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Biomedical subjects

K Hodohara

Publications and source records attributed to K Hodohara.

33 records · Page 2Linked to original sources

Thalassemia incidentally found by marked erythrocytosis due to an ochre mutation at codon 35 in a Japanese man.

We present a patient with beta-thalassemia minor diagnosed on the basis of the incidental findings of marked hypochromic and microcytic erythrocytosis. Hemoglobin analysis revealed increased hemoglobin (Hb) A2 levels and decreased beta/alpha synthesis ratio in both the propositus and his mother. Further molecular studies identified a single base substitution of TCA to TAA within codon 35 in heterozygous state, which creates a premature terminator resulting in a defect of effective beta globin synthesis. This is the first report of beta-thalassemia due to a nonsense mutation at codon 35 of beta-thalassemia gene in the Japanese population.

Adult↗

[A case of acute myelogenous leukemia accompanied with myelofibrosis and megakaryocyte-like giant bizarre blasts].

A 45-year-old man was admitted with high fever and leukocytosis in August 1993. The diagnosis of acute myelogenous leukemia (AML; M2) was made on the basis of morphological, cytochemical and immunological characteristics of the blasts in the bone marrow. The induction therapy with BHAC, daunorubicin, 6-MP was unsuccessful in achieving remission; the bone marrow biopsy specimen revealed the proliferation of the remaining leukemic cells and massive fibrosis accompanied with unusual megakaryocyte-like giant bizarre cells. These megakaryocyte-like giant cells were positive for myeloperoxidase and CD34, but not GPIIIa and factor VIII, indicating that those were derived from myelogenous stem cells. Following the low-dose Ara-C therapy, improvement of fibrosis and disappearance of these giant cells were observed in the bone marrow. After the reinduction therapy with high-dose Ara-C and MIT against markedly increased blasts, the patient died of systemic fungal infection. The presence of myelofibrosis and giant atypical blasts might allow resistance to therapy and poor prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

A simple method for predicting the cyclosporin A erythrocyte-to-plasma distribution ratio in blood, and its clinical assessment.

To adapt the monitoring of cyclosporin A (CyA) to clinical practice, we have developed a model to predict the CyA erythrocyte-to-plasma distribution ratio (CyA-EP), and evaluated its utility in clinical practice. We monitored CyA trough concentrations in whole blood and performed a series of biochemical tests during disease states in patients undergoing immunosuppressive therapy with CyA after transplantation. An estimate of CyA-EP (EPpr) was thus given by the following equation: EPpr = 6.0831 - 0.2944 x (TG+CHO) - 0.0037 x (CyAblood) - 0.0553 x (HCT) + 0.0463 x (BW) + 0.4447 x (CRE) - 0.0366 x (AGE). In this predictive model, EPpr is given as a function of the plasma lipid levels (TG+CHO, mM), the CyA concentration in whole blood (CyAblood, ng/ml), and the hematocrit (HCT, %), as well as the patient's body weight (BW, kg), serum creatinine (CRE, mg/dl) and age (AGE, years). The parameters TG+CHO, CyAblood, HCT, and AGE were negatively correlated with the CyA-EP, whereas BW and CRE exhibited a positive correlation. The predictive performance of this model was satisfactory for clinical use and changes in CyA-EP in transplant patients were obtained from monitoring CyA in whole blood and routine biochemical tests, without directly measuring CyA-EP. Since CyA-EP is an useful indicator for predicting a shift of CyA into tissues and its systemic clearance in plasma, our model to predict the CyA-EP will help the physician select a CyA regimen during immunosuppressive therapy in a variety of disease states after transplantation.

Adult↗

[Effect of combination chemotherapy for elderly patients with malignant lymphoma].

The remedial effect in elderly patients with malignant lymphoma in two groups treated with combination chemotherapy, one including doxorubicin (ADM) (A group) and the other excluding ADM (V group) were compared. Forty patients aged 65 years or more with malignant lymphoma were entered from January 1982 to December 1991. The A group was made up of 10 patients and the V group of 18 patients. As to pathological classification, two of the A group had low grade malignancy lymphoma, four had intermediate grade and three had high grade. Four of the V group had low grade, eight had intermediate grade and five had high grade. In terms of clinical stage, three of the A group were in stage II, 3 in stage III and 4 in stage IV. Two of the V group were in stage II, 7 in stage III and 9 in stage IV. The effective rate for the A group was 90% and the V group was 61%. The survival rate over five years in the A group was 37.5% and 21.8% in the V group. There were no adverse effects on the cardiovascular system in the A group. No significant differences of effects were shown in this study, however, the A group showed a higher tendency in terms of the CR rate and the survival rate. Cases of early death during chemotherapy were few and the quality of life of the patients was raised by discharge in the A group. Combination chemotherapy including ADM appears to be satisfactory in aged patients with malignant lymphoma.

Aged↗

Macrophage colony-stimulating factor (M-CSF) enhances complement component C3 production by human monocytes/macrophages.

The third complement component, C3, is an important factor in the host defense mechanism in which monocytes/macrophages participate as the primary phagocytes. Monocytes/macrophages are the principal extrahepatic producers of C3, and this C3 production is thought to be regulated by several cytokines. In the present study, we demonstrated that human macrophage colony-stimulating factor (M-CSF) enhanced C3 production by human peripheral monocytes in serum-free culture. Analytical immunoblot and ELISA showed that the presence of M-CSF increased the production of intracellular pro-C3 and extracellular C3 for 24 h in a dose-dependent manner. To confirm the rapid effect of M-CSF on C3 production, we performed metabolic labeling of C3 with [35S]methionine. The production of [35S]C3 for the first 6 h in the presence of M-CSF was also increased as compared to that in the absence of M-CSF. In addition to the previously reported effects of M-CSF on monocytes/macrophages, such as the enhancement of C3 receptor expression and C3 receptor-mediated phagocytosis, we consider that the effects of M-CSF demonstrated in this study are of importance in the local immune system organization of C3 and monocytes/macrophages.

Complement C3↗

Disseminated subcutaneous Nocardia asteroides abscesses in a patient after bone marrow transplantation.

We describe an unusual case of disseminated subcutaneous abscesses caused by Nocardia asteroides in a 17-year-old female with AML undergoing allogeneic BMT. She was receiving immunosuppressive therapy with CYA and a corticosteroid for acute GVHD, and maintenance therapy with ganciclovir for interstitial pneumonia (IP) caused by CMV, but was not neutropenic. The subcutaneous abscesses spread from the primary infection on her right anterior leg to both thighs, the left buttock, both upper arms, the left forearm and right shoulder, indicating hematogenous dissemination. Nocardia asteroides was identified from biopsy material in culture. The patient was successfully treated with a combination of trimethoprim/sulfamethoxazole (TMP/SMX) and minocycline, given for 3 months. The possibility of nocardiosis should be considered in the differential diagnosis of such patients.

Abscess↗

Trisomy 4 in a case of acute lymphocytic leukemia (L1).

Trisomy 4 has been identified previously as a chromosome abnormality associated with acute nonlymphocytic leukemia (ANLL) with myelomonocytic lineage and in myelodysplastic syndromes (MDS). We report a case of acute lymphocytic leukemia (ALL) (French-American-British, FAB L1) in a 42-year-old Japanese man, with trisomy 4 as the sole chromosomal anomaly. Immunophenotypically, the leukemic blasts demonstrated reactivity with CD2, CD5, and CD7 and indicated on early stage of T cell.

Adult↗

[Aplastic anemia successfully treated with erythropoietin and rhG-CSF].

A 32 year-old female admitted to our hospital with pancytopenia. The hematological data on admission were: RBC: 247 x 10(4)/microliters, Hb: 8.8 g/dl, Plts: 13,000/microliters, WBC: 2,500/microliters. Bone marrow aspirate and biopsied specimen showed marked hypocellularity without infiltration of abnormal cells. A diagnosis of aplastic anemia was made. Neither high-dose methyl-prednisolone pulse therapy nor anti-lymphocyte globulin were effective. With combination of oxymetholone (30 mg/day), recombinant erythropoietin (rHuEpo; 12,000 U/day, three times a week) and recombinant granulocyte-colony simulating factor (rHuG-CSF; 33 micrograms/day) for 3 months, remarkable improvements of hematological data were obtained. Her hemoglobin level reached 11.4 g/dl, and platelets count 49,000/microliters. However, 4 weeks after the withdrawal of erythropoietin and G-CSF administrations, her platelet count fell to 12,000/microliters. It was suggested that combination therapy with erythropoietin and G-CSF were effective for aplastic anemia.

Adult↗

[Multiple myeloma with a mass formation in a pacemaker pocket].

A 74-year-old female was diagnosed as having multiple myeloma in August 1989 and was treated with combined vincristine, melphalan and prednisolone. Subsequently, she was followed followed up in the outpatient clinic using interferon-alpha. On August 6, 1990, she had a transvenous demand pacemaker inserted because of severe atrioventricular block. The pulse generator was placed in a subcutaneous pocket in the left pectoral area. On February 3, 1991, she developed a mass overlying the pulse generator. This tumor was diagnosed as plasmacytoma by histological examinations. A myelogram showed 5.1% plasma cells with 5.5 x 10(4) nucleated cells/microliter. The amounts of serum protein and IgA M protein were 6.8 g/dl and 1.8 g/dl, respectively. The tumor responded to combined chemotherapy, but reenlarged to the initial size 3-4 weeks later. On August 6, 1991, this tumor, including the pulse generator was removed. By October 1991, the patient had systemic subcutaneous tumors and a right maxillary tumor suggesting the aggressive phase. On December 19, 1991, she died due to cardiac failure. In this paper the discussion focussed on the etiopathogenesis of plasmacytoma arising in the region of pulse generator pockets.

Aged↗

Flow cytometric assay for phagocytosis of human monocytes mediated via Fc gamma-receptors and complement receptor CR1 (CD35).

We developed a simple flow cytometric assay for phagocytosis by human monocytes that is mediated via Fc gamma receptors and the complement receptor CR1 (CD35), using fluorescent latex beads carrying IgG and complement components C4b and C3b. To prepare fluorescent latex beads carrying IgG(BA), BSA-coated latex beads (B) were incubated with diluted rabbit anti-BSA IgG. To bind complement components, BA-particles were incubated with whole human serum pretreated with K-76 monocarboxylic acid (K-76COOH). K-76COOH inhibits the activities of C5 and factor I (12,13), resulting in the deposition of C1,4b,2a,3b on BA-particles (BAC1,4b,2a,3b). Further incubation of BAC1,4b,2a,3b with EDTA-GVB at 37 degrees C gave particles carrying IgG and C4b,C3b (BAC4b,3b). The C3 fragment, C3b, was confirmed to present on BAC1,4a,2a,3b particles by SDS-PAGE and immunoblot, and these particles were calculated to have approximately 25,000-30,000 C3b molecules per particle. To evaluate the particle attachment, the phagocytic assay was performed with 3 microM cytochalasin D treated cells. The percent cells with ingested particles and the number of ingested particles/100 cells for 60 min were estimated, being 5.1% and 5.4 for B, 12.3% and 26.7 for BA, 42.5% and 108.7 for BAC4b,3b, and 42.6% and 112.5 for BAC1,4b,2a,3b, respectively.

Antigens, Differentiation↗

[Flow cytometric analysis of immunophagocytosis using sensitized fluorescent microspheres bearing C3b].

We analyzed the phagocytic activity of purified human monocytes using fluorescent latex beads sensitized with IgG or IgG.C3 by flow cytometry. To prepare IgG-sensitized latex beads (BA), BSA-coated latex beads (B) were incubated with diluted rabbit IgG anti-BSA. To bind complement components, BA were incubated with whole serum pretreated with K-76 monocarboxylic acid (K-76COOH). K-76COOH inhibits the activity of factor I and C5, resulting in deposition of C1, C4b, C2a, C3b on BA (BAC). Phagocytic activity was assessed by percent phagocytosis and phagocytic index (PI). To eliminate the effects of non-phagocytosed latex beads, subtraction of the data at 4 degrees C from 37 degrees C was performed. Percent phagocytosis for 60 min. was B 5.0%, BA 18.3%, and BAC 57.5%, and PI (ingested latex beads/100 cells) was B 7.9, BA 36.8, and BAC 152.7, respectively. In addition, K-76COOH caused dose dependent inhibition on IgG.C3 mediated phagocytosis. Comparison of inhibition pattern on BAC and BA indicated that K-76COOH directly inhibited C3.C3-receptor binding.

Complement C3b↗

A case of disseminated trichosporonosis: a case report and immunohistochemical identification of fungal elements.

Trichosporon beigelii was isolated from blood cultures of a 69-year-old Japanese male who had been treated for chronic myeloid leukaemia with cytotoxic agents and broad spectrum antibiotics. He died of sepsis 4 days after a positive blood culture was obtained. A postmortem examination revealed abundant budding yeasts and hyphae in sections of lung, liver, bone marrow and other organs. All the fungal elements in the sections were identified as Trichosporon species by their histological features and by immunohistochemical findings using rabbit antiserum raised against the strain isolated from the patient.

Aged↗

The site of cleavage in human alpha chains of IgA1 and IgA2:A2m(1) allotype paraproteins by the clostridial IGA protease.

Fc fragments of human immunoglobulin A(IgA) of IgA1 subclass and IgA2 subclass of A2m(1) allotype were prepared from IgA paraproteins by digestion with a protease from Clostridium sp. (M.O.-6). The N-terminal tetrapeptide of Val-Pro-Ser-Thr- for the Fc of IgA1 subclass, and that of Val-Pro-Pro-Pro- for the Fc of IgA2:A2m(1) allotype, were identified by sequence analysis. The site of cleavage by the protease was defined to be at the Pro-Val peptide bond, which is a common peptide bond present at 221-222 in both alpha chains. IgA of IgA2 subclass of A2m(2) allotype is resistant to the protease due to the different, Arg-Val, peptide bond at the same position.

Amino Acid Sequence↗

Clostridium ramosum, an IgA protease-producing species and its ecology in the human intestinal tract.

A bacterial strain isolated from feces of a patient with ulcerative colitis, which had been shown to produce a novel immunoglobulin A (IgA) protease (cleaving both the human IgA1 subclass and IgA2 subclass of A2m(1) allotype) extracellularly, was identified as Clostridium ramosum. By using a selective medium (propionate-rifampicin-gentamicin-colimycin-polymyxin medium) devised for C. ramosum, analysis of the population level of this organism was performed to determine its ecology in the human intestinal tract. C. ramosum was isolated in 20 of 25 fecal samples (80%) from patients with inflammatory bowel disease (I.B.D.) and in 112 of 135 samples (83%) from patients without I.B.D. (control group). C. ramosum was also isolated from 6 of 11 biopsy samples (55%) of the inflamed rectal mucosa from patients with ulcerative colitis and from five of 15 samples (33%) from the intact mucosa of the control group. The population levels of C. ramosum in most of the biopsy samples ranged from 2.3 to 5.0 log10 per gram. The IgA protease-positive C. ramosum was found in only four of 135 fecal samples (3%) and one of 15 biopsy samples (6.7%) from the control group. These results indicate that IgA protease-positive C. ramosum is not likely to play a role in the induction of I.B.D., unless the organism is first isolated from the patient with I.B.D.

Clostridium↗