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Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 919 records · Page 51Linked to original sources
PubMed1990

Efficient transformation of chicken embryo fibroblasts by c-Jun requires structural modification in coding and noncoding sequences.

To assess the transforming capability of the c-Jun protein, we introduced the chicken c-jun proto-oncogene into a replication competent avian retroviral expression vector (RCAS). Viral Jun efficiently transformed chicken embryo fibroblasts (CEFs) when expressed from this vector. Overexpression of c-Jun leads to transformation of CEFs with an efficiency that is 15- to 25-fold less than that seen for v-Jun, suggesting that v-Jun contains structural features that increase its oncogenic potential relative to c-Jun. There are four structural differences between v-Jun and c-Jun. To determine the relative contribution that each of these structural differences between v-Jun and c-Jun has on oncogenic activity, several deletion and substitution mutants were constructed. Each of these mutants was expressed in CEF and assayed for transformation by focus formation. Analysis of the results reveals that deletion of a region of 27 amino acids near the amino terminus of c-Jun and deletion of 3'-untranslated sequences are critical in activating the full oncogenic potential of Jun.

Amino Acid Sequence↗
PubMed1990

Cytocidal activity of a synthetic isoprenoid, N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine, and its potentiation of antitumor drugs against multidrug-resistant and sensitive cells in vitro.

A synthetic isoprenoid, N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine (SDB-ethylenediamine), inhibited the colony formation of multidrug-resistant mutant cell lines derived from Chinese hamster V79 (V79/ADM) and human hepatoma PLC/PRF/5 (PLC/COL) cells to a greater extent than that of the parental cells. When combined with other clinically useful antitumor agents, it potentiated the cytotoxic activity of almost all kinds of drugs tested including adriamycin (ADM), actinomycin D, vincristine, cytosine arabinoside, and 5-fluorouracil (5-FU), and the potentiation ratios were higher against V79/ADM cells than against V79/S cells. Among the antitumor agents tested, the activities of bleomycin-group antibiotics were more strongly enhanced by SDB-ethylenediamine and the potentiation was higher in the parental cells than in V79/ADM cells. SDB-ethylenediamine enhanced the uptake of ADM and daunorubicin into V79/ADM and its parental cells, but it did not increase the uptake of 5-FU or peplomycin, indicating that different mechanisms operate for potentiation in the cases of the latter drugs, i.e., not simply an increase of intracellular drug uptake. Two fragments of SDB-ethylenediamine, solanesol (polyprenoid moiety) and the diamine component (verapamil-like moiety), showed neither cytotoxic activity nor potentiator activity, even if they were mixed together, indicating that the steric conformation of intact SDB-ethylenediamine molecule is important for these two activities.

Animals↗
PubMed1990

Changes of ADP-ribosylation of GTP-binding protein by pertussis toxin in human platelets during long-term treatment of manic depression with lithium carbonate.

1. The study was done to determine whether long-term treatment with lithium carbonate affected the guanosine triphosphate (GTP)-binding protein in platelet membranes from patients with manic depression. 2. It was found that adenosine diphosphate (ADP)-ribosylation of inhibitory G-proteins (40-41 kDa) by pertussis toxin, islet-activating protein in the cell membranes increased about 45% when long-term treatment with lithium carbonate was stopped. 3. These results support the idea that one site for the therapeutic effects of lithium ions is G-proteins.

Adenosine Diphosphate↗
PubMed1990

A case of slowly progressive aphasia without generalized dementia in a Japanese patient.

A Japanese patient with a 4-year history of slowly progressive aphasia without generalized dementia is described. From 1985 on, this 61-yr-old right-handed dentist showed insidiously progressive deterioration in his speech and auditory comprehension, but has no memory disturbance, disorientation of space, time or persons, acalculia or other impairments in his behavior. His personality changes are unremarkable. He still treats patients at his clinic. General physical and neurological examinations were normal. CT and MRI (1.5T) scans showed widening of the left sylvian fissure and lateral ventricle without any vascular lesions. A PET scan demonstrated focal hypometabolism restricted to the left temporal lobe. The clinical course and picture of our patient corresponds, well to those of slowly progressive aphasia without generalized dementia, described by Mesulam.

Aphasia↗
PubMed1990

Changes in adhesion efficiency and vimentin distribution of fibroblasts from familial Alzheimer's disease patients.

Cultured fibroblasts from familial Alzheimer's disease patients were characterized. Familial Alzheimer fibroblasts showed the same appearance by phase microscopy and the same growth rate with the control fibroblasts cultured from the age-matched healthy control subjects. Fibroblasts cultured from familial Alzheimer's disease patients showed decreased efficiency in adhesion to substrata in limited periods. While 80% of the control fibroblasts finished adhesion within 30 minutes incubation, only 30% of Alzheimer fibroblasts completed adhesion within the same period. When fibroblasts from familial Alzheimer's disease were kept under serum-free media more than ten days, they showed a unique aberration of vimentin fiber distribution, while other cytoskeletal fibers were remained intact. It is indicated that fibroblasts cultured from patients with familial Alzheimer's disease can be used to study pathological processes which affect the cytoskeletal organization in the fibroblasts as well as in the cells of the central nervous system.

Alzheimer Disease↗
PubMed1990

Calcium-dependent chloride current in neurones of the rabbit pelvic parasympathetic ganglia.

1. Voltage-clamp recordings were made from neurones in rabbit vesical pelvic ganglia by using single microelectrodes filled with 2 M-caesium chloride. Neurones were superfused with Krebs solution containing 300 nM-tetrodotoxin and 50 mM-tetraethylammonium. 2. Depolarizing voltage jumps activated inward currents followed by slowly decaying inward tail currents at -30 to +30 mV, which were accompanied by a large increase in membrane conductance. Both the inward current and tail current were blocked by cobalt (2 mM) or in a Krebs solution containing zero calcium and 12 mM-magnesium. 3. Substitution of barium for calcium enhanced the inward current, while it strongly reduced the tail current. Strontium substitution still exhibited both the inward current and the tail current. 4. Lowering external chloride activity increased the tail current amplitudes without affecting an initial calcium current. The reversal potentials of the tail current, measured using a twin-pulse protocol, were -18 +/- 5 mV (mean +/- S.E.M., n = 8) and +5 +/- 3 mV (n = 5) in Krebs solution and low-chloride (62 mM) solution, respectively, suggesting a calcium-dependent chloride current. 5. Stilbene derivatives, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS, 0.01-1 mM) and 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS, 0.01-1 mM), reversibly and concentration dependently depressed the tail current without affecting the calcium current. 6. Transient (T) and sustained (N and L) types of calcium current were likely to co-exist in neurones of the rabbit pelvic ganglia. Calcium-dependent chloride current was activated by N- and L-type calcium currents but not by T-type current. 7. Activation of the tail current at 0 to +20 mV was described by a single-exponential function. The tail current decayed exponentially at a holding membrane potential of -70 mV. Tail decay time constants were dependent on voltage and duration of the step command. 8. Substantial activation of the calcium-dependent chloride conductance could occur during a post-tetanic after-potential when pelvic ganglia neurones fired action potentials repetitively.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1990

[Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, and antibiotics in severe and/or refractory infections in pediatrics].

A newly developed human immunoglobulin liquid preparation for intravenous injection was studied for efficacy, safety, and usefulness in treating severe and/or refractory infections in children receiving antibiotic treatment. It is suggested that C-425 is a useful intravenous preparation of human immunoglobulin for the treatment of severe and/or refractory infections in pediatrics. C-425 was administered to 87 inpatients with severe and/or refractory infections at 23 institutions nationwide. The Committee selected 61 cases for the present analysis. Physicians in charge judged clinical efficacy of C-425 to be "excellent" in 23 cases (40.4%), "good" in 24 (42.1%), "fair" in 7 (12.3%), "poor" in 3 (5.3%), and "unknown" in 4. The efficacy rate was calculated at 82.5% when the "excellent" and "good" cases were combined, and 94.7% when the "fair" cases were also included. According to the Committee's judgement, the efficacy of C-425 was "excellent" in 27 cases (44.3%), "good" in 18 (29.5%), "fair" in 7 (11.5%), and "poor" in 9 (14.8%). The efficacy rate was 73.8% when the "excellent" and "good" cases were combined. The rate increased to 85.2% when the "fair" cases were added. Organisms were identified in 31 cases, and the time course was followed in 19 instances. Organisms were eliminated in 12 cases (63.2%), decreased in number in 2 (10.5%), and persisted in 5 (26.3%). Eradication rate was 63.2%. One of the 87 patients died of fulminant hepatitis 2 days after the end of the treatment. The remaining 86 cases were analyzed for the safety of C-425. A skin rash was observed in one case. Laboratory examination revealed increase in transaminase levels in a total of 8 cases; both in GOT and GPT in 5, in GOT alone in 2, and in GPT alone in 1. These findings were not clinically important.

Anemia, Aplastic↗
PubMed1990

Evaluation of the susceptibility effect on the phase images of a simple gradient echo.

The phase shifts of a simple gradient echo (fast low-angle shot) were correlated with the local change in resonance frequency due to the differences in susceptibility among tissues (susceptibility effect). Susceptibility effects were considered theoretically, and the phase shifts for spherical and cylindrical configurations were calculated. A 1.5-T magnetic resonance unit and phantoms filled with solutions of copper chloride in water were used to obtain the phase images. The phase shifts of the simple gradient echo coincided with the values calculated with use of the sum of the macroscopic magnetic field and the cavity field of Lorentz. The authors conclude that the gap of the phase shifts at interfaces of tissues is useful in the evaluation of differences in magnetic susceptibility among tissues.

Cerebral Hemorrhage↗
PubMed1990

Augmentation of mouse immune functions by dietary restriction: an investigation up to 1 year of age.

Mice fed a 40% restricted diet until 1 year of age showed a 35% drop in body weight and markedly lower weights in the central lymphoid organs such as spleen and thymus than those of unrestricted mice. In contrast, the percentage of splenic Thy 1.2+ T cells was dramatically increased by dietary restriction. Splenic Ly 1+ T cells were also increased in the restricted mice. Spleen cells of the restricted mice revealed significantly higher responses not only in macrophage (MP)-dependent responses such as concanavalin A response and mixed-lymphocyte reaction but also in MP-independent T cell responses to recombinant interleukin 2 even at 1 year of age. These results strongly suggest that dietary restriction causes an enrichment of Thy 1.2+ T cells in spleen and augments the functions of T cells in mice.

Age Factors↗
PubMed1990

Osseous hemangioma arising in the facial bone.

Hemangiomas of bone are rare tumors in the facial region. In our own case, magnetic resonance imaging showed unique linear high-signal-intensity internal components in T1-weighted images. The histological study demonstrated that adipose tissue occurring in the stroma of the tumor caused the high signal intensity in T1-weighted images. We employed a vascularized calvarial bone flap to reconstruct the malar eminence after resection of the tumor.

Aged↗
PubMed1990

Effects of sodium iodate on experimental subretinal neovascularization in the primate.

We investigated the role of the retinal pigment epithelium (RPE) in the development of subretinal neovascularization (SRN) induced by bilateral laser photocoagulation of the retinas in monkeys. RPE function was affected by a unilateral carotid injection of sodium iodate, a selective RPE toxin, before laser photocoagulation. This caused severe RPE damage in the ipsilateral eye, but did not affect the contralateral eye. After laser photocoagulation no SRN was demonstrable clinically or histopathologically in the ipsilateral eye; in contrast, active SRN showing extensive fluorescein leakage was found in the contralateral eye. These results suggest that RPE may play a role in the development of laser-induced SRN.

Animals↗
PubMed1990

Activated macrophages in experimental subretinal neovascularization.

Laser-induced subretinal neovascularization (SRN) in monkey retinas was investigated by immunohistochemical techniques to identify the presence and location of activated macrophages. Retinal lesions were examined 3, 8 and 14 days after intensive argon laser treatment, and the distribution of interleukin-1 (IL-1)-containing cells in the lesions was determined by the orthogonal reconstruction of serial sections. Macrophages were present in the subretinal space of day 3 and day 8 lesions. These IL-1-containing cells were distributed about the area of rupture of Bruch's membrane and were quite common in lesions taken 3 days following laser treatment. While still apparent, the number was decreased at 8 days, and none were found 14 days after laser treatment. The temporal and spatial distribution of IL-1-staining macrophages paralleled the development of SRN, suggesting a relationship between the presence of activated macrophages and the initiation of neovascularization in this model.

Animals↗
PubMed1990

Learning impairment and microtubule-associated protein 2 decrease in gerbils under chronic cerebral hypoperfusion.

A coiled stainless steel wire clip was made that allowed us to chronically reduce cerebral blood flow in Mongolian gerbils. After 6 weeks of reduced cerebral blood flow in 15 experimental gerbils, we evaluated their learning ability and found it to be impaired relative to that in 15 control gerbils. Eight weeks after surgery, regional cerebral blood flow in the parietal cortex measured by the hydrogen clearance method in the experimental gerbils was 73-76% of that in the control gerbils. Light microscopy showed minimal histologic changes in the brains of the experimental gerbils. Concentrations of brain proteins analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that among water-soluble brain proteins, the concentrations of cytoskeletal proteins (microtubule-associated protein 2, calspectin, and clathrin) declined in the experimental gerbils. In particular, the concentration of microtubule-associated protein 2 declined significantly. Our findings show that the reduction of cerebral blood flow via carotid stenosis impairs the learning behavior in gerbils, with an associated decrease in the concentration of microtubule-associated protein 2. We believe that Mongolian gerbils with chronically reduced cerebral blood flow are a useful animal model of chronic brain hypoperfusion.

Animals↗
PubMed1990

Newly developed myocardial imaging by using single photon emission computed tomography (SPECT).

Thallium myocardial imaging is a useful technique to evaluate myocardial perfusion and myocardial viability in ischemic heart disease. However, myocardial imaging using single photon emission computed tomography (SPECT) and gamma-emitting radiopharmaceuticals has been recently developed for more precise evaluation of myocardial infarction and ischemia. The present study evaluates animal experiments and the clinical applications of these new myocardial imaging techniques. Areas considered on 1) myocardial necrosis assessed using 111In-antimyosin, 2) myocardial fatty acid metabolism assessed using 123I-beta-methyl-iodophenyl pentadecanoic acid (BMIPP) and 3) myocardial sympathetic neural activity assessed using 123I-metaiodobenzyl guanidine (MIBG). Dual energy SPECT using these new agents and thallium gives precise characterization of the myocardial tissue in the infarcted and ischemic area.

3-Iodobenzylguanidine↗
PubMed1990

Increase in colony stimulating factor (CSF) in serum and augmentation of CSF responsiveness of lymphoid mononuclear cells by acute Trypanosoma cruzi infection in mice.

Acute infection of Trypanosoma (T.) cruzi to C3H/HeN mice caused the induction of a higher level of serum colony stimulating factor (CSF) activity to support the proliferation of mouse bone marrow cells. The CSF activity reached a maximum 2 days after the infection and declined thereafter. Spleen cells of the T. cruzi-infected mice showed higher levels of responsiveness to CSF in L929-conditioned medium, mouse recombinant GM-CSF and infected mouse sera as compared with normal mouse spleen cells. The induction of CSF-responding cells became plateau 4 days after the infection and it decreased thereafter. In concomitant with the production of CSF activity in the infected mouse sera, large granular cells bearing high intensity of Mac-2 antigen increased in the infected mouse spleen. These cells were nylon nonadherent and displayed inhibitory effect on T cell response to Con A. These findings indicate that T. cruzi infection induces augmentation of in vivo CSF production, leading to the abnormal proliferation of CSF-responding cells and that augmented production of, and responsiveness to, CSF might be one of important mechanisms responsible for the induction of immune abnormalities in T. cruzi-infected mice.

Animals↗
PubMed1990

Properties of voltage-dependent barium currents in neurons of pelvic parasympathetic ganglia of rabbit.

Properties of voltage-dependent barium current (IBa) were examined in parasympathetic neurons of the rabbit urinary bladder, in vitro. Transient low-threshold IBa was evoked by voltage jump from a holding potential (Vh) of -100 to -50 mV. Additional transient high-threshold IBa appeared at potentials more positive than -30 mV. Long-lasting high-threshold IBa was evoked at 0 to -20 mV. High-threshold currents were blocked by omega-conotoxin but not by dihydropyridines.

Animals↗
PubMed1990

[Study of cytotoxicity of recombinant interleukin-2 (rIL-2) expanded tumor infiltrating lymphocytes (TIL) in renal cell cancer].

We studied subsets and cytotoxicity of recombinant interleukin-2 (rIL-2) expanded tumor infiltrating lymphocytes (TIL) from renal cell cancer (RCC) patients. TIL were successfully expanded in 13 of 14 RCC cases using anti-CD3 during initial 48 hours of culture. Percentages of CD8 positive cells among rIL-2 expanded TIL at 1 tp 4 week(s) of culture were 56.2 +/- 15.1% (range 26.2 to 79.8%, N = 13) and not necessarily predominant over CD4 positive cells. NK and LAK activities of TIL at 3 to 6 weeks of culture were 31.6 +/- 15.8% (range 1.4 to 57.4%, N = 9) and 16.6 +/- 11.6% (range 3.8 to 35.6%, N = 6), respectively. Autologous and allogeneic RCC cytotoxicity of TIL at 3 to 4 weeks of culture were 17.9 +/- 19.7% (range 0 to 47.6%, N = 4) and 18.9 +/- 14.8% (range 0 to 47.3%, N = 12), respectively. Since there was no statistical difference between them, autologous specific cytotoxicity was not demonstrated. From these results of present study, it is unlikely that most of effector cells of rIL-2 expanded TIL in autologous RCC lysis are major histocompatibility complex restricted cytotoxic T cells. And we concluded that it is doubtful that TIL is significantly superior over LAK cells in immunotherapy of human RCC.

Carcinoma, Renal Cell↗