Biomedical subjects

S Takada

Publications and source records attributed to S Takada.

At least 163 records · Page 9Linked to original sources

PubMed1994

Experimental control of axial pattern in the chick blastoderm by local expression of Wnt and activin: the role of HNK-1 positive cells.

Small grafts from transfected mammalian cell lines that secrete activin or express Wnt-1 RNA were made to the marginal zone of entire chick blastoderms in culture. Grafts from appropriate control cell lines produced no effects on development. The activin-secreting grafts, implanted before streak formation, could cause the streak to form opposite their marginal position even when this was 180 degrees distant around the blastoderm from the original presumptive streak site. Alternatively, opposed twin streaks were observed, one at the original presumptive site and one in relation to the graft. Wnt-expressing grafts implanted early could also reposition axis formation, but only to graft sites within approximately 100 degrees of angular distance from the host's presumptive streak origin. No Wnt-induced twinning was observed. Grafts of both experimental cell types intermixed were the most effective in reorientating, twinning, or globally disturbing the axial pattern and led to second axes with the least delay, relative to normal development, in reaching headfold stages. The incidence and distribution of cells positive for the epitope HNK-1 was investigated during early stages of normal and of experimentally twinned development. Only two nonhypoblast regions of HNK-1 expression were consistently observed in normal early development; a sector in the germ wall area opaca, behind the site of streak formation, and then a localised region of intensely, newly expressing cells arising in epiblast and in anteriormost parts of the (epiblast-derived) streak at the half-length streak stage. Both "activin only" and "activin/Wnt" mixed grafts, although not control grafts, became surrounded by new sectors of "germ wall" HNK-1 positivity. Such positivity may therefore mark a cell group with a signaling role (but no anatomical participation) in streak initiation. However, there was no change of the local background incidence of epiblastic HNK-1 positivity in the structure of streaks induced by "activin only" grafts. This indicates that most cells of the streak are specified by relatively local induction, rather than deriving from selective aggregation. Only grafts including the Wnt-expressing cells gave rise to obvious new HNK-1 expression within epiblast-derived cells anteriorly, as does the complete normal streak. This suggests that the Wnt class of response pathway can complement the activin one in producing rostrocaudally complete axial pattern, as has been suggested for amphibian development.

Activins↗

PubMed1994

Three sites of the hepatitis B virus X protein cooperatively interact with cellular proteins.

The X protein of hepatitis B virus is known to be a trans-activator of viral and cellular genes and to be a serine protease inhibitor as well. X protein has no DNA-binding activity, but is postulated to exert its trans-activation function by interacting with cellular proteins. To investigate interaction sites of X protein with cellular proteins, we carried out an immunoprecipitation inhibition assay using several different anti-X antibodies in the presence or absence of cellular proteins. Results elucidated three separate sites (aa 65-72, aa 105-115, and aa 131-142; U22, X1, and Z44 sites, respectively) of the X protein that cooperatively interacted with cellular proteins. Analyses with a series of mutant X proteins also supported the interactions at the U22, X1, and Z44 sites. Based on the CAT activity assay, the essential regions for the trans-activation function of X protein overlapped with these three interaction sites. Furthermore, these interaction sites also coincide with the structures necessary for the serine protease inhibitor activity. Thus, the trans-activation function and serine protease inhibitor activity of X protein may be exerted by interaction with cellular proteins through at least these three sites.

Allosteric Regulation↗

PubMed1994

Comparison of lesions induced by intra-articular injections of quinolones and compounds damaging cartilage components in rat femoral condyles.

Twenty-five microliters of a 2% saline solution of levofloxacin (LVFX) or ciprofloxacin (CPFX) was injected every other day for 2 wk into the knee joint space of CD rats (weighing 62.7-86.7 g) from the age of 3 wk. Early in the course of injection, histologic examination revealed chondrocyte necrosis without marked matrix change in the articular cartilage of the femoral condyles adjacent to the intercondylar groove. After 7 injections, the surface and intermediate zones of the articular cartilage showed extensive necrosis, sometimes with cavity formation in the center of the same portion. Papain completely depleted matrix basophilia in all zones throughout the condyle and caused cartilage necrosis with cavity formation. One injection of iodoacetic acid caused necrosis of almost all chondrocytes over the entire condyle, but chondrocytes sometimes remained alive in the portion where cavity formation was induced by quinolones. Chondroitinase depleted the matrix basophilia, and sometimes produced necrotic areas. DNA synthesis inhibitors n-ethylmaleimide, CPT-11, and etoposide (VP-16) caused chondrocyte necrosis, but never caused cavities in the articular cartilage. The DNA synthesis inhibitors n-ethylmaleimide, CPT-11, and hydroxyurea were administered concurrently with po LVFX administration and significantly increased the incidence of LVFX-induced cavity formation. n-Ethylmaleimide was the most effective of all the inhibitors. The quinolone-induced cavity formation is suggested to be site specific in the articular cartilage of rat femoral condyles. The depletion of matrix proteoglycans and chondrocyte necrosis may be necessary, although insufficient, to produce such lesions. Disruption of the collagen framework is suspected to contribute to their development. Involvement of altered DNA metabolism may play a role in the chondrocyte necrosis that occurs early in the specific sites.

Administration, Oral↗

PubMed1994

Functional reconstitution of Chlamydomonas outer dynein arms from alpha-beta and gamma subunits: requirement of a third factor.

The outer dynein arm of Chlamydomonas flagella, when isolated under Mg(2+)-free conditions, tends to dissociate into an 11 to 12S particle (12S dynein) containing the gamma heavy chain and a 21S particle (called 18S dynein) containing the alpha and beta heavy chains. We show here that functional outer arms can be reconstituted by the addition of 12S and 18S dyneins to the axonemes of the outer armless mutants oda1-oda6. A third factor that sediments at integral 7S is required for efficient reconstitution of the outer arms on the axonemes of oda1 and oda3. However, this factor is not necessary for reconstitution on the axonemes of oda2, oda4, oda5, and oda6. SDS-PAGE analysis indicates that the axonemes of the former two mutants lack a integral of 70-kD polypeptide that is present in those of the other mutants as well as in the 7S fraction from the wild-type extract. Furthermore, electron micrographs of axonemal cross sections revealed that the latter four mutants, but not oda1 or oda3, have small pointed structures on the outer doublets, at a position in cross section where outer arms normally occur. We suggest that the 7S factor constitutes the pointed structure on the outer doublets and facilitates attachment of the outer arm. The discovery of this structure raises a new question as to how the attachment site for the outer arm dynein is determined within the axoneme.

Animals↗

PubMed1994

Vasoconstrictors and renal protection induced by beta 1-selective adrenoceptor antagonist bisoprolol.

We investigated the role of the vasoconstrictors endothelin-1 (ET-1) and thromboxane in renal protection by the beta 1-selective adrenoceptor antagonist, bisoprolol, in Dahl salt-sensitive rats (Dahl S) and salt-resistant rats (Dahl R). Six-week bisoprolol treatment (20 mg/kg chow) reduced systolic blood pressure (SBP) by 14% in Dahl S rats fed a high-salt (4% NaCl) diet. This BP reduction was accompanied by a decrease in aortic wall thickness. ET-1 and thromboxane released from renal cortex was significantly decreased by 17 and 30% with bisoprolol, respectively. Other prostaglandin synthesis was unaffected. Renal function such as proteinuria, N-acetyl-beta-D-glucosaminidase (NAG) excretion, and glomerular filtration rate (GFR) was not influenced by bisoprolol. Morphologic investigation showed that bisoprolol significantly improved glomerular sclerosis by 29% and attenuated arterial damage by 71%, although tubular injury was not affected. The more severe the glomerulosclerotic lesions, the greater the generation of thromboxane and ET. The arterial lesions were positively correlated to thromboxane generation. These data indicate that long-term bisoprolol treatment reduces vasoconstrictive ET-1 and thromboxane generation and that these alterations may be partly responsible for the amelioration of glomerular and arterial injury in Dahl S rats.

Adrenergic beta-1 Receptor Antagonists↗

PubMed1994

New dihydropyridine calcium channel antagonist, pranidipine, attenuates hypertensive renal injury in Dahl salt-sensitive rats.

Interest in the cardiovascular protective effects of calcium channel antagonists has increased in the past decade. We investigated prevention of vascular wall remodeling by the long-acting calcium channel antagonist pranidipine in 12-week-old Dahl salt-sensitive (SS) rats with high-salt-induced (4% NaCl) hypertension. Six-week pranidipine treatment (60 mg/kg chow) decreased systolic blood pressure (SBP) by 22% in SS rats. This BP reduction was associated with decreases in cardiac mass and weight of the aortic wall. Glomerular filtration rate (GFR) was increased by 33%, but this did not lead to a decrease in urinary protein or NAG excretion. Morphologic investigation demonstrated striking resolution of arterial injury (medial necrosis and/or hyperplasia, inflammatory cell infiltration, and thrombus formation) by 87% after pranidipine treatment. Glomerular sclerosis was also attenuated by 61%, whereas tubular injury was improved by only 28%. These morphologic changes were reflected in the findings that the capacity of kidney homogenate for generating lipid peroxides was significantly decreased and that collagen levels and pattern type became similar to those of normotensive salt-resistant (SR) rats. Pranidipine also attenuated hypertensive vasculopathy in small arteries of the middle cerebral arteries. Thus, the calcium channel antagonist pranidipine can attenuate the vascular injury that occurs in salt-induced hypertension, a promising property that implicates its clinical usage, particularly in essential hypertension with cardiovascular complications.

Animals↗

PubMed1994

Quantitative analysis of genomic polymorphism of herpes simplex virus type 1 strains from six countries: studies of molecular evolution and molecular epidemiology of the virus.

Using the presence or absence of 63 variable restriction endonuclease (RE) sites selected from 225 sites with six REs, genomic polymorphism of 242 herpes simplex virus type 1 (HSV-1) strains from six countries (Japan, Korea, China, Sweden, U.S.A. and Kenya) was quantitatively analysed. Twenty-five of the 63 sites were found to differ between Korean and Kenyan strains. In contrast, only three and six sites were found to differ between isolates from Sweden and the U.S.A. and between those from Korea and China, respectively, suggesting that they are closely related to each other. In this way, characterization of 63 sites enabled us to categorize 186 distinct HSV-1 genotypes from 242 individuals. Some strains from Japan, Korea and China shared the same genotypes, indicating that they are phylogenetically closely related. Many significant correlation coefficients (magnitude of > 0.42; P < 0.01) between pairs of sites were found in isolates from the three Asian countries (Japan, Korea and China) as well as in those from Sweden and the U.S.A., suggesting that HSV-1 strains from within the same ethnic groups are evolutionarily closer. The average number of nucleotide substitutions per nucleotide, as defined by nucleotide diversity (pi), was estimated for HSV-1 genomes within (pi x or pi y) and between (pi xy) countries. On the basis of 225 sites, nucleotide diversity for Kenyan isolates was 0.0056, almost three times higher than that for Korean isolates, implying that Kenyan HSV-1 genomes are much more diverse than those from Korea. In addition, the diversity between HSV-1 isolates from different countries (pi xy) was highest between isolates from the three Asian countries and Kenya (0.0075 to 0.0081) and lowest among those from the three Asian countries (0.0032 to 0.0040). The mutation rate (lambda) for HSV-1 was estimated to be 3.5 x 10(-8)/site/year. All these findings show that the evolution of HSV-1 may be host-dependent and very slow.

Biological Evolution↗

PubMed1994

Wnt-3a regulates somite and tailbud formation in the mouse embryo.

Amphibian studies have implicated Wnt signaling in the regulation of mesoderm formation, although direct evidence is lacking. We have characterized the expression of 12 mammalian Wnt-genes, identifying three that are expressed during gastrulation. Only one of these, Wnt-3a, is expressed extensively in cells fated to give rise to embryonic mesoderm, at egg cylinder stages. A likely null allele of Wnt-3a was generated by gene targeting. All Wnt-3a-/Wnt-3a- embryos lack caudal somites, have a disrupted notochord, and fail to form a tailbud. Thus, Wnt-3a may regulate dorsal (somitic) mesoderm fate and is required, by late primitive steak stages, for generation of all new embryonic mesoderm. Wnt-3a is also expressed in the dorsal CNS. Mutant embryos show CNS dysmorphology and ectopic expression of a dorsal CNS marker. We suggest that dysmorphology is secondary to the mesodermal and axial defects and that dorsal patterning of the CNS may be regulated by inductive signals arising from surface ectoderm.

Animals↗

PubMed1994

Binding characteristics of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)-2-platin um(II) to DNA, RNA and protein molecules in HeLa cells and its lethal effect: comparison with cis- and trans-diamminedichloroplatinums(II).

HeLa S-3 cells were treated with 195mPt-radiolabeled (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)-2-platinum(II) (DWA2114R) under various conditions, and the relationship between the lethal effect of the agent and the number of platinum (Pt) atoms binding to DNA, RNA and proteins was examined. The values of mean lethal concentration for the cells treated with DWA2114 at 37 degrees C for 1, 2 and 3 h were 137.3, 75.10 and 51.17 microM, respectively. Cells were treated identically and the numbers of Pt atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells. In this way, the D0 values (D0, dose that would give an average of one lethal event per member of the population), expressed as the drug concentration, were substituted for the number of Pt atoms combined with each fraction. The target volumes, the efficacy of Pt atom to kill cells expressed as the reciprocals of the D0 values, were then calculated for each fraction. Our findings suggested that DNA was the primary target molecule for cell killing by DWA2114R. The target volumes for DNA were 3.36 x 10(4), 4.00 x 10(4) and 4.10 x 10(4) nucleotides for 1-, 2- and 3-h treated cells, respectively. The cell-killing effects of DWA2114R were lower than those of cis-diamminedichloroplatinum(II) (CDDP) by factors of 1.54, 1.42 and 2.51 for 1-, 2- and 3-h treatments at 37 degrees C, respectively, in terms of the target volume, while those in terms of the mean lethal dose (D0) were 14.8, 11.2 and 16.0, respectively. The efficacy of DWA2114R in killing the cells was 2.6 times greater than that of CDDP in the 3-h treatment at 0 degrees C.

Carboplatin↗

PubMed1994

The WD gene for Wilson's disease links to the hepatitis of LEC rats.

LEC rats develop an autosomal recessive hepatitis and subsequently liver cancer associated with copper accumulation in the liver similar to that of Wilson's disease. Using 71 backcross [(WKAH x LEC) x LEC] rats, linkage analysis of the hepatitis with the WD gene for Wilson's disease revealed identical segregation and no recombination event between these two genes. This result indicates that the WD gene is a prime candidate for the hts gene responsible for the hepatitis of LEC rats, and suggests that the hepatitis of LEC rats may be caused by a defect in a copper-transporting ATPase expressed in the liver.

Adenosine Triphosphatases↗

PubMed1994

Clinical study of azoospermia.

This study evaluated how many patients with azoospermia might have fertility potential using assisted conception techniques. A total of 102 male patients with azoospermia were included in the study. Thirteen patients had sex chromosomal abnormalities. Testicular biopsy performed in the other 89 patients showed incomplete spermatogenesis in 47 of them whereas 42 had complete spermatogenesis. In the latter 42 patients, distal vasography demonstrated bilateral obstruction of the excurrent ducts in 14 patients whereas no distal obstruction of the ducts was found in 28. The 89 patients were divided into three groups according to the findings of testicular biopsy and distal vasography. In the 14 patients with both complete spermatogenesis and distal obstruction of the excurrent ducts, surgical procedures are applicable. The pathogenesis of the 28 patients with complete spermatogenesis but without distal obstruction of the ducts should be clarified for further treatment.

Adult↗

PubMed1994

A case of recurrent intramural uterine stromal tumor with epithelial differentiation effectively treated with oral low-dose administration of etoposide.

A 66-year-old woman was diagnosed as having myoma of the uterus and total hysterectomy with bilateral salpingo-oophorectomy was performed. The histopathological findings were puzzling, and the case was finally diagnosed as intramural uterine stromal tumor with epithelial differentiation. Three years after the operation, a firm tumor developed in the pelvic cavity. Laparotomy failed to remove the tumor and neither CAP (cyclophosphamide 500 mg, adriamycin 50 mg, CDDP 70 mg) therapy nor radiation therapy was effective. Oral administration of etoposide (25 mg/day), however, showed PR (50% decrease) as determined by CT scanning, and ultrasonography, and no metastatic lesions were found. This tumor was coincident with the endometrial stromal tumor with epithelial elements classified by Clement and Scully. The histological feature of the tumors and the efficacy of oral etoposide therapy are discussed in this study.

Administration, Oral↗

PubMed1994

Occupational exposure to solvent mixtures: effects on health and metabolism.

Exposure monitoring by personal diffusive samplers, biological monitoring of toluene exposure by urinary hippuric acid determination, haematology, serum biochemistry for liver function, and a subjective symptom survey by questionnaire were conducted on 303 male solvent workers. They were exposed to a mixture of solvents including toluene (geometric mean 18 ppm), methyl ethyl ketone (MEK; 16 ppm), isopropyl alcohol (IPA; 7 ppm), and ethyl acetate (9 ppm). The intensity was mostly below unity using the additiveness formula based on current Japanese occupational exposure limits, but more than eight times unity at the maximum. The results were compared with the findings in 135 non-exposed male workers of similar ages. Haematology and liver function tests did not show any exposure related abnormality, and subjective symptoms were mostly related to central nervous system depression and local irritation. Further analysis suggested that the irritation effects were not related to exposure to MEK. Analysis of the relation between toluene exposure and hippuric acid excretion in urine showed that there was no metabolic interaction between MEK and toluene, or between IPA and toluene. Overall, therefore, it is concluded that there was no sign or symptom detected to suggest anything other than toluene toxicity, that there was no evidence to indicate any modification of toluene toxicity or metabolism due to coexposure, and that the additiveness assumption is reasonable for risk assessment for the combination of solvents under these exposure conditions.

1-Propanol↗

PubMed1994

Antihypertensive property and renal protection by shichimotsu-koka-to extract in salt-induced hypertension in Dahl strain rats.

We determined whether or not the kampo formula, Shichimotsu-koka-to extract, attenuates the development of salt-induced hypertension and provides renal protection against hypertensive injury in Dahl salt-sensitive (Dahl S) rats. A six-week treatment using this formula dose-dependently decreased the systolic blood pressure in Dahl S rats fed a high-salt (2% NaCl) diet. This blood pressure reduction was associated with a decrease in the thickness of the aortic wall. Renal function was not altered with this treatment; however, glomerular sclerotic lesions in the kidney were significantly attenuated. Neither arterial nor tubular lesions were affected. These data suggest that Shichimotsukoka-to extract exhibits an antihypertensive effect which is associated with partial resolution of glomerular sclerosis in the kidney.

Animals↗

PubMed1994

Effects of gonadotropin-releasing hormone agonist on steroidogenesis in the rat ovary.

To assess the regulatory roles of gonadotropin-releasing hormone (GnRH) in ovarian function, the kinetics of the ovarian GnRH receptor and the effects of the GnRH superagonist buserelin on steroidogenesis in ovarian cell culture were examined. Scatchard analysis of buserelin-binding to crude ovarian cell membrane revealed a specific high-affinity GnRH receptor. Buserelin together with follicle-stimulating hormone stimulated estradiol (E2) production in immature follicles in hypophysectomized and DES-treated rats. On the other hand, applied to developing follicles of rats treated with pregnant-mare-serum gonadotropin buserelin suppressed E2 production to terminate follicle maturation and simultaneously stimulated progesterone (P4) production to induce luteinization. With ovarian cells luteinized by human chorionic gonadotropin in vitro, buserelin suppressed production of both P4 and E2, leading to luteolysis. Buserelin affected steroid production by modulating activities of key enzymes in steroid synthesis. These findings indicate that buserelin action depended on the gonadotropin priming of ovarian cells, and suggest the possible involvement of GnRH in the regulation of steroidogenesis throughout the ovulatory cycle.

Animals↗

PubMed1994

The involvement of dopamine in the regulation of steroidogenesis in rat ovarian cells.

To investigate a role for dopamine (DA) in steroidogenesis in the rat ovary, ovarian cells of pregnant-mare-serum gonadotropin (PMSG)-treated rats were incubated with DA agonists, antagonists, adrenergic drugs and beta-blocker for 1 h. DA, norepinephrine (NE) and isoproterenol (Iso) increased the level of progesterone (P4) and cAMP in the conditioned medium. D1 agonists (SKF38393, SKF82526J, CY208-243) increased P4 secretion, while the D2 agonist, bromocriptine, showed no significant effect on P4 secretion. The effect of NE or Iso was inhibited by the beta-blocker propranolol (Pro), but was not suppressed by the D2 antagonist, domperidone. The effects of D1 agonists were suppressed by bulbocapnine (Bul), while neither Pro nor the D2 antagonist, domperidone, affected the levels of P4. The D1 receptor was demonstrated in the PMSG-treated rat ovary, and its Bmax was 1.33 fmol/mg tissue and the Kd was 0.357 nM. These results suggest that DA has a direct stimulatory effect on P4 secretion in PMSG-treated rat ovarian cells through they D1 receptor. The observed action may indicate a physiological role for DA in the regulation of ovarian functions in rats.

Animals↗

PubMed1994

Ovarian metastasis in patients with colorectal carcinoma.

The records of 159 patients who underwent surgical resection of colorectal cancer were reviewed to assess the incidence of ovarian metastasis and to define the role of oophorectomy. Four of these patients presented with metachronous metastases, and one patient had synchronous ovarian involvement. The incidence of ovarian involvement was higher in younger patients. While most patients with ovarian involvement had the primary tumor located at the rectosigmoid region, a similar distribution of the primary tumor was observed in patients without ovarian metastasis. The histological type and degree of differentiation was similar regardless of whether or not ovarian metastasis was present. Of the patient without ovarian metastasis, 57% presented with nodal metastases and 3.2% with peritoneal dissemination, while all patients with ovarian metastasis had nodal and peritoneal involvement. Our results suggest that histological type and degree of differentiation of the primary tumor do not influence likelihood of ovarian metastasis. However, the exposure of the tumor to the serosal surface and the subsequent peritoneal dissemination may be an important route by which malignant tumor cells reach the ovaries. However, due to the wide lymphatic involvement in patients with ovarian metastasis, the lymphatic route may be important as well. Thus, we consider that oophorectomy should be performed in all postmenopausal women, when the ovaries are macroscopically affected, and in premenopausal patients with Astler-Coller B2 tumors or over.

Adult↗

PubMed1994

Role of nuclear histone-H1 kinase in regeneration of rat liver.

The activities of nuclear histone-H1 kinase and C-kinase as well as the amount of phosphate bound to histone-H1 following partial hepatectomy were studied in rat. It was found that the nuclear histone-H1 kinase activity increased twice within 80 h, first 20 to 30 h, and second at 50 to 70 h after partial hepatectomy. The timing of increase of the enzyme activity correlated with increased amount of bound phosphate. On the other hand, the increase of the C-kinase activities occurred between 5 and 15 h after partial hepatectomy. Antibodies raised against human cdk2, human cyclin-A and mouse cdc2 kinase showed no detectable effect on the nuclear histone H1 kinase activity. These results suggest that phosphorylation of histone-H1 in liver regeneration may be catalysed by a putative kinase(s).

Animals↗