Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 78 year old female was found to have pancytopenia in February 1991. Bone marrow was normocellular with 11.7% blasts and showed dysmegakaryopoietic changes. A diagnosis of MDS (RAEB) was made and she was treated with transfusions and ubenimex. Leukemic transformation was noted in July. On Admission in October 1991, her laboratory examinations revealed the following: WBC 38,900/microliters with 93% blast, Hb 8.0 g/dl, Plt 2.1 x 10(4)/microliters, a hypercellular bone marrow with 74% blasts which were negative for myeloperoxidase (MPO) by light microscopy, but were positive by electron microscopy. Surface marker for CD13 was positive. These findings corresponded to M0 of the FAB subtype. Chromosome analysis revealed Ph1 chromosome with 46XX, t (9;22) (q34;q11) in 3 of 3 cells examined, Southern analysis showed the rearrangement of the break point cluster region (bcr). Reverse transcriptase polymerase chain reaction technique demonstrated the presence of major bcr/abl mRNA. She was treated with transfusions and methyl-prednisolone. Her blast counts declined and Ph1 chromosome was only positive in 1 of 12 metaphases examined. She died of pneumonia in December 1991. Eleven cases with MDS showing Ph1 chromosome have previously been reported. The observations indicate that Ph1 chromosome positive acute leukemias were heterogenous in nature.
 ...
PMID:[RAEB transformed into AML (M0) showing Ph1 chromosome and rearrangement of major cluster region]. 825 8

A 59-year-old male, who was treated with artificial pneumothorax for pulmonary tuberculosis 42 years previously, presented with a painful mass in the left lateral chest wall and lymph node swelling in the left neck. A chest CT-scan revealed a tumor shadow extending from the outer chest wall to the pleural cavity containing pus surrounded by calcified pleura. 67Ga scintigraphy showed accumulation of the radionuclide in the left lateral chest and left neck. Biopsy specimen obtained from both the chest tumor and cervical lymph node revealed diffuse large cell lymphoma. Immunostaining failed to demonstrate CD1, CD3, CD4, CD8, CD13, CD20, immunoglobulin, alpha, gamma, mu, delta, kappa and lambda chains, indicating null cell characteristics. Chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, prednisolone and bleomycin and irradiation resulted in a temporary decrease of the tumor and lymph nodes, but the patient died of pneumonia 14 months after the onset of disease. Since the levels of serum lactate dehydrogenase and immunosuppressive acidic protein varied in parallel to the disease activity, they appeared to be useful for the assessment of therapeutic effects during the clinical course. Approximately 100 cases of non-Hodgkin's lymphoma developing after tuberculous pyothorax have been reported in this country, among which the incidence of null cell type is exceedingly rare.
 ...
PMID:[Null-cell non-Hodgkin's lymphoma presenting with a mass in the chest wall after tuberculous pyothorax]. 829 30

A 67-year-old female was admitted with fatigue. Peripheral blood examination showed severe pancytopenia. Bone marrow biopsy revealed hypoplastic marrow. She was diagnosed as having aplastic anemia. Steroid pulse therapy was not effective. After treatment with erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF), blasts which were positive for CD13, CD33, CD34 and HLA-DR and negative for myeloperoxidase appeared in the peripheral blood. At this time, bone marrow biopsy revealed myelofibrosis with increased blasts. Chromosome analysis showed 46XX, add (1) (p36), add (1) (q44), -2, -5, del (7) (q11), -12, +3mar. She died of pneumonia despite chemotherapy with etoposide. Administration of EPO and G-CSF may have led to the rapid development of leukemia and myelofibrosis.
 ...
PMID:[Transformation of aplastic anemia to acute myeloid leukemia with myelofibrosis following treatment with granulocyte colony-stimulating factor and erythropoietin]. 877 84

We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin seemed to be the primary site. A 21-year-old woman's initial symptom was a skin nodule on the right cheek. She also had tumors in the nasopharynx, and the bone marrow subsequently became involved. No lymphadenopathy was present. She experienced complete remission after dose-intensified therapy with cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone (CHOP), but the disease relapsed in the central nervous system 6 months later. An 81-year-old man experienced an 11-month history of skin nodules in the left forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He died of pneumonia during chemotherapy. The malignant cells of the 2 patients had similar morphologic features, with a monocytoid nucleus and no cytoplasmic granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+, CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations. The DNA of Epstein-Barr virus was not detected from the bone marrow cells by polymerase chain reaction. Only 3 other cases with similar phenotypes have been reported; all had skin lesions. Although the origin of these cells remains unknown, we propose that this is a distinct clinicopathologic entity.
 ...
PMID:A cutaneous agranular CD2- CD4+ CD56+ "lymphoma": report of two cases and review of the literature. 1043 11

This article describes a rare case of bone marrow transplantation (BMT) from an unrelated donor (URD) in an adult Japanese male with Down syndrome (DS) diagnosed as having acute mixed lineage leukemia. Examination of peripheral blood demonstrated WBC 6.2 x 10(9)/l with 45.5% blasts at admission. Leukemic blasts with positive peroxidase stain, but negative periodic acid-Schiff stain comprised 91.6% on bone marrow specimen. Surface marker analysis of these blasts showed the following: CD3(-), CD5(-), CD7(-), CD10(+), CD19(+), CD13(+), CD14(-), CD33(+), CD34(+), CD41a(-), and CD56(-). Based on these data, he was diagnosed as having acute mixed lineage (myeloid and B-lymphoid lineage) leukemia. He achieved complete remission (CR) by lymphoid-oriented chemotherapy performed after ineffective myeloid-oriented therapy. After four courses of consolidation chemotherapy for lymphoid lineage blasts, recurrence due to proliferation of myeloblasts had occurred. Thereafter, a second CR was obtained by low dose cytosine arabinoside (AraC) therapy. As this patient was considered to have a high risk of relapse, we selected allogeneic BMT from URD. Severe stomatitis due to methotrexate (MTX) occurred probably due to altered pharmacokinetics usually observed in DS patients. Though acute graft-versus-host disease (GVHD) of systemic skin (grade II) and pneumonia were observed during neutropenia due to the post-conditioning regimen, he could be discharged from our hospital on the 135th day after BMT. On day 205 post-BMT, however, bronchiolitis obliterans (BO) occurred as a chronic GVHD disorder. Despite therapy with prednisolone and FK506, he died on day 400 post-BMT because of respiratory failure due to BO. In DS patients, superfluous toxicities due to MTX and AraC treatment have been reported, and these toxicities have been considered due to altered pharmacokinetics in patients with DS. This patient could tolerate the transplant conditioning regimen commonly used in patients without DS.
 ...
PMID:Unrelated donor bone marrow transplantation for acute mixed lineage (myeloid and B-lymphoid lineage) leukemia in an adult with Down syndrome. 1270 27

This article describes the first case of acute myeloid leukemia (AML) in a healthy donor at 14 months after granulocyte colony-stimulating factor (G-CSF)-primed peripheral blood stem cell (PBSC) harvest. In September 2001, a healthy 61-year-old female was given G-CSF prior to PBSC harvest for her brother with multiple myeloma. In spite of successful engraftment, the recipient died from a disease relapse. In November 2002, the donor, admitted with high fever and leukocytosis with 98.5% blastoid cells, was diagnosed as having AML (M1). Her leukemia cells were positive for CD13, CD33, and G-CSF receptor without chromosomal abnormality and responded to G-CSF in vitro. During chemotherapy, she died of progressive pneumonia. If our case is truly the first, the incidence of leukemia in donors may not be higher than that of naturally occurring leukemia. However, efforts towards an international long-term study, or at least to report every case similar to ours, would be required to be conclusive.
 ...
PMID:Acute myelogenous leukemia in a donor after granulocyte colony-stimulating factor-primed peripheral blood stem cell harvest. 1471 37

A 77-year-old man was referred to our hospital because of elevated LDH and leukoblastosis in the peripheral blood in June 2002. Physical examination revealed neither hepatosplenomegaly nor superficial lymphadenopathy. A bone marrow film showed dysmegakaryocytopoiesis with many micromegakaryocytes and MPO-positive blasts appearing in 20-30% of NCC. A diagnosis of MDS (RAEB-t) was made. Blastic cells were positive for CD13, 33, 34 and HLA-DR. Karyotypic analysis at diagnosis revealed 46XY, inv(3) (q21q26), t(9;22) (q34; q11) and minor-BCR/ABL chimeric m-RNA was detected by RT-PCR. Mild chemotherapy (low dose Ara-C etc) was given but the disease progressed to the AML stage with thrombocytosis in August. In September imatinib was given because of Ph positivity, but the effect was transient. In October massive leukocytosis with myeloblastosis was uncontrollable. In December 2002 the patient died of pneumonia, after a total course of 7.5 months. This rare case with Ph chromosome and 3q21q26 syndrome showed a poor prognosis as previously reported.
 ...
PMID:[3q21q26 syndrome with minor-BCR/ABL type Ph chromosome]. 1497 33

Infection with human coronavirus 229E (HCoV-229E) is associated with the common cold and may result in pneumonia in immunocompromised patients. The viral spike (S) protein is incorporated into the viral envelope and mediates infectious entry of HCoV-229E into host cells, a process that depends on the activation of the S-protein by host cell proteases. However, the proteases responsible for HCoV-229E activation are incompletely defined. Here we show that the type II transmembrane serine proteases TMPRSS2 and HAT cleave the HCoV-229E S-protein (229E-S) and augment 229E-S-driven cell-cell fusion, suggesting that TMPRSS2 and HAT can activate 229E-S. Indeed, engineered expression of TMPRSS2 and HAT rendered 229E-S-driven virus-cell fusion insensitive to an inhibitor of cathepsin L, a protease previously shown to facilitate HCoV-229E infection. Inhibition of endogenous cathepsin L or TMPRSS2 demonstrated that both proteases can activate 229E-S for entry into cells that are naturally susceptible to infection. In addition, evidence was obtained that activation by TMPRSS2 rescues 229E-S-dependent cell entry from inhibition by IFITM proteins. Finally, immunohistochemistry revealed that TMPRSS2 is coexpressed with CD13, the HCoV-229E receptor, in human airway epithelial (HAE) cells, and that CD13(+) TMPRSS2(+) cells are preferentially targeted by HCoV-229E, suggesting that TMPRSS2 can activate HCoV-229E in infected humans. In sum, our results indicate that HCoV-229E can employ redundant proteolytic pathways to ensure its activation in host cells. In addition, our observations and previous work suggest that diverse human respiratory viruses are activated by TMPRSS2, which may constitute a target for antiviral intervention.
 ...
PMID:TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium. 2353 51