PubMed Health⌕ Search

Biomedical subjects

Gail Amir

Publications and source records attributed to Gail Amir.

At least 19 recordsLinked to original sources
PubMed2006

CD4+CXCR4highCD69+ T cells accumulate in lung adenocarcinoma.

The chemokine receptor CXCR4 is involved in the growth and metastasis of tumor cells. However, the expression of its ligand, the chemokine CXCL12, in tumors and its role in regulating the accumulation of immune cells within the tumors is not clear. Using ELISA and immunohistochemistry we found that CXCL12 is expressed in the majority of nonsmall cell lung cancer tissue sections obtained from stage IA to IIB nonsmall cell lung cancer patients undergoing operation. Histopathologic examination of these sections indicated that high CXCL12 expression correlated with increased tumor inflammation. In addition, disease recurrence rates in a subgroup of adenocarcinoma patients showed a tendency to correlate with high CXCL12 expression in the tumor. Isolation of adenocarcinoma-infiltrating immune cells demonstrated an increase in the percentage of CD4+CD69+CXCR4+ T cells as compared with normal lung tissue. About 30% of these cells expressed the regulatory T cell markers CD25high and FoxP3. The percentage of CD8 T cells within the tumor did not change, however; the percentage of NK and NK T cells was significantly reduced. In correlation with CXCR4 expression, CD4 T cells showed increased migration in response to CXCL12 compared with CD8 T cells and NK cells. Overall, these observations suggest that CXCL12 expression may influence tumor progression by shaping the immune cell population infiltrating lung adenocarcinoma tumors.

Adenocarcinoma↗
PubMed2006

Epithelial cell apoptosis by fas ligand-positive myofibroblasts in lung fibrosis.

The Fas/Fas ligand (FasL) apoptotic pathway has been shown to be involved in bleomycin-induced lung fibrosis. We examined the hypothesis that myofibroblasts from fibrotic lungs possess a cytotoxic phenotype that causes apoptosis of epithelial cells via the Fas/FasL pathway. We show in vivo epithelial cell apoptosis and associated upregulation of Fas and apoptotic Fas pathway genes in epithelial cells of lungs with bleomycin-induced fibrosis. In addition, we show that FasL surface molecules are overexpressed on alpha-SMA-positive cells in mice with bleomycin-induced fibrosis, and in humans with idiopathic pulmonary fibrosis. This enables the molecules to kill Fas-positive epithelial cells. In contrast, FasL-deficient myofibroblasts lose this myofibroblast cytotoxic phenotype, both in vivo and in vitro. In vivo, there was no bleomycin-induced epithelial cell apoptosis, as assessed by specific M30 staining in chimeric FasL-deficient mice that lacked FasL-positive myofibroblasts. In vitro, FasL-positive, but not FasL-negative myofibroblasts, induce mouse lung epithelial cell apoptosis. Thus myofibroblast cytotoxicity may underlie the absence of re-epithelialization, resulting in persistent lung fibrosis.

Animals↗
PubMed2005

Undifferentiated sarcoma of the pulmonary artery mimicking pulmonary thromboembolic disease.

Primary pulmonary artery sarcoma is an uncommon tumor. Mandelstamm in 1923 was the first to describe the disease in an autopsy. Since then, less than 200 cases were reported. The incidence is 0.001-0.03%, they are always highly malignant sarcoma, and women are involved twice as often as men. The presentation is often cough, dyspnea, and chest pain, and patients are usually diagnosed as suffering from pulmonary emboli, and primary tumor of the pulmonary artery is not usually considered in the differential diagnosis. The diagnosis of pulmonary artery sarcoma is made of the "clot" resected during pulmonary artery thrombendarterectomy. Our suggestion is that in patients with unilateral pulmonary artery occlusive disease, no evidence of positive hypercoagulability tests, and no history of thromboembolism, a high suspicion of pulmonary artery sarcoma should be kept in mind, and an angiographic-guided biopsy from the intra-arterial occlusive material should be considered. The treatment is surgery. The survival without operation is less than 2 months. Some patients were treated with adjuvant chemotherapy. We report on a woman with undifferentiated sarcoma of the pulmonary artery, mimicking chronic pulmonary artery emboli. This case illustrates the need to consider malignancy in the differential diagnosis of patients having pulmonary emboli.

Aged↗
PubMed2005

Natural ozone scavenger prevents asthma in sensitized rats.

The assumption that ozone is not only a strong oxidant, but also an important inflammatory mediator, is heavily supported by the ample literature on the pulmonary toxicity and biological effects of environmental ozone and by the recent discovery that antibodies, human neutrophils, and inflammatory lesions catalyze the formation of ozone in vivo. We hypothesized that the pulmonary inflammation in asthma involves a vicious circle of ozone production and recruitment of white blood cells, which produce more ozone. Accordingly, we predicted that electron-rich olefins, which are known ozone scavengers, could be used for prophylactic treatment of asthma. In particular, volatile, unsaturated monoterpenes, could saturate the pulmonary membranes and thereby equip the airways with local chemical protection against either exogenous or endogenous ozone. Here we present experimental evidence using a sensitized rat model to support this hypothesis. Examination of the pulmonary function of sensitized rats that inhaled either limonene (unsaturated, ozone scavenger) or eucalyptol (saturated, inert to ozone) showed that limonene inhalation significantly prevents bronchial obstruction while eucalyptol inhalation does not cause any effect. The anti-inflammatory effect of limonene was also evident from pathological parameters, such as diminished peribronchiolar and perivascular inflammatory infiltrates.

Administration, Inhalation↗
PubMed2005

Obstructing tracheal pulmonary Langerhans cell histiocytosis.

Pulmonary Langerhans cell histiocytosis, also known as eosinophilic granuloma, is an uncommon interstitial lung disease. A solitary nodule, usually parenchymal, may rarely be the only manifestation of the disease. We describe a case of Langerhans cell histiocytosis presenting as an obstructing tracheal lesion in a 55-year-old woman. Following complete resection of the lesion via flexible bronchoscopy, full recovery was achieved. This case represents a unique cause for tracheal obstruction, as well as an unreported manifestation of pulmonary Langerhans cell histiocytosis.

Female↗
PubMed2005

Simultaneous donor marrow cell transplantation with reduced intensity conditioning prevents tracheal allograft obliteration in a bronchiolitis obliterans murine model.

STUDY OBJECTIVES: Prolonged survival of transplanted kidney or liver allografts has been associated with prolonged chimerism resulting from donor-origin leukocytes carried within the allograft parenchyma. The present study, performed in a murine model, examined whether simultaneous administration of donor bone marrow cells after reduced intensity conditioning allows acceptance of heterotopic tracheal allografts and prevents the formation of the airway fibroproliferative lesion, which mimics bronchiolitis obliterans (BO). METHODS: Allogeneic tracheal allografts from C57BL/6 mice were grafted subcutaneously into BALB/c mice (n = 6) [day 0]. Conditioning consisted of total lymphoid irradiation (200 cGy) at day - 1, donor marrow cells (3 x 10(7)) administered IV on day 0, intraperitoneal cyclophosphamide (200 mg/kg) on day 1 to eliminate alloreactive marrow cells, followed by a repeated dose of donor marrow cells on day 2. Control groups consisted of one group (n = 4) that underwent similar conditioning without donor marrow cells, and another group (n = 4) that received syngeneic BALB/c marrow cells. None of these groups were administered maintenance immunosuppression. Grafts were harvested and histopathology findings were evaluated semiquantitatively at day 28, day 55, and day 95. RESULTS: Tracheal allografts from donor marrow cell recipients still maintained a patent airway with intact airway epithelium at 95 days after transplant. However, grafts from control animals not receiving donor marrow cells or mice administered syngeneic marrow cells had lumen obliteration by 28 days after transplant. Chimerism in animals receiving allogeneic bone marrow was confirmed. Graft vs host disease did not develop in animals receiving allogeneic marrow cells. CONCLUSIONS: Further investigation may verify this approach to be applicable for the prevention of posttransplantation BO.

Animals↗
PubMed2004

Late-delayed cerebral involvement in systemic non-Hodgkin lymphoma: a second primary tumor or a tardy recurrence?

BACKGROUND: Central nervous system involvement is a well recognized complication of systemic non-Hodgkin lymphoma. Most central nervous system recurrences occur within the first 2 years after the initial diagnosis and are considered to represent clonally related recurrence of systemic disease. The authors attempted to investigate the clonal relation between the late-delayed central nervous system involvement and the original systemic tumor. METHODS: The authors studied archival, formalin fixed, paraffin embedded tissue samples from 8 patients with isolated cerebral involvement diagnosed > 3 years after their initial presentation with aggressive, systemic, B-cell non-Hodgkin lymphoma. The rearranged immunoglobulin heavy-chain variable region genes (VH) from both sites were amplified by polymerase chain reaction and were sequenced when necessary. RESULTS: In three of five patients who had interpretable results, a distinct, monoclonal, VH family-specific band profile was obtained from the cerebral and systemic lymphoma. In the other two patients, a similar VH band pattern was observed and also was compared using direct sequencing, which demonstrated sequence differences between tumors from the two sites. CONCLUSIONS: Clonal variance between the cerebral and systemic lymphoma in these patients suggested the possibility that some instances of late-delayed recurrence in the central nervous system represent a second, new B-cell lymphoma rather than a true recurrence of the original systemic tumor, a finding that may have significant clinical and biologic implications.

Adult↗
PubMed2004

Rapidly progressive diffuse large B-cell lymphoma with initial clinical presentation mimicking seronegative Wegener's granulomatosis.

Here we present a 40-yr-old male patient with an aggressive B-cell lymphoma, who presented 2 yr earlier with polyarthritis, and was responsive to steroids and oral methotrexate. Thereafter he developed skin and lung lesions which on biopsy consisted of mixed 'inflammatory' infiltrates with granulomatous vasculitis. A diagnosis of seronegative Wegener's granulomatosis was made and the patient received a combination of prednisone and cyclophosphamide with clinical improvement and clearance of the radiological lesions in the lungs. The patient was now completely asymptomatic for 1 yr, but then generalized lymphadenopathy appeared, which was shown by histopathology to be large B-cell lymphoma, also involving the bone marrow. Despite intensive chemotherapy, his disease could not be controlled because of primary chemoresistance, which was perhaps in some way related to exposure to the suboptimal doses of chemotherapy given during the 'inflammatory' period before the diagnosis of lymphoma was established. This case illustrates the occasional difficulty in distinguishing between extranodal lymphoproliferative diseases and autoimmune disorders especially when clonality cannot be proved. It also shows the possible risk of 'masking' a true lymphoma by treating non-malignant diseases with immunosuppressive agents, which may eventually contribute to the development of chemoresistant lymphoma.

Adult↗
PubMed2003

Disseminated Mycobacterium kansasii infection with pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia.

A 64-year-old woman with chronic myelogenous leukemia (CML) was admitted due to prolonged fever and lung infiltrates. An open lung biopsy was required to make the diagnosis of pulmonary alveolar proteinosis (PAP) and infection with Mycobacterium kansasii. She was treated successfully with combined antimycobacterial therapy for 14 months. However, the leukemia progressed and the patient developed recurrent bilateral lung infiltrates. Blood and bronchoalveolar fluid cultures yielded growth of Acinetobacter. She died shortly thereafter due to septic shock. The relationship between M. kansasii infection, PAP, and abnormal host defense in CML is discussed.

Fatal Outcome↗
PubMed2003

The haematopoietic specific signal transducer Vav1 is expressed in a subset of human neuroblastomas.

Vav1 is a signal transducer protein expressed exclusively in the haematopoietic system, where it plays a pivotal role in growth factor-induced differentiation and proliferation. Vav1 couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, leading to cell differentiation and/or proliferation. Vav1 was originally detected as an oncogene, but its involvement in human malignancies has not been reported thus far. We report here that Vav1 is expressed in a neuroblastoma cell line, SK-N-MC. Molecular analysis indicated that there are no gross rearrangements or mutations in the Vav1 gene in SK-N-MC cells. Vav1 protein from SK-N-MC cells was similar to wild-type Vav1 in apparent molecular weight, phosphorylation state, and ability to associate with active EGFR. We also analysed the expression of Vav1 in 42 specimens of human neuroblastoma. Vav1 was expressed in the majority of these tumours. Our results suggest that Vav1 may play a role in the neoplastic process in a subset of neuroblastomas.

Blotting, Northern↗
PubMed2003

Retreatment with rituximab alone induces sustained remission in a patient with follicular lymphoma with multiple extranodal sites of involvement, relapsing soon after primary treatment with fludarabine-rituximab.

Two recent studies have shown that retreatment of patients with relapsed indolent NHL with rituximab (RI) can be as effective as primary treatment, provided the lymphoma was initially responsive to primary RI therapy. From the available data, it remains unknown as to whether this approach is also effective for extranodal relapse. Here, we describe a 47-year-old male with stage 4B follicular lymphoma (FL), initially also involving skin, who achieved complete remission (CR) after a combination of fludarabine, cyclophosphamide and RI that lasted only 5 months. He soon relapsed with systemic disease and a number of extranodal sites including liver, lungs and bone marrow. After retreatment with RI alone (four cycles, 375 mg/m(2)), the patient achieved a second CR. Another four infusions of RI were given 6 months later as maintenance therapy. The duration of CR is already 18 months longer than the first CR. This case illustrates the fact that even in relapsed advanced FL, with multiple sites of extranodal disease, RI given as a single agent may be extremely effective in achieving an additional meaningful complete response.

Antibodies, Monoclonal↗
PubMed2003

Primary ALK positive anaplastic large cell lymphoma of the pancreas.

Here we present an unusual case of anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALCL), appearing as a primary tumor of the pancreas which invaded into the adjacent duodenal wall, causing upper gastrointestinal bleeding. After complete resection of the tumor (Whipple's operation), the patient received 4 cycles of CHOP chemotherapy. Currently, 2 years after diagnosis the patient still remains lymphoma free. Primary ALCL of the pancreas is very rare and has only been reported on one previous occasion. Nevertheless, lymphoma should be considered in the differential diagnosis of pancreatic tumors and an attempt to obtain tissue diagnosis is always necessary before continuing with radical surgery, especially in young patients.

Adult↗
PubMed2003

Fatal hemophagocytic syndrome in a patient with panniculitis-like T-cell lymphoma and no clinical evidence of disease.

Panniculitis-like T-cell lymphoma is an uncommon type of extranodal T-cell lymphoma which presents clinically with subcutaneous nodules. The clinical course can either be indolent or rapidly progressive, often complicated by hemophagocytic syndrome. We report a patient with primary subcutaneous disease and initial complete response to combination chemotherapy. The patient experienced an early relapse which responded to salvage chemotherapy. However, she died shortly thereafter with hemophagocytic syndrome, polymicrobial sepsis and systemic fungal infection. At autopsy there was no evidence of lymphoma in the bone marrow or other organs. We emphasize that a fatal hemophagocytic syndrome can occur despite minimal or even without evidence: of clinically active lymphoma as demonstrated by autopsy in this case.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Acute myocardial infarction as the presenting symptom of acute myeloblastic leukemia with extreme hyperleukocytosis.

This case report deals with an unusual leukostatic complication in a 56-year-old woman with acute myeloblastic leukemia (AML) and extreme hyperleukocytosis (316 x 10(9)/L) who presented with acute myocardial infarction (MI). After leukopheresis the patient achieved hemodynamic stabilization and rapid neurologic recovery of encephalopathy that had also developed after the infarction. Considering the central role of WBC in the remodeling of post MI myocardial tissue, it was obvious that administration of chemotherapy with its subsequent inevitable pancytopenia could impose an increased risk for further cardiac complications including myocardial rupture. Nevertheless, cytarabine-based induction chemotherapy was initiated 3 days after admission, and she achieved prolonged complete remission. Coronary angiography disclosed segmental atherosclerosis, but the only significant obstruction was in the right coronary artery. The patient died with relapsed leukemia 7 years later without recurrence of any cardiac symptoms or signs. Autopsy disclosed segmental coronary atherosclerosis involving the LAD (60% obstruction), suggesting that atherosclerosis was a predisposing risk factor. Additional compromise to blood perfusion due to leukostasis had led to this unusual complication of AML involving a major vessel. This is the first documented case of leukostasis causing coronary artery occlusion as well as the first report of successful induction chemotherapy for AML during a myocardial infarction.

Aminoglycosides↗
PubMed2002

Large-cell transformation of chronic lymphocytic leukemia and follicular lymphoma during or soon after treatment with fludarabine-rituximab-containing regimens: natural history- or therapy-related complication?

Novel therapeutic regimens containing purine analogs and monoclonal antibodies have led to significant improvement in the course of indolent lymphoproliferative diseases (LPD). Complete clinical and even molecular remissions have been achieved in an increasing proportion of patients. In parallel to their tumor cytotoxic effect, these agents are inevitably associated with prolonged immunosuppression inherent to their mechanism of antilymphocytic activity. Until now, attention has been paid mainly to opportunistic infection occurring as a result of the above drug-induced immunosuppression and less to other possible complications, such as malignancy or tumor progression in the immunocompromised host. Here we briefly report nine patients with previously treated indolent LPD in whom the onset of large-cell transformation occurred during or shortly after the initiation of regimens containing these agents before transformation occurred. One patient had received rituximab alone, three fludarabine-containing regimens and five received sequential regimens containing both agents. This

Adult↗