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Biomedical subjects

K Matsunami

Publications and source records attributed to K Matsunami.

At least 19 recordsLinked to original sources
PubMed1992

Evidence of a role for phosphatidylinositol synthesis in human amnion cell proliferation.

Phosphatidylinositol (PtdIns) is the key precursor of phosphoinositide-derived intracellular mediators. The effects of changing the rate of PtdIns synthesis on mitogenic activity of human amnion-derived WISH cells were investigated. Incubation of the cells with [3H]inositol caused a time- and dose-dependent PtdIns labeling. Exogenous Ca2+ inhibited [3H]inositol incorporation in a dose-dependent fashion; half-maximal inhibition occurred with 0.3-1.0 mM Ca2+. In contrast, removal of cytosolic Ca2+ by ionophore A23187 and 1 mM EGTA induced enhancement of the PtdIns labeling as a function of A23187 concentration, perhaps through release of inhibitory effects of endogenous Ca2+. The A23187-stimulated PtdIns labeling with [3H]inositol was not abolished by additional unlabeled inositol, suggesting that [3H]inositol labeling of PtdIns occurred mainly through de novo synthesis catalyzed by PtdIns synthase (EC 2.7.8.11). In cells with PtdIns synthase activity decreased by exogenous Ca2+, [3H]thymidine incorporation was also inhibited, while A23187 caused dose-dependent enhancement of thymidine incorporation. The changes in PtdIns synthase activity occurred in parallel with changes in mitogenic activity caused by increasing the dose of exogenous Ca2+ or A23187. A similar lowering of mitogenic activity was observed upon suppression of PtdIns synthase by pemirolast potassium (9-methyl-3-1H-tetrazol-5yl-4H-pyrido[1,2-a]pyridin-4-one potassium) via a Ca(2+)-independent mechanism. These data demonstrate that changes in PtdIns synthase activity by some agents acting via different mechanisms are associated with parallel changes in thymidine incorporation, and suggest that PtdIns production is tightly coupled to cell proliferation in human amnion cells.

Amnion↗
PubMed1992

Enhancement of growth-promoting activity in extract from uterine cancers by protein kinase C in human endometrial fibroblasts.

Uterine cervical and corpus cancers have been reported to synthesize and secrete a putative peptide mitogen, which elicits a potent proliferative response in fibroblasts by a mechanism independent of phosphoinositide turnover. The extract from human uterine cervical cancer stimulated [3H]thymidine incorporation into human endometrial fibroblasts in a dose-dependent manner. Concomitant exposure of the fibroblasts to thrombin or fibroblast growth factor (FGF) led to synergistic enhancement of the extract-stimulated [3H]thymidine incorporation into fibroblasts. An apparent maximal activity of the extract in the presence of thrombin or FGF was 2-fold higher than that in the absence of them, implying that thrombin or FGF acted at a stage after the interaction of the mitogen in the extract with its specific receptor. Insulin or epidermal growth factor failed to augment the growth-promoting activity in the extract. The stimulatory action of thrombin or FGF was mimicked by protein kinase C activators, phorbol-12-myristate-13-acetate (PMA) or 1-oleoyl-2-acetyl glycerol, but not by Ca2+ ionophore A23187. When the fibroblasts were first exposed to the extract for 4 h and then to PMA, PMA succeeded to augment the mitogenic activity in the same manner. The identical effects of protein kinase C activators with thrombin or FGF suggested that both types of ligand share a similar signaling cascade of action, activation of protein kinase C. These results demonstrated that the growth-promoting activity in uterine cancer extract could be enhanced by the agents which promote phosphoinositide metabolism through activation of protein kinase C. These findings could give a new insight into pathophysiology of the interaction between malignant cells and their stromal cells, fibroblasts.

Endometrium↗
PubMed1991

ECG analysis of golden hamsters exposed to long-term -Gz conditions: ordinary and pathological findings.

Changes of ECG due to long and intense -Gz acceleration was investigated in anesthetized Syrian golden hamsters. The R-R interval decreased (heart rate increased) slightly at the very initial phase of steady -Gz load. However, the R-R interval increased during the rest of the whole steady -Gz period. The P-R interval increased with a smaller -Gz load (-4 and -6 Gz), but it decreased with a larger -Gz (-8 and -10 Gz). The size of the QRS complex was measured as R amplitude. It decreased in all -Gz conditions. Effects were a little different for smaller and larger -Gz, as was observed in the case of P-R changes. Pathological ECGs were frequently observed. They were: (1) Arrhythmia of heart rate with or without atrio-ventricular blocks. (2) Abnormal P wave; e.g., splitting, flattening, or abolition of P wave. (3) Alteration of the QRS complex in amplitude or contour. (4) Changes in ST-T components. In spite of all these changes, however, it should be noted that several Syrian golden hamsters could tolerate up to -10 Gz for as long as 1,000 s.

Acceleration↗
PubMed1991

The vestibulo-autonomic function viewed from cardiac responses in centrifuged monkeys.

Vestibulo-autonomic function was examined as the change of cardiac parameters (HR and SV) to +Gz and -Gx accelerations for 1,000 s in intact and bilaterally labyrinthectomized monkeys. Under anesthetized conditions, HR and SV slightly changed to +2Gz acceleration in both monkeys. In +3Gz acceleration, changes were remarkable and significant. HR increased in intact monkeys by as much as 30% while it decreased in labyrinthectomized monkeys, although a moderate initial increase was observed. SV decreased in intact as well as labyrinthectomized monkeys, but the reduction was significant and larger for the latter. This implies that vestibular input could modulate autonomic function. For larger +Gz, both intact and labyrinthectomized monkeys could tolerate no more due to severe cardiac dysfunction (rapid HR and SV decrease) which appeared soon after +4Gz application. In case of -Gx application, HR increased, although slightly, in proportion to the amplitude of applied -Gx in both monkeys, with less changes in labyrinthectomized ones. SV hardly changed in smaller -Gx, while it increased in larger -Gx. Difference between intact and labyrinthectomized monkeys was observed in -6Gx and -8Gx conditions.

Acceleration↗
PubMed1991

Suppression of growth-promoting activity in extract from human uterine cancer by cyclic AMP-mediated mechanism.

Uterine cervical and corpus cancers have been reported to synthesize and secrete the putative peptide mitogen, which elicits a potent proliferative response in the fibroblasts [Res. Commun. Chem. Pathol. Pharmacol. 66, 477-480 (1989)]. The extract from human cervical cancers stimulated [H]thymidine incorporation into human endometrial fibroblasts in a dose-dependent manner. Concomitant exposure of the fibroblasts to dibutyryl cyclic AMP (cAMP) of forskolin, the mitogenic activity of the extract was suppressed by 60%. A higher concentration of the extract did not overcome the inhibitory effects of them, implying that they acted at a stage after the mitogen in extract and specific receptor interaction. These results demonstrated that the growth-promoting activity in cervical cancer extract could be under negative control through cAMP-dependent mechanism.

Bucladesine↗
PubMed1991

Development of skill of children in the performance of the family computer game "Super Mario Brothers".

The development of skill of children in the performance of a family computer game (Super Mario Brothers) was investigated among three groups of different age: kindergarten children (6 years old) and primary school children (9 and 12 years old). The skill to perform the game with either hand was evaluated by the mean scores gained by the children. In the normal (right and dominant) situation, the mean score improved significantly with advancement of age. Similar was true in the reversed (left hand dominant) situation, but more distinctly. The mean scores were significantly higher in the normal than in the reversed situations. The experienced children were superior to the inexperienced children in playing the game. The correlation between the reaction time and the game score was also investigated with the same subjects for the 9- and 12-year-old school children. Almost no correlation could be elucidated.

Age Factors↗
PubMed1990

Inhibitory action of estradiol on growth promoting activity in extract from uterine cancers.

Extracts from uterine cervical and body cancers, but not from benign tumor or intact tissues tested, were found to contain a growth-promoting activity which induced the proliferation of human endometrial fibroblasts. Exposure of cultured fibroblasts to the cancer extracts increased the rate of [3H]thymidine incorporation in a dose-dependent manner. The activity was heat-labile, and not inactivated by removal of lipid-soluble material suggesting that the activity is associated with a protein. When the fibroblasts were preincubated with estradiol for 12 hours, but not for 1 hour, the extract-induced fibroblast proliferation was suppressed. The inhibitory effect of estradiol was dose related (EC50: 10nM) and non-competitive, suggesting that the steroid may reduce the sensitivity of fibroblasts to the extracts. This is the first report to provide direct evidence that estradiol may play an inhibitory role in the action of growth factor-like peptide produced from malignant tumors.

Cell Division↗
PubMed1990

Evidence for tight coupling of phospholipase activation and Ca2+ influx during acrosome reaction of golden hamster spermatozoa.

1. Phospholipases have been proposed to play a key role in sperm acrosome reaction. To examine the activation mechanism of phospholipases and subsequently sperm fertilizing capacity. Ca2+ fluxes and phospholipid turnover (breakdown and synthesis) were investigated in golden hamster spermatozoa during acrosome reaction. 2. Upon exposure of the spermatozoa to 1.7 mM Ca2+, a net uptake by the cells occurred in two distinguishable phases. 3. Depletion of extracellular Ca2+ by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) at a time that an initial Ca2+ uptake was observed to reach almost steady-state, prevented the secondary Ca2+ uptake and acrosome reaction. 4. The time course of an initial Ca2+ uptake seemed to precede that of the acrosome reaction. 5. Incubation of the spermatozoa with Ca2+ in the presence of [3H]glycerol induced a rapid increase in labeling of phosphatidic acid, a key intermediate of phosphinositide turnover initiated by the action of phospholipase C, which appeared to parallel the time course of a first phase of Ca2+. 6. Phospholipase A2 activation, detected by lysophospholipid formation, slightly delayed the initial events of first Ca2+ uptake and phosphatidic acid production. 7. It is concluded that first Ca2+ entry into the cells, associated with phosphatidic acid production, activates a phospholipase A2, leading to the production of substances, like lysophospholipids and fatty acids, which may contribute to acrosome reaction.

Acrosome↗
PubMed1990

Relative effects of xylazine-atropine, xylazine-atropine-ketamine, and xylazine-atropine-pentobarbital combinations and time-course effects of the latter two combinations on brain stem auditory-evoked potentials in dogs.

Brain stem auditory-evoked potentials (BAEP) were recorded in 4 dogs to analyze the relationship between acoustic stimulus intensities and peak latencies of each wave, and to investigate the relative effects of xylazine-atropine, xylazine-atropine-ketamine, and xylazine-atropine-pentobarbital combinations and the time-course effects of the latter 2 drug combinations on BAEP. Click stimulations fixed at a stimulus rate of 10/s and a frequency of 4 kHz were delivered at intensities ranging from 10- to 110-dB sound pressure level (SPL) in 10-dB steps for analyzing the relationship between the acoustic stimulus intensities and the peak latencies and at an intensity of 110-dB SPL for investigating the effects of the sedative and anesthetic drug combinations and their time-course effects on BAEP. Waves I to VI were identified with stimulus intensity of greater than or equal to 50-dB SPL. Wave VII was observed in some records, but was excluded from statistical analysis. As stimulus intensity was increased from 50- to 110-dB SPL, the latency decreased for all waves during xylazine-atropine-ketamine anesthesia. There were no statistically significant differences in the peak latencies of each wave in BAEP among xylazine-atropine, xylazine-atropine-ketamine, and xylazine-atropine-pentobarbital combinations 20 minutes after drug administration, except that the latency of wave VI during xylazine-atropine sedation was significantly (P less than 0.01) shorter than that detected during xylazine-atropine-ketamine or xylazine-atropine-pentobarbital anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1989

Mode of [14C] 2-deoxy-D-glucose uptake into retrosplenial cortex and other memory-related structures of the monkey during a delayed response.

Physiological studies on the monkey retrosplenial (RS) cortex have been few, and its functional role remains to be investigated. In the present study, activity of the RS cortex was investigated using radioactive 2-DG while the monkey was performing a visual tracking task with a delay (a delayed-response task) for 45 minutes. A remarkable increase in 2-DG uptake was observed equally in the left as well as in the right RS cortex. The anterior nucleus of the thalamus also showed increased 2-DG uptake. In addition, other memory-related structures (prefrontal cortex, dorsomedial nucleus of the thalamus, amygdala and hippocampus) showed a similar increase in 2-DG uptake compared to control monkeys, though their respective absolute values were different from one another. Since the RS cortex receives afferents from the anterior nucleus of the thalamus, which is one of the main nuclei of the Papez circuit, it is assumed that the RS cortex is important in memory function. Therefore, the remarkable increase in 2-DG uptake in the present study could reflect some aspects of memory or learning processes required to perform the delayed response.

Animals↗
PubMed1989

A putative growth factor in extract from uterine cancers.

Extracts from uterine cervical and corpus cancers, but not from benign tumor or intact tissues tested, were found to contain a growth-promoting activity which induced the proliferation of human endometrial fibroblasts. Exposure of cultured fibroblasts to the cancer extracts increased the rate of [3H]thymidine incorporation in a dose-dependent manner. The activity was heat-labil, and not inacticated by removal lipid-soluble fraction, suggesting that the activity is associated with a protein. However, the cancer extract failed to stimulate phosphoinositide turnover. The substance(s) present in the uterine cancer extracts may activate endometrial fibroblasts proliferation through the transmembrane signaling mechanisms other than phosphoinositide turnover. The bindings of previously identified growth factors including somatomedine C, thrombin, insulin, fibroblast growth factor were not inhibited by the extracts. This is the first report to provide direct evidence that malignant uterine tumor may produce and secrete a putative growth factor-like peptide.

Adenocarcinoma↗
PubMed1987

Neuronal activity in nuclei pontis and reticularis tegmenti pontis related to forelimb movements of the monkey.

The activity of the pontine nucleus (PN) neuron was recorded in 3 monkeys moving a handle alternately from start to target zones in a simple extension-flexion movement at the wrist. Of 73 PN neurons related to the task, 44 were related to movement, 19 to handle holding and 5 to both movement and holding of the handle. Of the 44 movement-related neurons, 16 were related to flexion, 22 to extension, and 6 to both. In 37 of 54 analyzed movements of the PN neurons which were related to movements, or to both movements and handle holding, the change of the activity occurred before the movement. However, in most of these cases (24/37), discharge occurred less than 100 ms earlier than the start of the movement. In the remaining one-third of movements (17/54), neurons discharged after the onset of the movement. Locations of the 73 neurons were histologically verified in the pontine nucleus. Somewhat similar observations were made of 14 cells located in the nucleus reticularis tegmenti pontis (NRTP). Considering that the majority of movement-related PN and NRTP neurons discharged immediately before or even after the onset of movement, these neurons may play a role in the execution of movement, at least of a simple movement, rather than in the initiation or planning of movement.

Animals↗
PubMed1986

[Fundamental and clinical studies of imipenem/cilastatin sodium in the field of obstetrics and gynecology].

To evaluate the penetration of imipenem/cilastatin sodium (MK-0787/MK-0791) into the female genital organ, concentrations of MK-0787/MK-0791 in antecubital vein blood, portio vaginalis, myometrium, endometrium, ovary and oviduct of patients who underwent simple hysterectomy and in the pelvic dead space exudate of patients who underwent radical operations for cancer of the uterine cervix were determined and analyzed using a two-compartment model. Concentrations at the end of a 30 minutes drip infusion of 500 mg/500 mg of MK-0787/MK-0791 were 48.38/52.69 micrograms/ml in plasma from the antecubital vein, 9.46/14.92 micrograms/g in the portio vaginalis, 14.10/9.79 micrograms/g in the myometrium, 6.47/11.42 micrograms/g in the endometrium, 14.72/13.30 micrograms/g in the ovary and 10.59/13.62 micrograms/g in the oviduct. Maximum concentrations of MK-0787 and MK-0791 in the pelvic dead space exudated were 10.66 micrograms/ml at 1.33 hours and 12.74 micrograms/ml at 1.15 hours after the start of the drip infusion, respectively. The concentration in plasma from the antecubital vein after an infusion of 1,000 mg/1,000 mg of MK-0787/MK-0791 reached 68.37/61.57 micrograms/ml at the end of a 60 minutes drip infusion, and the maximum concentration of MK-0787 in the pelvic dead space exudate was 20.02 micrograms/ml at 1.50 hours after the start of the drip infusion and that of MK-0791 was 14.90 micrograms/ml at 2.01 hours after the start of the drip infusion. MK-0787/MK-0791 was administered to 9 patients with obstetric and gynecological infections, and clinical efficacies were found to be excellent in 1, good in 6, and poor in 2 patients.

Adult↗