Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a study of 870 individual patients with either lymphocytosis (excluding known lymphoproliferative disease), increased proportions of blood lymphocytes with granular morphology (LGL), or neutropenia, 14 cases were found with abnormally increased CD3+CD4+CD8+ components. Eleven of these were further investigated and 10 shown in follow-up studies to be persistent in nature. Morphological assessments revealed increased LGL in 9/11 cases, and in seven of these > 50% lymphocytes had discernable cytoplasmic granulation. Immunophenotypic studies indicated that CD8 expression by CD4+ lymphocytes in these patients was of low density (CD8dim+), and that both the CD4+CD8- and CD4+CD8dim+ fractions in each patient was characterized by a CD11b+CD16-CD56+CD57+ composite NK-associated (NKa) phenotype (in contrast to normal CD4+CD8- blood lymphocytes and CD4+CD8+ thymocytes which were consistently CD11b-CD16-CD56-CD57-). TCR genotypic studies revealed rearranged components (beta plus gamma, or beta alone) in 5/11 cases, but there were no obvious relationships between TCR configuration (including rearranged band densities) and immunophenotypes, absolute lymphocyte or neutrophil numbers, the proportions of blood LGL, or the proportions of CD4+ cells coexpressing CD8. The occurrence of identical NKa phenotypic profiles in both germline and rearranged TCR cases does, however, suggest the possibility of an evolutionary process from a non-clonal expansion to a clonal state. Serum studies, including soluble CD4, CD8 and IL2-R concentrations and autoantibody investigations, of representative germline and rearranged TCR cases failed to indicate any consistent abnormalities, but there was some suggestion for the existence of a chronic reactive process in some of the patients with germline TCR. These findings suggest that expanded LGL/NKa+ components with phenotypic evidence of CD4/CD8 coexpression should be regarded as a distinct diagnostic category and that persistent CD4+CD8+ abnormalities with germline TCR should be monitored for possible clonal transition.
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PMID:A distinct large granular lymphocyte (LGL)/NK-associated (NKa) abnormality characterized by membrane CD4 and CD8 coexpression. The Yorkshire Leukaemia Group. 136 95

For the disease of the granular lymphocytes (GL) that contain azurophilic granules to proliferate in the peripheral blood, which is often complicated by anemia or neutropenia and which generally develop into chronic disease, the new designation of granular lymphocyte-proliferative disorders (GLPD) is being proposed. This disease include T-GL having CD3 antigen which forms a complex with T cell Ag receptor (TCR-alpha beta), and NK-GL which is CD3-negative but CD16- or NKH-1-positive, having non-MHC-restricted cytotoxicity. The two cases presented here demonstrate the characteristics of T-GL or NK-GL, however, while one case with NK-GL showed spontaneous decrease of GL, improvement of neutropenia and anemia without any treatment, the other case with T-GL became intractable and required repeated blood transfusion. On such differences in the clinical development of the disease, we have conducted investigations including a review of the literature to see whether there is any correlation between the characteristics of the proliferating cells and pathologic conditions of the disease, and whether this disease is indeed tumorous.
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PMID:[NK- and T-cell granular lymphocyte-proliferative disorders]. 238 Oct 62

Repeated analysis of peripheral blood lymphocytes (PBLs) from a patient with large granular lymphocytosis, neutropenia, and rheumatoid arthritis revealed that approximately 45% of PBLs displayed the following phenotype: CD3+, CD4-, CD8-, CD16+, HNK-1-, WT31-. This population was purified for further analysis by depletion with anti-CD4 and anti-CD8 monoclonal antibodies (MoAbs). Southern blot analysis showed preferential rearrangements of the V gamma 9 genes. Northern blot demonstrated the presence of V gamma 9 mRNA transcripts. With MoAbs directed against either the V gamma 9 peptide (Ti gamma A) or the delta chain of the gamma delta T-cell receptor (TCR delta 1), we further demonstrated that those cell surfaces expressed both V gamma 9 and a delta gene product. In addition, analysis of the gamma gene rearrangements on six clones derived from this population demonstrated a unique rearrangement on a single chromosome, strongly suggesting the monoclonality of this T-cell population. Significant cytotoxic activity against K562, U937 was observed only after an in vitro culture period with interleukin-2 (IL-2), whereas no specific inhibitory effect on autologous bone marrow (BM) CFU-G was noted.
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PMID:Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder. 254 20

A 58-year-old male with a 10-years history of thymoma was admitted to our hospital because of the respiratory infection. Hepatosplenomegaly and systemic lymphadenopathy were revealed on physical examination. Chest roentgenogram showed a large anterior mediastinal tumor and a right pleural effusion. Blood examination showed Hb 11.5 g/dl, leucocyte count 1,600/microliters (1% neutrophils, 34% monocytes, 65% lymphocytes) and platelet count 11.2 x 10(4)/microliters. The lymphocytes in the peripheral blood and pleural fluid were mostly small agranular mature lymphocytes and CD2+ 3+ 4- 8+. A monoclonal rearrangement of TCR beta chain gene was found using Southern blot analysis of the lymphocytes in the peripheral blood and pleural fluid. The CFU-GM colony formation by bone marrow cells was normal, and not suppressed by the patient's serum or peripheral blood lymphocytes. Neutrophil-associated IgG was increased with a direct immunofluorescence test. Serum IgG level was slightly decreased. Radiation therapy for thymoma exerted no effect. Treatment with prednisolone 60 mg daily resulted in complete disappearance of the pleural effusion and partial improvement of hepatosplenomegaly, thymoma and neutropenia. Histological examination of the thymoma revealed predominantly spindle cell type. He is still in good condition 21 months after diagnosis. This case seems to represent neoplastic proliferation of mature CD8+ T cells associated with thymoma.
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PMID:[CD8+ agranular lymphocyte proliferative disorder with T-cell receptor beta-chain gene rearrangement associated with thymoma and neutropenia]. 255 91

A patient with neutropenia and life-threatening infections secondary to T-gamma lymphoproliferative disease, who did not respond to treatment with recombinant human G-CSF (filgrastim), was treated with filgrastin plus cyclosporine A (CyA). The patient achieved a good response in the absolute neutrophil count and subsequently required a dose reduction in the filgrastim. The patient was eventually discontinued from the CyA but continues on filgrastim alone. While on therapy, the large granular lymphocytes disappeared from the circulation and the beta-TCR rearrangement, which was present prior to beginning therapy, became undetectable. The patient had no significant toxicity to the CyA or the filgrastim and he has not experienced any serious infections or required hospitalization. Filgrastim has proven to be relatively nontoxic and of some benefit to patients with this disease and should probably be utilized first when treatment is necessary. However, if improvement is not observed, these findings suggest that a trial of the combination of CyA plus filgrastim may be beneficial.
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PMID:Treatment of chronic neutropenia associated with large granular lymphocytosis with cyclosporine A and filgrastim. 748 4

There is increasing evidence that haemopoietic growth factors are effective in reversal of neutropenia associated with large granular lymphocytes (LGLs) proliferation. A 19-year-old woman with CD3+/TCR gamma delta+, CD4-, CD8- LGL proliferation and severe neutropenia repeatedly developed blood eosinophilia, fever and dyspnoea after administration of GM-CSF. Acute eosinophilic pneumonia with a lobar lung infiltrate pleural effusion, and marked bronchoalveolar lavage fluid eosinophilia was diagnosed. Treatment with corticosteroids and discontinuation of GM-CSF lead to rapid improvement. In addition, haematological analysis revealed that H*1 Technicon, a widely-used automated cell counter, may misinterpret eosinophils erroneously as neutrophils, therefore examination of blood smears to prevent eosinophil-mediated toxicity during GM-CSF treatment is recommended.
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PMID:GM-CSF-induced acute eosinophilic pneumonia. 766 82

A survey of 870 different adult blood samples (primarily from patients with non-haematological disorders) found that 269 (31%) had increased proportions (> 25%) and/or absolute numbers (> 1.0 x 10(9)/l) of morphologically-defined large granular lymphocytes (LGL), and/or phenotypically-defined NK-associated (NKa) cells. Of these, 112 were re-analysed at least 6 months after initial presentation and were classified as 'persistent' (92/112) or 'transient' (20/112) according to whether or not the original abnormality was still present. Lymphocyte counts in most patients with persistent abnormalities were within normal limits (18/92) or slightly increased (68/92), with only six having a lymphocytosis exceeding 10.0 x 10(9)/l. With the exception of five persistent LGL expansions in which the granular lymphocytes did not express NKa determinants (designated LGL+NKa-), the remaining 87 cases could be phenotypically grouped according to their primary abnormality as CD8+NKa+ (n = 33), CD4+ NKa+ (n = 14), CD8dim+NKa+ (n = 7) or CD8-NKa+ (n = 33). TCR genotypic studies in 58 patients showed that the 16 patients with rearranged TCR components were restricted to the CD8+NKa+ group and that, in most of these, the CD8+ fraction showed abnormal relative CD16/CD56 expression. Persistent neutropenia (n = 15) also appeared to be associated with primary abnormalities of CD8+NKa+ cells (12/15), with 10 of these additionally showing rearranged TCR genes. In contrast, persistently increased CD8dim+NKa+ and CD8-NKa+ components did not appear to phenotypically differ from their corresponding 'counterparts' in normal bloods or in patients with transient LGL/NKa+ abnormalities. This survey has therefore established that persistent LGL/NKa+ abnormalities are considerably more common than suggested in published work, that a high proportion of patients with expanded CD8+NKa+ components, with quite diverse clinical histories, show evidence of clonal lymphoid populations, and that the clonal nature of such disorders appears to be associated with abnormal NKa phenotypic patterns.
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PMID:Transient and persistent expansions of large granular lymphocytes (LGL) and NK-associated (NKa) cells: the Yorkshire Leukaemia Group Study. 848 57

This study reports the clinical, haematological and immunophenotypic features of a series of 25 patients with clonal expansions of large granular lymphocytes (LGL)/NK-associated (NKa) cells. These showed a male predominance (16:9) with a median age of 67 (range 38-91) years; four had a documented history of rheumatoid arthritis, a further 18 had diverse clinical disorders, and the remaining three were clinically well. Mild anaemia was found in approximately half the patients and a lymphocytosis (seen in approximately 70% of the cases) was usually modest (< 10.0 x 10(9)/l). Neutropenia was the most frequently observed feature, and this was typically persistent in nature. Serum studies revealed few consistent features although positive rheumatoid factor and increased soluble CD8 levels were noted in 67% and 87% of those cases tested. Phenotypically, all cases were CD2+CD3+CD8+ and expressed membrane TCR alpha beta chains; most (17/22) were additionally CD5+ and (19/22) CD7+. The staining intensities of CD5 and CD7 antigens were however lower than that of normal CD4+ and CD8+ blood lymphocytes. Expression of NKa antigens was variable although 16/22 cases were CD16+CD56- and 19/22 were CD57+. Clonal CD3+CD8+ LGL/NKa expansions with a CD16+CD56+ composite phenotype were not seen in this patient series. Analyses of 'activation' antigens showed a consistent lack of CD25 expression by CD3+ cells, but increased CD3/Ia co-expression was found in a high proportion (19/25) of cases. Studies of CD45R isoform expression by CD8+ LGL/NKa cell fractions revealed a consistent CD45RA+RO- profile for all cases tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clonal CD3+CD8+ large granular lymphocyte (LGL)/NK-associated (NKa) expansions: primary malignancies or secondary reactive phenomena? 858 Aug

The association of large granular lymphocyte leukemia (LGL-L) with hepatocellular carcinoma in a 55-year-old patient is described. An increased number of LGL was seen on peripheral blood smears. The immunophenotype was CD3+, CD4-, CD8+, and a study of the TCR gene rearrangement indicated the monoclonal nature of the proliferation. A liver mass was detected on CT scan and an ultrasound-guided fine needle biopsy revealed the presence of hepatocholangiocellular elements. A right hepatectomy was performed. Major neutropenia persisted despite corticosteroids and granulocyte colony-stimulating growth factor (G-CSF) therapy. Methotrexate at 20 mg/week failed to control lymphocytosis after three months of treatment. A new nodule of hepatocarcinoma reappeared twelve months after surgery and a liver resection was performed.
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PMID:Large granular lymphocyte leukemia associated with hepatocellular carcinoma: a case report. 864 51

In the majority of clonal expansions of CD3+ large granular lymphocytes (LGL), referred to as T-LGL leukemia, patients have a chronic disease, often manifested by severe neutropenia, rheumatoid arthritis, and mild to moderate splenomegaly. The characteristic leukemic phenotype is CD3+, CD8+, CD16+, CD57+ and CD56-. Here we report an unusual case of T-LGL (CD3cyt+, CD3surface-, CD16+, CD56-) with clinicopathological features (acute presentation, large tumor mass, and systemic illness with highLGL counts at diagnosis) similar to those described for patients with CD3-natural killer (NK)-LGL leukemia. Two distinct stages of maturation arrest were observed: in the lymph node abnormal cells were CD4+, CD8+ whereas the majority of circulating leukemic cells expressed only CD8. TCR gamma (TCR gamma) gene configuration demonstrated that these originated from the same T cell clone, suggesting a maturation process between the two populations, or preferential passage of CD8 single positive cells into the blood.
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PMID:Aggressive acute CD3+, CD56- T cell large granular lymphocyte leukemia with two stages of maturation arrest. 875 72


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