Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 433 records · Page 24Linked to original sources

PubMed1994

[Penetration of the esophageal and gastric ulcers to the cardioaortic system following hiatus hernia: a lethal complication in the severely-handicapped].

Among the severely-handicapped, hiatus hernia (HH) and/or gastroesophageal regurgitation (GER) are not uncommon. We report here three patients with HH and/or GER. Two of them died of massive hemorrhage in the alimentary tract from the heart or the thoracic aorta due to penetration of the gastric or esophageal ulcer. The third patient died of pneumonia, but autopsy proved multiple esophageal ulcers, one of which reached the wall of the brachiocephalic artery without penetration. We propose that proper treatment for HH and/or GER is required for the severely-handicapped, including surgical intervention, before their general conditions become worse and decompensatory.

Adult↗

PubMed1994

[Intermittent intraarterial infusion chemotherapy using a subcutaneously implanted reservoir in patients with hepatoma].

Hepatocellular carcinomas that should not be treated with transarterial embolization (TAE) were treated with intermittent intraarterial infusion chemotherapy using a subcutaneously implanted reservoir. Among 37 patients, in whom objective evaluation of the initial response was possible, 3 cases of CR, 12 of PR, 10 of NC and 12 of PD were obtained. The response rate was 40.5%. Culminate 1 year survival rates were 80.0% for responders (CR + PR), 4.5% for non-responders (NC + PD) and 35.1% as an average for all patients. The survival in responder patients was better than in non-responders (p < 0.001). To determine the role of this therapy we divided the cases into two groups by anamnesis of TAE and investigated the initial response and prognosis based on the grade of portal vein invasion in each group. In one group of 18 patients, who had not been treated with TAE, there were no relationships between the grade of portal vein invasion and the initial response and between the grade of portal vein invasion and the prognosis. In this group the initial response was better in patients whose one shot infusion chemotherapy immediately before intermittent intraarterial infusion chemotherapy had been effective than in the others. In the other group of 19 patients, who had been treated with TAE, the initial response and prognosis were better in patients with lower grades of portal vein invasion (Vp0-2) than in those with the highest grade (Vp3).

Carcinoma, Hepatocellular↗

PubMed1994

[Clinical study of anti-phospholipid antibody in patients with sarcoidosis].

Serum antibodies against five types of phospholipids were measured by enzyme-linked immunosorbent assay (ELISA) in 55 patients with sarcoidosis. In 21 cases (38%), either IgG antibodies or IgM antibodies were detected. These antibodies were thought to mainly be infective type. This positive rate was significantly higher than that (7%) of the control group (70 cases) (p < 0.01). As to the immunoglobulin classes, 5 cases had IgG antibodies only, 11 cases had IgM antibodies only, and 5 cases had both IgG and IgM antibodies. No correlation was observed between the occurrence of anti-phospholipid antibodies (APL-Ab) and disease activity of sarcoidosis. Significant correlations were found between the occurrence of APL-Ab and skin lesions, many extrathoracic organ lesions and the persistence of abnormal chest X-ray findings for over 2 years and 5 years. From these data, it is suggested that the presence of APL-Ab is associated with prolonged disease activity of sarcoidosis.

Antibodies, Antiphospholipid↗

PubMed1994

[Malignant lymphoma with various neuropsychological symptoms].

A case of malignant lymphoma presented with various neuropsychological symptoms which made it difficult to achieve the diagnosis and therapy. A 9-year-old boy was referred to our hospital with complaints of psychological symptoms, impairment of consciousness and generalized convulsive seizures. A lumbar puncture revealed infiltration of numerous blasts which were positive for immature B cell markers. CT scan showed a mass in the right ethmoidal sinus, but no space occupying lesion in the brain. The tumor cells in the right ethmoidal sinus had the same phenotypes as those in the CSF. Thus a diagnosis of non-Hodgkin's lymphoma, developing in the right ethmoidal sinus and infiltrating into the central nervous system, was established. The blast cells in the liquor and the tumor of the right ethmoidal sinus disappeared after induction of systemic chemotherapy, irradiation and intrathecal chemotherapy. However, intracranial bleeding occurred during the chemotherapy. He died of respiratory failure 10 months after the start of treatment.

Child↗

PubMed1994

[Levels of soluble CD4 and soluble CD8 in patients with sarcoidosis].

Levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) in serum and bronchoalveolar lavage fluid (BALF) were determined in 36 patients with sarcoidosis and 20 healthy controls by an ELISA method. In addition, the possible sources of sCD4 and sCD8 were examined in detail. The sCD4 levels in serum did not differ significantly between sarcoidosis patients and controls. The sCD8 levels in the sera of sarcoidosis patients with a high serum angiotensin-converting enzyme (ACE) level were significantly higher than those of patients with a normal serum ACE level (413 +/- 148 U/ml vs. 297 +/- 76 U/ml, p < 0.01). The high ACE group also had significantly increased serum sCD8 levels as compared to controls (323 +/- 111 U/ml, p < 0.05). In the sarcoidosis patients, the mean serum sCD8 level was 308 +/- 46 U/ml in stage 0, 339 +/- 107 U/ml in stage I, 557 +/- 141 U/ml in stage II, and 474 +/- 211 U/ml in stage III. The stage II group had a significantly higher sCD8 level than either the stage 0 or I groups (p < 0.05). In the sarcoidosis patients, the sCD8 level correlated significantly with the level of either ACE or soluble Interleukin-2 receptor in serum (p < 0.05). The sCD4 level in BALF was significantly higher in sarcoidosis patients than in controls (4.10 +/- 1.90 U/ml vs. 2.39 +/- 0.12 U/ml, p < 0.01), while the sCD8 level in BALF tended to be higher in sarcoidosis patients than in controls (4.31 +/- 4.39 U/ml vs. 2.02 +/- 1.52 U/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Platelets-induced stimulation of endothelin-1 production and inhibition by phosphoramidon.

The effects of platelets on endothelin-1 (ET-1) production were examined by using cultured bovine pulmonary artery endothelial cells (ECs). Platelets (6 x 10(6) to 2 x 10(9) platelets/ml) prepared from rat peripheral arterial blood markedly stimulated immunoreactive (IR)-ET release from ECs into the culture medium, in a time-and platelet number-dependent manner. High-performance liquid chromatography analysis of the culture supernatant following exposure to platelets revealed one major IR-ET component corresponding to the elution position of synthetic ET-1. Northern blot analysis showed that platelets enhanced prepro ET-1 mRNA expression in the ECs. Increased IR-ET release was observed with the supernatant obtained after incubation of platelets, and this increment was significantly inhibited by transforming growth factor-beta 1 neutralizing antibody. Phosphoramidon, an ET converting enzyme inhibitor, significantly decreased the amount of IR-ET accumulating in the culture medium of ECs, incubated with or without platelets, and the decreasing effect of phosphoramidon in the presence of platelets was greater than that in their absence. A similar effectiveness of phosphoramidon was seen when transforming growth factor-beta 1 was used instead of platelets. Thus, platelets appear to stimulate the endothelial production of ET-1 in vitro, probably through a release of transforming growth factor-beta 1. We also suggest that the inhibition of ET converting enzyme by phosphoramidon is more effective in the augmented condition of ET-1 production than in the basal condition.

Animals↗

PubMed1993

Bovine serum albumin-doxorubicin conjugate overcomes multidrug resistance in a rat hepatoma.

A bovine serum albumin-conjugated doxorubicin via the glutaraldehyde bridge (BSA-DXR conjugate) showed potent dose-dependent inhibition of cell growth against daunorubicin-resistant AH66 (AH66DR) cells as well as parental AH66 (AH66P) cells in vitro as compared to treatment with DXR or BSA-glutaraldehyde conjugate without DXR (BSA-GA). In the culture of AH66DR with BSA-DXR conjugate, drug accumulation in the AH66DR cells increased as a function of time up to 24 h reaching approximately the same drug level as AH66P cells treated with DXR. The intracellular accumulation of the BSA-DXR conjugate was inhibited by the addition of ammonium chloride, while that of DXR alone was not inhibited. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate or pharmacologically active DXR adduct remained in the cells at a relatively high concentration over a 36-h time period. The life-prolonging effect of the conjugate was assessed using rats inoculated i.p. with AH66P or AH66DR. The rats were treated with the BSA-DXR conjugate, DXR, a mixture of DXR with BSA, or BSA-GA by either the i.p. or i.v. route. Treatment with DXR had no significant surviving effect as compared to that with saline in AH66P-bearing rats. By contrast, BSA-DXR conjugate showed a significant life-prolonging effect as compared with DXR alone in the same degree both in AH66P- and AH66DR-bearing rats. BSA-GA did not show any toxicity in vivo as well as in vitro. These results indicate that the BSA-DXR conjugate allows DXR to escape from the multidrug resistance mechanism.

Animals↗

PubMed1993

Increase in ubiquitin conjugates dependent on ischemic damage.

Insoluble ubiquitin conjugates (UC) in the mitochondrial fraction of the gerbil cortex were analyzed following transient forebrain ischemia. At 1 h of reperfusion after 2-10 min of ischemia, UC increased as the duration of ischemia was prolonged. Pre-treatment with pentobarbital, rather than post-treatment immediately after recirculation, reduced the increase of UC at 1 h of reperfusion following 5 min of ischemia. Pentobarbital had no effect on in vitro ubiquitination of heat-denatured lysozyme by the extract of gerbil cortex. These results suggest that increase in UC is dependent on ischemic damage and pentobarbital attenuates the increase of UC by relieving injury during ischemia.

Adenosine Triphosphate↗

PubMed1993

Inhibitory effect of nonenzymatic glycation on ubiquitination and ubiquitin-mediated degradation of lysozyme.

We examined ubiquitination and ubiquitin-mediated degradation of glycated protein by rabbit reticulocyte lysate fraction II (ubiquitin-free preparation). Non-glycated lysozyme and three glycated lysozyme preparations with different glucose binding ratios were used as substrates. Glycation sites of the lysozyme were mostly the epsilon-NH2 group of lysine residues, since modification at the alpha-NH2 group of the amino terminal was not detectable. Ubiquitin was conjugated with three glycated lysozyme preparations, which contained 1.4, 2.8 and 4.5 mol glucose per mol, by fraction II supplemented with hemin. The extent of formed conjugates was reduced 81, 72 and 56% of those of ubiquitin-non-glycated lysozyme conjugates, respectively. Additionally, ubiquitin-mediated degradation of the resultant conjugates was reduced and their respective rates were 97, 56 and 19% of that of the non-glycated lysozyme. These results indicated that both ubiquitin conjugation and ubiquitin-mediated degradation of the lysozyme were inhibited by nonenzymatic glucose binding to the lysozyme.

Electrophoresis, Polyacrylamide Gel↗

PubMed1993

Effect of interleukin-6 on cell proliferation of FRTL-5 cells.

We studied the effects of interleukin-6(IL-6) on DNA synthesis and cyclic AMP production in rat thyroid FRTL-5 cells. When cells were incubated with IL-6 in the presence or absence of IGF-I, cell proliferation was not observed. By contrast, IL-6 stimulated DNA synthesis in a dose dependent manner when TSH was added concomitantly. On the other hand, IL-6 did not modulate the cAMP accumulation in the presence or absence of TSH. These data demonstrate that, like IGF-I, IL-6 may be able to act as a growth factor through activation of a mitogenic signal transduction pathway different from A-kinase in FRTL-5 cells.

Animals↗

PubMed1993

Functional regulation of GTP-binding protein coupled to insulin-like growth factor-I receptor by lithium during G1 phase of the rat thyroid cell cycle.

The regulatory effects of lithium on the function of pertussis toxin-sensitive GTP-binding (G(i))-proteins located on the mitogenic pathway activated by insulin-like growth factor-I (IGF-I) in FRTL-5 cells were studied. Addition of GTP-gamma-S to the thyroid stimulating hormone-primed cell membranes resulted in a decreased affinity of IGF-I receptor binding, and the dissociation constant (Kd) increased from 0.46 nM to 3.1 nM. Moreover, IGF-I stimulated GTP-gamma-S binding to a 40-kDa protein, and pertussis toxin (PT) attenuated the stimulatory effect of IGF-I on the same protein. Lithium lowered the affinity of IGF-I receptor binding and the Kd (3.4 nM) was in the same range as that in the presence of GTP-gamma-S. The inhibitory effect of lithium was markedly abolished by pretreatment with PT. Lithium attenuated the amounts of ADP-rebosylation of the 40-kDa protein by PT. In addition, lithium stimulated Ca2+ entry, similar to that by IGF-I, and induced cell proliferation via a PT-sensitive step. These findings suggest that lithium may be capable of modulating the function of G(i)-proteins coupled to IGF-I receptors during the G1 phase of the FRTL-5 cell cycle.

Adenosine Diphosphate Ribose↗

PubMed1993

Genistein, a tyrosine kinase inhibitor, blocks the cell cycle progression but not Ca2+ influx induced by BAY K8644 in FRTL-5 cells.

IGF-I, when added to TSH-primed FRTL-5 cells, induces a long lasting Ca2+ influx and then DNA synthesis. Ca2+ channel agonist, BAYK 8644, is capable to mimic these effects on cell proliferation. We studied the effect of genistein, a specific tyrosine kinase inhibitor, on BAY K8644- or IGF-I- induced cell cycle progression in FRTL-5 cells. Genistein inhibited DNA synthesis induced by BAY K8644 and by IGF-I. In contrast, Ca2+ influx stimulated by BAY K8644 was not inhibited. These data demonstrate that the signal transduction pathway induced by BAY K8644 or IGF-I may possibly involve genistein-sensitive process at the downstream step of Ca2+ entry.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1993

Malignant lymphoma originating from the earliest T-lineage precursor cell.

The earliest T-lineage precursor cells with a CD3-CD4+CD8- phenotype and germline-state T-cell receptor (TCR) genes have recently been identified in the murine thymus. We report a case of malignant lymphoma that was considered to originate from the human counterpart of this newly defined murine T-cell population. The surface phenotype of the lymphoma cells was CD2+CD3-CD4+CD8-CD25-CD34-CD44+HLA-DR+. TCR-beta, -gamma, -delta chain genes and immunoglobulin heavy and light chain genes were all in a germline state. These characteristics were markedly similar to those of the murine earliest T-lineage precursor cells. The present case thus strongly suggests the presence of the human counterpart of this novel murine T-cell population.

Adolescent↗

PubMed1993

Pharmacokinetic study of a tripeptide HIV-1 protease inhibitor, KNI-174, in rats after intravenous and intraduodenal administrations.

Recently, as a new type of anti-AIDS drug, an HIV-1 protease inhibitor, KNI-174, has been synthesized; it shows a potent and selective HIV-1 protease inhibitory activity in vitro. In this study, we developed an HPLC assay system for KNI-174 in rat plasma and examined the pharmacokinetics of KNI-174 in rats using this assay method after both intravenous (i.v.) and intraduodenal (i.d.) administrations to obtain the disposition characteristics and bioavailability of this new anti-AIDS drug. This HPLC assay method is specific to KNI-174 and the standard curve was linear from 0.02 to 30 micrograms ml-1 plasma. After i.v. administration, 10.0 mg kg-1, KNI-174 disappeared from the rats' plasma in a three-exponential decay. The mean terminal elimination half-life, t1/2 lambda z, was 3.97 +/- 0.19 (S.E.) h, the total body clearance, CLtot, was 9.53 +/- 1.08 ml min-1 and the distribution volume at steady state, Vd,ss, was 7070 +/- 960 ml kg-1. In the case of the i.d. administration, 10.0 mg kg-1, the mean peak plasma concentration, Cmax, and the peak time, tmax, were 0.196 +/- 0.076 micrograms ml-1 and 0.444 +/- 0.193 h, respectively. The bioavailability of KNI-174 till infinity, BA(0-infinity), was 5.37 per cent. Because the IC50 of KNI-174 against HIV-1 in PHA-PBM was 138 ng ml-1, the time needed for maintaining the concentrations above IC50 after a single i.d. administration of KNI-174 is estimated to be 0.350 +/- 0.184 h.

Animals↗

PubMed1993

Distribution characteristics of immunosuppressants FK506 and cyclosporin A in the blood compartment.

Using two representative immunosuppressants, FK506 (FK) and cyclosporin A (CyA), of which the mechanism of pharmacological action is the same although there is a great difference in the pharmacological intensity, the distribution characteristics were studied in both in vivo and in vitro experiments using rat, dog, and human blood. Blood samples were fractionated by means of sedimentation in Ficoll-Paque, and the drug contents in the diluted plasma fraction, erythrocyte fraction, and lymphocyte fraction were measured by an HPLC method. FK distributes to the lymphocyte fraction to a level about three times greater than that of CyA, while CyA distributes to the erythrocyte fraction to a level ten times that of FK. The distribution pattern of these fractions was independent of the drug concentration and species after correcting the drug concentration in each fraction with the blood drug concentration. The uptakes of FK and CyA in the isolated lymphocytes obtained from the rat spleen and human peripheral blood were also studied. The amount of FK taken up by the spleen lymphocytes is five times greater than that of CyA. In the case of the uptake study using human peripheral blood lymphocytes, the concentration of FK in the lymphocyte is 100-fold higher than that of CyA. This difference in the lymphocyte level between the two immunosuppressants is thought to be one of the reasons why FK is more potent than CyA, a difference of about 100-fold in the in vitro pharmacological study and about tenfold in the in vivo organ transplantation experiments.

Animals↗

PubMed1993

Comparison of a new orally potent tripeptide HIV-1 protease inhibitor (anti-AIDS drug) based on pharmacokinetic characteristics in rats after intravenous and intraduodenal administrations.

Recently, a series of KNI compounds such as KNI-227 and KNI-272 has been synthesized and shows potent and selective HIV-1 protease inhibitory activity in vitro. In this study, we developed an HPLC assay system for KNI-227 and KNI-272 in rat plasma and examined the pharmacokinetic characteristics in rats after both intravenous (i.v.) and intraduodenal (i.d.) administrations to obtain the disposition characteristics and bioavailabilities of these new anti-AIDS drugs. After i.v. administration of KNI-227, 10.0 mg kg-1, the mean terminal elimination half-life, t1/2 lambda zeta, was 0.808 +/- 0.161(SE) h, the total body clearance, CLtot, was 11.7 +/- 3.3 ml min-1 and the distribution volume at steady state (Vd,ss) was 1410 +/- 460 ml kg-1. On the other hand, after i.v. administration of KNI-272, 10.0 mg kg-1, t1/2 lambda zeta was 2.86 +/- 0.78 h, CLtot was 15.3 +/- 1.4 ml min-1 and Vd,ss was 3440 +/- 670 ml kg-1. In the case of the i.d. administration of drugs, the mean peak plasma concentrations, Cmax, of KNI-227 and KNI-272 were 0.374 +/- 0.110 microgram ml-1 and 0.900 +/- 0.093 micrograms ml-1, respectively. The bioavailabilities (BA) of KNI-227 and KNI-272 to infinity, BA(0-infinity), were 5.90% and 42.3%, respectively. As compared with the lead compound, KNI-174, the BA of KNI-272 was improved about 10 times. Although the anti-AIDS virus activity of these two drugs has not been investigated in vivo, KNI-272 is expected to be a better candidate for oral anti-AIDS therapies.

Animals↗

PubMed1993

cAMP stimulates human immunodeficiency virus (HIV-1) from latently infected cells of monocyte-macrophage lineage: synergism with TNF-alpha.

The present experiments were designed to study whether GTP binding protein activation and the resulting cAMP plays any role in HIV replication. The results showed that cholera toxin (CT) enhanced HIV replication dose dependently in myelo-monocytic cell lines latently infected with HIV-1, U1 and J22HL-60. Three- to 4-fold enhancement of virus production was observed in U1 cells and 4- to 11-fold enhancement in J22HL-60 cells 4 days after treatment with 100 ng/ml of CT. The increment of intracellular cAMP accumulation was parallel with HIV augmentation by CT in both cells. Even at the low concentration 0.1 ng/ml, TNF enhanced virus production to about an 80-fold higher level than the untreated U1 control cells as described previously (11). However, a synergistic effect (80- to 238-fold enhancement) was observed, when TNF-alpha and CT were added together to U1 cells. Similar synergism was seen in J22HL-60 cells. HIV antigen positive cells and gp120 expression were also increased to a similar degree. Phosphodiesterase inhibitor IBMX had no effect on HIV production alone, but potentiated HIV induction by CT and TNF. Adenylate cyclase activator, forskolin (FK), at 100 microM also significantly augmented HIV production (> 4-fold) and potentiated TNF induction in J22HL-60 and U1 cells. On the other hand, CT did not show any effect on HIV replication as well as TNF induction in HIV-1-infected T cell line. Northern blot experiment confirmed that this enhancement was mediated through the activation of HIV transcription. These data suggest that cAMP augments HIV replication and potentiates TNF induction in a particular monocyte-macrophage system.

1-Methyl-3-isobutylxanthine↗

PubMed1993

The clinical course and prognosis of patients with severe, moderate or mild sarcoidosis.

During 1978-1990, 346 patients with sarcoidosis were enrolled in our institute. Of 346 patients, 295 patients were eligible for evaluation on the clinical course and prognosis. According of their clinical presentations, they were classified into 3 groups; severe, moderate and mild sarcoidosis. Of the 295 patients, 27 (9.2%) were classified as severe sarcoidosis who developed serious illness including involvement of the heart (8), lung (6), muscles (5), eyes (3), central nervous system (CNS) (3) or liver (2). The mean interval between the onset of disease to severe disability was 58.3 months. The interval was particularly long in those patients who presented with either pulmonary (100.8 months) or liver sarcoidosis (108 months). Of the 27 patients with severe sarcoidosis, 8 (29.6%) gradually became worse towards the end of their clinical course despite only mild clinical signs and symptoms at the first presentation. Therefore, the initial clinical symptoms and findings, including ocular involvement. ECG abnormalities, negative reaction to PPD, high value of serum angiotensin converting enzyme (ACE) and a small number of lymphocytes in peripheral blood, were not useful in predicting prognosis. The relationship between the maximum serum ACE value during the clinical course and the duration of the active phase was statistically significant in the 123 patients who were monitored throughout their course, suggesting that the maximum serum ACE may be a marker for assessing prognosis. Corticosteroid was administered to 76 patients (22%) with serious systemic involvement. They included 26 (96.4%) of the 27 severe sarcoidosis and 50 (37.9%) of the 132 moderate sarcoidosis. Patients with mild sarcoidosis did not receive corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗