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Biomedical subjects

H Hara

Publications and source records attributed to H Hara.

At least 631 records · Page 35Linked to original sources

Prevention of hippocampus neuronal damage in ischemic gerbils by a novel lipid peroxidation inhibitor (quinazoline derivative).

We investigated the effect of a novel quinazoline derivative (KB-5666), a lipid peroxidation inhibitor, on ischemic neuronal damage using Mongolian gerbils. The animals were sacrificed 7 or 30 days after 5 min of forebrain ischemia induced by bilateral common carotid artery occlusion. Morphologic changes, a microtubule-associated protein 2 (MAP2) immunohistochemical study and quantitative autoradiographic study using [3H]phorbol 12, 13-dibutyrate ([3H]PDBu) were evaluated in the hippocampus after ischemia. KB-5666 (3-50 mg/kg, i.v.) showed protective effects against neuronal death of the CA1 subfield 5 min before ischemia, immediately or 1 hr after ischemia, but not 4 hr after ischemia. KB-5666 (i.p.) also showed protective effects in a dose-dependent manner immediately after ischemia. Furthermore, KB-5666 dose-dependently prevented a marked decrease in microtubule-associated protein 2 immunoreactivity in the dendritic fields of the CA1 pyramidal cells after ischemia. The [3H]PDBu binding activity in the stratum oriens and the stratum lacunosum-moleculare of the CA1 subfield was reduced by 19 and 30%, respectively, 7 days after ischemia. [3H]PDBu binding sites were unchanged in the stratum oriens in the CA3 subfield. By contrast, in the molecular layer of the dentate gyrus, the [3H]PDBu binding activity increased by 15%. KB-5666 (i.v.) prevented a decrease in the [3H]PDBu binding activity in the stratum oriens and stratum lacunosum-moleculare of the CA1 subfield and an increase in the molecular layer of the dentate gyrus. These histologic, immunohistochemical and receptor-autoradiographic data indicate that KB-5666 protects the brain from both cellular and functional consequences of ischemia.

Animals↗

[Bone marrow transplantation for MDS].

Five patients with myelodysplastic syndrome (RA: 4 cases, RAEB in T: 1 case) were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Median age was 20-y-o (11-31-y-o). All patients were prepared with cyclophosphamide and total body irradiation. Engraftment was documented in all patients. One patients (case 4, 31-y-o female) died of brain hemorrhage due to the thrombocytopenia refractory to platelet transfusion because of anti-platelet antibody in 34 days after BMT. A patient with RAEB in T was also died of respiratory failure from interstitial pneumonia on Day 173. One patient (case 1, 22-y-o, female) progressively became granulocytopenic and thrombocytopenic status after BMT. She suffered from life-threatening infection and then received a second bone marrow cell infusion from the same donor without any preparative conditioning. These results suggest that BMT could be the treatment of choice for MDS, especially for the patients with RA who have poor prognostic factors including life-threatening cytopenia and or cytogenetical abnormalities.

Adolescent↗

[Administration of haptoglobin in ABO incompatible bone marrow transplantation].

Haptoglobin was administered i.v. in 2 cases of ABO incompatible bone marrow transplantation for the prevention of hemoglobinuria due to acute hemolysis. The first case was a 25-year-old woman with severe aplastic anemia. The transplantation was both major and minor mismatch, where the donor was type A and the recipient was type B. The second case was a 31-year-old man with chronic phase of chronic myelogenous leukemia. The transplantation was major mismatch, where the donor was type B and the recipient was type O. After the administrations of haptoglobin 8,000 units we transfused bone marrow infusates from which incompatible erythrocytes were removed. Though prominent hemoglobinemia was observed in both cases, the serum haptoglobin values were not saturated and hemoglobinuria was not detectable. Haptoglobin appears to be useful for the prevention of acute renal failure associated with acute hemolysis in ABO incompatible bone marrow transplantation. Intravenous haptoglobin supplement therapy makes transplantation safer and may contribute to improve the recovery rate of total nucleated bone marrow cells after the erythrocyte depletion without worrying much about their contamination.

ABO Blood-Group System↗

[A case of polycythemia vera associated with idiopathic interstitial pneumonia successfully treated by alkylating agents].

A 62-year-old female was referred to our division because of general fatigue, low grade fever and exertional dyspnea for 2 months. Laboratory data and chest roentgenograms on admission revealed polycythemia vera associated with idiopathic interstitial pneumonia. Alkylating therapy with carboquone and cyclophosphamide resulted in the improvement of abnormalities on chest X-ray films which had previously shown decreased lung fields and abnormal interstitial shadows, as well as hematological abnormalities. Six months later, the results of the patient's pulmonary function tests and arterial blood gas analysis became within normal limits. Little information about polycythemia vera associated with idiopathic interstitial pneumonia is available. This case indicated that alkylating therapy with no steroidal combination is effective for idiopathic interstitial pneumonia.

Alkylating Agents↗

[A study of the coexistence of pulmonary tuberculosis and bronchogenic carcinoma: results of a questionnaire in Chugoku and Shikoku areas].

A study to obtain information on the relation between tuberculosis and carcinoma of the lung was carried out in 24 hospitals in Chugoku and Shikoku areas during the period from January 1979 to December 1988 using a questionnaire. As a result of this survey, 142 cases of coexisting active pulmonary tuberculosis and bronchogenic carcinoma were reported during the period. The incidence of coexisting cases was 2.32% of patients with pulmonary tuberculosis and 2.22% of patients with bronchogenic carcinoma. The foci of tuberculosis and carcinoma were found more often in the same lobe than in different lobes. The proportions of histological types of bronchogenic carcinoma were as follows: squamous cell carcinoma 43.9%, adenocarcinoma 36.0%, small cell carcinoma 16.5% and large cell carcinoma 3.6%. These findings were not significantly different from those in the general population. No significant difference in the proportions of histological types was found by coexisting lobe. some cases indicated that coexisting tuberculosis gave a favorable influence to the prognosis of lung cancer.

Carcinoma, Bronchogenic↗

[Valve thrombosis of St. Jude Medical prosthesis; report of three cases].

Three cases with valve thrombosis of St. Jude Medical prosthesis (SJM valve) are reported. Incidence of valve thrombosis of SJM valve was 0.15%/patient-year. Cineradiography was useful to make the diagnosis. SJM valves were implanted with the hinges anatomically oriented in mitral position, and in both aortic and tricuspid positions with the leaflet opening parallel to the ventricular septum. Therefore, we recommend that SJM valve should be placed with the hinge antianatomically oriented in mitral position, and in both aortic and tricuspid positions with the leaflet opening to be perpendicular to the interventricular septum, respectively.

Adult↗

Human pulmonary infection with Corynebacterium equi.

A 28 year old man with no underlying disease developed a cavity and multiple nodules in the lung from which Corynebacterium equi was isolated. He experimented with organic solvents and microorganisms including Corynebacterium species for several years. Computed tomography of his pulmonary lesions revealed that these nodules were related to the bronchial tree. Histologically, the lesions were compatible with nonspecific inflammatory changes. The clinician must suspect the pulmonary infections with Corynebacterium species even if the patient has no underlying disease.

Actinomycetales Infections↗

[Selection of a prosthetic valve for mitral valve replacement].

The early and the late results of mitral valve replacement were retrospectively evaluated to delineate the concept of selection of the prosthetic valve for the mitral position. The mitral valve was replaced with porcine bioprosthesis (P-B) in 102 patients and with St. Jude Medical prosthesis (SJM) in 341 patients between 1975 and 1987. Operative mortality was 5.3% for the SJM and 8.8% for the P-B group (N.S.). Cumulative duration of follow up was 1479.8 patient-years for the SJM and 888.9 patient-years for the P-B group. Actuarial survival rate was 90% for the SJM at 9 years and 81%, 76% for the P-B group at 10 and 13 years (N.S.). Freedom from valve-related death was 94% for the SJM at 9 years and 94% for the P-B at 13 years (N.S.). Thrombo-embolic complications occurred at an incidence of 0.47%/patient-years (p-y) for the SJM and 0.67%/p-y for the P-B group (N.S.). Freedom from prosthetic valve dysfunction due to primary tissue failure (PTE) lowered rapidly after the seventh postoperative year from 88% to 35% in the P-B group. Prosthetic valve dysfunction free rate was significantly lower in the P-B group compared with the SJM between the seventh post operative year and ninth postoperative year (p less than 0.01). From this analysis, we believe that the SJM prosthesis is suitable cardiac valve prosthesis to the mitral position.

Adolescent↗

[Surgical treatment of massive pulmonary embolism--the time of the operation and its effectiveness].

The records of 6 patients undergoing pulmonary embolectomy for massive pulmonary embolism (MPE) at Kurume University Hospital during 17 years were reviewed to determine the management of surgery. The patients consisted of 2 men and 4 women. The patients' ages ranged from 29 to 68 years (mean age, 49.3 years). The records showed that one patient died of brain death after operation and the others survived. All the patients complained of chest pain, anterior chest discomfort and dyspnea. Sudden syncope was observed in 2 patients. Artificial mechanical ventilation was performed preoperatively on 3 patients. Right ventricular load was demonstrated on electrocardiograms and ultrasonograms. Pulmonary angiograms were attempted on two patients and one of them had cardiac arrest during this examination. MPE was suspected by perfusion defect of 50% to 80% of pulmonary vasculature demonstrated on lung perfusion scintigram in 4 patients. Open pulmonary embolectomy with cardiopulmonary bypass (CPB) was performed on all patients using crystalloid cardioplegia and topical cooling. Intraoperative pulmonary angiograms were performed in 4 patients to prevent residual thromboemboli. Since most thromboemboli originate below the level of the vena cava, acute double ligation of the vena cava just below the renal vein was performed to control recurrent embolism. Oral anticoagulant, warfarin, was administered for 3 months after embolectomy as prophylaxis against postoperative recurrent embolism. It is our opinion that an aggressive attitude toward pulmonary embolectomy on CPB is necessary to save lives of MPE patients. This surgical procedure is very easy and safe.

Adult↗

[Surgical treatment of supravalvular aortic stenosis].

Five surgically treated cases of supravalvular aortic stenosis were reported. Preoperative cardiac catheterization revealed marked left ventricular-aortic pressure gradient ranged from 20 to 180 mmHg (median, 80.2 mmHg) and retrograde aortogram showed localized (hourglass type) supravalvular aortic stenosis in all cases. A traditional diamond shaped patch aortoplasty was used to relieve supravalvular aortic stenosis in 1 case and an extended aortoplasty was used in last 4 cases. Pressure gradients were almost disappeared postoperatively with good surgical result. The extended aortoplasty is considered to be more reasonable than the traditional aortoplasty in relieving constriction symmetrically and restoring normal relationship of the aortic valve cusps and coronary ostia. The operative indication and selection of the operative procedures for supravalvular aortic stenosis were briefly discussed.

Adolescent↗

Enhancement of colony-forming activity of granulocyte-macrophage colony-stimulating factor by monocytes in vitro.

Human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) stimulated granulocyte-macrophage (GM) colony formation from human marrow mononuclear cells (MMCs) in a dose-dependent manner in methylcellulose culture. When phagocytes were depleted from MMCs, GM colony formation from the phagocyte-depleted (PD) MMCs by hrGM-CSF markedly decreased. Experiments in which PD-MMCs were cultured with hrGM-CSF and adherent cells showed that 94% (on day 7 and day 14) of the colonies from PD-MMCs were dependent on the presence of adherent cells. In contrast, the ability of granulocyte colony-stimulating factor (G-CSF) to form colonies was not affected by phagocyte depletion. To check for the presence or absence of progenitors that could form GM colonies in direct response to hrGM-CSF, single-cell culture of hematopoietic progenitor cell surface antigen (My-10)-positive PD-MMCs was carried out using a flow cytometer and an Autoclone System. In duplicate experiments, 0.7% and 3.5% (day 7) or 3.6% and 3.9% (day 14) of My-10-positive PD-MMCs formed GM colonies in response to hrGM-CSF and 5.1% and 6.0% (day 7) of My-10-positive PD-MMCs formed GM colonies in response to G-CSF. This was clear evidence for the presence of progenitors directly responding to hrGM-CSF. Also observed was a synergistic effect on GM colony formation in which more My-10-positive PD-MMCs stimulated by hrGM-CSF and G-CSF could form GM colonies than the sum of those stimulated by each separately. This enhancing effect of colony-forming activity of hrGM-CSF by adherent cells and the single cell culture experiment were reproduced in serum-free culture system.

Antigens, Surface↗

Enhanced tumor growth and metastatic spread of an MH134 variant lacking a part of the MM antigen: a possible role of antibody-dependent cellular cytotoxicity in control of tumor growth and metastases.

The role of antibody-dependent cellular cytotoxicity (ADCC) in host defense against tumor growth and metastasis was investigated with MH134, an MM antigen-positive murine hepatoma, and MH134-M, a variant with enhanced tumorigenesis and metastasis, in syngeneic C3H/HeN mice. When inoculated subcutaneously into C3H/HeN mice, MH134-M tumors grew more rapidly than did MH134 tumors and consistently metastasized to the draining lymph nodes, whereas MH134 tumors did not. Also, MH134-M exhibited a significantly greater lung colonization potential than did MH134, when inoculated intravenously into C3H/HeN mice. In BALB/c nu/nu mice, however, solid MH134 tumors grew and metastasized to the same extent as MH134-M, indicating that there is no significant intrinsic difference between these two tumor lines in proliferative or metastatic capacity. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting, performed after SDS-PAGE analysis of cellular extracts with a monoclonal antibody (MAb) that recognizes a part of the MM-antigen, revealed that the cells of MH134-M lack at least a part of the MM antigen. Sera of C3H/HeN mice bearing solid MH134 tumors were found to contain anti-MM-antigen antibodies, when tested by immunoblotting of SDS-PAGE-developed materials. Cytotoxicity testing in which thioglycollate-induced peritoneal macrophages were used as effector cells revealed that antibodies present in sera strongly induced ADCC to MH134 but not to MH134-M. On the other hand, sera of MH134-M tumor-bearing C3H/HeN mice neither contained anti-MM-antigen antibodies nor induced ADCC to MH134 or MH134-M tumor cells. Intravenous injection of carrageenan into C3H/HeN mice bearing solid MH134 tumors significantly enhanced tumor growth, whereas the growth of subcutaneously injected MH134-M tumors was not influenced by this treatment. These results suggest that the enhanced tumorigenesis and metastasis of the MH134-M line in C3H/HeN mice are based, at least in part, on significant loss of the MM antigen and the resultant inability to induce ADCC-triggering antibody production during tumor growth.

Animals↗

Macrophage-mediated N-nitrosation of thioproline and proline.

Thioproline (Thiazolidine-4-carboxylic acid) and proline were nitrosated by stimulated mouse macrophages in vitro. A macrophage cell line (J774.1, 1.0 x 10(6)/well, 1 ml) was incubated with Escherichia coli lipopolysaccharide, interferon-gamma and thioproline (5 mM) or proline (5 mM). After 72 hr incubation at 37 degrees C, 4 microM N-nitrosothioproline was produced. The amount of N-nitrosoproline was much lower than that of N-nitrosothioproline. Thioproline and proline inhibited the formation of carcinogenic N-nitrosomorpholine. N-nitrosothioproline and N-nitrosoproline are found as major N-nitroso compounds in human urine. Macrophage mediated N-nitrosation may contribute to the formation of these N-nitrosamino acids in the human body.

Animals↗

Establishment of ascitic tumor of human pre-B acute lymphoblastic leukemia in nonconditioned nude mice.

In the present study, an ascitic tumor of NALM-6, a human pre-B acute lymphoblastic leukemia cell line, was established in nude mice which had not been subjected to any preconditioning such as X-irradiation and/or splenectomy. The ascitic tumor was also established in X-irradiated mice. Under various conditions, the tumor transplantability was 100%. NALM-6 cells were initially inoculated i.p. into 8-day-old nude mice after being admixed with X-irradiated HT-1080, a human fibrosarcoma cell line. Then, the in vivo grown (for 10 wk) tumor cells were serially transplanted i.p. into X-irradiated adult (10 to 12 wk old) nude mice. After the serial passages, we succeeded in establishing a highly transplantable NALM-6 ascitic tumor in nonpreconditioned as well as X-irradiated nude mice without the addition of HT-1080 cells. The ascitic tumor cells do not lose transplantability after in vitro culture for 20 days. Cellular radioimmunoassay and fluorescence-activated cell sorter analysis indicated that the in vivo established NALM-6 tumor cells retained the antigenic phenotype of the parental NALM-6 cells. Titration experiments revealed a reciprocal relationship between survival time of the mice and the number of tumor cells inoculated. When appropriate numbers of tumor cells (e.g., 4 x 10(6) cells) were used for the inoculation, survival times of individual mice fell within a relatively narrow range; this narrow range will facilitate the experiments where the present tumor model is used for evaluating the in vivo efficacy of antitumor agents. The present ascitic tumor models, particularly the one established in nonpreconditioned nude mice, will be useful for evaluating the in vivo efficacy of anti-human leukemia agents as well as for studying the in vivo biological behavior of the transplanted leukemia cells.

Animals↗

Decreased expression of interleukin-2 binding molecules (p70/75) in T cells from patients with systemic lupus erythematosus.

Using radiolabeled interleukin-2 (IL-2), affinity cross-linking and binding assays revealed that the expression of intermediate-affinity IL-2 binding molecules (p70/75) on freshly prepared T cells from patients with systemic lupus erythematosus (SLE) was significantly decreased in comparison with that in normal subjects. The proliferative response of T cells to high doses of IL-2 was also reduced in patients with SLE. The decreased expression of p70/75 reflects the hyporesponsiveness to IL-2 of T cells in patients with SLE.

Adult↗

Axonal tracing of autonomic nerve fibers to the superficial temporal artery in the rat.

The origin of nerve fibers to the superficial temporal artery of the rat was studied by retrograde tracing with the fluorescent dye True Blue (TB). Application of TB to the rat superficial temporal artery labeled perikarya in the superior cervical ganglion, the otic ganglion, the sphenopalatine ganglion, the jugular-nodose ganglionic complex, and the trigeminal ganglion. The labeled perikarya were located in ipsilateral ganglia; a few neuronal somata were, in addition, seen in contralateral ganglia. Judging from the number of labeled nerve cell bodies the majority of fibers contributing to the perivascular innervation originate from the superior cervical, sphenopalatine and trigeminal ganglia. A moderate labeling was seen in the otic ganglion, whereas only few perikarya were labeled in the jugular-nodose ganglionic complex. Furthermore, TB-labeled perikarya were examined for the presence of neuropeptides. In the superior cervical ganglion, all TB-labeled nerve cell bodies contained neuropeptide Y. In the sphenopalatine and otic ganglia, the majority of the labeled perikarya were endowed with vasoactive intestinal polypeptide. In the trigeminal ganglion, the majority of the TB-labeled nerve cell bodies displayed calcitonin gene-related peptide, while a small population of the TB-labeled neuronal elements contained, in addition, substance P. In conclusion, these findings indicate that the majority of peptide-containing nerve fibers to the superficial temporal artery originate in ipsilateral cranial ganglia; a few fibers, however, may originate in contralateral ganglia.

Animals↗