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Biomedical subjects

K Kitagawa

Publications and source records attributed to K Kitagawa.

At least 253 records · Page 14Linked to original sources

Changes of c-mos expression in response to 2-O-tetradecanoylphorbol-13-acetate in undifferentiated teratocarcinoma cells.

Treatment of the cells of the 311 cell line, a pluripotent mouse teratocarcinoma cell line, with 12-O-tetradecanoylphorbol-13-acetate (TPA) modulates c-mos expression. Transient suppression of 6.1 and 4.6 kilobases (kb) transcripts and activation of 1.8 transcript indicate that TPA mediates concurrently positive and negative regulation of c-mos transcription. The results show that the c-mos gene is a TPA-modulated gene. In addition, a TPA-responsive element (GTGACTCA), which exists in the 5'-flanking region of c-mos gene of Balb/c mice [1,2], is suggested to be involved in this response. However, these changes were not accompanied by early marker changes associated with endodermal cell differentiation, i.e., morphological change, induction of plasminogen activator and suppression of glucose transport activity.

3-O-Methylglucose↗

Phase I clinical studies of 7432-S, a new oral cephalosporin: safety and pharmacokinetics.

Phase I clinical studies of 7432-S, a new oral cephalosporin, including a randomized placebo-controlled trial were conducted with 40 healthy volunteers. In single-dose studies, 7432-S was orally administered at doses of 25, 50, 100, and 200 mg. The mean plasma levels peaked at 2.1 to 3.0 hours and reached 1.9, 3.6, 5.6, and 11.6 micrograms/ml, respectively. Linear correlation was observed between plasma AUC values and doses given. The half-lives of the plasma levels were 0.88 to 2.26 hours with a mean of 1.53 +/- 0.33 hours. The mean urinary recoveries were 67.5 to 75.2% of the dose within 24 hours. 7432-S was partially metabolized to 7432-S-trans which was excreted in urine at 7.2 to 9.2% of the doses. Study of the meal effect showed that AUC values and peak levels were not altered although the time to the peak levels was slightly prolonged. In multiple-dose studies, 100 mg of 7432-S twice daily for 2 weeks and 200 mg twice daily for 1 week were administered and there was no abnormal accumulation of 7432-S in plasma throughout the study. No significant differences were observed in plasma levels and urinary recoveries between single- and multiple-dose regimens. Clinical symptoms, physical tests, laboratory parameters, and fecal levels of vitamins K1 and K2 were in normal ranges. 7432-S was concluded to be safe and well tolerated.

Administration, Oral↗

Levallorphan and dynorphin improve motor dysfunction in Mongolian gerbils with unilateral carotid occlusion: the first application of the inclined plane method in the experimental cerebral ischemia.

Levallorphan and dynorphin were effective on the motor dysfunction in the gerbil model of unilateral cerebral ischemia. The effect of opioids, levallorphan (mixed agonist-antagonist), dynorphin (kappa-receptor agonist) and naloxone (mu-receptor antagonist), on neurological impairment was evaluated using the unilateral cerebral ischemia model of gerbil. Motor function was evaluated quantitatively by using the inclined plane method. Both levallorphan-treated group and dynorphin-treated group showed a significant improvement of the motor dysfunction compared with saline-control group. On the other hand, naloxone-treated group did not differ from saline-control group. The beneficial effect of these opioids on motor dysfunction might be mediated by the kappa-opioid receptor. This study also showed the potential usefulness of the inclined plane method for the investigation on the cerebral ischemia.

Animals↗

Changes in aerobic and anaerobic ATP-synthesizing activities in hypoxic mouse brain.

The changes in cerebral metabolism in mice in severe hypoxia were investigated by analyses of changes in the levels of energy metabolites and near-infrared spectrophotometric assessment of the states of hemoglobin and cytochrome oxidase. Under 4.4% O2, the contribution of anaerobic ATP production was at most about 20% of the demand. However, the cerebral ATP level was kept at the control level until about 1 min before death. Pentobarbital anesthesia, which reduced the cerebral rate of metabolism, prolonged the survival time, although anaerobic ATP production still did not support ATP demand. Under these conditions, deoxygenation of hemoglobin and reduction of cytochrome oxidase proceeded rapidly within 1 min. Hemoglobin reached the maximum state of deoxygenation in the middle phase of hypoxia, with no further change until death. However, cytochrome oxidase was reduced slowly with one phase of partial reoxidation due to increase of cerebral blood volume, and reached the completely reduced state at death. From these results it was concluded that the aerobic ATP synthesis, which supplied more than 80% of the cerebral demand, decreased gradually because of limitation of oxygen supply, and that the failure of oxidative phosphorylation to meet demand triggered the decrease in the cellular ATP level that led to death.

Adenosine Diphosphate↗

Primary retroperitoneal teratoma in an adult: ultrasonographic, computer tomographic and magnetic resonance imaging demonstrations.

A 25-year-old male patient with a primary retroperitoneal teratoma is described. The chief complaint was right hypochondralgia during exercise for seven days. Various diagnostic imagings disclosed an expansive, heterogeneous and fat-rich mass associated with multiple cystic lesions in the right suprarenal fossa. Sagittal, transaxial and coronal magnetic resonance imaging scan visualized the extent and character of the tumor very clearly. Histological examination of the tumor removed through a thoracoabdominal approach showed cystic teratoma with out malignant transformations.

Adult↗

Inhibition by pertussis toxin of fibroblast growth factor-stimulated hexose transport in Swiss 3T3 cells.

Addition of fibroblast growth factor to quiescent cultures of Swiss 3T3 cells stimulated the membrane transport of 2-deoxyglucose. Treatment of the cells with pertussis toxin (islet-activating protein) inhibited fibroblast growth factor-stimulated hexose transport. 5'-Guanylyl imidodiphosphate (p[NH]ppG), a non hydrolyzable analogue of GTP, increased the number of hexose carriers in the plasma membrane of saponin-permeabilized cells. These results suggest that guanine nucleotide binding protein may be involved in the regulation of hexose transport system by fibroblast growth factor in Swiss 3T3 cells.

Affinity Labels↗

Ca2+-dependent translocation of hexose carrier in mouse fibroblast Swiss 3T3 cells.

Ca2+-induced translocation of hexose carriers from microsomal membrane to plasma membrane was demonstrated in saponin-permeabilized Swiss 3T3 cells by a specific D-glucose-inhibitable cytochalasin B-binding assay. The number of hexose carriers in the plasma membrane and the hexose transport activity in intact cells were also compared. The incubation of permeabilized cells with 10 microM Ca2+ at 37 degrees C rapidly increased the number of D-glucose-inhibitable cytochalasin B-binding sites in the plasma membrane from 13 to 40 pmol/mg protein and concomitantly decreased that in the microsomal membrane from 66 to 36 pmol/mg protein, each with a half-time of approx. 2 min. Furthermore, when Ca2+-stimulated cells were exposed to 50 microM EGTA, the effect of Ca2+ on the translocation of D-glucose-inhibitable cytochalasin B-binding sites was reversed with a half-time of approx. 5 min. The concentration of Ca2+ required for the half-maximal effect was approx 500 nM. The magnitude of the stimulatory effect of D-glucose-inhibitable cytochalasin B-binding sites in the plasma membrane closely correlated with the magnitude of stimulatory action of Ca2+ on 3-O-methylglucose transport in the intact cells. These results suggest that Ca2+ regulates the activity of hexose transport across the plasma membrane through a rapid and reversible translocation of hexose carrier between microsomal and plasma membranes of mouse fibroblast Swiss 3T3 cells.

3-O-Methylglucose↗

Insulin-like effect of dichloroacetic acid on hexose transport in Swiss 3T3 cells.

Hexose transport in Swiss 3T3 cells was increased by treatment with dichloroacetic acid as well as by treatment with insulin. Neither extra- nor intracellular Ca2+ was found to be involved in their stimulatory action. On the other hand, the removal of intracellular Mg2+ resulted in a loss of the stimulation. These results suggest that dichloroacetic acid stimulates the hexose transport in Mg2+-dependent manner, similar to that of insulin.

3-O-Methylglucose↗

Suppression of c-mos expression in teratocarcinoma cells with a new type of inducer of differentiation, 3,5-di-tert-butylchalcone 4'-carboxylic acid.

The treatment of 311 cells, a pluripotent mouse teratocarcinoma cell line, with a new type of inducer, 3,5-di-tert-butylchalcone 4'-carboxylic acid (Ch55), results in the suppression of the c-mos gene, accompanied by early marker changes associated with cell differentiation, i.e., the enhanced secretion of plasminogen activator and the decrease in peanut agglutinin receptors and glucose transport. This indicates that Ch55 is a potent inducer of teratocarcinoma cells and suppresses c-mos expression.

3-O-Methylglucose↗

Comparisons of blood and urinary responses to cold exposures in young and older men and women.

Minimally dressed men and women between 20 and 72 years old rested for 2 hr in 28, 20, 15, and 10 degrees C room temperatures (Ta). Older women maintained core temperatures during all exposures, partially due to rapid increases in metabolism. Regardless of Ta, blood glucose levels were higher in older than younger women during the first hour of the exposures (p less than .05). Free fatty acid levels in older women were double those of others (p less than .001). Epinephrine levels were 25% higher in men than women (p less than .05). Cortisol levels were 30% higher in younger than older adults, regardless of sex (p less than .01). All measurements, and norepinephrine, were elevated in all groups during the 10 degrees C exposure. Rapid increases in metabolism in older women during cold exposure may have been facilitated by substrate availability. This advantage may have resulted from greater utilization of cortisol and epinephrine, increased catecholamine sensitivity, or hormonal changes consequent to menopause.

Adaptation, Physiological↗

Synthesis of porcine neuropeptide Y(NPY) in solution.

The porcine neuropeptide Y (NPY), a 36-residue peptide amide, was synthesized by assembling six peptide fragments followed by thioanisole-mediated deprotection with trifluoromethanesulfonic acid in trifluoroacetic acid. beta-Cycloheptyl aspartate, Asp(OChp), was employed to suppress base-catalyzed succinimide formation. When administered to dogs, the purified peptide (10 micrograms/kg) caused prolonged increase of systemic arterial blood pressure and decreased pancreatic blood flow.

Animals↗

Capsaicin enhances the non-adrenergic twitch response of rat vas deferens.

1 Capsaicin (Cap) enhanced the twitch response of the epididymal and prostatic portions of rat vas deferens induced by field stimulation at 0.1 Hz. The effect of Cap was reproducible and showed no desensitization. 2 Prazosin, and pretreatment with reserpine or Cap did not affect the potentiating effect of Cap, whereas pretreatment with 6-hydroxydopamine abolished the action of Cap. 3 Cap tended to attenuate the contractions induced by noradrenaline, tyramine and ATP. 4 Like Cap, substance K and substance P augmented the twitch response without causing desensitization, but their effects differed somewhat from that of Cap. Calcitonin gene-related peptide inhibited the twitch response. 5 These results suggest that Cap enhances a stimulation-induced, prazosin-resistant non-adrenergic twitch response of rat vas deferens through an as yet undefined prejunctional mechanism. This mechanism is possibly mediated by some peptide released in response to Cap from sensory neurones, which in turn acts on sympathetic nerves and increases stimulation-induced release of a mediator or cotransmitter responsible for the non-adrenergic twitch response. However, the possibility that Cap has a direct action on sympathetic nerves cannot be ruled out.

Animals↗

Possible involvement of a Na+/H+ antiporter in the stimulation of hexose transport in Swiss 3T3 cells by a phorbol ester and growth factors.

Phorbol-12,13-dibutyrate, epidermal growth factor, and insulin raised the intracellular pH ([pH]i), presumably through the activation of a Na+/H+ antiporter. Addition of amiloride or replacement of extra-cellular Na+ by choline which abolishes the cytoplasmic alkalinization prevented the stimulation of hexose transport by these agents. Furthermore, monensin, a Na+/H+ ionophore which increases the [pH]i, stimulated hexose transport. This stimulation was also prevented by the replacement of extra-cellular Na+ by choline. These observations suggest that stimulation of the Na+/H+ antiporter may have stimulated the increase in hexose transport.

Amiloride↗