Neopterin production in posttraumatic stress disorder before and after pharmacotherapy

Post-traumatic stress disorder (PTSD) has been associated with decreased neopterin levels. In the present study, we evaluated whether this low neopterin levels would normalize following pharmacotherapy with sertraline in PTSD. Fourteen patients with PTSD and 14 controls were enrolled in the study. A clinical evaluation and measurements of neopterin levels before and after sertraline treatment were performed. In addition, all patients were assessed with the Clinician Administered PTSD Scale (CAPS). The mean neopterin levels were significantly lower in the patient group than control group at baseline and were negatively correlated with the duration of illness, or severity of illness. Sertraline treatment decreased the symptoms of PTSD; however this was not accompanied by a significant increase in neopterin production. In conclusion, our results reveal that the failure for neopterin to normalize through symptom alleviation suggests that either neopterin may be a trait marker of the illness, or that more sustained treatment is necessary to elevate the neopterin production. Received: 30 September 2002 / Accepted: 12 December 2002 Correspondence to Dr. Murad Atmaca     

High levels of delayed radiation-induced apoptosis observed in lymphoblastoid cell lines from ataxia-telangiectasia patients

PURPOSE: Cells from ataxia-telangiectasia (A-T) patients are extremely sensitive to radiation but display decreased apoptosis, as measured during the first 3 days following radiation. To explain this apparent contradiction, we examined apoptosis in normal and A-T cells at late time points following radiation, under the assumption that radiation-induced apoptosis is delayed in the A-T cells. METHODS AND MATERIALS: Blood cells and lymphoblastoid cell lines from A-T patients, as well as healthy donors, were irradiated with X-rays. Apoptosis was measured at different time points (up to 7 and 30 days for lymphocytes and lymphoblastoid cells, respectively) using a flow cytometric method based on the reduction of intracellular DNA content (sub-G1 population). RESULTS: Compared to normal cells, CD4 and CD8 A-T lymphocytes displayed constantly reduced levels of radiation-induced apoptosis for up to 7 days after treatment. A-T lymphoblastoid cells, however, displayed a delayed and prolonged apoptosis. CONCLUSION: A-T lymphoblastoid cells show high levels of delayed radiation-induced apoptosis, which may contribute to the high cellular radiosensitivity displayed by the A-T phenotype. ATM (the gene mutated in A-T) plays different roles in the apoptotic response to ionizing radiation in quiescent lymphocytes and proliferative lymphoblastoid cells.     

Limited stage I and II follicular non-Hodgkin's lymphoma: the Nebraska Lymphoma Study Group experience

The purpose of this study was to evaluate the outcome and prognostic factors of patients with limited stage follicular non-Hodgkin's lymphoma treated prospectively by the Nebraska Lymphoma Study Group (NLSG). Forty previously untreated patients, median age 64 years, with limited stage follicular lymphoma were prospectively treated according to the protocols of the NLSG between January 1980 and December 1990. The follicular large cell type represents 75% of the cases, and 14 of the biopsies also had a diffuse component (composite lymphoma). The initial treatment was radiation therapy (RT) to the involved field in 15 patients, anthracycline-containing combination chemotherapy (CT) in 20, and combined RT and CT in 5. Thirty-seven patients (92.5%) achieved a complete remission (CR). The median follow-up is 120 months (range, 20 to 214). Of the 37 patients achieving a CR, 7 patients are alive in first CR, one died due to sepsis, another because of a myeloproliferative disorder at 77 months following chemotherapy, 6 died because of unrelated causes in first CR. Twenty-two patients relapsed between 1 to 128 months following a CR. The estimated 10-year event-free survival is 21% (95% CI: 7 to 35). Two patients received no or palliative therapy after relapse and both died of progressive disease. Nineteen patients received salvage therapy and 15 achieved a second remission. The median survival after first relapse is 55 months. The estimated 10-year overall survival is 44% (95% CI: 28 to 60). Various factors including sex, histologic subtype, stage, and degree of follicularity do not influence the overall survival or event-free survival. CT with or without RT resulted in a better trend for 10-year event-free survival in stage IA patients compared to RT alone but estimated 10-year overall survival is no different. The overall survival is worse in the > or = 60 age group but this difference is not evident if data is adjusted for cause specific death. In conclusion, limited stage follicular lymphoma has an excellent initial response to radiation therapy or chemotherapy; however the recurrence rate is high and cure is limited.     

MicroRNA expression patterns of tumors in early-onset colorectal cancer patients

Background

The expression of microRNAs (miRNAs) may differ in tumors from patients with different ethnic origins and ages. The aims of the present study were to clarify the appropriate alterations of miRNA expression associated with the early stages of carcinogenesis in early-onset Turkish colorectal cancer (CRC) patients and to define specific biomarkers that could be used as new diagnostic and prognostic markers for this population.

Materials and methods

The expression profiles of 38 different miRNAs associated with CRC were evaluated using miRNA polymerase chain reaction arrays in tumors and surgical margin tissue samples from 40 sporadic early-onset Turkish CRC patients. The relationships between the miRNA expression profiles and the characteristics of the tumors and patients were evaluated.

Results

The expression of miR-106a was found to be upregulated, and miR-143 and miR-125b levels were found to be downregulated in tumor tissues compared with the normal tissues. The high expression level of miR-106a (2.93-fold; P = 0.031) and low expression level of miR-125b (2.42-fold; P = 0.063) were observed in tumors with lymph node metastases compared with the normal colorectal mucosa samples. However, the deregulation of these miRNAs was not significantly associated with survival (log-rank P > 0.05).

Conclusions

The present results implied that miR-106a and the miR-125b were associated with the formation and invasion of colorectal tumors. Thus, these miRNAs might be used as significant prognostic factors and indicators of early-stage CRC. Further studies and validations are required; these miRNAs may provide novel molecular targets for CRC treatment.     

Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes

Two major types of lymphocytosis of large granular lymphocytes (LGLs) were observed. The proliferating LGLs in each type had distinct immunophenotypes, functional characteristics, and probably belonged to different cell lineages. The more common form (Type A) consisted of cells derived from the T cell lineage and had the T suppressor/cytotoxic phenotype (T11+, T3+, T8+). The expression of the Leu 7 and HLA-DR antigen was variable. These cells did not have natural killer (NK) function but showed a variable degree of antibody-dependent cell-mediated cytotoxic (ADCC) activity. Neutropenia was invariably present and rheumatoid arthritis and autoantibodies were frequent associations. These lymphocytes had many similarities to the major type of LGLs present in normal adult bone marrow. The other type of LGL lymphocytosis (Type B) consisted of cells lacking the antigens T3 and T8 but expressing M1 and NKH1. These cells possessed strong NK and ADCC activity but their cell lineage was not clear. Neutropenia and autoimmune phenomena were not detected. The cytochemical characteristics of the LGL granules from both types of patients were similar but differences in ultrastructure were observed. LGLs from Type B patients proliferated in the presence of Interleukin 2 (IL-2) and 12- O-tetradecanoyl-phorbol-13 acetate (TPA). Significant changes in their basic T11+, T3-, T8- phenotype were not observed. IL-2 and TPA, however, had profound influence on the NK function of the cells with enhancement in the case of IL-2 and marked suppression when stimulated by TPA.     

Increased surface expression of the membrane glycoprotein IIb/IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation

Platelet activation altered the binding of three monoclonal antibodies (monovalent Fab' fragment) directed against the glycoprotein (GP) IIb/IIIa complex. An increased binding of two- to threefold occurred after stimulation with thrombin or phorbol myristate acetate (PMA), with slight but significant increase in the dissociation constants (Kd) of two antibodies (LJ-CP8 and LJ-P9). In contrast, no statistically significant changes were observed with ADP-stimulated platelets. The increased binding of LJ-CP3, but not of the other two antibodies, to activated platelets decreased by 30% to 40% in the presence of EDTA at 22 to 25 degrees C. Platelets stimulated by thrombin or PMA bound more fibrinogen than did those stimulated by ADP, and significant differences in the extent but not in the affinity of fibrinogen binding were observed with various platelet agonists. When the pool of GP IIb/IIIa molecules exposed on the surface of unstimulated platelets was reacted with the monoclonal antibody LJ-CP3 to block ADP-induced fibrinogen binding and platelet aggregation, stimulation with thrombin or PMA still induced substantial binding of antibody and fibrinogen, and aggregation ensued. Therefore, platelets exposed to "strong" agonists exhibit an increased number of surface-oriented epitopes associated with GP IIb/IIIa. The GP IIb/IIIa molecules bearing these newly exposed epitopes are functional in that they can bind fibrinogen and mediate platelet aggregation.     

Gastric antral stricture in a patient with chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare disorder of phagocytic cell oxidative metabolism. Patients have recurrent infections with catalase-positive organisms and granulomatous lesions throughout the body. Gastric antrum can be an occult site of involvement. We describe a four-year old boy with chronic granulomatous disease who was admitted with the complaints of persistent vomiting and weight loss. Gastric antral narrowing was diagnosed according to radiological findings. Treatment with steroid and antibiotics yielded a good clinical response in 15 days with a relief of the obstruction. This case report emphasizes the beneficial effect of this form of therapy in preventing life-threatening obstruction of vital organs in CGD.     

Transient hypogammaglobulinemia of infancy: Clinical and immunologic features of 40 new cases

BACKGROUND: Transient hypogammaglobulinemia of infancy (THI) results from a delay in the maturation of immunoglobulin production. METHODS: The clinical and immunologic data of 40 patients with THI are presented. Clinically, the majority of patients presented with recurrent respiratory infections and otitis media, bronchitis and/or bronchial asthma and recurrent gastroenteritis. RESULTS: Ten of 40 children had isolated low IgG; isolated low IgA and isolated low IgM were detected in one and three patients, respectively. At initial evaluation, levels of all three immunoglobluins were low in nine patients. Ten patients had diminished IgG and IgA levels, six had diminished IgA and IgM levels and one had low IgG and IgM levels. Two patients were given intravenous immunoglobulin replacement therapy for 1 year. None of the patients has experienced serious infections during their follow-up period. CONCLUSIONS: Prospective evaluation of patients (age range 5-60 months) revealed that immunoglobulin levels in 33 patients recovered before 36 months of age. Seven patients still had low immunoglobluin levels at 40-57 months of age. Three of these patients had low levels of both IgG and IgA, while two patients had low IgM levels and a further two patients had low IgA levels.     

The analysis of eosinophil and lymphocyte phenotype following single dose of high-dose methylprednisolone in two siblings with marked hypereosinophilia.

The effect of single high-dose methylprednisolone (HDMP) on eosinophil and lymphocyte phenotype in two siblings with marked hypereosinophilia was investigated. Since conventional dose steroids failed to produce a haematological and clinical response in case one, both children were given HDMP (20 mg/kg/day). Eosinophils and lymphocytes showed an activated state before treatment, characterized by marked expression of CD11b, CD18, CD45RO on eosinophils and increased HLA-DR, CD95, CD18, CD38 on lymphocytes. Twenty-four hours after administration of HDMP a dramatic reduction in peripheral blood eosinophil count was observed in both patients associated with phenotypic changes characterized by decreased expression of CD11b, CD18, CD13 and increased CD95 expression in one. Furthermore, HDMP treatment induced a drop in the expression of CD95 and CD18 on lymphocytes. These changes may suggest a suppressive role for HDMP on eosinophil and lymphocyte activation which may have contributed to the haematological and clinical response.