvovirus B19 and CMV with activation signs. It is not excluded that parallel influence of Parvovirus B19 on erythrocytic hemopoiesis growth and that of CMV on lymphocytic-monocytis cells aggravates immunodeficiency and promotes development of infection complications.
 ...
PMID:[Laboratory diagnosis of cytomegaloviral infection in patients with anemia and hemoblastosis in the Omsk region]. 1258 56

To determine the clinical characteristics and outcome of patients with chronic hepatitis C virus (HCV) infection presenting severe autoimmune cytopenia unrelated to interferon alpha therapy, we analyzed characteristics and outcomes of 35 patients with HCV (16 from our departments and 19 from the literature). We considered active autoimmune hemolytic anemia (AHA) as a decrease of at least 2 g/dL in hemoglobin levels, an increase of at least 0.6 mg/dL in the serum unconjugated bilirubin level, a reticulocyte count >5%, and a positive direct Coombs test. Severe neutropenia was defined as a neutrophil count <0.5 x 10(9)/L, and severe thrombocytopenia as a platelet count <30 x 10(9)/L. We identified the following cytopenias: AHA (17 cases), severe thrombocytopenia (16 cases), aplastic anemia (2 cases), severe neutropenia (1 case), refractory sideroblastic anemia (1 case), and pure red cell aplasia (1 case). Three patients simultaneously presented 2 types of severe cytopenias. Twenty-seven patients (77%) were female and 8 (23%) male, with a mean age at diagnosis of cytopenia of 51.7 years (range, 18-84 yr). Immunologic markers were detected in 19 (68%) of 28 patients, the most frequent being hypocomplementemia in 16 (57%), cryoglobulins in 15 (54%), antinuclear antibodies in 12 (43%), and rheumatoid factor in 5 (18%). Other associated processes were autoimmune diseases in 14 (50%) of 28 and human immunodeficiency virus (HIV) coinfection in 3 (9%) of 32. We found clinical and immunologic differences between HCV patients with AHA and those with severe thrombocytopenia. Patients with HCV-related AHA showed a higher prevalence of associated autoimmune diseases (71%), cryoglobulins (67%), and cirrhosis (59%). All had a good response to corticosteroids, but a poor prognosis (47% mortality). In contrast, patients with HCV-related severe thrombocytopenia had a lower prevalence of associated autoimmune diseases (11%), a poorer response to corticosteroids (55%), and lower mortality (6%), with HIV/HBV coinfections in some patients. The 35 cases presented demonstrate that different types of immune-mediated cytopenias may be severe and clinically significant in patients with HCV infection. Hemolytic anemia and severe thrombocytopenia were the most frequent cytopenias observed. Most patients responded well to corticosteroids, although a higher rate of mortality was observed in those with liver cirrhosis.
 ...
PMID:Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 35 cases. 1264 Jan 85

Allogeneic haematopoietic stem cell transplantation (i.e. bone marrow or peripheral blood stem cell transplantation) is a common procedure in the treatment of various haematological disorders such as aplastic anaemia, (pre)leukaemias, some malignant lymphomas, multiple myeloma and immunodeficiency states. Many of these patients develop erythematous skin lesions following transplantation. Although graft- versus-host disease is the major differential diagnosis in these situations, many other causes of erythema are encountered. The large number of transplant patients means that more and more pathologists are confronted with the challenging problem of making a correct diagnosis in these situations. In this review article we therefore describe the different causes of erythema and their differential diagnoses. In most cases the clinical presentation is related to the microscopical features. Besides acute and chronic graft-versus-host disease, we discuss the (common) drug reactions and non-specific features such as Sweet's syndrome, erythema nodosum and eosinophilic folliculitis. In addition, we deal with the recurrence of original diseases and infections. With this knowledge every pathologist should feel comfortable when looking at skin biopsies of patients after haematological stem cell transplantation.
 ...
PMID:Differential diagnosis of skin lesions after allogeneic haematopoietic stem cell transplantation. 1265 43

The method of immune-enzyme assay was used to examine 113 patients with secondary immunodeficiency, including 16 HIV-infected drug-addicts (group 1), 36 patients with cytomegalovirus infection (CMVI) and with immunoregating index CD4/CD8 below 1.0 (group 2), 30 patients with CMVI and with CD4/CD8 below 1.2 (group 3) and 31 patients with aplastic anemia and with anemia of unclear genesis (group 4), for parvovirus infection caused by parvovirus B19. As for groups 1 and 4, the antibodies were detected in 50 and 48.4% of cases; it is noteworthy that an active parvovirus infection was registered in the above groups more often than in groups 2 and 3. There were patients with the antibodies in group 2 by 1.8 times more than in group 3. It is suggested that the simultaneous impact of HIV, CMV and parvoviruses significantly aggravates the immunodeficiency and contributes to a more severe clinical course.
 ...
PMID:[Diagnosis of parvovirus B19 infection in patients with secondary immunodeficiency diseases]. 1282 4

Persistent infection with human parvovirus B19 (B19) is primarily associated with chronic bone marrow failure in immunocompromised patients, but occasionally this organism may also affect immunocompetent hosts. B19 is also suggested as a causative agent of organ failure during bone marrow transplantation (BMT). We herein report the case of a 9-year-old girl with no previous history of immunodeficiency who developed severe aplastic anemia concurrent with B19 persistent infection. Both immunoglobulin (Ig)M antibody to B19 and B19 DNA identified by real-time polymerase chain reaction were found in the patient's serum at time of diagnosis of aplastic anemia. No giant proerythroblasts were found in her bone marrow at diagnosis. Although intravenous administration of Ig (IVIg) reduced serum B19 DNA, the aplastic status of her bone marrow did not improve. Both aplastic anemia and persistent B19 viremia were successfully treated by BMT from an HLA-identical sibling donor. Serum B19 DNA increased temporarily after BMT; however, neither organ nor marrow failure was observed. B19 DNA disappeared from the serum 2 months after BMT, suggesting that a normal immune response was restored by BMT and terminated the B19 viremia. During BMT, use of high-titer IVIg for B19 might prevent B19-associated organ failure.
 ...
PMID:Successful bone marrow transplantation for severe aplastic anemia in a patient with persistent human parvovirus B19 infection. 1521 70

Fetal tissue is the richest source of primordial stem cells and has several properties that make it particularly useful for transplantation. It is superior to adult (mature) tissue in certain respects. First, fetal cells are capable of proliferating faster and more often than mature, fully differentiated cells. This means that these donor cells are able to quickly reverse the lost function of the host. In addition, these fetal cells can often differentiate in response to the environmental cues around them. This is because of their location--they can grow, elongate, migrate, and establish functional connections with other cells around them in the host. It has been found that fetal tissue is not easily rejected by the recipient due to the low levels of histocompatibility antigens in the fetal tissue. At the same time, angiogenic and trophic factors are at high levels, enhancing their ability to grow once they are transplanted. Since early fetal hematopoietic tissue lacks lymphocytes, graft vs host reactions are minimized. Fetal cells tend to survive excision, dissection, and grafting better because they generally do not have long extensions or strong intercellular connections. Finally, fetal tissue can survive at lower oxygen levels than mature cells. This would make them more resistant to the ischemic conditions found during transplantation or in vitro situations. Studies on fetal cell/tissue transplant have been encouraging. Fetal tissue can be used in different indications, for instance, fetal liver transplants may be used in combating aplastic anemia, placental umbilical cord whole blood transfusion can serve as an emergency alternative to adult whole blood transfusion, fetal adrenal transplant has been tried in combating intractable pain in arthritis, and fetal thymic transplant in combating leucopenia in non-Hodgkin's lymhoma and other immunodeficiency conditions like DiGeorge Syndrome, only to name a few. Fetal brain tissue transplant has also been done in a heterotopic site and the proliferation of the tissue has been observed. Neurotransplantation with fetal tissue in Parkinsonism shows positive results in some globally accepted studies. There are futuristic potential uses of fetal tissue in bioengineering through coating/seedling of fetal tissue on implants, stents and other artificial surgical life-saving devices to improve their functioning, and it may also extend the life of these costly gadgets. By properly using pre-HLA fetal tissue seedling in orthopedic, thoracic and also neurosurgical appliances, there could be a reduction of long-term irritation sequelae of the implant and the host interphase, and thus, a better device, i.e., a more biofriendly interphase could be developed. This may help in the reduction of pseudomembrane formation, loss of patency and other resultant TH2 reactions of the host system.
 ...
PMID:Fetal cell/tissue therapy in adult disease: a new horizon in regenerative medicine. 1549 Oct 58

X-linked lymphoproliferative syndrome (XLP) is a rare, often fatal, primary immunodeficiency disease characterized by an abnormal response to Epstein-Barr virus (EBV) infection. The gene responsible for XLP has been identified as SH2D1A/DSHP/SLAM-associated protein (SAP). The major clinical manifestations include fulminant infectious mononucleosis, lymphoproliferative disorder, and dysgammaglobulinemia. Affected males uncommonly present with lymphocytic vasculitis in addition to aplastic anemia. In this study, we describe a Japanese XLP patient who presented with hypogammaglobulinemia following acute EBV-induced infectious mononucleosis in the infancy and later had systemic lymphocytic vasculitis and hemophagocytic lymphohistiocytosis in the adulthood, which resolved by steroid pulse therapy. The patient's SAP gene was found to harbor a missense mutation (His8Asp), presumably resulting in defective expression of SAP in T cells. Biopsy specimens of lung and skin disclosed that CD8+ T cells predominantly infiltrated vascular vessels. However, immunohistochemical examination showed that EBV-infected cells were not identifiable in the vessels. We propose that T-cell-mediated immune dysregulation in XLP can cause vasculitis by EBV infection-unrelated mechanism.
 ...
PMID:X-linked lymphoproliferative syndrome presenting with systemic lymphocytic vasculitis. 1568 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>