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Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 379 records · Page 21Linked to original sources
PubMed1996

Pharmacological studies on antidiarrheal effects of Hange-shashin-to.

We attempted to characterize the antidiarrheal action of Hange-shashin-to (TJ-14), a kampo medicine, by comparing its action with that of loperamide. The oral administration of TJ-14 caused the dose-dependent suppression of castor oil-induced diarrhea at 250 to 1000 mg/kg. No significant repression was noted by TJ-14 even at 1000 mg/kg, p.o. for diarrhea induced by pilocarpine, serotonin or barium chloride. Oral treatment with loperamide at 5 mg/kg markedly suppressed diarrhea induced by castor oil and barium chloride. Contractions of isolated guinea pig ileum in response to acetylcholine (1 x 10(-7) g/ml), histamine (1 x 10(-7) g/ml) or barium chloride (3 x 10(-4) g/ml) were little affected by TJ-14 at 10(-4) g/ml. The responses elicited by the three contractive drugs were dose-dependently suppressed by loperamide. TJ-14 did not affect the small intestinal transit even at an oral dose of 1000 mg/kg. On the other hand, the small intestinal transit was significantly suppressed by loperamide (5 mg/kg, p.o.). These results indicate that TJ-14 can effectively control castor oil-induced diarrhea, and that its antidiarrheal action was not based on the suppression of intestinal motility.

Animals↗
PubMed1996

Synthesis and antitumor activities of 5'-O-aminoacyl-3'-O-benzyl derivatives of 2'-deoxy-5-fluorouridine and related compounds.

Various O-alkyl derivatives of 2'-deoxy-5-fluorouridine (FUdR) were synthesized and their antitumor activities in mice bearing sarcoma 180 (s.c.-p.o.) were evaluated in terms of the ED50 values (mg/kg/d). Most of these compounds were superior to FUdR in antitumor activity. In particular, the antitumor activity of 3'-O-(p-chloro-benzyl)-FUdR (3e) (ED50 = 0.87 mg/kg/d) was as much as 100 times that of FUdR (ED50 = 84 mg/kg/d). Further, various 5'-O-aminoacyl derivatives of 3e were synthesized and evaluated in terms of ED50 value and therapeutic index (T.I.). Both the ED50 value (0.41 mg/kg/d) and the T.I. (4.18) of 3'-O-(p-chlorobenzyl)-5'-O-glycyl-FUdR hydrochloride (6a) were significantly improved, compared with those of 3e and FUdR. FUdR plasma concentration after a single p.o. dosing of 6a was maintained for as long as 24 h.

Animals↗
PubMed1996

Central alveolar hypoventilation syndrome (Ondine's curse) with gastroesophageal reflux.

Congenital central hypoventilation syndrome (Ondine's curse) is a rare disorder with lack of automatic control of ventilation during sleep. We have reported a case of Ondine's curse in a patient who underwent Nissen's fundoplication for gastroesophageal reflux (GER) at age 5 months. Ventilatory challenge test during sleep was done to confirm central alveolar hypoventilation. This female patient, without cor pulmonale, was a good candidate for diaphragm pacing. Thus, the patient underwent implantation of a diaphragm pacer at age 3 years; she had required mechanical ventilation since birth. Diagnosis, pathogenesis, and problems in the setting of diaphragm pacing for an infant are discussed.

Child, Preschool↗
PubMed1996

PMA and ionomycin differently affect atrial natriuretic peptide stimulated cyclic GMP production in rat mesangial cells.

How 4 beta-phorbol 12-myristate 13-acetate (PMA) and ionomycin (Io), a calcium ionophore, affect on the atrial natriuretic peptide (ANP) stimulated cyclic-3',5'-guanosine monophosphate (cGMP) production in cultured rat mesangial cells was examined. Cultured mesangial cells were prepared by isolated glomeruli from Sprague Dawley rats employing the sieving method and were used between the 3rd and 15th passage for experiments. cGMP and protein contents were measured by radioimmunoassay and Lowry method. Incubations with effectors were carried out either in the presence or absence of 0.5 mM 1-methyl-3-isobutyl-xanthine (MIX). The intracellular concentration of calcium ([Ca2+]i) was determined by using the Fura-2 method. Pretreatment with PMA, an activator of protein kinase C (PKC), attenuated ANP stimulated cGMP production in a time- and dose-dependent fashion, while alpha PDD (an inactive analog of PMA) did not inhibit cGMP production. PMA inhibition was reversed by addition of staurosporine, a protein kinase C inhibitor. Io attenuated ANP stimulated cGMP production in the absence but not in the presence of MIX. These findings suggested that PMA acts on ANP receptor or guanylate cyclase via activation of PKC in rat mesangial cells. Io may inhibit ANP stimulated cGMP production via activation of cyclic nucleotide phosphodiesterase.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Ethosuximide-induced lupus-like syndrome with renal involvement.

A 20-year-old man developed fever and urinary abnormalities with positive antinuclear antibody (ANA) two months after the start of ethosuximide. A renal biopsy showed mild mesangial cell proliferation and cellular crescents predominantly occupying a vascular pole in 7 out of 80 (8.8%) glomeruli. In the arteriole, mainly in close proximity to the glomerulus, proliferation of smooth muscle cells and luminal narrowing were observed. Discontinuation of ethosuximide led to the disappearance of fever, ANA and urinary abnormalities. These findings are strongly suggestive of a causal relationship between ethosuximide and a lupus-like syndrome with peculiar renal involvement.

Adult↗
PubMed1996

[Prolongation of survival and antitumor activity of antitumor drugs in murine cancer cachexia model].

We examined the activity of UFT, ADM and MMC, which are used for colon tumors, in terms of their prolongation of the survival period, growth inhibition of the primary tumor and improvement of cachexia in murine cancer cachexia model. The mean survival period of Colon 26, mouse adenocarcinoma bearing mice was 25.0 +/- 4.9 days. The maximal ILS value of the UFT administered group was 103.2%, against 7.2 and 26.0%, respectively, ADM and MMC maximal ILS value. For therapeutic activity of hypercalcemia, UFT was superior to other drugs, although all drugs showed equivalent tumor growth inhibitory activity. These findings indicate that UFT can prolong the survival period due to improvement of cancer cachexia. Therefore, we measured plasma interleukin-6 (IL-6) and found that UFT-administration lowered the plasma IL-6 level more than other drugs. Moreover, the prostaglandin E2 (PGE2) level in the tumor was significantly decreased only by UFT-administration. Since PGE2 has been shown to enhance IL-6 production from Colon 26 in vitro, it was speculated that UFT improve cachexia and prolongs life by decreased IL-6 resulting from decreased PGE2.

Animals↗
PubMed1996

[Quantitative analysis of clinical usefulness of CRT monitor diagnosis by using previous and current chest images with simulated lung nodules].

We quantitatively evaluated the clinical usefulness of CRT diagnosis by using previous and current chest images with simulated lung nodules. Sixty normal chest X-ray films consisting of previous and current chest images were digitized. Simulated nodules prepared by a computer workstation were added on lung fields of the 30 current images. Observer performance tests were carried out with six radiologists to evaluate the detection of simulated lung nodules in CRT and hard copy film with previous and current images, and with only current films. ROC analyses indicated that the detection accuracy in CRT diagnosis with current and previous images was greater than that in CRT diagnosis with only a current image. In addition, there was no statistically significant difference between CRT and hard copy film diagnoses if current and previous images were employed for the diagnosis of simulated lung nodules. We believe that CRT diagnosis is as useful as hard copy film diagnosis for the evaluation of pulmonary nodules by using previous and current chest images.

Data Display↗
PubMed1996

Macrophages and neutrophils infiltrating into the liver are responsible for tissue factor expression in a rabbit model of acute obstructive cholangitis.

Acute obstructive cholangitis (AOC) is one of the most fatal outcomes in sepsis, and frequently complicates disseminated intravascular coagulation (DIC). Recently we found that the plasma tissue factor (TF) level increased and changed in parallel with plasma markers of DIC in patients with AOC. To elucidate the role of TF in the pathogenesis of coagulopathy in AOC, we investigated the plasma levels of TF and its localization by immunohistochemical staining in rabbit models of AOC. Plasma TF activity significantly increased 3 h after the insult (0.63 +/- 0.1¿9 U/ml; p < 0.01) compared with that beforehand (0.05 +/- 0.02 U/ml), then reached a maximum level at 6 h (0.94 +/- 0.16 U/ml). The fluctuations in plasma TF activity correlated with those of the coagulation parameters including platelet count, fibrinogen, prothrombin time, and antithrombin III activity. Immunohistochemically, enhanced expression of TF was mainly detected in macrophages and neutrophils that had infiltrated into the liver sinusoids and around the bile duct, but not in the sinusoidal endothelial cells. A double immunofluorescence study revealed the concomitant presence of TF and fibrin at sites where macrophages and neutrophils had conglomerated. However, we could not detect an apparent change in TF expression in the lung or kidney. These data suggest that macrophages and neutrophils infiltrating into the liver sinusoids and around the bile duct play a pivotal role in TF expression, leading to coagulopathy in the acute phase of obstructive cholangitis in rabbits.

Acute Disease↗
PubMed1996

Computerized electro-nystagmography.

A computerized electro-nystagmography (ENG) system was developed on the basis of a new idea for the performance of ENG. In this system, all the functions of conventional ENG was performed by a personal computer (PC) except for the initial setting of an analog amplifier. The eye movement signals from the ENG amplifier were displayed on the graphic screen and recorded on a magnetic or magneto-optical disc. By using a special graphic screen, eye movements, even fine nystagmus, can be more clearly observed than they can on the PC's conventional graphic screen. Examiners can select the most suitable display condition according to the specific purpose(s) of the ENG examination. As a laser printer prints the recorded eye movements simultaneously with data sampling, we can observe eye movements in the same manner as on the recorded paper of a conventional ENG. Moreover, this system has a very powerful function for the analysis of such nystagmus responses as caloric test, VOR test and optokinetic nystagmus and it can be gotten at a lower cost than conventional ENG. These technical and economical features indicate that the computerized ENG system is a very useful and convenient device for observing, recording and analyzing ENG examinations.

Audiometry, Evoked Response↗
PubMed1996

[Inhibition of prostate cancer growth in nude mice by hormone and chemotherapy].

The combined effect of hormone and cytotoxic therapy on the growth of prostate cancer PC-3 in nude mice was investigated. PC-3 cell was derived from the bone metastasis of a hormone-refractory prostate cancer. Each group consisted of seven animals. After the inoculation of cancer cells, diethylstilbestrol (DES: 20 mg/kg) and futraful with uracil (UFT: 20 mg/kg) were administered for 25 days. DES and UFT synergically inhibited the growth. DES had no effect as a single agent on the growth of a hormone-independent cell line (KM20C) derived from human colon cancer. It also had no additive effect when given with UFT.

Animals↗
PubMed1996

[Clinical effect of intra-arterial carboplatin-combined chemotherapy for advanced uterine cervical cancer and increased tissue platinum levels with Lipo PGE1 administration before chemotherapy].

Combination chemotherapy including carboplatin was administered intraarterially from the internal iliac artery as neoadjuvant chemotherapy to nine patients with advanced uterine cervical cancer. Two or three courses were repeated at intervals of 3 weeks. And to investigate whether the administration of Lipo PGE1 with the action of vasodilation before intra-arterial chemotherapy increases tissue levels of anticancer agents, 7 out of 9 patients were treated with Lipo PGE1, followed by arterial infusion chemotherapy. After infusion, tissue platinum (Pt) concentrations were measured by flameless atomic absorption spectrophotometry. Three of 9 patients with measurable tumor had a complete response and 6 had a partial response. Tissue Pt concentrations reached maximum levels 2-6 hours after intra-arterial chemotherapy. Tissue Pt levels of the patients with pretreatment of Lipo PGE1 were significantly higher than those without pretreatment (p < 0.01). It seems likely that Lipo PGE1 administration before intra-arterial chemotherapy is useful for the enhancement of tissue levels of anticancer agents as well as the clinical effects.

Adenocarcinoma↗
PubMed1996

[Male life expectancy and prolongation of life expectancy were lowest in small towns in Japan].

The relationship between size of population and life expectancy of residents was investigated in 652 cities in Japan, using municipal life tables for 1985 and 1990. The following findings were seen: 1) Population size and life expectancy Life expectancy of males at age 0, 20 and 40 was lowest in small towns with a population less than 30,000 (except for age 40 in 1985), and highest in cities with a population of 70,000-199,999 in 1985 and 1990. Life expectancy of females at age 0, 20, 40 and 65 did not significantly vary with size of population in 1985 and 1990. 2) Population size and prolongation of life expectancy (1985-1990) Life expectancy was prolonged in males by 1.02, 0.88, 0.86 and 0.66 years at age 0, 20, 40 and 65, respectively. The prolongation of life expectancy of males at age 0, 20 and 40 was smallest in small towns with a population less than 30,000. Life expectancy was prolonged in females by 1.41, 1.32, 1.29 and 1.12 years at age 0, 20, 40 and 65, respectively. The prolongation of life expectancy was shortest at birth for females who lived in cities with a population of 50,000-59,999. 3) Socioeconomic factors and prolongation of life expectancy The prolongation of life expectancy of males was related to the entrance rate for high school and inversely related to the unemployment rate. The prolongation of life expectancy of females was not related to any of the socioeconomic factors studied.

Adult↗
PubMed1995

Targeted disruption of H2B-V encoding a particular H2B histone variant causes changes in protein patterns on two-dimensional polyacrylamide gel electrophoresis in the DT40 chicken B cell line.

The chicken H2B gene family comprises eight members (H2B-I to H2B-VIII), which are all located in two major histone gene clusters. All of them have been shown to encode four different protein variants (classes I to IV). In the DT40 chicken B cell line, the H2B-V gene, encoding the class III H2B variant, constituted about 10% of the total intracellular mRNA from all the H2B genes. To study the nature of this particular variant in vivo, we generated heterozygous (H2B-V, +/-) and homozygous (H2B-V, -/-) DT40 mutants by targeted integration. The remaining H2B genes were shown to be expressed more in these mutants than in the wild-type cell lines. The growth rate of DT40 cells was unchanged in the absence of the H2B-V gene. Two-dimensional polyacrylamide gel electrophoresis showed that the protein patterns were, on the whole, similar between the wild-type and homozygous cell lines. However, within this constant background, some cellular proteins disappeared or decreased quantitatively in the homozygous mutants, and several other proteins increased or newly appeared. These results suggest that the class III H2B variant participates negatively or positively in regulation of the expression of particular genes that encode the proteins that vary in DT40 cells. This type of regulation is possibly mediated through alterations in nucleosome structure over the restricted regions involving the putative genes of the DT40 genome.

Animals↗
PubMed1995

Determination of schizandrin in human plasma by gas chromatography-mass spectrometry.

Schizandrin (SZ) is one of the lignan components from Schisandra fruits. A highly sensitive and precise method for the determination of SZ in human plasma was developed involving selected-ion monitoring with gas chromatography-mass spectrometry using a fused-silica capillary column. A 0.1-ml plasma sample was used for solid-phase extraction. A good linear relationship was obtained in the concentration range studied (2.0-500 ng/ml) and the method was sufficiently accurate and precise to support clinical pharmacokinetic studies. After oral administration of SZ at a dose of 15 mg to healthy male subjects, the average value of the maximum plasma concentration of SZ was 96.1 +/- 14.1 ng/ml. The plasma concentration of this substance could be monitored for 8 h after administration.

Cyclooctanes↗
PubMed1995

Targeted disruption of an H3-IV/H3-V gene pair causes increased expression of the remaining H3 genes in the chicken DT40 cell line.

The chicken H3 gene family contains 12 members (H3-I to H3-XII). Nine of them belong to two major histone gene clusters, but the genomic locations of the others are unknown. In the DT40 chicken B cell line, H3-IV and H3-V, which are located in inverted orientation and share a 3'-untranslated region of 531 bp, produce about 24% of the steady-state level of total mRNAs from all the H3 genes. To study the nature of these two genes, we carried out targeted integration into DT40 cells of constructs of the H3-IV/H3-V locus. Analysis of the stable transfectants showed that the growth rate of DT40 cells was unchanged in the absence of two copies of the H3-IV/H3-V locus. Furthermore, the remaining H3 genes were shown to be expressed more in the mutants lacking one or two H3-IV/H3-V alleles than DT40 cells, and the steady-state level of total H3 mRNAs remained constant in all the mutant cell lines tested. The levels of mRNAs from the H2B and H1 genes, which are located close to the H3 genes, were unchanged. These results demonstrate that the chicken H3 gene family has the ability to compensate for disruption of H3-IV/H3-V, which are normally responsible for about 24% of total H3 mRNAs.

Alleles↗
PubMed1995

Myogenic regulatory factors can activate TATA-containing promoter elements via an E-box independent mechanism.

We have studied the effect of several myogenic regulatory factors on the activity of the promoter for a mouse gene encoding a skeletal myosin heavy chain (MyHC) expressed in adult (type IIB) muscle fibers. Co-transfection of myogenic factors is necessary for activity of the IIB promoter in mouse C2 myotubes in culture but not in quail myotubes in culture. Although this promoter contains one E-box within the first 192 base pairs upstream of the transcriptional start site, mutations in this motif demonstrate that it is not required for the transactivation effect of the myogenic factors. Analysis of other mutants suggests that the MEF2 and MHox DNA-binding factor binds to an evolutionarily conserved AT-rich motif. In addition, the IIB promoter appears to require the conserved TATA motif (CTATAAAAG) in order to be activated by the AT-rich sequences. The IIB promoter constructs produce RNA transcripts which begin at the natural site of transcriptional initiation in quail myotubes and in mouse C2 myotubes after co-transfection with myogenic factors; a second, minor, start site is also used in the co-transfected C2 myotubes. Results obtained after transfection of the mouse IIB promoter constructs in quail myotube cultures suggest that the overexpression of myogenic factors in C2 cultures does not result in an environment in which the control of IIB MyHC promoter activity is aberrant. Therefore, either the myogenic factors themselves, or other proteins induced by them, seem to interact directly with the basal transcription seem to interact directly with the basal transcription machinery to allow muscle-specific gene expression.

Animals↗