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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 901 records · Page 50Linked to original sources

Influence of fixed fibroblasts on glycosaminoglycan synthesis of human gastric carcinoma cells in vitro.

The influence of fixed fibroblasts on the glycosaminoglycan (GAG) synthesis of gastric carcinoma cells was examined by incubation along with [3H]glucosamine. In well-differentiated adenocarcinoma cells, the amount of 3H-GAG in the interface material between the carcinoma cells and the fixed fibroblasts was much larger (about twenty times) than in the interface between the carcinoma cells and the bare culture plates, and 3H-GAG consisted mainly of heparan sulfate, with a small amount of dermatan sulfate and chondroitin sulfate. On the other hand, in poorly differentiated carcinoma cells, the amount of 3H-GAG in the interface material produced by the carcinoma cells on the fibroblast was almost the same as on the bare culture dish. In a conventional monolayer culture, well-differentiated adenocarcinoma cells produced a much greater amount of GAG, consisting mainly of dermatan sulfate, chondroitin sulfate and heparan sulfate, than poorly differentiated carcinoma cells. Almost the same amount of hyaluronic acid was secreted into the medium by both types of carcinoma cells.

Adenocarcinoma↗

Development of responses by facial expressions and eye movements in neonates and young infants.

Eye movements and facial expressions were assessed in 177 normal neonates and infants under 150 days of age after the examiner gazed into their eyes for 20 seconds. Blinking to a threatening stimulus and turning of the eyes towards a red object near the examiner's face were tested. The eye movements abruptly changed from fine nystagmoid movements to distinct rolling movements suggesting observation of the examiner's face after 70-80 days of age. Rapid turning of the eyes towards the red object also appeared from the same age, while blinking developed gradually after 40 days of age. Most infants under 80-90 days of age knitted their brows and showed esophoria in response to the examiner's face or facial movements, but such responses gradually disappeared after 90 days of age when social smiles developed. Eye movements and facial expressions during early infancy are very informative in developmental evaluations.

Blinking↗

Increase in norepinephrine-induced formation of phosphatidic acid in rat vas deferens after denervation.

Surgical denervation of rat vas deferens causes supersensitivity in that the tissue sensitivity and the maximum response to a variety of agonists increase. To understand the molecular mechanism of supersensitivity in smooth muscle, norepinephrine(NE)-induced alteration in phospholipid metabolism was studied using control and denervated vasa deferentia. When the tissue was stimulated by NE, only [32P]Pi incorporation into phosphatidic acid(PA) was increased in proportion to the increase in NE concentration without any significant effect on that into other phospholipids. This PA labeling was significantly accelerated by denervation. In the denervated tissue, PA labeling was stimulated by lower concentrations of NE and the maximum response to NE was increased compared to the control. The breakdown of phosphatidylinositol 4-monophosphate(DPI) and phosphatidylinositol 4,5-diphosphate (TPI) was also accelerated by NE. But the influence of denervation on this NE-induced DPI and TPI was not marked. Therefore, it is likely that denervation clearly enhanced NE-induced PA labeling without an appreciable effect on that of the other phospholipids. Furthermore, the absolute amount of PA was also increased by NE, and this increase was exaggerated by denervation. Considering that PA can behave as a Ca2+ ionophore in the plasma membrane, these results suggest that the stimulated accumulation of PA plays an important role in receptor-linked supersensitivity in smooth muscle.

Animals↗

Traxanox augments immune response to lipopolysaccharide in inbred mice: role of macrophages.

Both C57BL/6 and BALB/c mice were immunized intravenously with lipopolysaccharide (LPS, 10 micrograms/mouse) on day 0, and hemolytic plaque forming cells (HPFC) in the spleen were assayed on day 4. Traxanox given orally at a dose of 30 mg/kg augmented the HPFC production to LPS in both mice. This agent (3-30 mg/kg) restored significantly the suppressed HPFC production to LPS in the BALB/c mice pretreated with carrageenan (0.03 mg/mouse), but did not restore it in the BALB/c mice pretreated with cyclophosphamide (25 mg/kg). The transfer of spleen adherent cells of the mice immunized with LPS and treated with traxanox to the syngeneic mice resulted in a significant increase in the HPFC production to LPS. The HPFC production to trinitrophenylated polyvinylpyrrolidone, a T cell-independent antigen was not affected by the treatment with traxanox or carrageenan. These results suggest that traxanox has a capacity to augment the immune response by affecting macrophage function.

Adjuvants, Immunologic↗

Effects of 8-(2-fluoroethyl)-3 alpha-hydroxy-1 alpha H, 5 alpha H-tropaniumbromide benzilate (Ba598Br) on allergy- and drug-induced asthmas.

The effects of Ba598Br, a new atropine derivative possessing a quarternary ammonium salt structure, on the canine airway, including its antiasthmatic effects, were investigated. The in vivo airway resistance was determined using the modified Konzett-Rössler method. Inhalation of 0.01% of Ba598Br had an inhibitory effect against acetyl-choline (ACh, 10 micrograms/kg i.v.)-evoked bronchoconstriction. The effect of Ba598Br was more powerful and longer lasting than that of the same dose of atropine. Pretreatment with Ba598Br (0.3%) and atropine (0.3%) by inhalation produced a remarkable inhibitory effect on the asthmatic bronchoconstriction induced by inhalation of Ascaris suum antigen in naturally sensitized dogs. In this case, Ba598Br showed a potency of approx. twice that of atropine as estimated from the inhibitory percent. On the other hand, in the case of posttreatment (drugs being inhaled after the antigen inhalation), both drugs showed inhibitory effects of equal degree. As for the effects on increased airway secretion at the time of asthmatic attack, both drugs inhibited the excessive secretions without any remarkable change in the viscosity of the secretions. Inhalation of 0.3% Ba598Br showed a powerful antihistamine action with respect to histamine (Hist, 3 micrograms/kg i.v.)-induced bronchoconstriction after the bilateral cervical vagi and superior laryngeal nerves were amputated. However, almost no effect could be observed with the same dose of atropine. Both Ba598Br and atropine showed relaxing actions of the same degree against ACh contraction on the isolated canine trachea, bronchus and bronchiole preparations, with a particularly strong relaxation being observed in the bronchiole. On the other hand, Ba598Br showed relaxing actions against histamine-induced contractions, which were more powerful than those of atropine, in the bronchus and bronchiole. From the above findings, it is suggested that the Ba598Br inhalation brings about antiasthmatic effects by its persistent, powerful anticholinergic actions and its transient but powerful antihistamine actions.

Animals↗

Transmembrane macromolecule rotation model--molecular hypothesis of membrane excitation.

A hypothesis concerning the molecular changes in the nerve cell membrane during excitation is presented. Based upon established principles about the interaction of hydrophobic and hydrophilic ligands and upon recent facts concerning the contraction of neurofilaments, the hypothesis accounts for both the initiation of the action potential and its conduction along the nerve axon without attenuation. The hypothesis can be summarized as follows: When acetylcholine combines with the acetylcholine receptor (AchR) alpha subunit, hydrophobic subsites are exposed at the bound surface of AchR. Since hydrophobic portions are quite unstable, the subsites move to the center of the membrane, which is hydrophobic. It is postulated that the rotation of receptor subunits makes the center an ion channel. Ca++ flowing in through the ion channel causes the undercoating filaments to contract and this contraction results in the conduction of an action potential along the axon. The contraction of the undercoating filaments induces transmembrane rotation of globular protein connected to the filaments. At right angles to the axon the force of the hydrophobic bond between membrane macromolecules is so strong that many cylindrical lipid structures are formed. The gaps between the rotatory cylinders serve as ion channels. Ca++ passing through the ion channels allows for the conduction of an action potential without attenuation.

Acetylcholine↗

[General pharmacological actions of traxanox sodium. II. Effects on the cardiovascular system].

The effects of traxanox, an anti-allergic drug, on the cardiovascular system were studied in both anesthetized dogs and cats and in isolated heart preparations from guinea-pigs. In anesthetized dogs, a very small dose of traxanox (0.01 mg/kg, i.v.) had no effect, but 0.1--30 mg/kg caused an increase in respiratory rate, hypotension, bradycardia, a transient decrease followed by an increase in renal blood flow, and a decrease in femoral blood flow. These effects were abolished by vagal block, indicating they are mediated via vagal afferents. In contrast, oral administration of traxanox (100 mg/kg) had no effect on the blood pressure or heart rate of anesthetized dogs. In anesthetized cats, traxanox (3 and 30 mg/kg, i.v.) caused a slight increase in blood pressure, but showed no effect on respiratory rate and heart rate. Both traxanox and theophylline (10(-4)M) caused increases in the beat rate of the atria and the contractile force of the papillary muscle in isolated preparations from guinea-pigs, and they potentiated the positive chronotropic and inotropic responses induced by isoproterenol. On the other hand, in anesthetized and vagotomized dogs, traxanox (3 and 10 mg/kg, i.v.) affected neither the left ventricular contractile force nor the hypotension and positive inotropic and chronotropic responses produced by isoproterenol. Administration of theophylline alone (3 and 10 mg/kg, i.v.) caused hypotension and increases in contractile force and heart rate, but it did not enhance the responses produced by isoproterenol. At doses of 1 and 10 mg/kg (i.v.), traxanox had little effect on either pressor or chronotropic responses to norepinephrine, epinephrine, DMPP and stellate cardiac nerve stimulation. The same doses of traxanox slightly reduced the depressor and chronotropic responses to isoproterenol, acetylcholine and vagus nerve stimulation. These findings suggest that traxanox had no effect on the cardiovascular systems of the animals studied in the dose range (1--5 mg/kg, p.o.) showing anti-allergic activity.

Anesthesia↗

[Effect of traxanox sodium on SRS-A release in bronchial and peritoneal anaphylaxis].

The effect of traxanox on SRS-A release was examined in vivo and compared with that of disodium cromoglycate (DSCG). Intravenous antigen challenge produced an intense anaphylactic bronchoconstriction that showed a peak time of 5 min in egg albumin-sensitized guinea pigs pretreated with three agents, mepyramine (2.5 mg/kg, i.v.), indomethacin (1 mg/kg, i.v.) and propranolol (0.05 mg/kg, i.v.). This bronchoconstriction was almost completely inhibited by additional pretreatment with an SRS-A antagonist, FPL 55712 (2.5 mg/kg, i.v.). A lipoxygenase inhibitor, BW755C (10 mg/kg, i.v.), also significantly inhibited this reaction. These results indicate that this anaphylactic bronchoconstriction is due to the release of endogenous SRS-A. In this model, traxanox (5 and 10 mg/kg, i.v.) showed a dose-related inhibition, but DSCG (10 mg/kg, i.v.) did not. FPL 55712 (1 mg/kg, i.v.) administered at the peak time of the bronchoconstriction caused a relaxation. Traxanox, on the other hand, failed to relax this reaction. In IgE-mediated rat passive peritoneal anaphylaxis (PPA), traxanox (0.01--10 micrograms/rat, i.p.) inhibited the release of SRS-A and histamine dose-dependently. This inhibitory effect was about 10--20 times as potent as that of DSCG. In addition, both traxanox (0.1 microgram/rat, i.p.) and DSCG (1 microgram/rat, i.p.) showed a synergistic effect in combination with isoproterenol (0.01 microgram/rat, i.p.) and an additive effect with theophylline (100 micrograms/rat, i.p.) in inhibiting the release of SRS-A in rat PPA. These results suggest that traxanox inhibits the release of SRS-A in vivo, so that it may be clinically effective in treating patients with allergic bronchial asthma.

Anaphylaxis↗

Postjunctional supersensitivity of the smooth muscle of the rat vas deferens induced by calmodulin-antagonizing drugs applied locally to the hypogastric plexus.

Local application of 100 micrograms of chlorpromazine hydrochloride (CPZ) to the hypogastric plexus of the rat produced supersensitivity of the smooth muscle of the vas deferens. In comparison with surgical denervation, CPZ produced a similar increase in the maximum response but less leftward shift of the dose-response curves to norepinephrine. The changes in dose response curves to methacholine and potassium induced by CPZ were substantially similar to those induced by denervation. Virtually identical supersensitivity was brought about in the rat vas deferens by the same treatment with other drugs which possess calmodulin-antagonizing actions. CPZ produced no change in norepinephrine content of the tissue. Contractile responses of the tissue to tyramine were markedly potentiated by CPZ, but the responses to nerve stimulation were not significantly altered except for that at the lowest frequency. In electrophysiologic studies, while spontaneous junction potentials could be detected in all of the impaled cells, they occurred with lesser frequency and smaller amplitude in all of the impaled cells in the CPZ-treated rat vas deferens than in the control tissue. Nevertheless, the junction and action potentials could be induced by nerve stimulation in all smooth muscle cells. The results indicate that CPZ and also other drugs used in the present study produced postjunctional supersensitivity accompanied by a large increase in the maximum response, but almost no prejunctional supersensitivity in the rat vas deferens.

Animals↗

[Clinical experience with cefotiam in the otorhinolaryngologic field].

Clinical investigation with cefotiam (CTM) was performed, the following results were obtained. CTM was administered to 18 cases of infectious diseases in the otorhinolaryngologic field. Clinical results were excellent in 7 cases, good in 5 cases, fair in 4 cases and poor in 2 cases. Clinical efficacy was 66.7%. No side reactions were noted in any cases.

Adult↗

Facilitation of intrathoracic operations by means of high-frequency ventilation.

Gas exchange was measured in eight patients undergoing high-frequency ventilation (HFV) during intrathoracic operations for lung cancer. HFV facilitated the operation because the exposed lung moved only slightly to ventilate and stayed in a less expanded state. Intermittent positive-pressure breathing (IPPB) (control) was switched to HFV 20 minutes after the pleural cavity was opened. HFV either was conducted alone (HFV alone) or was superimposed on a hypoventilation equal to the dead space (HFV on VD). The driving pressure and frequency of HFV were set at 0.5 kg/cm2 using 3, 6, and 12 Hz with an FI02 of 0.50. The only statistically significant difference in arterial PO2 between IPPB and HFV occurred when the HFV alone was used at 12 Hz. Significant differences in arterial PCO2 values existed between IPPB and HFV alone when the HFV was at 6 and 12 Hz, and between HFV alone and HFV on VD at 12 Hz. The arterial pH values were lower at 6 and 12 Hz in HFV alone and were significantly different from pH values during IPPB. Acidosis was due to the respiratory component of HFV only. The metabolic component remained unchanged. It was concluded that the gas exchange was adequately maintained at 3 Hz during HFV alone. The intrathoracic operation was facilitated by less movement as the frequency increased, although the lung volume tended to expand. The gas exchange, particularly the elimination of carbon dioxide, worsened during the use of HFV alone. However, HFV on VD continued to maintain an adequate gas exchange and facilitate the operation.

Adult↗

[Effect of cysteine ethylester hydrochloride (Cystanin) on host defense mechanism].

Cysteine ethylester (10 approximately 100 mg/kg, p.o.) augmented the production of hemolytic plaque-forming cells (HPFC) to sheep red blood cells and lipopolysaccharide in the spleen of mice. It showed no effect, however, on the HPFC production to trinitrophenylated polyvinylpyrrolidone; and it had no activity as a polyclonal B cell activator like lipopolysaccharide. Cysteine ethylester at a concentration of 3 microM or more potentiated the phagocytosis of yeast by the peritoneal polymorphonuclear leukocytes of rats. This activity was less potent than that of levamisole and D-penicillamine. It also potentiated the reduction of nitroblue tetrazolium (NBT) by blood leukocytes prepared from guinea pigs and a human being. This activity was more potent than that of levamisole and D-penicillamine. Furthermore, cysteine ethylester at doses showing an immunopotentiating activity protected irradiated mice from death by spontaneous infection. These findings suggest that this drug may have a capacity to potentiate the host defense mechanisms.

Adjuvants, Immunologic↗

Roles of poly(ADP-ribose) synthesis in repair and replication in normal human, Cockayne syndrome, and xeroderma pigmentosum fibroblasts after UV irradiation.

Roles of poly(ADP-ribose) in repair and replication were studied in UV-irradiated normal, xeroderma pigmentosum (XP), and Cockayne syndrome (CS) fibroblasts. UV radiation reduced cellular NAD with concurrent synthesis of poly-(ADP-ribose) in a dose-dependent manner in normal and CS cells, but not in XP cells. Enzymatic incision of DNA of UV-irradiated XP cells by T4-endonuclease V activated poly(ADP-ribose) polymerase. Methyl methanesulfonate (MMS) also reduced the cellular NAD in all the above strains. However, inhibitors of poly(ADP-ribose) synthesis did not affect UV-induced unscheduled DNA synthesis (UDS) and UV and MMS survivals. Thus, poly(ADP-ribose) synthesis may have a chromatin-stabilizing effect, but not the key role in excision repair of UV damage, unlike in the repair of dimethyl sulfate alkylation. CS cells were deficient in the NAD pool and in the recovery of post-UV DNA synthesis, which were rescued by an exogenous supply of NAD. Such normalization in CS cells was inhibited by excess nicotinamide as in normal cells, suggesting that replicon reinitiation may require specific poly(ADP-ribosyl)ation in UV-irradiated human cells.

Benzamides↗