Search PubMed⌕ Search

Biomedical subjects

M Hirokawa

Publications and source records attributed to M Hirokawa.

At least 145 records · Page 8Linked to original sources

Successful hematopoietic reconstitution with granulocyte colony-stimulating factor in a patient with hypoplastic acute myelogenous leukemia.

We describe a 68-year-old Japanese male with hypoplastic acute myelogenous leukemia (AML) who achieved complete hematological reconstitution following granulocyte colony-stimulating factor (G-CSF) administration. The patient had pancytopenia and the bone marrow was hypocellular with 19 to 36% peroxidase-positive blasts without morphological abnormalities suggestive of myelodysplasia. After receiving G-CSF as a supportive therapy for pneumonia, the blood count became normal and the bone marrow was normocellular with less than 5% of blasts. Without subsequent chemotherapy, he relapsed as a form of overt leukemia and died of pneumonia. Chemotherapy may be necessary to maintain remission in hypoplastic AML after hematopoietic reconstitution by G-CSF.

Aged↗

[Carcinoma of the renal pelvis and ureter following bladder carcinoma].

We followed 135 primary bladder carcinoma patients for at least 3 years. Subsequent carcinomas of the upper urinary tract were found in 5 patients (3.7 per cent) an average of 67 months after an initial treatment of the bladder tumors. Two patients underwent radical cystectomy and the remaining 3 patients received transurethral resections or partial cystectomy five to seven times for bladder lesions. Primary bladder tumor was multiple in all and one of them was accompanied by carcinoma in situ in the bladder and urethra. Except for one patient who presented with gross hematuria, four patients had no symptoms referable to the upper urinary tract tumor. However two of them had high stage disease. Positive urinary cytology was observed in only one patient. All patients underwent nephroureterectomy and the four got well but one died of acute heart failure. Regular urinary cytology and IVP should be done for an extended period of time for early detection of renal pelvic and ureter cancers in patients who had multiple and recurrent bladder cancers.

Adult↗

Signal transduction by B7/BB1 expressed on activated T lymphocytes: cross-linking of B7/BB1 induces protein tyrosine phosphorylation and synergizes with signalling through T-cell receptor/CD3.

We report here that B7/BB1 molecules expressed on activated T lymphocytes are involved in signal transduction. Anti-B7/BB1 monoclonal antibody (mAb) enhanced allogeneic proliferative responses against three different B lymphoma lines in a dose-dependent manner, while the same mAb inhibited T-cell response against allogeneic T cells expressing B7/BB1. Induction of B7/BB1 expression on T cells with allogeneic stimulation was confirmed by flow cytometric analysis. With the purified preactivated T cells as responder cells, anti-B7/BB1 mAb costimulated these primed T cells with coimmobilized anti-CD3 mAb. Moreover, cross-linking of B7/BB1 molecules induced protein tyrosine phosphorylation in preactivated T cells with a phosphorylation pattern distinct from those induced by signalling through other T-cell molecules. These results suggest that B7/BB1 molecules function not only as costimulatory ligands expressed on antigen-presenting cells but as receptors on T cells to transduce the costimulatory signals into the cells and may play a role for T-cell-T-cell interactions leading to clonal expansion of activated T lymphocytes. However, the physiological relevance of our finding remains to be explored.

Antibodies, Monoclonal↗

Autoantibodies against 70-kDa heat shock proteins (HSP70) in allogeneic bone marrow transplant recipients.

We report that autoantibodies against the 70-kDa heat shock protein family (HSP70) were detected in allogeneic bone marrow transplant recipients. Antibodies to HSP70 family proteins were detected in three out of 14 recipients of an allogeneic marrow graft but in none of the seven patients receiving autologous peripheral blood stem cell transplant (PBSCT). Immunoblotting analysis combined with two-dimensional SDS-PAGE revealed that these patients had antibodies to a constitutive 73-kDa/pI 5.5 heat shock protein (HSP73) and to a stress-inducible 72-kDa/pI 5.6 protein (HSP72). This is the first report, to our knowledge, describing the presence of autoantibody against HSP73 in allogeneic marrow transplant recipients. Our results may provide additional insight into the etiology and the pathophysiology of allogeneic transplant-related disorders.

Adolescent↗

The role of transforming growth factor beta in the generation of suppression: an interaction between CD8+ T and NK cells.

CD8+ T cells have suppressor effector functions, but the mechanisms involved in the generation of this activity are poorly understood. We report that natural killer (NK) cells have an important role in the acquisition of this function. CD8+ cells induce NK cells to produce transforming growth factor-beta (TGF-beta) which, in turn, stimulates CD8+ T cells to become suppressors of antibody production. Using a monocyte-dependent and -independent method to induce antibody production, we first observed that the addition of NK cells to CD8+ cells was required for optimal suppression. Next, we determined that the interaction of CD8+ T cells with NK cells resulted in a striking increase NK cell TGF-beta mRNA and its production. This cytokine appeared to be involved in the induction of T suppressor cell activity since: (a) anti-TGF-beta 1 completely abrogated the suppression of immunoglobulin G synthesis; (b) TGF-beta 1 could substitute for NK cells in inducing CD8+ T cells to develop suppressor activity; and (c) a short exposure of T cells to TGF-beta 1 in the absence of B cells was sufficient for the generation of suppressor activity by CD8+ T cells. Interferon gamma did not have this property. These studies provide strong evidence that in addition to its suppressive properties, TGF-beta is involved in the generation of CD8+ T suppressor effector cells. Because NK cell function is decreased in many autoimmune diseases, these cells may fail to interact properly with these individuals' CD8+ cells in generating suppressors of aggressive anti-self responses.

Adult↗

Nucleolar organizer regions in bladder cancer: application to urinary cytology.

OBJECTIVES: We investigated the relationship between the numbers of nucleolar organizer regions (NORs) in nonmalignant reactive cells and those in transitional cell carcinomas using urinary exfoliated cell specimens. Another aim of this study was to determine whether higher numbers of NORs are correlated with tumors with higher pathologic grade. METHODS: Nucleolar organizer regions, which are important for regulating protein synthesis, were counted by means of a silver staining technique in urinary exfoliated cells from 34 patients with transitional cell carcinoma (TCC) and in 30 patients with other urologic diseases (controls). RESULTS: The number of argyrophilic proteins of the nucleolar organizer region (Ag-NORs) per cell (mean +/- SD) was 2.9 +/- 0.5 in the control group and 5.5 +/- 1.9 in patients with TCC, which was significantly higher than that in the controls (p < 0.001). It was 4.0 +/- 1.0 in patients with grade 1 TCC, 5.4 +/- 2.0 in those with grade 2 TCC, and 6.5 +/- 1.2 in those with grade 3 TCC. Although no statistically significant difference was observed between the groups, the patients with grade 2 TCCs with higher numbers of Ag-NORs showed a tendency to have more diffuse and/or invasive lesions. CONCLUSIONS: This method is simple and quick, and can identify low-grade malignancy. It could be used as a tool for further grading of grade 2 TCCs and for determining prognosis.

Adult↗

Intramyocardial angiomyolipoma.

We report a case of cardiac angiomyolipoma in a 48-year-old woman who went to the hospital because of shortness of breath. Cardiac ultrasonography showed a right atrial mass, which was surgically removed. Pathologic examination revealed a 6-cm-diameter, dome-shaped mass composed of a mixture of blood vessels, smooth muscle, and fat. Because of its distinctive morphology and location, we diagnosed it as an intramyocardial angiomyolipoma. There was no evidence of tuberous sclerosis. Since excision of the mass, the patient has remained well without recurrence for 20 months. Angiomyolipomas usually develop in the kidney; extrarenal occurrence is rare. To date, no case of a cardiac angiomyolipoma has been reported in the English literature. The histogenesis of angiomyolipoma is uncertain, but it is most likely hamartomatous in nature.

Angiomyolipoma↗

A case of skin metastasis from follicular thyroid carcinoma.

We present a case of skin metastasis from follicular thyroid carcinoma which developed on the scalp of a 72-year-old man. The lesion was noticed 1 month after a surgical excision of the primary thyroid carcinoma and gradually enlarged during the past 11 months. A biopsy from the nodule showed mostly well-differentiated thyroid follicular structures with colloid material. Tumor cells showed mild variation of nuclear size and shape in almost all areas. We performed immunohistochemistry using antithyroglobulin antibody, which established the diagnosis of a metastatic lesion from thyroid follicular carcinoma. Total thyroidectomy and 131I radiotherapy were performed. No further metastasis has been discovered during the last 18 months.

Adenocarcinoma, Follicular↗

Confluent and reticulated papillomatosis: a case with concurrent acanthosis nigricans associated with obesity and insulin resistance.

A 19-year-old Japanese man with confluent and reticulated papillomatosis (CRP) is presented. He was an obese and dark-complexioned man, who had impaired glucose tolerance and hyperinsulinemia. The clinical and histological findings were consistent with the diagnosis of CRP. He also had acanthosis nigricans (AN) on his axillae and nape. Neither spores nor hyphae were detected from scales; antifungal treatment had no benefit. Although the reduction of his weight was unsuccessful, oral etretinate therapy resulted in considerable improvement of both CRP and AN. We reviewed previous case reports in terms of the relation between CRP and AN. Although the two conditions are usually differentiated because of their distinctive clinical features, a close relationship was noted between CRP and AN.

Acanthosis Nigricans↗

Autoreactive T cell-dependent polyclonal hypergammaglobulinemia in mantle cell lymphoma.

We investigated the mechanism of polyclonal B cell differentiation in mantle cell lymphoma (MCL) using peripheral blood mononuclear cells (PBMC) from a patient with MCL in leukemic stage presenting polyclonal hypergammaglobulinemia. Patient T cells not only responded to autologous non-T cells but induced polyclonal production of IgG in vitro. Flow cytometric analysis of PBMC showed the increased conversion of CD4+ T cells from the naive to the memory state. We propose the possible mechanism that autoreactive T cells may be involved in polyclonal B cell differentiation in this monoclonal B cell disorder.

B-Lymphocytes↗

Parachordoma of the buttock: an immunohistochemical case study and review.

We report a case of parachordoma occurring in the buttock of a 43-year-old man, and review 20 cases of parachordoma reported in the English literature. The tumor in our case was grossly 3 cm in dimension, solid, lobulated and grayish-white in color. Microscopically, the tumor consisted of epithelioid and spindle cells, and fibromyxoid stroma. The epithelioid cells were immunohistochemically positive for vimentin, S-100 protein, neuron-specific enolase, keratin, carcinoembryonic antigen and epithelial membrane antigen, and negative for HMB45. These findings are similar to those for chordoma rather than extraskeletal myxoid chrondrosarcoma. Although the etiopathogenesis of parachordoma remains obscure, Schwann cells or some other neuron-related cell origin are suspected.

Adult↗

[A case of malignant pheochromocytoma with high levels of serum neuron-specific enolase (NSE) and calcitonin].

A 71-year-old woman was admitted with the chief complaint of headache, lumbago and slight fever. Computerized tomographic (CT) scan demonstrated a large soft tissue mass with multiple cystic necrosis in the right adrenal region. The plasma norepinephrine concentration was excessive and serum levels of neuron-specific enolase (NSE), calcitonin and parathormone were elevated. MIBG scintigraphy showed a high uptake in the same region. Under the diagnosis of pheochromocytoma without distant metastasis, right adrenalectomy was performed. The tumor was removed en bloc with right kidney and a part of the liver because of inflammatory adhesion. The histological examination revealed benign pheochromocytoma. After the operation, norepinephrine and calcitonin decreased to normal but the levels of NSE and PTH remained high. One year after operation, chest X-ray revealed multiple lung metastases and after 1.5 years she died of respiratory failure. Autopsy revealed multiple lung and bone metastases and a liver metastasis, parathyroid glands showed hyperplasia but the thyroid gland showed no abnormal change. This clinical course suggests that serum NSE might be a useful tumor marker for differentiating malignant pheochromocytoma from benign one, and this tumor producing calcitonin caused secondary hyperparathyroidism.

Adrenal Gland Neoplasms↗

Successful vidarabine therapy for adenovirus type 11-associated acute hemorrhagic cystitis after allogeneic bone marrow transplantation.

A 36-year-old man underwent an allogeneic BMT for acute lymphoblastic leukemia. Eighteen days later the patient developed sudden onset of painful, gross hematuria due to adenovirus type 11 infection that did not respond to conservative therapy. There was an increase in serum creatinine levels and delayed recovery of the platelet count, associated with hemophagocytosis. After obtaining informed consent, vidarabine, which has been shown to be active against adenovirus in vitro, was started. The patient's symptoms improved within a few days of vidarabine therapy and urine cultures for adenovirus became negative. No serious adverse effects were observed. Vidarabine may be one therapeutic option in life-threatening adenovirus infection.

Adenovirus Infections, Human↗

[Acute monoblastic leukemia (M5a) with dysmegakaryocytopoiesis associated with t(16;21) (p11;q22)].

We report a 24-year-old woman who had acute monoblastic leukemia associated with t(16;21) (p11;q22). She was referred to our hospital in April 1992 because of high fever and hemorrhagic diathesis. Physical examination on admission showed no hepatosplenomegaly. The hemoglobin was 5.1g/dl, platelet count 1.7 x 10(4)/microliters, the white blood cell count 18,700/microliters. Bone marrow aspirate showed that 86% of nucleated cells were monoblasts which were positive for peroxidase and alpha-naphtyl butyrate esterase. She was diagnosed as having M5a. Dysmegakaryopoiesis, such as micromegakaryocytes and megakaryocytes with multiple small separated nuclei, was seen in the bone marrow. Chromosomal analysis revealed t(16;21). Complete remission was achieved after two courses of BHAC-DMP therapy, but dysmegakaryopoietic features remained. She relapsed in September 1992. Review of the literature and this patient indicate that acute nonlymphocytic leukemia with t(16;21) is associated with multilineage leukemic differentiation.

Adult↗

Mechanisms of allogeneic stimulation induced tumor necrosis factor-alpha (TNF-alpha) production.

We investigated the mechanisms of allogeneic stimulation induced TNF-alpha production in vitro by using human peripheral blood mononuclear cells (PBMC) and Daudi lymphoblastoid B-cells. PBMC produced TNF-alpha in response to mitomycin C-treated or paraformaldehyde-fixed Daudi cells, reaching a peak level after 4-6 h of culture. Monocytes were identified as the major source of TNF-alpha produced during allogeneic cell interaction. The second potent producer of TNF-alpha was E-rosette non-forming natural killer cells. Purified T-cells did not produce significant levels of TNF-alpha, even in the presence of IL-1 and IL-6. Interleukin-4 (IL-4) down-regulated TNF-alpha production by monocytes, but in contrast interferon-gamma (IFN-gamma) moderately enhanced TNF-alpha production. Our results indicate that monocytes are mainly responsible for the production of TNF-alpha in response to allogeneic stimulation, and T-cells modulate monocyte function by their soluble factors.

Adult↗

Analysis of discordant test results among five second-generation assays for anti-hepatitis C virus antibodies also tested by polymerase chain reaction-RNA assay and other laboratory and clinical tests for hepatitis.

The diagnostic performances of five commercially available second-generation assays for anti-hepatitis C virus antibody, two enzyme-linked immunosorbent assays, one enzyme immunoassay, and two particle agglutination assays (passive hemagglutination assay and particle agglutination assay), were evaluated. Among 104 samples from healthy subjects and 300 consecutive samples from patient ordered for routine determinations of anti-hepatitis C virus antibody in serum, assay results showed variable degrees of discordance for 17 samples (4.2%). These 17 samples were further tested by an immunoblot assay, the polymerase chain reaction-RNA assay, and the hemagglutination inhibition assay. Four of the 17 samples were regarded as true positive, since all supplementary assays and clinical data indicated active hepatitis C virus infection. Another five samples were considered false positive because no confirmatory evidence was obtained from the laboratory analysis or clinical data. The remaining eight samples were negative for hepatitis C virus RNA, but the results of the other supplementary tests were indeterminate. Some of these samples with indeterminate results may have been from patients with subclinical cases of disease who spontaneously recovered from hepatitis with persistent anti-hepatitis C virus antibody in their sera.

Adult↗

Ph+ acute myelogenous leukemia with t(7;11)(p15;p15) and clonal evolution in relapse after bone marrow transplantation.

A 20-year-old female with Ph+ acute myelogenous leukemia (M2) associated with t(7;11)(p15;p15) is reported. Bone marrow aspirates were hypercellular with leukemic cells including Auer rods. Chromosome analysis showed t(7;11) and the Ph chromosome. After complete remission, normal karyotype was restored. Normal male karyotypic cells replaced the bone marrow following allogeneic bone marrow transplantation from her brother. On day 358, cytogenetic study at relapse revealed 14q+ as an additional change and clearly showed that the abnormal clone was derived from the patient, because metaphases with XX were all of abnormal karyotype and those with XY were normal.

Adult↗