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Biomedical subjects

T Hotta

Publications and source records attributed to T Hotta.

At least 289 records · Page 16Linked to original sources

Effect of recombinant human tumor necrosis factor on the colony growth of human leukemia progenitor cells and normal hematopoietic progenitor cells.

The effects of recombinant human tumor necrosis factor (rH-TNF) on the colony growth of human leukemia progenitor cells (L-CFU), granulocyte-macrophage progenitor cells (CFU-GM), and erythroid progenitor cells (BFU-E) were studied. L-CFU was assayed with leukemia cells obtained from patients with acute myelogenous leukemia. CFU-GM and BFU-E were assayed with bone marrow cells obtained from hematologically normal donors and patients with acute leukemia or non-Hodgkin's lymphoma in complete remission. A dose-dependent growth inhibition of L-CFU as well as CFU-GM and BFU-E was observed by rH-TNF at concentrations of 1 to 100 U/mL. The inhibitory effect on L-CFU was significantly greater than that on CFU-GM. No correlation was observed between the inhibitory effect on L-CFU and the number of colonies formed in the cultures without rH-TNF. Preincubation of the progenitor cells in culture medium containing 20% fetal calf serum with up to 1,000 U/mL of rH-TNF for 24 hours did not result in the inhibition of colony growth of L-CFU or CFU-GM. The inhibitory effect of rH-TNF was neutralized by an anti-rH-TNF murine monoclonal antibody.

Female↗

Lipopolysaccharide-induced colitis in rabbits.

An experimental animal model of human ulcerative colitis using lipopolysaccharide (LPS) was studied. Rabbits were skin-sensitized by LPS and challenged with intrarectal instillation of LPS after 1% formalin enema. The course of experimental colitis was followed by performing serial colonofiberscopic examinations and biopsy. Petechiae appeared from the 8th hour, and ulcers and bleeding on the 3rd day. Mild macroscopic changes continued for about 2 weeks. By repeating the LPS enema after the initial treatment, the colitis was maintained for over 1 month. Control groups without formalin enema revealed no macroscopic changes, and the groups with only formalin enema showed mild transient changes. The endotoxin level in the blood during the experiment increased (36 pg/ml) at 24 h after the treatment in the LPS-sensitized group, while non-sensitized control rabbits had higher levels of endotoxin. Though fibrinogen and PTT levels had increased at 24 and 72 h, these levels were marked in the control rabbits. The direct reaction of LPS was minimal, and local immune reaction by LPS seems to play an important role in the perpetuation of experimental colitis. Tissue fibrinolysis of the colon increased significantly as the mucosal damage appeared. This experimental colitis with LPS may be useful as a model of human ulcerative colitis.

Animals↗

Granulopoiesis-supporting effects of marrow stromal cells in continuous culture from patients with primary myelofibrosis.

The granulopoiesis-supporting effects of marrow adherent cells from seven patients with primary myelofibrosis (PMF) were studied by a continuous allogeneic co-culture system in which the survival of donor granulocyte-macrophage colony-forming cells (CFU-GM) depends upon the supporting ability of adherent cells. Marrow adherent cells from all these seven patients were able to sustain the same number of CFU-GM as those from control subjects. Cytochemical studies showed that colonies grown from cells sustained on fibrous marrow adherent cell layers were predominantly neutrophilic, as were those in control cultures, although many eosinophil colonies grew from patients' bone marrow. These results indicate that marrow stromal cells from PMF patients function normally in their ability to support granulopoiesis.

Adult↗

[Hemodilutional therapy in raised intracranial pressure; observations in a case of cerebral infarction associated with polycythemia vera].

A 36-year-old man presented with sudden onset of hemorrhagic cerebral infarction in association with polycythemia vera. On admission this patient manifested semicomatous state and left hemiplegia which were gradually progressed. X ray CT demonstrated a severe hemorrhagic infarction in right MCA territory accompanying marked shift of midline structures. Cerebral angiograms represented occlusion of right MCA showing floating emboli in the internal carotid. Hematocrit value was found to be high as 61.2 per cent. Elevated ICP levels were noted by means of epidural pressure monitoring. Deterioration of patient status was considered to be based on impairment of cerebral circulation due to hemostasis by elevated blood viscosity. In addition to administration of mannitol solution, intermittent exsanguinations, 1000 ml in total amount, were performed and hematocrit levels were corrected by hemodilution. Consciousness level was remarkably improved in accordance with reduction of ICP, which well corresponded to values of hematocrit. Level of ICP and tissue perfusion are convinced to be strongly affected by hemorheological factor in the state of raised ICP.

Adult↗

Separation of an inhibitor of erythropoiesis in "middle molecules" from hemodialysate from patients with chronic renal failure.

A "middle molecule" inhibitor of erythropoiesis in patients with chronic renal failure was separated from a large amount of hemodialysate. Hemodialysate was passed through Amberlite XAD-4 resin, Sephadex G-50 gel, and DEAE-Sephadex A-25, followed by reversed-phase liquid chromatography. The erythroid colony assay (CFU-E) was used to detect the inhibitory effect of the sample solution. Certain fractions from the DEAE-Sephadex A-25 column showed a dose-related inhibition of CFU-E formation as great as that of standard spermine. The inhibitory effect of these fractions decreased to the control value after proteolytic digestion. The inhibitor was eluted from the liquid-chromatographic column by a solvent gradient containing 390 to 425 mL of methanol per liter. These results suggest there is an inhibitor of CFU-E with a relative molecular mass of 1000 to 10 000 and an active site composed of peptide. This technique may prove useful for separation of the inhibitor of erythropoiesis in uremic body fluid.

Animals↗

Enhanced colony formation of human hemopoietic stem cells in reduced oxygen tension.

In general, cell cultures, including hemopoietic stem cells, are produced in an atmosphere of various CO2 concentrations in air, although most cells in vivo proliferate and differentiate at lower oxygen tensions. We therefore investigated the effect of reduced oxygen tension on the in vitro colony growth of committed and multipotential hemopoietic progenitor cells from human bone marrow. All hemopoietic progenitor cells (CFU-mix, BFU-E, CFU-E, and CFU-GM) investigated showed enhanced colony growth at lower oxygen tension. CFU-E showed the highest enhancement, followed in order by BFU-E, CFU-mix and CFU-GM. At reduced oxygen tension, the sensitivity of early and late erythroid progenitor cells to erythropoietin was significantly increased, and this can be one of the mechanisms for the enhanced colony growth of erythroid progenitors. In the colony growth of CFU-GM, plating efficiency was also enhanced by the predominant increment of neutrophilic colonies. The lowering of oxygen tension would presumably reduce oxygen toxicity and result in the increased colony growth of human bone marrow stem cells, although the precise mechanisms of oxygen toxicity at the level of hemopoietic stem cells have yet to be elucidated. However, this clonal culture system, using a low oxygen tension, can be a useful means for elucidating the regulatory mechanisms involved in the proliferation and differentiation of hemopoietic progenitor cells in physiological and pathological conditions.

Bone Marrow↗

[A case of spontaneous carotid-cavernous fistula disappearing following irradiation].

A case of spontaneous carotid-cavernous fistula, which completely disappeared following irradiation (45 Gy), is reported. A 59-year-old woman was admitted on October 10, 1983, with a history of doplopia and recurrent retrobulbar and occipital pain. On admission, neurological examination showed no neurological deficit, and right cerebral angiography demonstrated a dural internal carotid-cavernous fistula fed by the meningohypophyseal trunk and drained into the inferior petrosal sinus. In spite of the conservative management, right oculomotor palsy and hypesthesia corresponding to the division of ophthalmic branch of the right trigeminal nerve was developed. On November 22, liniac irradiation to the region of fistula (30 days, total dose, 45 Gy) was started. Symptoms and signs gradually improved 3 weeks after irradiation and completely disappeared 3 months after irradiation. Carotid-cavernous fistula was no longer demonstrated by the cerebral angiography 7 months after irradiation. Two years after onset, no recurrence of symptoms was observed.

Arteriovenous Fistula↗

Gastric anti-ulcer and cytoprotective properties of 2-(3,4-dimethoxyphenyl)-5-methyl-thiazolidine-4-one in rat experimental ulcers.

Anti-ulcer properties of 2-(3,4-dimethoxyphenyl)-5-methylthiazolidine-4-one (KM-1146) were investigated on various experimental ulcers in comparison with cimetidine. While both KM-1146 and cimetidine at the same dose were comparative on the preventive effects of Shay- and stress-ulcers, KM-1146 was more effective against different necrotizing agents such as 0.2N NaOH and 99.5% ethanol at non-antisecretory dose. KM-1146 50 mg significantly accelerated the healing of acetic acid-induced ulcers while cimetidine 200 mg had no effect. KM-1146 increased rat gastric mucosal blood flow as measured by hydrogen gas clearance and prevented a decrease of gastric mucus gel thickness induced by water immersion restraint stress. These studies indicate that KM-1146 exerts cytoprotective action even in anti-secretory dose in addition to a significant anti-ulcer action which is comparable to cimetidine.

Acetates↗

Cloning of sequences induced and suppressed by administration of PSK, antitumor protein-bound polysaccharide.

To elucidate the effects of PSK, a protein-bound polysaccharide from Coriolus versicolor, on gene expression in tumor cells, we prepared cDNA clone libraries from PSK-treated and untreated cells of a rat ascites hepatoma line, AH66, which was previously shown to be susceptible to the antitumor action of this compound. Two PSK-induced and one suppressed cDNA clones were selected from these libraries by using a differential colony hybridization and RNA blot hybridization. PSK was thus shown to have a direct effect on the transcription and consequently on the translation of tumor cells.

Animals↗

Granulocytic and stromal progenitors in the bone marrow of patients with primary myelofibrosis.

Quantitative and qualitative changes in granulocyte-macrophage (CFU-GM) and fibroblast colony-forming cells (CFU-F) were studied in 7 patients with primary myelofibrosis (MF). Marrow cells were collected from bone biopsy specimens after treatment with collagenase. The number of CFU-GM correlated with the amount of haemopoietic tissue noted in the bone marrow histology and ranged between 0-400/mg of bone. CFU-F were increased in 2 patients with moderate fibrosis. Circulating CFU-GM were increased in all patients studied (169-3749/ml of blood). There was no significant correlation between the number of CFU-GM in the bone marrow and that in the blood. Cytochemical studies showed a high incidence in eosinophil progenitors in the bone marrow and especially in the blood of patients with MF. These data suggest a functional abnormality of myeloid progenitors in this disease.

Aged↗

Functional changes in marrow stromal cells in aplastic anaemia.

To determine whether or not abnormalities exist in the bone marrow stroma in aplastic anaemia, we analysed the ability of marrow stromal cells to support haemopoiesis using a long-term culture system. Marrow stromal cell layers from 3 of 9 patients with this disorder failed to maintain granulocyte-macrophage colony-forming cells in vitro. The stromal dysfunction was reversible in 1 patient who recovered after androgen therapy. The results of the present study add to the available evidence for a functional defect of marrow microenvironments in some cases of aplastic anaemia.

Adolescent↗