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Biomedical subjects

T Otsuka

Publications and source records attributed to T Otsuka.

At least 19 recordsLinked to original sources

Long-term survival of human myeloid progenitor cells induced by a mouse bone marrow stromal cell line.

Mouse endothelial-adipocyte cell line (14F1.1), which induces proliferation of mouse stem cells in culture, is also capable of supporting long-term survival in culture of human myeloid progenitor cells; colony forming unit-granulocyte/macrophage (CFU-GM) was recovered from cultures incubated with the 14F1.1 cell line after over a month of incubation. The CFU-GM population increased beyond the input number, whereas, in control cultures initiated without stromal cells, the number of progenitors gradually declined. Addition of a relatively low concentration of human colony-stimulating factors (CSFs) into the cultures promoted the formation of "cobblestone areas," where mouse stroma and human hemopoietic cells closely interacted. 14F1.1 supernatant alone did not support the survival of human CFU-GM but synergized with the function of human granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate adherent macrophage proliferation.

Animals

Use of a synthetic protease inhibitor for the treatment of L-asparaginase-induced acute pancreatitis complicated by disseminated intravascular coagulation.

In two patients receiving L-asparaginase therapy, severe acute pancreatitis complicated by disseminated intravascular coagulation (DIC) developed. In both cases it was successfully treated with continuous infusion of a synthetic protease inhibitor, nafamostat mesilate. In this report, we briefly discuss the clinical efficacy of the synthetic protease inhibitor in treating such cases.

Acute Disease

Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions.

Levels of serum granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with various leukocyte disorders were estimated by enzyme-linked immunosorbent assay (ELISA). Some cases of acute myelogenous leukemia and aplastic anemia showed elevated serum levels of G-CSF and/or GM-CSF, whereas almost all of 23 healthy controls showed G-CSF and GM-CSF levels lower than 100 pg/ml. High levels of both types of CSF were noted in patients with granulocytosis due to infection. These levels became lower after resolution of the infection. Daily changes in serum CSF levels were also examined in a patient with autoimmune neutropenia, and it was found that the peripheral neutrophilic granulocyte count changed almost in parallel with the serum G-CSF level but not with GM-CSF, following the pattern with a delay of about 4-5 h, suggesting the possibility that G-CSF mainly regulates peripheral neutrophil circulation.

Adult

Structure-function studies of HIV-1: influence of long terminal repeat U3 region sequences on virus production.

DNA sequence analyses of several human immunodeficiency virus (HIV) isolates revealed extensive genetic diversity in the env gene and, to a lesser extent, in other regions of the viral genome, including the long terminal repeat (LTR) sequences. Since the LTRs contain elements responsible for the control of transcription, the difference in the LTR region may play a crucial role in the overall replication rate of HIV. To evaluate the role of the LTR, we have constructed a number of infectious hybrid HIV molecular clones containing LTRs from different proviral DNAs linked to the body of the viral genome, and analyzed them in a transient expression system. Both parental and hybrid proviral DNAs were transfected into human rhabdomyosarcoma cells for monitoring virus production. Proviral DNA designate pZ6 (HIVZr6) showed a high level of virus in the medium of the transfected culture in comparison to the pHXB2 (HIVHTLV-III) and pARV (HIVSF-2) DNAs. Hybrid proviral DNAs containing viral genes from pZ6, linked to LTR U3 sequences of pHXB2 and pARV at the 5' end, showed virus production similar to the levels observed with pZ6. These results indicate that the extent of virus production does not correlate with the LTR U3 sequences, and may involve other regions of the viral genome.

Base Sequence

Case report: nifedipine-rifampicin interaction attenuates the effect on blood pressure in a patient with essential hypertension.

A 72-year-old woman with 5-year history of essential hypertension developed peritoneal tuberculosis. The patient's hypertension, which had been well-controlled by long-acting nifedipine, deteriorated after the administration of rifampicin, an antitubercular agent. During use of nifedipine and rifampicin, both the peak plasma concentration and the area under the curve of nifedipine decreased markedly to about 40% of those without rifampicin. The findings suggest that rifampicin may increase the elimination of nifedipine, presumably by induction of its hepatic metabolism. Nisoldipine, another calcium antagonist, also failed to lower the patient's blood pressure, when given in combination with rifampicin. Taken together, these findings indicate that more caution should be urged when calcium antagonist is prescribed along with rifampicin.

Adrenergic alpha-Antagonists

[Epidemiological study of Staphylococcus aureus isolated from the Japanese National University and Medical College Hospitals with coagulase typing, and production of enterotoxins and toxic shock syndrome toxin-1].

Coagulase typing, staphylococcus enterotoxins (SE) A to E or toxic shock syndrome toxin-1 (TSST = 1) production, and susceptibility to Oxacillin (MPIPC) were examined in 430 strains of S. aureus, which were isolated from clinical specimen of 43 Japanese National University or Medical College Hospitals during the one month period of August in 1990. Methicillin-resistant Staphylococcus aureus (MRSA): more than 4 mmg/ml of minimum inhibitory concentration for MPIPC in Mueller-Hinton broth containing 2% NaCl, occupied 58.6% of all the S. aureus, and more than 60% of the strains from admitted patients in all the areas of Japan except Hokkaidoh. Coagulase type II, SEC and TSST-1 producing strains were most frequently detected, 34.5% of all the MRSA. This kind of strain was distributed mainly in the eastern part of the Honshyu island, and showed high percentage especially in the Tohhoku and the Chyubu area. The second most frequent kind of MRSA was coagulase type II, no SE nor TSST-1 producing one, 15.4%, which was distributed mainly in the western part of Japan. Coagulase type IV, SEA producing MRSA strains and Coagulase type II, SEA, SEC and TSST-1 producing strains were detected in relatively high incidence, 10.3% and 8.7% respectively. Coagulase type III, no SE nor TSST-1 producing MRSAs demonstrated characteristic distribution, and were detected only in the western part of Japan, presenting the highest incidence in the Shikoku Island.

Bacterial Toxins

Analysis of the viral determinants underlying replication kinetics and cellular tropism of human immunodeficiency virus.

Human immunodeficiency viruses (HIVs) isolated from infected individuals show genetic and biological diversity. To delineate the genetic determinants underlying specific biological characteristics such as rate of replication and cellular tropism, generation of hybrid HIV using viruses which exhibit distinct biological feature is essential. We have used three different infectious HIV proviral DNAs, designated pZ6, pHXB2 and pARV, derived from HIVZr6, HIVHTLV-IIIB and HIVSF-2 strains, respectively, to construct hybrid HIV. Proviral DNAs differed in their ability to direct the synthesis of viral particles upon transfection into cells and the viruses derived from the molecular clones exhibited different cellular tropism. Three different methods were utilized to generate hybrid HIV, including construction of hybrid proviral DNA using molecular techniques, intracellular ligation of viral DNA fragments and the homologous recombination approach. The chimeric proviral DNAs with exchanges involving only the long terminal repeat (LTR) region indicated that LTR does not exert influence on the overall level of virus production despite extensive differences in the U3 region of the LTR. Regarding the cellular tropism of HIV, the virus derived from pHXB2 productively infected CEMx174 cells. On the other hand, pARV-derived virus did not show productive infection of CEMx174 cells. The hybrid HIV containing the 3'-end of the genome from pARV and the 5'-end of the genome from pHXB2 was effective in infecting CEMx174 cells. However, the converse hybrid containing the 5'-pARV and the 3'-pHXB2 was not effective in infecting CEMx174 cells. These results suggest that differences in the genes outside of env and nef may play a role in the ability of virus to infect a certain cell type.

Base Sequence

A new angiogenesis inhibitor, FR-111142.

FR-111142 is a new angiogenesis inhibitor produced by a fungus Scolecobasidium arenarium F-2015. FR-111142 inhibited endothelial cell proliferation in vitro and angiogenesis in the growing chick chorioallantoic membrane model in vivo. Further, FR-111142 also suppressed the solid tumor growth in mice.

Allantois

Epstein-Barr virus BCRF1 gene product (viral interleukin 10) inhibits superoxide anion production by human monocytes.

Due to its similar biological activities to interleukin 10 (IL-10), Epstein-Barr virus (EBV) BCRF1 gene product (viral IL-10: vIL-10) has recently been recognized as an analogue of authentic IL-10. Preincubation of human monocytes with vIL-10, like human IL-10, induced smaller amounts of interferon-gamma (IFN-gamma) mRNA in activated human peripheral blood mononuclear cells (PBMNCs) than nonpreincubation, indicating that vIL-10 acts principally on monocytes. Since the activation of monocytes and their generation of oxidative products are regulated by various cytokines, we examined the effects of vIL-10 on superoxide anion (O2-) production by human PBMNCs and monocytes. Not only PBMNCs but also monocytes preincubated with vIL-10 showed a smaller production of O2-. Inhibition was achieved in a dose-dependent fashion and increased gradually after incubation with vIL-10. Additions of IFN-gamma, macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), which prime monocyte activation and induce O2- production, were also affected by the reciprocal effect of vIL-10. Thus, vIL-10 production by EBV-infected cells may be involved in the development of EBV-related disorders.

Base Sequence

[The role of bronchial responsiveness to leukotrienes in antigen-induced immediate and late asthmatic response].

In order to clarify the role of leukotriene in the antigen-induced asthmatic response, we carried out mite-antigen, leukotriene D4 (LTD4) and histamine inhalation tests in 21 mite-sensitive atopic asthma patients, and investigated the relationship between the bronchial responsiveness to mite (PD20-Mite) and that to LTD4 and histamine (PD20-LTD4, PD20-Hist). We then compared PD20-LTD4 and PD20-Hist between the groups with and without late asthmatic response (LAR), and investigated the relationship between the peak percentage fall of FEV1.0 in LAR (magnitude of LAR) and PD20-LTD4 and PD20-Hist. There were significant correlations between PD20-LTD4 and PD20-Mite (r = 0.590, p < 0.01), and between PD20-Hist and PD20-Mite (r = 0.669, p < 0.001). The bronchial responsiveness to LTD4 and histamine was significantly higher in the group with LAR. In addition, PD20-LTD4 showed a significant negative correlation with the magnitude of LAR (r = 0.724, p < 0.001). Furthermore we analyzed the relationship between PD20-LTD and the ratio of the magnitude of LAR to that of IAR (immediate asthmatic response), because there was a significant correlation between the magnitude of IAR and that of LAR (r = 0.842, p < 0.001) in 16 asthmatic patients with dual asthmatic response, and found that the correlation coefficient was also very high (r = -0.836, p < 0.001). These results suggest an important role of leukotriene in the antigen-induced asthmatic response.

Adolescent

Antitumor effect of thermosensitive CDDP-liposomes on human osteosarcoma cells in culture.

We have administered cis-diamminedichloroplatinum (II) (CDDP) containing thermosensitive liposome and simultaneous hyperthermia into human osteosarcoma cells (OST) and studied the antitumor effects. Experiments were conducted under the following three different culture conditions as follows, (1) drug treatment alone, (2) hyperthermia after drug treatment, and (3) simultaneous hyperthermia and drug treatment. Antitumor effects were estimated by inhibition of DNA synthesis and decrease in cell growth rates. The antitumor action of simultaneous hyperthermia and drug treatments was the most dominant and synergistic among three experimental conditions. Accumulation of cellular platinum from thermosensitive CDDP-liposomes was markedly enhanced by hyperthermia. Flow cytometric analysis of the cell cycle indicated that CDDP-liposomes only under the simultaneous application of hyperthermia released free CDDP, and evoked cell accumulation in S and G 2/M phase. The results suggested that thermosensitive CDDP-liposomes were not taken up into cells by endocytosis, and released free CDDP into culture media under hyperthermia at 42 degrees C. From these, we have concluded that administration of thermosensitive CDDP-liposomes and simultaneous local hyperthermia could be a promising method for the treatment of osteosarcoma especially in the extremities.

Cisplatin

[Clinical study of intracranial pressure and auditory brain stem response in the cases of diffuse axonal injury].

The course of intracranial pressure (ICP) and the finding of auditory brain stem response (ABR) was discussed in the cases diagnosed as diffuse axonal injury (DAI) established by Gennarelli. ICP was measured in twenty-six cases which were divided into three groups according to the course of ICP: Group (1), in which ICP remained below 20 mmHg (group I, 9 cases). Group (2), in which ICP rose above 20 mmHg but was controlled by therapy (group II, 8 cases). Group (3), in which ICP rose above 20 mmHg and could not be controlled by any therapies (group III, 9 cases). Glasgow outcome scale 3 months after the injury in the cases of group I and II was severe disability (SD) and/or persistent vegetative state (PVS), but all of the cases in group III died. The findings of serial ABR were divided into 3 groups. These were group A (2 cases) which showed normal record, group B (5 cases) which showed elongation of latencies between the first and fifth waves, and group C (5 cases) in which there was no response in ABR. GOS in group A or B was SD and/or PVS, but all of the cases in group C were shown to be dead in GOS. Our studies suggest that the level of ICP in DAI is rather higher than that published in previous reports, and the continuous measurements of ICP and serial records of ABR are useful for evaluating the outcome of DAI.

Adolescent

[Clinical experience with recently produced devices for use in spinal surgery].

The authors reported their clinical experience with devices, which have been recently introduced for spinal surgery. The main roles of such devices are to correct malalignment of the spine and stabilize the spinal instability. Although Harrington's device has been widely used since 1962, its use is gradually decreasing due to its having several weak points, such as its low resistance to distorting forces and its imperfect ability to correct malalignment of the spine. In the present manuscript, the authors describe clinical experience with three kinds of spinal devices. They are Steffee's transpedicular screw for 5 cases of lumbar spondylolisthesis, Roosen-Trauschel compression clamp for 2 cases of atlanto-axial dislocation and Kaneda's device for one case of metastatic T-11 tumor. Good fixation was obtained in 4 cases using Steffee's devices. The injury of the nerve root is one of the most serious disadvantages in this device. Although Roosen-Trauschel compression clamp needs improvement in some aspect, it was able to bring about good stabilization without using sublaminar wiring, which may be a dangerous procedure in the cervical region. Kaneda's device seemed to be useful for the thoracolumbar lesion. Although it needs a relatively radical approach, such as thoracotomy, Kaneda's device brought about good stabilization and corrected the kyphosis. The devices, which are described in the present manuscript, will probably play important roles in spinal surgery in the future.

Adult

[Surgical treatment of pulmonary aspergilloma--with modified conservative operation].

During the past 10 years 26 patients were operated on for pulmonary aspergilloma (20 males and six females, mean age of 55.8 years). Lung resections were performed on 13 cases (Group 1). Conservative operations were performed on the remaining cases, including one bilateral operation case (Group 2). New paragraph. The operative techniques in Group 1 were: lobectomy 11 cases of lobectomy, one case of partial resection; and one case of segmental resection. The operative techniques for Group 2 were; five cases of thoracoplasty and cavernoplasty; three cases of thoracoplasty plus cavernoplasty and muscle flap; three cases of thoracoplasty and muscle flap; one case of thoracoplasty and air-plombage; and two cases of cavernoplasty. A second operation was required in four and seven cases in Groups 1 and 2, respectively, and a third operation in two and four cases respectively. The conservative technique was used in all of additional operations required. The mean operation time and amount of blood loss were 262 min and 1,943 ml for Group 1 and 170 min and 918 ml for Group 2-being shorter and lesser for Group 2. Both the operation time and blood loss were reduced during the second and third operations. Reduction of %VC after the first operation was also less remarkable for Group 2 (-9.6%, No = 9). The advantage of using a conservative technique is that successful results can be expected without insult to the hilus and mediastinal surface in cases with compromised pulmonary functions, or in those cases which pneumonectomy or resection is difficult because of the risk of massive bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of nonweight bearing on the hip.

To evaluate the effects of nonweight bearing on joints (weight-free range, five to 92 months), bilateral hips of 20 patients with amputated lower limbs or nonunion of the femur were studied clinically and roentgenographically. The nonweight-bearing side showed a roentgenographic narrowing of the joint space of 10% or more as compared with the weight-bearing side in one half of the patients, and marked narrowing of 30% or more was observed in six patients. The degree of narrowing correlated with the degree of osteopenia expressed as a femur score. The joint space narrowing was notable in those who had onset of the nonweight-bearing state at ages younger than 20 years. None of the patients who showed narrowing of the joint space had pain or motor restriction of the hip. These findings suggest that a nonweight-bearing state of normally weight-bearing joints causes deranged homeostasis of articular cartilage, which leads to its thinning.

Adolescent

[Magnetic resonance imaging in diffuse brain injury].

Forty cases diagnosed as diffuse brain injury (DBI) were studied by magnetic resonance imaging (MRI) performed within 3 days after injury. These cases were divided into two groups, which were the concussion group and diffuse axonal injury (DAI) group established by Gennarelli. There were no findings on computerized tomography (CT) in the concussion group except for two cases which had a brain edema or subarachnoid hemorrhage. But on MRI, high intensity areas on T2 weighted imaging were demonstrated in the cerebral white matter in this group. Many lesions in this group were thought to be edemas of the cerebral white matter, because of the fact that, on serial MRI, they were isointense. In mild types of DAI, the lesions on MRI were located only in the cerebral white matter, whereas, in the severe types of DAI, lesions were located in the basal ganglia, the corpus callosum, the dorsal part of the brain stem as well as in the cerebral white matter. As for CT findings, parenchymal lesions were not visualized especially in mild DAI. Our results suggested that the lesions in cerebral concussion were edemas in cerebral white matter. In mild DAI they were non-hemorrhagic contusion; and in severe DAI they were hemorrhagic contusions in the cerebral white matter, the basal ganglia, the corpus callosum or the dorsal part of the brain stem.

Adolescent