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Biomedical subjects

T Hotta

Publications and source records attributed to T Hotta.

At least 253 records · Page 14Linked to original sources

[Occurrence of cytoplasmic bridge between erythroblasts--morphology and frequency in hematological disease].

Peculiar cytoplasmic connection between erythroblasts was observed in the smear preparation of human bone marrow; a pair of erythroblasts in the resting stage was connected by "cytoplasmic bridge" which is very thin and sometimes long compared with the telophase bridge appeared in the usual cytokinesis. Electron microscopy revealed that small amount of microtubules were running along in the cytoplasmic bridge but mid-body was not seen. Plasma membrane about the middle of the bridge bulged to form "bulging ring". Erythroblasts in various differentiating stages were connected by the cytoplasmic bridge and the stage of each pair was almost the same. The occurrence of the cytoplasmic bridge between erythroblasts was evaluated in the smear preparations of human bone marrow with hematological diseases or normal conditions. In the normal bone marrow, the mean value was 8.1 +/- 3.6% (n = 33). In patients suffered from autoimmune hemolytic anemia, it was 4.3 +/- 2.3% (n = 12), aplastic anemia, 3.2 +/- 2.1% (n = 6) and paroxysmal nocturnal hemoglobinuria, 5.0 +/- 1.4% (n = 3). While in the erythroleukemia the occurrence was very low showing 0.2 +/- 0.1% (n = 3) of total erythroblasts. In MDS, RAEB (2.5 +/- 2.4%) and RA (2.9 +/- 2.2+%) showed statistically significant lower occurrence. In the normal bone marrow the occurrence was higher, so the formation of cytoplasmic bridge could be essential for a normal proliferation of erythroblasts.

Adolescent↗

[Etoposide delivery to malignant brain tumors by induced hypertension with angiotensin II].

Etoposide delivery to 9L gliosarcoma model in Fischer 344 rats was evaluated. Etoposide 2 mg/body was given intravenously (IV) or intracarotidly with (IHIC) or without (IC) intravenously administrated angiotensin II. Mean etoposide concentration of tumors was 5.08 micrograms/g for IHIC group, 2.27 micrograms/g for IC group and 0.70 micrograms/g for IV group. The difference in etoposide concentration between IHIC group and IV group was statistically significant (p less than 0.05). In addition, etoposide concentrations of the normal brain tissues were lower than concurrent plasma concentrations in all groups. The etoposide concentration was increased in the tumor and very low in the normal brain tissues in Fischer 344 rats with 9L gliosarcoma by induced hypertension with angiotensin II. These studies might suggest that intraarterial chemotherapy by induced hypertension with angiotensin II was useful on treatment of malignant brain tumors.

Angiotensin II↗

[Abnormal cluster formation in a patient with myelodysplastic syndrome with trisomy-11--periodical approach by colony assay].

59 year old female was admitted to Nagoya Memorial Hospital for anemia unknown etiology after the work up of the gastrointestinal tract. Peripheral blood count at admission was as follows: WBC 2,400/microliters, RBC 321 X 10(4)/microliters, Hb 9.8 g/dl, Ht 30.1%, Plt 8.2 X 10(4)/microliters, which showed pancytopenia with normocytic, normochromic anemia. She had no hepatosplenomegaly, vitamin B12 nor folate deficiency. Bone marrow was hyperplastic and showed trilineage megalodysplastic changes. The diagnosis of myelodysplastic syndrome (Refractory anemia) was made. Progenitor assay showed no colony formation of BFU-E but showed normal growth of CFU-GM colony and cluster. She had chromosomal abnormality of 47, XX, + 11. Administrated anabolic steroid, prednine and activated vitamin D3 were not effective and she died of brain hemorrhage in April 1987. Colony assay at this stage showed numerous leukemic clusters and no normal colonies. Re-performed chromosome assay showed 47, XX, + 11. There are only a few reports of trisomy-11 in a patient with MDS. Especially we could follow this case till her leukemic transformation by colony assay.

Anemia, Refractory, with Excess of Blasts↗

[Mitral valvuloplasty for mitral regurgitation due to torn chordae of the posterior leaflet].

Four patients with mitral regurgitation due to torn chordae of the mitral posterior leaflet underwent mitral valvuloplasty. Standard operation was McGoon's procedure which was sometimes combined with Kay's annulorrhaphy. There were no sign of mitral insufficiency and/or stenosis in all patients revealed by the post-operative cardiac catheterization and all of them are on good health. Then, our plans of mitral posterior valvuloplasty for mitral regurgitation are as follows: A resected area is not beyond 33% of the posterior leaflet and the target mitral valve area after valvuloplasty is 2.8 cm2.

Adult↗

Problems associated with the EEA stapling technique for esophagojejunostomy after total gastrectomy.

Since November 1980, the EEA stapling device has been used to create an end-to-side esophagojejunostomy in 238 patients who underwent total gastrectomy. Failures in the stapling technique were divided into two groups: immediate and delayed. Immediate failures were observed and corrected at the time of surgery. In ten cases, the muscular layer of the esophagus was disrupted, and in three the mucosal layer of the jejunum was disrupted. There were 18 delayed complications: eight cases of anastomotic leakage (3.4%), and ten of stenosis (4.2%). The leakage in one case was classified as major, and those in the other seven as minor. Of the ten stenosis cases, there were five of membranous stricture, four of granular stricture, and one of narrowing after major leakage healing. Only this last case required further surgical treatment. The other nine were successfully dilated either endoscopically or by bougienage.

Adult↗

In vitro bone marrow toxicity of nucleoside analogs against human immunodeficiency virus.

3'-Azido-2',3'-dideoxythymidine is known to cause severe anemia and neutropenia. Although these are rare for 2',3'-dideoxycytidine, it frequently impairs thrombocytogenesis. These differential myelossuppressive features correlated well with the in vitro toxicities of the drugs for a megakaryoblastic cell line and for colony formation of erythroid and granulocytic cells.

Antiviral Agents↗

[Salvage chemotherapy with a combination of VP-16, ifosfamide, procarbazine, prednisolone, bleomycin and methotrexate (VIPP-BM) for refractory malignant lymphoma].

Twenty patients with refractory malignant lymphoma were treated with a combination of VP-16, ifosfamide, procarbazine, prednisolone, bleomycin and methotrexate (VIPP-BM) as salvage chemotherapy. These patients were either resistant to front-line therapy or refractory in their relapses. Two patients (10%) achieved a complete remission and eleven patients (55%) attained a partial remission. An overall response rate was 65%. Major toxicities were myelosuppression, nausea and vomiting, and mucositis. However they were well tolerated. This regimen has been effective in the treatment for the patients with refractory lymphoma.

Adolescent↗

[Clinical study of combination chemotherapy with mitomycin C, vindesine and cisplatin (MVP therapy) in advanced non-small cell lung cancer].

Thirty-seven patients with inoperable non-small cell lung cancer were treated with the combination chemotherapy (MVP therapy) with mitomycin C (8 mg/m2), vindesine (3 mg/m2 X 2) and cisplatin (60 mg/m2). The partial responders were 13 cases (35%), and the median survival time was 271 days. In this study the cisplatin dose was less than in any other report of "MVP" therapy. But both the response rate and the median survival time did not differ from those reported elsewhere. The side effects (bone marrow suppression, renal toxicity, etc.) were mild, and did not prevent the continuance of this therapy. Thus, we could repeat more than 6 courses of "MVP" therapy for 8 patients. Nowadays, it is difficult to obtain complete responders with any chemotherapy for inoperable non-small cell lung cancer. To prolong lives of patients and maintain good quality of life, we recommend chemotherapy with low toxicity in often-repeatable courses.

Adult↗

Antitumor effect of recombinant human lymphotoxin on a tumor line of human malignant glioma.

We examined the antitumor effect of recombinant human lymphotoxin (rHuLT) on a xenotransplantable human malignant glioma line. Tumor-bearing nude mice were treated with rHuLT for three weeks following four schedules: intratumoral injection of rHuLT 20,000 units once a week, twice a week, intravenous injection once a week and twice a week. The inhibition rate of tumor growth was 98.8%, 99.1%, 92.1% and 98.8%, respectively. Histologically, necrotic lesions were observed in the tumors of all treated mice. Thrombo-obstructive changes of tumor vessels were also seen in the tumors of mice after intravenous injection of rHuLT. None of the mice died as a result of this treatment in spite of significant body weight loss. These results indicate that rHuLT has a strong antitumor effect on a xenotransplantable human malignant glioma line.

Animals↗

[Initial symptoms of hematemesis from gastric varix with chromosomal abnormalities of t(2; 8) and 14q+ in a patient with acute lymphoblastic leukemia (FAB: L3)].

A 71-year-old woman was hospitalized because of hematemesis on December 1, 1987. Her white blood cell (WBC) count was 41,200/microliters with 48% of lymphoblasts, and the bone marrow was hypercellular with more than 90% of blasts. The diagnosis of acute lymphoblastic leukemia (ALL) (FAB: L3) was made by morphologic, cytochemical and immunologic studies of the blasts. The examination of fiber gastroscope revealed remarkable varix in the stomach, suggesting portal hypertension accompanied by infiltration of leukemic cells into reticulo-endothelial system. She died of respiratory failure because of bleeding into the trachea. The autopsy disclosed the massive infiltration of leukemic cells into the whole organs. In the chromosome study of the peripheral blood, t(2; 8) and 14q+ were observed, and these chromosomal abnormalities are relatively unusual in patients with Burkitt's lymphoma.

Aged↗

[Limb salvage procedures in malignant bone tumors of the extremities, with special reference to the various reconstructive procedures of bone defects].

The outcomes of 31 cases of limb salvage procedures for malignant bone tumors performed between 1974 and August 1988 were investigated. The age at operation ranged from 7 to 76. Thirteen cases were growing children under 15. The site of lesions were humerus in 6 cases, femur in 20, tibia in 3 and fibula in 2. Pathological diagnoses were osteosarcoma in 19, chondrosarcoma in 5 and others in 7. Reconstructive procedures were performed in 28 cases, consisting of endoprosthetic replacements in 18, vascularized fibula grafts in 6 and free autogenous bone grafts in 4. Two cases of osteosarcoma recurred, and amputations were performed. Six cases died of pulmonary metastases, while 22 cases (71%) are alive and free of disease. Functional results depended mainly on the size and site of resection rather than on the reconstructive procedures, and were generally good in the proximal femur and fibula, and poor in the distal femur and proximal tibia. Discrepancy in the length of lower limbs occurred in 8 cases of growing children; 5 of 6 vascularized fibula grafts showed thickening of the grafted bones, and one of them grew by 2.5 cm in length. Endoprosthetic replacements are adequate for hip and shoulder regions, and for low grade sarcoma which does not require chemotherapy or irradiation. Free autogenous bone grafts are good for narrow defect of bone, and cases of arthrodesis of joint. Vascularized fibula grafts are adequate for the upper limb, and lower limb of growing child.

Adolescent↗

[So-called Ph1-negative chronic myelogenous leukemia with a mosaic pattern of trisomy 8 and normal karyotypes--report of 2 cases].

Two cases of Ph1-negative chronic myelogenous leukemia (CML) are described, they were 66-year-old female and 73-year-old male. Both patients shared all of the following features: presence of anemia, thrombocytopenia and leukocytosis with every stage of neutrophilic differentiation, hypercellular bone marrow with hyperplasia of the degranulated neutrophilic series, diminished neutrophilic alkaline phosphatase, elevated serum lysozyme and vitamin B12 level, mosaic pattern of trisomy 8 and normal karyotypes in chromosome analysis, and markedly increased number of CFU-GM. In addition, bcr rearrangement by Southern blot hybridization was not demonstrated in these patients. The diagnosis of chronic myelomonocytic leukemia was not verified, however, because of the absence of monocytosis in peripheral blood. The existence of so-called Ph1-negative CML like these two cases as a diagnostic entity must be further studied.

Aged↗

[Treatment with sulbactam/cefoperazone of severe infections in patients with hematological disorders].

Infectious episodes in 90 patients with hematological disorders were treated with sulbactam/cefoperazone (SBT/CPZ), a new combination drug of a potent beta-lactamase inhibitor, sodium sulbactam, and a third generation cephalosporin, sodium cefoperazone. Clinical responses to the SBT/CPZ regimen were excellent in 23 cases, good in 30 cases, fair in 11 cases, and poor in 26 cases. The overall efficacy rate (percentage of cases showing excellent or good responses) was 58.9%. Efficacy rates classified according to different infections were: 80% in documented sepsis, 57.6% in suspected sepsis, 61.1% in pneumonia and 50% in other infections. One episode of side effect was encountered with redness and itching of skin. Hepatic disorders were observed in 3 cases. These adverse reactions, however, were not serious. These results indicate that SBT/CPZ has a high therapeutic efficacy to severe infections in patients with hematological disorders.

Adolescent↗

[Growth inhibition of erythroid colonies by autologous sera and the clinical effect of erythropoietin in chronic renal disease].

We investigated the inhibitory effect of autologous sera on erythroid colony formation (CFU-E) of bone marrow cells from patients with chronic renal disease and the clinical effect of recombinant erythropoietin. Colonies formed in cultures using autologous serum (AS) decreased in 15 among 30 cases as compared with those using fetal calf serum (FCS). This inhibitory effect of autologous sera was diminished by treatment with activated charcoal in all these cases. The degree of hemoglobin increase after administration of recombinant erythropoietin appeared to correlate with the intensity of inhibitory activity of AS. These data indicate the clinical significance of the inhibitor(s) of erythropoiesis in uremic sera and suggest that the clinical effects of erythropoietin in this disease are further improved if the inhibitor(s) can be effectively removed.

Adult↗

Serological and biochemical characterization of surface antigen expressed on human myeloid cells and identification of six distinct antigen systems.

Six distinct surface antigens selectively expressed on human myeloid cells were defined with ten murine monoclonal antibodies. Four antigens (GAp95, GAp170, GAp160-220, GAp145-200) are expressed on protein molecules and one antigen (GANGL) is detected in neutral glycolipids. The biochemical nature of the remaining one (GA8.9) is unknown. GAp95 and GANGL are expressed on relatively mature myeloid cells, whereas GAp160-220 is expressed on immature myeloid cells. GAp170 and GAp145-200 are expressed on a wide range of myeloid cells. GA8.9 was found on NKM-1, a cell line of acute myelomonocytic leukemia, and also on some acute nonlymphocytic leukemia cells.

Antibodies, Monoclonal↗

Activated charcoal diminishes the lot difference of fetal bovine sera in erythroid colony formation of human bone marrow cells.

Using normal bone marrow as target cells, we assayed the colony-forming efficiency of early and late erythroid progenitor cells and granulocyte-macrophage progenitor cells using several different lots of fetal bovine serum (FBS). There was a marked difference in the ability of these sera to support colony formation, particularly in erythroid colony assays. When adsorbed by activated charcoal, all these sera supported erythroid colony formation more efficiently than before adsorption. There was no significant effect of charcoal adsorption of FBS on granulocyte-macrophage colony formation. Gel-filtration study showed that charcoal adsorption diminished low-molecular-weight fractions by less than 5000 Da. The inhibitory activity of this fraction was heat labile and Pronase sensitive. Concentrated samples obtained from these fractions inhibited erythroid colony formation in a dose-dependent manner. These results suggest that low-molecular-weight inhibitors that are relatively specific to erythropoiesis play a critical role in the lot differences of FBS for erythroid colony formation.

Adsorption↗

Functional and morphological differentiation induction of a human megakaryoblastic leukemia cell line (MEG-01s) by phorbol diesters.

The effect of differentiation induction by a tumor-promoting phorbol diester, 12-O-tetradecanoylphorbol-13-acetate (TPA) on a clonal human megakaryoblastic cell line, MEG-O1s, was investigated, and a prominent response was demonstrated. The cells became weakly adherent, developed conspicuous cytoplasmic blebs, and displayed mature megakaryocytic characteristics by light microscopy such as the development of azurophilic cytoplasmic granules and a mosaic pattern of oxyphilic patches, multiplication of nuclei, and enhancement of the PAS reaction and alpha-naphthyl acetate esterase staining. Ultrastructural studies demonstrated the development of prominent cytoplasmic blebs, budding of blebs, and multiplication of nuclei. Numerous granules with central nucleoids that are similar to alpha granules had developed as well as granules with high electron density and clearly demarcated zones. Surface marker analysis revealed a moderate increase in IgG Fc receptor levels and a profound decrease in C3 receptor sites. By an immunofluorescent technique using monoclonal and polyclonal antibodies, a dramatic change in the expression of several megakaryocyte-platelet-specific proteins was demonstrated. All the proteins that had been expressed before induction such as platelet glycoprotein (GP) IIb/IIIa, fibrinogen, von Willebrand factor, factor XIIIA, beta-thromboglobulin (beta-TG), and HLA class 1 antigen were profoundly enhanced after induction by TPA. Induction by TPA led to the expression of fibronectin and factor V, which were not detected on nontreated cells. An ultrastructural immunoperoxidase study demonstrated platelet GPIb and GPIIb/IIIa in both plasma membranes and protein synthesis areas such as perinuclear cisternae and endoplasmic reticulum after TPA induction. beta-TG was also observed in some cytoplasmic granules of TPA-treated cells. TPA remarkably increased the secretion of beta-TG into the culture medium of MEG-01s. Ploidy was also increased from 2C to 4C to 4C to 8C. Similar maturation of MEG-01s was induced by other phorbol diester analogues such as phorbol-12,13-dibutyrate, but not by phorbol itself. These results indicate that phorbol diester, TPA, can bring about differentiation and maturation of a human megakaryoblastic cell line (MEG-01s) and that MEG-01s cells will provide a useful model for studying megakaryocytic differentiation and numerous megakaryocyte-platelet-specific proteins.

Antibodies, Monoclonal↗