[Chronic fatigue syndrome].
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Fatigue Syndrome, Chronic↗
Biomedical subjects
T Kitani
Publications and source records attributed to T Kitani.
Deficient surface expression of glycosylphosphatidylinositol-anchored proteins in B cell lines established from patients with paroxysmal nocturnal hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired type hemolytic disorder. Hematopoietic cells of patients with PNH are deficient in glycosylphosphatidylinositol (GPI) anchored membrane proteins. Since some membrane-bound complement inhibitors, such as CD59 and decay accelerating factor (DAF), are GPI anchored proteins, abnormal cells from patients with PNH are sensitive to complement attack. Their myeloid and erythroid cells are affected more than their lymphoid cells. Patients whose B cells were severely deficient in GPI anchored proteins were chosen to establish cell lines by Epstein-Barr virus mediated transformation. The lines established (SS-1-, TK-1-, and TK-14- cell lines) had the following characteristics of PNH. First, GPI anchored proteins were completely absent from the surface of SS-1- and TK-14- cells, and were expressed at very low levels on TK-1- cells, whereas polypeptide anchored proteins were normally expressed on these three lines. Secondly, DAF mRNAs of the SS-1- cell line were qualitatively and quantitatively indistinguishable from those of a control, wild-type cell line. Third, pro-CD59 and pro-DAF molecules were detected intracellularly in these cell lines, their pro-CD59 being smaller and more hydrophilic than that from a wild-type cell line. These cell lines should be useful in further studies on the pathogenesis of PNH.
Antigens, CD↗
Monocytes appearing repeatedly after chemotherapies had an identical rearrangement pattern of immunoglobulin with leukemic blasts in a patient with CD13+ acute lymphoblastic leukemia.
We recently encountered a patient with acute lymphoblastic leukemia (ALL) who showed temporal monocytosis of an unusually high cell count (5,000-30,000 monocytoid cells/microliter) five times after treatment with different chemotherapies. The leukemic cells expressed B-cell-associated antigens, CD19 and CD10, E-rosette receptor, CD2 and monocyte/myeloid antigen, CD13 simultaneously. They were peroxidase-negative. One week after the initiation of conventional chemotherapy for ALL, the leukemic blasts had disappeared. Alternatively, monocytoid cells appeared along with the recovery from nadir status. They showed several features of monocytes; they were weakly dot-positive for nonspecific esterase, reactive with CD14 and CD13 and Fc gamma-receptor-positive. Furthermore, they migrated into a fungally infected joint space. Features incompatible with normal monocytes were the absence of peroxidase reactivity, the expression of B-cell-associated antigens, CD19 and CD10 and E-rosette receptor, CD2. Southern blot hybridization analysis revealed an unexpected result that HindIII digested DNA from both leukemic blasts and monocytoid cells had the same rearranged band of IgH. Thus, an identical clonality of monocytoid cells, temporally appearing after chemotherapies and leukemic lymphoblasts, was determined in this patient with CD13+ ALL.
Antigens, CD↗
[Chronic fatigue syndrome: the present concept and historical perspective].
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Endocrine System Diseases↗
[Diagnostic criteria for chronic fatigue syndrome by the CFS Study Group in Japan].
Much interest recently has been given to chronic fatigue syndrome (CFS) in Japan as other countries. The CFS Study Group sponsored by the Ministry of Health and Welfare has been developed since April 1991, A diagnostic criteria for CFS was newly proposed by this group. The criteria is substantially based upon the working case definition, which was made by Holmes and colleagues in 1988. There are some modification from CDC working case definition; the criteria of probable cases of CFS was defined, and postinfectious CFS was also given.
Fatigue Syndrome, Chronic↗
Transformation of large granular lymphocytic leukemia during the course of a reactivated human herpesvirus-6 infection.
A patient with CD3+ large granular lymphocytic (LGL) leukemia developed transformation (TF). The phenotype of the leukemic cells was CD3+, CD4+ and CD8-. The leukemic cell count increased rapidly; the cells became large and the nuclear outline, which had been reniform, became lobulated. Anti-HTLV-1 and anti-HIV antibodies were negative in the serum of the patient and no HTLV-1 specific sequences were detected in the cDNA of the leukemic cells by polymerase chain reaction (PCR). Comparison of the karyotype abnormality of the leukemic cells before and after TF revealed an abnormality of the 21 trisomy in 90% of mitotic cells of the patient. Analysis of the cell cycle revealed that 13.7% of the leukemic cells were in DNA synthesis phase which was not previously found. The titer of anti-human herpesvirus-6 (HHV-6) immunoglobulin G which had been high at chronic phase (1:1640 compared to normal titer of less than 1:160), became 1:20,000 at TF. The titer of anti-HHV-6 immunoglobulin M also increased from less than 1:4 at the chronic phase to 1:120 at TF (normal value less than 1:4). A HHV-6-specific DNA sequence was detected by PCR in the peripheral mononuclear cells collected at TF but not at the chronic phase. These data suggests that TF occurs not only in CD3-negative but also in CD3-positive LGL leukemia. HHV-6 reactivation is therefore a possible cause in immunocompromised hosts whose general conditions are deteriorated.
Aged↗
[Symptoms, signs and laboratory findings in patients with chronic fatigue syndrome].
This review summarizes the symptoms, signs and laboratory abnormalities seen in 59 patients with chronic fatigue syndrome (CFS), 2 patients with post-infectious CFS and in 26 patients with possible CFS whose illnesses fulfill the criteria proposed by the study group of the Ministry of Welfare, Japan. The characteristic symptoms and signs of CFS are prolonged generalized fatigue following exercise, headache, neuropsychological symptoms, sleep disturbance and mild fever. In possible CFS patients, the frequency of mild fever, muscle weakness, myalgia and headache is low. Our standard hematologic and laboratory tests revealed a few abnormality in patients with CFS. The characteristic abnormality in CFS patients is the low values of 17-Ketosteroid-Sulfates/creatinine in morning urine and the acylcarnitine deficiency. It seems likely that this deficiency of acylcarnitine induces an energy deficit in the skeletal muscle, resulting in general fatigue, myalgia, muscle weakness and postexertional malaise in CFS patients. Virologic studies revealed no evidence of retrovirus infection with HTLV-1, HTLV-2 and HIV, but the reactivation of HHV-6 infection was apparent.
Adolescent↗
[Evaluation of hypercoagulable state in patients with malignancies by using prothrombin fragment F1 + 2].
In order to elucidate the activation of the coagulation cascade in patients with malignant neoplasms, we measured the levels of plasma prothrombin fragment F1 + 2, which is liberated in the process of thrombin generation. Twenty healthy adults (Group A), 29 patients with malignancies not complicated with DIC (Group B) and 4 patients with DIC (Group C) were evaluated. The values of F1 + 2 in Group C (2.38 +/- 0.55 nmol/l) were significantly higher (p < 0.01) than those in Group A (0.52 +/- 0.19 nmol/l) and B (0.86 +/- 0.68 nmol/l). Many patients in Group B showed higher levels of F1 + 2 compared to normal subjects, however, no significant differences were found between Group A and B. With respect to other coagulation molecular markers such as TAT, D-Dimer and PIC, F1 + 2 levels revealed positive correlation to those levels. Concerning the clinical course of DIC, elevated levels of F1 + 2 normalized much rapidly than those of TAT and D-Dimer by continuous administration of heparin. In conclusion, the measurement of plasma F1 + 2 is important in monitoring the activation of coagulation system in patients with malignancies, especially with respect to early detection and treatment of DIC.
Aged↗
[Clinical effects of cefodizime in severe infections complicated with hematological diseases. Hanshin Infection Study Group].
One hundred thirty-eight patients with severe infections accompanying hematological diseases were treated with cefodizime (CDZM). CDZM was administered by intravenous injection at daily doses ranging from 2 g to 8 g for about 3 to 18 days. Clinical efficacies of CDZM were excellent in 30 cases, good in 37 cases, fair in 1 case and poor in 53 cases. The efficacy rate was 55.4%. The efficacy rate was 56.4% in patients from whom causative organisms were not identified. The efficacy rate against Gram-negative bacteria (66.7%) was higher than that against Gram-positive bacteria (28.6%). No significant differences in the efficacy rates were found among groups of patients with different initial neutrophil counts (less than 100, 100-499, and over 500/microliters). Skin eruption caused by CDZM was observed in 2 patients (1.5%). Hepatic disorders, renal dysfunction and urinary test abnormality (protein and urobilinogen) were observed in 7 (5.0%), 1 (0.7%) and 1 (0.7%), respectively. Therefore, CDZM was considered to be a clinically useful antibiotic for severe infections complicated with hematological diseases.
Adolescent↗
[Therapeutic effects of cefuzonam against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].
Cefuzonam (CZON) was used to treat severe infections in 151 patients with hematopoietic disorders, and its efficacy and safety were assessed. The drug was given in doses of 2.0 to 6.0 g a day, divided into 2 or 3, intravenously by injection or infusion. The clinical effects were excellent in 34 cases, good in 40 cases, fair in 5 cases, and poor in 57 cases. Therefore, the results were excellent or good in 54.4% of the patients treated. The efficacy rates were 43.8 and 35.9% for groups of patients whose neutrophil counts were 500/microliters or less and 100/microliters or less, respectively. It was excellent or good in 70.6% of patients in whom causative agents were identified, and in 66.7 and 80.0% of patients infected with Gram-negative and -positive bacilli, respectively. The efficacy rate for patients infected with unidentified agents was 52.1%. The rate for patients who had received other antibiotics previously was 41.5%. The rate for patients having received only one antibiotic for the preceding treatment was 50.0%. Six (3.9%) of the treated patients experienced adverse effects including changes in laboratory test results observed in 4.
Adolescent↗
[Therapeutic effects of meropenem against severe infections in patients with hematopoietic disorders. Hanshin Study Group of Hematopoietic Disorders and Infection].
The efficacy and the safety of meropenem (MEPM), a newly developed carbapenem antibiotic, were investigated in 150 patients with severe infections complicated with hematopoietic disorders. 1. Clinical responses in 132 patients who were evaluable for effectiveness were excellent in 33 patients, good in 45, fair in 10 and poor in 44, with an efficacy rate of 59.1%. 2. The efficacy rate in patients who had previously been treated with the other antibiotics was 51.2%, while that in patients who had not been thus treated was 62.9%. 3. The efficacy rate in patients whose neutrophil counts increased during the therapy with MEPM was higher than that in patients whose neutrophil counts did not increase. The efficacy rate in patients whose neutrophil counts during the therapy were below 100/mm3 was 48.1%. 4. Out of 150 cases, side effects were observed in 4 patients, 3 with eruption and 1 with jaundice. Abnormalities in laboratory test results on liver functions were noted in 8 patients. These results indicate that MEPM is an effective and safe antibiotic for the treatment of severe infections in patients with hematopoietic disorders.
Adolescent↗
[Large granular lymphocytic leukemia].
We investigated the surface markers, cell-function, clonality, and the association of IL-2 receptors and a second messenger of src family of tyrosine kinase p56lck in IL-2 signal transduction of the leukemic cells of 12 patients with large granular lymphocytic leukemia (LGL leukemia). The leukemic cells of 5 patients were CD3+ and 5 of them were CD3-. In three patients with CD3- leukemia examined, one showed karyotype abnormality of 46, XY, -10, +mar and the delta gene of TCR was rearranged in one patient. The TCR of the leukemic cells of a patient MH with CD3+, CD4 and CD8 (double positive marker: DP) recognised rabbit IgG presented by macrophages. The recognition was class II restricted. We examined the expression pattern of CD8 subunits and found that DP leukemic cells commonly expressed CD8 alpha+ beta-. These results suggested that DP leukemic cells were CD4+ T cells and expressed CD8 alpha secondarily. The p75 IL-2 receptors were detected, however, the modulation of p56lck in the process of IL-2 signal transduction were not found out. There was no association between p75 and p56lck when leukemic LGL cells proliferated on stimulation with IL-2.
Antigens, CD↗
[Late phase II study of MST-16 (sobuzoxane) efficacy for malignant lymphoma].
A late phase II study with MST-16 for malignant lymphoma was performed with the collaboration of 11 institutions belonging to the Hanshin Hematological Disease Treatment Research Group. Out of a total 40 patients entered into the study, 37 cases (33 of NHL and 4 HD) were evaluated for efficacy and 27 cases for side effects. The response rate was 29.7% (2 cases of CR and 9 PR). The factors affecting response rate were histological classification, phenotype of tumor cell surface and stage of disease. Bone marrow suppression and G-I disorders were the main toxicities observed, but they disappeared by the cessation of MST-16 treatment.
Adult↗
[Improvement with interferon-alpha therapy and splenectomy in hairy cell leukemia of European-American type].
A 61-year-old man was admitted to our hospital in April 18, 1988, with dyspnea and gingival bleeding. Physical examination revealed marked splenomegaly, and peripheral blood showed severe pancytopenia with 38% abnormal mononuclear cells. The abnormal cells were characterized by a hairy appearance under a phase contrast microscopy, and strong tartrate-resistant acid phosphatase activity. These cells reacted with CD19, CD25 and CD11c monoclonal antibodies by the immunostaining method. Bone marrow aspiration failed and bone marrow biopsy revealed diffuse proliferation of hairy cells (HC) with moderate fibrosis. In addition, the staining pattern of HC peroxidase is similar to that found in megakaryocyte series. He was diagnosed as HCL of the European-American type based on these findings. Interferon (IFN)-alpha was administered at a daily dosage of 3 x 10(6) IU by intramuscular injection. Although splenomegaly and hematological conditions improved gradually, he received splenectomy because of his incomplete hematological improvement. Normalization of peripheral blood cell counts and a marked decrease of HC in bone marrow were obtained. Tubuloreticular structure and tubular confronting cisternae were seen in peripheral mononuclear cells during IFN therapy.
Combined Modality Therapy↗
[A study of combination chemotherapy (BHAC-ACVP) for adult acute lymphocytic leukemia. Hanshin Co-operative Study Group of Hematological Malignancies].
Twenty-nine adult patients with acute lymphocytic leukemia (ALL) were treated with combination chemotherapy consisting of behenoyl-ara-C, adriamycin, cyclophosphamide, vindesine and prednisolone (BHAC-ACVP regimen). Complete remission (CR) was obtained in 7 of 13 (54%) of the previously untreated, and 4 of 16 (25%) of the previously treated patients. Six of 10 (60%) L1 and 5 of 17 (29%) L2 patients achieved CR. Side effects such as nausea, GPT elevation and fever were observed, but these were not severe in most cases. The result indicates that BH-AC is useful for the treatment of adult patients with ALL.
Antineoplastic Combined Chemotherapy Protocols↗
HTLV-I associated myelopathy (HAM) after blood transfusion in a patient with CD2+ hairy cell leukemia.
Hairy cell leukemia complicating hemolytic anemia developed in a 46-year-old woman. Morphologically and cytochemically typical hairy cells were found to express both CD20 and CD2 antigens. Expression of surface IgG of kappa-chain type and the rearrangement of Ig but not T-cell receptor beta genes confirmed a B-cell origin of the leukemia. Blood transfusion was followed by disappearance of the hemolysis and a marked improvement of the leukemia. However, the patient developed progressive spastic spinal paraplegia about seven months after transfusion and was diagnosed as having HTLV-I associated myelopathy (HAM) by the demonstration of HTLV-I antibodies in serum and cerebrospinal fluid. HTLV-I infection via the transfusion may have been involved in the hematologic improvement seen in this patient. Autopsy showed demyelination, vacuolar degeneration, gliosis, and perivascular cuffing in the white matter of spinal cord without evidence of leukemic infiltration.
Anemia, Hemolytic↗
Membrane expression of decay-accelerating factor on neutrophils from normal individuals and patients with paroxysmal nocturnal hemoglobinuria.
Decay-accelerating factor (DAF), a complement-regulating glycoprotein, was found to be a maturational protein for normal neutrophils, and a remarkable correlation was found between the DAF level and alkaline phosphatase activity in neutrophils. We studied the relationship between the amount of DAF on the membrane and cell maturity in total nucleated bone marrow (BM) cells, mature BM and peripheral blood (PB) neutrophils from normal subjects, and patients with paroxysmal nocturnal hemoglobinuria (PNH) using a fluorescence-activated cell sorter with anti-DAF monoclonal antibodies. Percentage distributions of differentiating neutrophils from normal total nucleated BM cells showed that the proportion of immature cells (myeloblasts plus promyelocytes) decreased, while that of mature ones (bands plus segmented forms) increased as the fluorescence intensity increased. For PB neutrophils, no apparent correlation was found between DAF expression and cell maturity. This may have resulted from margination of the fully matured neutrophils with a high amount of DAF. In PNH patients who have low levels of DAF, this study showed that DAF expression in their neutrophils differs from that in normal subjects, and abnormalities occur in PNH cells from a very early stem-cell stage.
Alkaline Phosphatase↗
Acetylcholinesterase and lymphocyte function-associated antigen 3 found on decay-accelerating factor-negative erythrocytes from some patients with paroxysmal nocturnal hemoglobinuria are lost during erythrocyte aging.
Erythrocytes from patients with paroxysmal nocturnal hemoglobinuria are deficient in decay-accelerating factor (DAF), a factor called C8-binding protein or homologous restriction factor, acetylcholinesterase (AchE), and lymphocyte function-associated antigen 3 (LFA-3). These proteins share a common feature that glycan-inositolphospholipid anchors the protein to the membrane, suggesting that an abnormality related to this glycolipid causes multiple protein deficiencies. The relationship between the DAF, AchE, and LFA-3 defects was studied by fluorescent flow cytometric analysis. In five patients, DAF-negative erythrocytes were also AchE-negative. In three patients, a fraction of DAF-negative erythrocytes expressed subnormal levels of AchE, indicating that AchE was synthesized in these DAF-negative cells. Erythrocytes from the patients having DAF-negative, AchE-positive cells were separated according to density and analyzed for expression of DAF and AchE. Both proteins decreased with increase of cell density, suggesting that DAF-negative, AchE-positive cells become AchE-negative during erythrocyte maturation by losing AchE. A low level of LFA-3 was found on DAF-negative erythrocytes from one patient and decreased with erythrocyte maturation. These results support an idea that complete deficiency of glycan-inositolphospholipid-anchored proteins on erythrocytes could result from abnormally early termination of surface recruitment of these proteins, and subsequent dilution through cell divisions and loss from the surface.
Acetylcholinesterase↗