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Biomedical subjects

K Sugimoto

Publications and source records attributed to K Sugimoto.

At least 181 records · Page 10Linked to original sources
PubMed1999

Administration time-dependent effect of nitrendipine on the reduction of cardiac hypertrophy in spontaneously hypertensive rats.

The influence of administration time of nitrendipine on the regression of cardiac mass was studied in spontaneously hypertensive rats (SHR). Nitrendipine (100 mg/kg) was given once daily at 10 AM or 10 PM for 16 weeks. Similar reductions of the trough blood pressure were observed in both groups. Cardiac biventricular mass in the animals dosed at 10 PM was significantly less than that in the vehicle-treated rats, whereas in the rats dosed at 10 AM no significant reduction was noted in the cardiac mass. These data suggest that the administration time of nitrendipine has a different effect on the regression of cardiac hypertrophy in SHR.

Animals↗
PubMed1999

Visualization of prekinetochore locus on the centromeric region of highly extended chromatin fibers: does kinetochore autoantigen CENP-C constitute a kinetochore organizing center?

Kinetochore is morphologically defined as a trilaminated, highly differentiated structure at the primary constriction of mitotic chromosomes. This subcellular organella is assumed to be composed of DNA and proteins. Immunoelectron microscopy has shown that centromere autoantigens CENP-C and CENP-B localize to the kinetochore inner plate and the underlying centromeric region respectively. We previously indicated that both are DNA-binding proteins that constitute centromeric heterochromatin throughout the cell cycle. Here, we tried to elucidate how these molecules are involved in the kinetochore/centromere organization in vivo by analyzing their morphological behavior in nuclei. Using immunofluorescence microscopy, we found that CENP-C remained as round discrete dots, whereas CENP-B displayed larger surrounding materials. To examine the CENP-C-binding locus on the genome, we prepared highly extended chromatin fibers and performed simultaneous immunofluorescence and fluorescence in situ hybridization. We obsreved that centromeric alphoid DNA, targeted by CENP-B, was highly dispersed, whereas the CENP-C antigen persisted as small dots well situated on the fibers. These features reminded us of the 'ball and cup' structure that had been presented for 'prekinetochore'. We propose here that CENP-C constitutes a 'kinetochore organizing center' tightly associating with DNA, whereas CENP-B heterochromatin offers the solid support during kinetochore maturation.

Animals↗
PubMed1999

Effects of candesartan cilexetil on oxidative state and renal function in 5/6 nephrectomized rats.

We have investigated the influence of a novel angiotensin II type 1 receptor antagonist, candesartan cilexetil, on the oxidative state of renal tissue and renal function in 5/6 nephrectomized rats, and compared its effects with those of an angiotensin-converting enzyme inhibitor, enalapril. Candesartan cilexetil (1 and 5 mg/kg per day), enalapril (5 mg/kg per day) and vehicle were orally administered once daily for 16 weeks after 5/6 nephrectomy. There was a marked degree of proteinuria evident prior to treatment, an average of 5.69 mg/mg creatinine in the nephrectomized rats, vs 1 to 2 mg/mg creatinine in the control group matched for species and body weight. Inhibition of development of proteinuria by candesartan cilexetil was dose dependent. Enalapril also significantly blunted the rise in urinary protein. Malondi-aldehyde content in the homogenate from the renal cortex increased significantly in the nephrectomized rats compared to control animals. This elevation of malondi-aldehyde content was unaffected by administration of either candesartan cilexetil or enalapril. Antioxidative enzyme (glutathione peroxidase, superoxide dismutase, and catalase) activities in the renal tissue were not affected by any active treatment. Elevation of lipid peroxide in remnant renal tissue suggests that oxidative stress may contribute to the progression of renal injury in the nephrectomized rats. Neither candesartan cilexetil nor enalapril affected antioxidant defenses in renal tissue in nephrectomized rats, indicating that mechanisms other than alteration in oxidative stress are involved in the renoprotective effects of candesartan cilexetil and enalapril.

Angiotensin Receptor Antagonists↗
PubMed1999

Inhibition of p34cdc2 dephosphorylation in DNA damage- and topoisomerase II inactivation-induced G2 arrests in HL-60 cells.

Doxorubicin induces DNA breakage by stabilizing a cleavable topoisomerase II-DNA complex. In contrast, topoisomerase II catalytic inhibitor ICRF-193 and uncoupling inhibitor aclarubicin interfere with the cleavable complex formation. We analysed combination effects of these drugs using two-dimensional flow cytometry of DNA content and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling assay. Both ICRF-193 and aclarubicin attenuated the cytotoxic effect of doxorubicin on HL-60 cells (85% and 46% maximum reduction, respectively), which suggested that doxorubicin exerts its cytotoxic effect at least partially through the topoisomerase II-dependent DNA cleavage. Doxorubicin and ICRF-193 both induced G2 arrest in HL-60 cells, by which they may have reduced the cytotoxic effect of vincristine. Indeed, although ICRF-193 inhibited doxorubicin-induced apoptosis, ICRF-193 and doxorubicin cooperated in arresting HL-60 cells at G2 phase. These results indicated that G2 arrest was caused not only by DNA damage but also through a DNA damage-free, topoisomerase II inactivation-induced pathway. Western blot analysis showed that both types of G2 arrest were mediated by the inhibition of p34cdc2 dephosphorylation.

Antineoplastic Agents↗
PubMed1999

A 13-bp cis-regulatory element in the LTR promoter of the tobacco retrotransposon Tto1 is involved in responsiveness to tissue culture, wounding, methyl jasmonate and fungal elicitors.

The tobacco Tto1 is one of the few active LTR-retrotransposons of plants, and its transposition is activated by tissue culture and is primarily regulated at the transcriptional level. The expression of Tto1 RNA can also be activated by various stresses, including viral infection, wounding, and treatment with jasmonate, a signal molecule of plant defence responses. It is shown here that the Tto1 LTR promoter is responsible for a high level of expression in cultured tissues of transgenic tobacco plants. We demonstrate that a 13-bp repeated motif (TGGTAGGTGAGAT) in the LTR functions as a cis-regulatory element, which confers the responsiveness to tissue culture, wounding and methyl jasmonate. Fungal elicitors also activate the promoter containing multiple copies of the 13-bp motif. Expression mediated by the 13-bp motif is activated markedly by okadaic acid and moderately by K252a, so that both phosphorylation and dephosphorylation of proteins are possibly involved in the signalling pathways. Interestingly, the 13-bp motif contains a conserved motif, Box L (also called AC-I or H-box like sequence) which has been shown to be involved in the expression of phenylpropanoid synthetic genes. Moreover, extended homologies are found between promoters of Tto1 and an asparagus defence gene, AoPR1, suggesting a possibility that the ancient insertion of an ancestral Tto1-related retrotransposon has provided some of the promoter/regulatory sequences, including the 13-bp motif-related sequence, of the AoPR1 gene. Based on the structural and functional similarity between the two promoters, a possible evolutionary role of the regulatory sequences of LTR-retrotransposons is discussed.

Acetates↗
PubMed1999

Hyperlipidaemia and the progression of nephropathy in OLETF rats: effect of angiotensin-converting enzyme inhibitor, enalapril.

1. The influence of angiotensin-converting enzyme (ACE) inhibitor is investigated in enalapril on renal function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneously non-insulin-dependent diabetes (NIDDM). 2. Enalapril (5 mg/kg) or vehicle was administered once daily by gastric gavage to 22-week-old male OLETF rats for 32 weeks. Blood pressure, albuminuria, creatinine clearance, plasma glucose, serum insulin and lipids were determined before and during the treatment. Renal haemodynamics was examined at the end of the treatment. 3. Enalapril lowered blood pressure mildly but significantly. In the vehicle-treated rats, urinary albumin excretion increased from 0.75 +/- 0.16 mg/mg creatinine (Cr) to 8.65 +/- 0.78 mg/mg Cr. Enalapril significantly blunted the development of albuminuria from 0.66 +/- 0.12 mg/mg Cr to 5.19 +/- 0.67 mg/mg Cr (P < 0.008) without significant influence on creatinine clearances. Enalapril also significantly blunted the rise in serum cholesterol and triglyceride prior to the development of massive albuminuria. Enalapril did not affect bodyweight, plasma glucose or insulin levels. Renal haemodynamics assessed by inulin and p-aminohippuric acid clearances were similar in both groups at the end of the treatment. 4. These results reconfirmed that the ACE inhibitor has protective effects on nephropathy in NIDDM. Massive albuminuria was preceded by increase in serum lipids in OLETF rats, which supports the view that hyperlipidaemia exacerbates glomerular injury in chronic renal disease. Enalapril attenuated the rise in serum lipids, suggesting that the beneficial effects of the compound on renal injury in OLETF rats might also be mediated through the action of affecting serum lipids.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Angiotensin II in human veins: development of rapid desensitization and effect of indomethacin.

1. The present study investigated whether rapid desensitization (tachyphylaxis) develops after exposure of human hand veins to angiotensin (Ang)II and whether pretreatment with indomethacin affects its development. 2. Venoconstrictor responses to increasing (2-256 ng/min) and constant (50 ng/min) doses of AngII and noradrenaline (NA) infusion were obtained in six healthy male subjects using the dorsal hand vein technique. After pretreatment with indomethacin and placebo, venoconstrictor responses to 50 ng/min AngII infusion were obtained in eight healthy male subjects. 3. The maximal mean (+/- SD) venoconstrictor response to NA (obtained with 256 ng/min NA) was 93.1 +/- 4.7%, whereas that to AngII (obtained with doses between 16 and 128 ng/min) was 43.8 +/- 12.2%. Continuous infusion of NA induced constant venoconstriction, whereas the venoconstrictor response to AngII peaked 3 min after the beginning of infusion and, thereafter, was attenuated. 4. Venoconstriction in response to constant AngII infusion after indomethacin pretreatment was significantly larger than that after placebo from 6 to 18 min after the initiation of infusion. 5. These findings show that rapid desensitization to AngII develops in human hand veins and this is compatible with the hypothesis that vasodilator prostaglandins are involved in the development of this desensitization.

Adult↗
PubMed1999

Functional domain structure of human heterochromatin protein HP1(Hsalpha): involvement of internal DNA-binding and C-terminal self-association domains in the formation of discrete dots in interphase nuclei.

Human heterochromatin protein HP1(Hsalpha) possesses two evolutionarily conserved regions in the N- and C-terminal halves, so-called chromo and chromo-shadow domains, and DNA-binding domain in the internal non-conserved region. Here, to examine its in vivo properties, we expressed HP1(Hsalpha) as a fusion product with green fluorescent protein in human cells. HP1(Hsalpha) was observed to form discrete dots in interphase nuclei and to localize in the centromeric region of metaphase chromosomes by fluorescence microscopy. Interestingly, this dot-forming activity was also found in the N-terminal half retaining the chromo and DNA-binding domains and in the C-terminal chromo-shadow domain. However, the chromo domain alone stained nuclei homogeneously. To correlate this dot-forming activity with self-associating activity in vitro, the chromo and chromo-shadow domain peptides were independently expressed in Escherichia coli, affinity purified, and chemically cross-linked with glutaraldehyde. In a SDS-polyacrylamide gel, the former mainly produced a dimer, while the latter produced a ladder of bands up to a tetramer. When passed through a gel filtration column in a native state, these peptides were exclusively separated as a dimer and a tetramer, respectively. These results suggested that the internal DNA-binding and C-terminal chromo-shadow domains are both involved in heterochromatin formation in vivo.

Binding Sites↗
PubMed1999

Identification of aggrecanase activity in medium of cartilage culture.

Erosion of cartilage is a major feature of joint diseases, i.e., osteoarthritis and rheumatoid arthritis, which leads with time to a loss of joint function. Proteolytic cleavage of the aggrecan core protein is a key event in the progress of these joint diseases. Aggrecan degradation has been believed to be mediated by a putative proteinase, aggrecanase. We identified aggrecanase activity in conditioned medium from explant culture of bovine nasal cartilage stimulated by retinoic acid. The activity was partially purified more than 10,000-fold. The enzyme cleaves at the aggrecanase site (Glu(373)-Ala(374)) but not at the MMP site (Asn(341)-Phe(342)) in the interglobular domain of the aggrecan. It also cleaves at Glu(1971)-Leu(1972), which is located in the gap region in the chondroitin sulfate attachment region prior to the aggrecanase site. The enzyme is a typical Ca(2+)-dependent metalloproteinase with a unique salt-dependency and is inhibited by several hydroxamate-based inhibitors for matrix metalloproteinases. Heparin and chondroitin sulfate inhibited the enzyme in a dose-dependent manner, suggesting that the large carbohydorate in aggrecan is important for substrate recognition by aggrecanase.

Animals↗
PubMed1999

Long-term results of arthrodesis for osteoarthritis of the ankle.

A bone graft in the shape of a triangular prism was taken from the anterior surface of the tibia and used in the arthrodesis in 43 joints of 42 patients with primary and secondary osteoarthritis of the ankle. The modified anterior sliding inlay graft method was used. The average period of external immobilization was 5.8 weeks (range, 27-84 days), and followup ranged from 2 years 4 months to 14 years 11 months (average, 7 years 2 months). Nonunion was detected in three (7%) patients: one patient returned to work without additional treatment, and the other two patients underwent followup surgery within 7 months, and bony union was achieved. The final rate of nonunion was 2.3%. After the operation, excellent alleviation of pain was obtained. However, dorsiflexion of the foot decreased from the preoperative average value of 10.5 degrees to the postoperative value of 4.2 degrees, and plantar flexion also decreased from the preoperative value of 24.7 degrees to the postoperative value of 14 degrees. In addition, the range of motion of the subtalar and Chopart joints gradually improved with little effect on daily living activities. The most appropriate position of arthrodesis of the ankle appears to be in the neutral position between dorsal and plantar flexion. In addition, the varus and valgus angle of the hindfoot should be in a neutral or slightly valgus position. Degenerative arthritis developed and advanced in the subtalar joint in 32.5% of the patients, and these degenerative changes were exacerbated in many patients if such changes were present before surgery. Tibial stress fracture occurred in two (4.7%) patients as a complication that was specific to the current surgical method. Thus, the surgical procedure was modified to prevent the onset of tibial stress fracture.

Activities of Daily Living↗
PubMed1999

Role of a complex containing Rad17, Mec3, and Ddc1 in the yeast DNA damage checkpoint pathway.

Genetic analysis has suggested that RAD17, RAD24, MEC3, and DDC1 play similar roles in the DNA damage checkpoint control in budding yeast. These genes are required for DNA damage-induced Rad53 phosphorylation and considered to function upstream of RAD53 in the DNA damage checkpoint pathway. Here we identify Mec3 as a protein that associates with Rad17 in a two-hybrid screen and demonstrate that Rad17 and Mec3 interact physically in vivo. The amino terminus of Rad17 is required for its interaction with Mec3, and the protein encoded by the rad17-1 allele, containing a missense mutation at the amino terminus, is defective for its interaction with Mec3 in vivo. Ddc1 interacts physically and cosediments with both Rad17 and Mec3, indicating that these three proteins form a complex. On the other hand, Rad24 is not found to associate with Rad17, Mec3, and Ddc1. DDC1 overexpression can partially suppress the phenotypes of the rad24Delta mutation: sensitivity to DNA damage, defect in the DNA damage checkpoint and decrease in DNA damage-induced phosphorylation of Rad53. Taken together, our results suggest that Rad17, Mec3, and Ddc1 form a complex which functions downstream of Rad24 in the DNA damage checkpoint pathway.

Alleles↗
PubMed1999

Hindfoot alignment of hallux valgus evaluated by a weightbearing subtalar x-ray view.

A new radiographic view was proposed to evaluate alignment of the hindfoot under weightbearing condition. The ankle joint and the middle and posterior facets of the subtalar joint were clearly visualized in all radiographs. A comparative study was made of 104 feet with hallux valgus in 58 female patients and 67 normal feet in 57 normal female subjects (control group). The mean value of the angle between the axis of the tibia and a line on the surface of the ankle joint on the talus was significantly larger in the group with hallux valgus than in the control group. Likewise, the mean value of the angle between the axis of the tibia and a line on the surface of the posterior facet of the subtalar joint on the calcaneus in the group with hallux valgus was 95.3 degrees, significantly larger than the 87.9 degrees in the control group. These findings showed that the ankle joint and the posterior facet of the subtalar joint in hallux valgus have valgus deviation. The hindfoot in a foot with hallux valgus has a tendency toward pronation. No previous study has measured the inclination of the posterior facet of the subtalar joint directly in weightbearing.

Adolescent↗
PubMed1999

A comparison of the antagonistic activities of tamsulosin and terazosin against human vascular alpha1-adrenoceptors.

Tamsulosin, a selective alpha1A-adrenoceptor antagonist, and terazosin, a non-selective one, are effective for the treatment of urinary disturbance due to benign prostatic hypertrophy. In the present study, their alpha1-adrenoceptor-blocking effects on blood vessels, which may cause orthostatic hypotension, were investigated in 10 healthy males. After the subjects took orally 0.2 mg of tamsulosin, 1 mg of terazosin or a lactate capsule as the control in a randomized cross-over fashion, their finger tip vasoconstrictor response to cold stimulation and vasoconstrictor response of the dorsal hand vein to increasing doses of phenylephrine were examined. The finger tip vasoconstrictor response was significantly reduced and the infusion rate of phenylephrine producing a half-maximal constriction was significantly increased by terazosin, but tamsulosin had no significant effect on these parameters. These data suggest that the usual dose of tamsulosin exerts little alpha1-adrenoceptor-blocking activity on blood vessels, and orthostatic episodes might be mild, if any, during the treatment with tamsulosin.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

Development of the ball-and-socket ankle as assessed by radiography and arthrography. A long-term follow-up report.

We studied the development of ball-and-socket deformity of the ankle by arthrography and radiography in 14 ankles of ten patients with congenital longitudinal deficiency of the fibula accompanied by various anomalies. The mean follow-up was for 18 years 10 months. In three ankles in infants less than one year old the lateral and medial sides of the ankle were already slightly round. In another seven ankles the ball-and-socket appearance developed before the age of five years. This was thought to be due to osseous coalition which limits eversion and inversion. In another four ankles in children who were over the age of one year at the initial examination, the deformity was demonstrated by arthrography and radiography at their first examination. Ball-and-socket deformity accompanied by tarsal coalition is an acquired deformity secondary to limitation of movement of the subtalar and midtarsal joints. It has completely developed by about five years of age.

Adolescent↗
PubMed1999

Levothyroxine-induced liver dysfunction in a primary hypothyroid patient.

Here we report a case of levothyroxine-induced liver dysfunction. T4 (levothyroxine) has been more commonly used for the treatment of hypothyroidism than T3 active hormone (triiodothyronine), because with the former drug a stabler plasma concentration is obtained after oral administration. Although there are few reports on levothyroxine-induced liver dysfunction, we treated a primary hypothyroid patient with high serum aminotransferase after administration of levothyroxine. Liver dysfunction was improved after cessation of the drug administration. Antibody to T4 was found in the serum of the patient after this event. From clinical course and laboratory data of the patient, the episode of liver damage was considered to be induced by levothyroxine. We then administrated triiodothyronine, and it did not induce liver dysfunction. Changing levothyroxine to triiodothyronine resulted in a successful clinical course in this case, as re-administration of the doubtful drug is strictly limited.

Adolescent↗