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Biomedical subjects

K Matsunami

Publications and source records attributed to K Matsunami.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

[Fundamental and clinical evaluation of ceftazidime in the perinatal period].

Following an intravenous injection of ceftazidime (CAZ) 1 g, the ratio of transfer of the drug into a fetus was 59.9%, and umbilical serum concentrations of the drug reached the peak of 18.2 micrograms/ml at 1.5 hours, and were slightly higher than maternal serum concentrations at 2.93 hours and after, with half-life of 1.37 hours, the same as in maternal serum. Following an intravenous injection of CAZ 1 g, concentrations of CAZ in mother's milk at 2 hours after injection were 1.16 micrograms/ml on the 4th day of the treatment of CAZ, and 0.86 micrograms/ml on the 7th day. The CAZ was administered to cases of premature rupture of membrane. The prophylactic efficacy against puerperal infections in mothers was 92%, and that against fetal infections in neonates was 96.7%. The CAZ was also administered after cesarean section, and the prophylactic efficacy against postoperative infections was 93.3%. Neither subjective/objective adverse effects nor abnormal laboratory findings for which CAZ was suspected were observed in any mothers or neonates. From the above results demonstrating satisfactory maternal transfer into fetuses and the high degree of safety in fetuses and neonates, as well as its high antibacterial activity, CAZ is considered to be a useful drug for the treatment of perinatal infections.

Adult↗

[Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology].

Aztreonam (AZT) was studied for the transfer into the pelvic dead space exudate in 5 patients who received radical hysterectomy due to uterocervical cancer, and for the clinical efficacy in the treatment of 5 cases of obstetrical and gynecological infections. Transfer into the pelvic dead space exudate Data analysis was performed by the simulation curves prepared from pharmacokinetic parameters using the two-compartment model. On examination, the serum concentration of cubital venous serum was found to be 53.20 micrograms/ml at 1 hour after the start of 1-hour intravenous drip infusion of 1 g of AZT. Also, the shifting concentration of the pelvic dead space exudate was found to have reached its peak value of 12.79 micrograms/ml at 3.22 hours after the start of the infusion, and still showed the value of more than 7 micrograms/ml even at 8 hours after the start of the infusion. The AUC was 112.81 micrograms X hr/ml. Clinical evaluation AZT was administered at a daily dose of 2-4 g in 2 divided doses by intravenous injection and intravenous drip infusion for 60 minutes. Clinical efficacy of the 5 patients with acute and moderate degree obstetrical and gynecological infections was; excellent in 1 case, good in 3 cases and poor in 1 case, with the overall efficacy rate of 80.0%.

Adult↗

[Fundamental studies of cefoxitin in the field of obstetrics and gynecology].

The concentration of cefoxitin (CFX, Merxin) in dead space exudate was studied in 14 patients following total extirpation of diffuse uterine cervical cancer. A two-compartment model was used for the analysis. The results obtained were as follows: Calculated maximum concentrations of CFX in the pelvic dead space exudate were 26.55 micrograms/ml at 2.11 hours, 31.07 micrograms/mg at 2.01 hours and 51.51 micrograms/ml at 2.10 hours after 1 hour intravenous drip infusions of CFX 2, 3 and 4 g, respectively. These concentrations were higher than the MIC80 of 12.5 micrograms/ml against E. coli and B. fragilis and were maintained for a sufficient period of time. Based on the results of this study, CFX is considered to be an important and valuable drug in the field of obstetrics and gynecology.

Adult↗

[Fundamental and clinical studies of cefpimizole in obstetrics and gynecology].

Cefpimizole (AC-1370) concentrations in the pelvic dead space exudate were determined in patients under-going curative resection of carcinoma of the uterine cervix to study the transfer of the drug into the female genital organs, and the results were statistically analyzed, using the two-compartment model. When 1 g of AC-1370 was administered by intravenous drip infusion over 1 hour, the AC-1370 concentration in the serum from the antecubital vein reached a level of 129.09 micrograms/ml at 1 hour of intravenous drip infusion, and the AC-1370 concentration in the pelvic dead space exudate reached a peak of 30.32 micrograms/ml at 2.51 hours of intravenous drip infusion, and remained at not less than 12 micrograms/ml 8 hours after the beginning of the drip infusion, with the area under the curve (AUC) for the AC-1370 concentration in the pelvic dead space exudate being 213.66 micrograms X hr/ml. Seven patients with obstetrical and gynecological infections were treated with 1 g of AC-1370 by intravenous drip infusion over 1 hour, 2 approximately 3 times daily. Although the patients all had rather mild infections, the treatment was effective in all of them. The findings in this study proved a dose of 1 g of AC-1370 at a time to be sufficiently effective in mild cases, but in view of the transfer of the drug into tissues, it seemed necessary to administer 2 g of the drug at a time in severe cases.

Adult↗

Effects of stimulation of corpus callosum on precentral neuron activity in the awake monkey.

The effects of stimulation of the corpus callosum (CC) on precentral neurons were studied in monkeys performing motor tasks with either forelimb. Of a total of 246 precentral neurons that were tested with CC stimulation, 70 were orthodromically and 12 were antidromically activated. The percentages of neurons orthodromically activated by CC stimulation were the same in pyramidal tract neurons (PTNs) (31%) and non-PTNs (31%). The mean latency of neuronal activation by CC stimulation was similar in PTNs and non-PTNs. Precentral neurons were divided into two groups with respect to muscular contractions evoked by intracortical stimulation: neurons related to finger, wrist, and elbow movements (distal group) and those related to shoulder or axial movements (proximal group). The percentages of neurons orthodromically activated by CC stimulation were similar in both groups; 25% in distal and 29% in proximal groups. However, the mean latency of orthodromic CC activation was significantly shorter for the proximal than for the distal group. Precentral neurons were classified into three groups; neurons related to finger and/or wrist movement tasks (F-W group), those related to arm movement tasks in addition to finger and/or wrist tasks (F, W + A group), and those related to arm movements only (A group). The percentages of neurons orthodromically activated by CC stimulation were similar in the three groups. The mean latencies of neuronal activities were a little longer in the F-W group than in the A group or the F, W + A group. Precentral neurons were classified into three groups in relation to ipsilateral or contralateral forelimb movements: neurons related to ipsilateral movements (ipsi neurons, n = 13), those related to ipsilateral as well as contralateral movements (bilat neurons, n = 50) and those related to contralateral movements (contra neurons, n = 136). The percentages of neurons orthodromically activated by CC stimulation were 15 (2/13, ipsi neurons), 24.0 (12/50, bilat neurons), and 25.0% (34/136, contra neurons), respectively. The mean latencies of neuronal activation were compared between two groups; one group was composed of ipsi and bilat neurons, and the other group was of contra neurons. The mean latency was a little shorter for the ipsi + bilat group than for the contra group.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗