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Biomedical subjects

Norifumi Tsukamoto

Publications and source records attributed to Norifumi Tsukamoto.

At least 19 recordsLinked to original sources
PubMed2006

Identification of inherited macrothrombocytopenias based on mean platelet volume among patients diagnosed with idiopathic thrombocytopenia.

Inherited macrothrombocytopenia is a rare illness that is often misdiagnosed as idiopathic thrombocytopenia (ITP), a more widespread acquired disease. Automated blood cell counters in routine clinical use usually miss giant platelets and underestimate mean platelet volume (MPV). Incorrect diagnoses might expose patients to a risk of unnecessary treatment. The ADVIA 120 hematology counter efficiently detects large platelets based on two-dimensional laser light scatter. The present study measures and re-evaluates MPV using the ADVIA 120 in 112 patients who had initially been diagnosed with ITP. We identified 11 unrelated patients as having probable macrothrombocytopenia (average MPV of 19.2+/-3.8 fL; normal range 7.8-10.2). Functional, phenotypical and DNA analyses confirmed that three of these patients had Bernard-Soulier syndrome and one had MYH9-related disease, both of which are the most common forms of inherited macrothrombocytopenia. We stress that a conventional automated hematology analyzer had overlooked giant platelets in these patients, and that all of them had received high-dose steroid therapy and/or splenectomy before this study according to a diagnosis of ITP. Thus, checking MPV using the ADVIA 120 in thrombocytopenic patients is a useful method of correctly diagnosing inherited macrothrombocytopenia, and thus avoiding patient exposure to unnecessary and sometimes toxic treatment.

Adult↗
PubMed2006

X-linked agammaglobulinemia diagnosed in adulthood: a case report.

X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency caused by mutations in Bruton's tyrosine kinase (BTK). Patients typically become symptomatic during infancy or early childhood and develop recurrent bacterial infections. We report a Japanese case of XLA diagnosed in a patient who was 27 years of age and who had no history of severe infection. The patient's serum immunoglobulin (Ig) G, IgA, and IgM levels were 132,7, and 17 mg/dL, respectively. The percentage of positive cells for CD19 and CD20 was 0.03% and 0.02%, respectively. The patient's brother and sister had no abnormalities. Flow cytometric analysis showed a partially reduced expression of BTK protein in the patient's peripheral monocytes. Sequencing of the BTK. gene revealed a missense mutation (230C>T,T33I). Given this data, this patient was diagnosed as having rare, late onset XLA with a missense mutation in the BTK gene.

Adult↗
PubMed2006

Sacroiliitis as an initial manifestation of acute myelogenous leukemia.

Sacroiliitis is the most pathognomonic and earliest manifestation of ankylosing spondylitis. We herein report a 28-year-old female patient who presented with sacroiliitis as an initial manifestation of acute myelogenous leukemia (AML). She had a 3-month history of anemia and walking difficulty. Bone marrow findings revealed an increase of blasts with trilineage dysplasia. Although she was initially diagnosed with myelodysplastic syndrome (MDS), blasts rapidly increased and AML developed 1 month after the diagnosis of MDS with Sacroiliitis. Induction chemotherapy failed to induce a complete remission of AML, but it did effectively treat the sacroiliitis. However, the sacroiliitis relapsed when the leukemia cells progressed thereafter. Oral corticosteroids helped ameliorate the sacroiliitis. She underwent bone marrow transplantation (BMT) from an HLA-identical sister during a nonremission period; however, the leukemic cells began to rapidly increase from day 30 after BMT. The close relationship between the occurrence of sacroiliitis and AML suggested that autoimmune sacroiliitis was a paraneoplastic phenomenon of AML in this patient. Although autoimmune disorders develop in a substantial number of MDS patients, they are rarely observed in de novo AML. No previous report has described sacroiliitis as the initial manifestation of de novo AML.

Adrenal Cortex Hormones↗
PubMed2006

[Plasmacytoma with multiple hypervascular lesions revealed by angiography in a patient with multiple myeloma].

A 68-year-old woman suffering from a left iliac tumor and severe back pain was admitted to another hospital in May 1999. The bone X-ray, CT scan and MRI demonstrated a 7 cm x 5 cm left iliac tumor with osteolysis and she was transferred to our hospital. Angiography demonstrated multiple hypervascular lesions in the left ilium, lumbar vertebrae, left ischium, left pubis and left rib. The tumor was resected and diagnosed as a plasmacytoma. Immunoelectrophoresis did not show any M-protein in the serum and urine, but the patient was diagnosed as having a non-secretory or low producing multiple myeloma because of the presence of 42.8% of abnormal plasma cells in the bone marrow aspirate. Her symptoms improved following 3 courses of MCNU-VMP therapy and the bone marrow plasma cells decreased to less than 5%. She was discharged and treated as an outpatient but relapsed and died of chemotherapy-resistant myeloma. We report this case because macro-angiogenesis in a multiple myeloma demonstrated by angiography is rare and interesting.

Aged↗
PubMed2006

[Reversible posterior leukoencephalopathy syndrome probably caused by L-asparaginase].

A 46-year-old male with refractory biphenotypic acute leukemia was treated with doxorubicin (days 1-3, 15-17), vincristine (days 1, 8, 15, 22), prednisolone (days 1-28), and L-asparaginase (L-ASP: days 15-28) as reinduction therapy. Physical examination revealed normotensive state and normal consciousness. On the 27th day, systemic seizures developed with mild hypertension (BP 151/98 mmHg). Computed tomography (CT) imaging of the brain showed areas of hypodensity in the bilateral white matter, and in the occipital and posterior parietal areas. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) showed some high intensity area involving the white matter, but also involving the cortex in the same area. Because the patient's condition progressed into unconsciousness and apnea from recurrent seizures, a respirator and anticonvulsants were needed. Four days later, the patient's general condition dramatically improved. There were no abnormal findings on MRI, and we diagnosed the cause of the seizures as reversible posterior leukoencephalopathy syndrome (RPLS). In adults, RPLS caused by chemotherapy is rare, especially L-ASP. Our patient did not have any previous history of convulsion up to the LAdVP, which brought on the seizures. It was considered that the RPLS might be caused by L-ASP, which had been given to this patient for the first time and was being given to him at the time of developing the seizures. RPLS is one of the causes of neurologic complications by L-ASP.

Acute Disease↗
PubMed2006

[Deep vein thrombosis and pulmonary embolism in a patient with multiple myeloma treated with thalidomide and dexamethasone].

A 51-year-old man visited our hospital because of fever in 2003. With the discovery of the presence of a chest wall tumor, pleural effusion and M-protein, and increased plasma cells in the bone marrow, a diagnosis of multiple myeloma was established. Since the effect of combination chemotherapy followed by tandem auto-PBSCT lasted only one year, thalidomide and dexamethasone administration was started in November 2004. However, three months later, his lower limbs became swollen. Elevation of fibrin degradation product (FDP) and computed tomography findings suggested deep vein thrombosis and pulmonary embolism. With heparin and warfarin, these thromboses disappeared. Furthermore, chemotherapy strategies in addition to thalidomide were safely performed with anti-coagulation therapy. As thalidomide has become an accepted component in therapeutic strategies for multiple myeloma, careful attention must be paid to the prevention of thrombosis.

Angiogenesis Inhibitors↗
PubMed2005

Distinctive immunoglobulin VH gene usage in Japanese patients with chronic lymphocytic leukemia.

The incidence of chronic lymphocytic leukemia (CLL) is low in Asian countries including Japan, while CLL is the most common type of leukemia in the west. To elucidate which factors contribute to the low frequency of CLL in Japan, we investigated immunoglobulin (Ig) heavy chain gene usage and somatic hypermutation status in 44 Japanese patients with CLL. Only one of these patients used V(H)1-69. The finding is in striking contrast to data from western countries, where the frequency of CLL expressing V(H)1-69 ranges from 12 to 21%.

Adult↗
PubMed2005

Long-term persistence of host cells detected by X-chromosome gene-based assay in patients undergoing gender-mismatched hematopoietic stem cell transplantation.

Using our recently developed human androgen receptor (HUMARA) gene-based chimerism assay, long-term chimerism was investigated in female patients who underwent hematopoietic stem cell transplantation (HCT) with cells from male donors. After restriction digestion of samples, we detected a small number of female-derived cells within a large population of male-derived cells, with a sensitivity from 0.1% to 0.05%. Chimerism was examined in four patients with myeloid malignancies: two patients with acute myeloid leukemia (AML) from myelodysplastic syndrome (MDS), and one patient each with AML M3 and AML M4. All patients underwent myeloablative conditioning regimens and exhibited good clinical results during a median follow-up period of 6.6 years (range, 3.4-7.5 years). Female-derived cells were detected throughout the entire follow-up period in all bone marrow samples, but they became undetectable in the peripheral blood samples of 3 patients. Moreover, the HUMARA band pattern suggests that these residual host cells were normal cells. This study confirms the usefulness of the HUMARA gene-based assay, which showed that patients undergoing HCT frequently show mixed chimerism (MC) for a long period, especially in bone marrow, although the possibility of contamination by host stromal cells cannot be excluded.

Adult↗
PubMed2005

High Th1/Th2 ratio in patients with multiple myeloma.

To determine the clinical significance of the T helper 1(Th1)/T helper 2 (Th2) ratio in multiple myeloma, the intracellular IFN-gamma and IL-4 were analyzed by flow cytometry in 56 patients with multiple myeloma. The mean Th1/Th2 ratio of cases in the initial diagnosis phase and the refractory phase were higher than that of the control group. The mean serum beta-2-microglobulin in the high Th1/Th2 subgroup was significantly higher than that in the normal Th1/Th2 subgroup (P < 0.05). In conclusion, the Th1/Th2 ratio was closely related to the disease status of multiple myeloma.

Adult↗
PubMed2005

Pericardial graft vs. host disease in a patient with myelodysplastic syndrome following peripheral blood stem cell transplantation.

A patient with myelodysplastic syndrome developed pericardial effusion 20 month after allogenic peripheral blood stem cell transplantation. Sclerotic and erythematous skin lesions were observed over the face and extremities, and a diagnosis of chronic graft vs. host disease (GVHD) was made based on skin biopsy findings. Pericardial fluid contained numerous CD8+/HLA-DR+ lymphocytes, but no leukaemic cells. Tumour necrosis factor alpha (TNFalpha) and soluble Fas (sFas) levels were highly elevated in both the effusion and serum. The patient was treated with methylprednisolone and tacrolimus. Skin GVHD improved rapidly associated with resolution of pericardial effusion and reductions in cytokine levels. We concluded that pericardial effusion was due to pericarditis and was a manifestation of chronic GVHD in this patient, and that cytotoxic lymphocytes and specific cytokines played significant roles.

Adult↗
PubMed2005

Thiopurine methyltransferase genotype and phenotype status in Japanese patients with systemic lupus erythematosus.

We investigated the genotypic status of thiopurine methyltransferase (TPMT) polymorphism to evaluate the possible risk of the toxicity of azathioprine (AZA) in 68 patients with systemic lupus erythematosus (SLE). The allele frequency of TPMT mutation in the SLE group (2.9%) was higher than that in 174 Japanese healthy volunteers (1.1%), although it did not reach statistically significant difference (p=0.23). The mean value of TPMT activities in 51 subjects with TPMT*1/*1 was 40% higher than that of 4 subjects with TPMT*1/*3C in SLE group (18.1+/-6.1 nmol/h/ml packed red blood cells (pRBC) versus 13.2+/-3.2 nmol/h/ml pRBC; p=0.11). Two out of 4 SLE patients with TPMT*1/*3C had been treated with AZA, and one patient showed a leucopenia. The TPMT genotyping before AZA treatment is recommended for Japanese SLE patient group to avoid the AZA-induced adverse events, although detection of the patient with low TPMT activity by genotyping is still imperfect.

Adolescent↗
PubMed2005

Genotyping of thiopurine methyltransferase using pyrosequencing.

Thiopurine methyltransferase (TPMT) metabolizes thiopurine drugs which are used in the treatment of leukemia and some autoimmune diseases. Previously, 11 mutant alleles of TPMT gene (TPMT*1S, *2, *3A, *3B, *3C, *3D, *4, *5, *6, *7, and *8) have been reported. These mutant alleles may cause life-threatening toxicity in patients exposed to thiopurine drugs, 6-mercaptopurine and azathioprine. We have developed a rapid and accurate protocol for TPMT genotype determination using Pyrosequencing(TM) technology in 96 Japanese subjects. Five fragments of the TPMT gene (exon 4, 5, 7, 8, 10) were amplified by PCR, and the 10 single-nucleotide polymorphisms (SNPs) for TPMT*1S, *2, *3A, *3B, *3C, *3D, *4, *5, *6, *7, and *8 were sequenced. The results of this pyrosequencing method corresponded exactly with those of the DNA sequencing method using BigDye terminator chemistry. We have demonstrated that typing of 10 SNPs can be performed within 30 min. Pyrosequencing has a wide application in the large-scale identification of individual TPMT genotypes.

Adult↗
PubMed2005

[Unclassified mature T cell leukemia with cerebriform nuclei].

A 53 year-old male visited our hospital for evaluation of his leukocytosis, which was first diagnosed more than 6 years previously. He was asymptomatic and there were no remarkable findings on physical and laboratory examinations except for the lymphocytosis. Abnormal lymphocytes with deep folded nuclei were seen on light microscopy, whose phenotype was CD3+, CD4-, CD8-, CD7-, CD16 , CD56-, CD45RO+ and CD45RA- . Electron microscopy revealed 'cerebriform nuclei' which were characteristic of Sézary cells. Adult T cell leukemia (ATL) and Sézary syndrome (SS) were ruled out because of the negative HTLV-1 test and the absence of skin lesions, respectively. T-prolymphocytic leukemia (T-PLL), which is characterized by a marked increase in leukocytes having a CD7-phenotype and a progressive fatal course, was also excluded. Recently, the TCL1 onco-protein has been shown to be overexpressed in progressive T-PLL but not in other mature T cell leukemias including Sézary syndrome. Peripheral mononuclear cells in the present patient did not overexpress TCL1. In its morphology and phenotypes, our case resembled 'Sézary cell leukemia (SCL)' but the clinical course was much more indolent. This case did not match any of the mature T cell leukemias defined in the WHO classification.

Cell Nucleus↗