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Biomedical subjects

M Fujimoto

Publications and source records attributed to M Fujimoto.

At least 415 records · Page 23Linked to original sources
PubMed1989

Comparison of vascular and platelet thromboxane A2/prostaglandin H2 receptors in the pig.

We compared the properties of vascular and platelet thromboxane A2/prostaglandin H2 receptors in the pig. The binding profiles of U46619, several prostaglandins and thromboxane A2/prostaglandin H2 receptor antagonists to the aorta and platelet receptors were almost the same irrespective of whether the agonist ([3H]U46619) or the antagonist ([3H]SQ29,548) radioligand was used, except that the receptor density in the latter was 4 times higher than that in the aorta. The antagonists suppressed U46619-induced contraction of pig coronary artery and secondary aggregation of platelets at potencies comparable to their KI values in the binding experiments. On the other hand, the responses of the artery specimens to U46619 and the prostaglandins differed from those of the platelets. Thus, the binding sites in the vascular and platelet receptors seem to be the same or quite similar, but there seem to be different mechanism(s) leading the agonistic binding signal to final responses.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

Effects of the kallikrein-kinin system on phasic coronary vasospasm in dogs.

It is well known that kinins are liberated from kininogen in blood during angina attack to maintain blood flow in coronary artery. We examined the effects of bradykinin, one of kinins, on the coronary artery other than vasodilation. The isolated canine coronary artery ring was suspended in gassed (95% O2, 5% CO2) Krebs-Henseleit buffer at 37 degrees C in vitro. The experimental phasic contraction of coronary artery was induced by 6 x 10(-4)M of 3,4-diaminopyridine which decreases K conductance (Y. Uchida, Jpn. Circ. J: 49, 128, 1985). The effect of bradykinin and other substances on the cycle length of contraction (CL), the peak tension of contraction phase (PT) and the tension during relaxation phase (RT) were observed. The phasic contraction was eliminated by 10(-7)M nifedipine and 10(-6)M diltiazem which block voltage dependent Ca channels. These Ca blockers reduced PT, but slightly increased CL, and weakly reduced RT. The phasic contraction was also eliminated by 10(-6)M bradykinin. However, bradykinin, unlike Ca blockers, did not reduce PT, but markedly prolonged CL and decreased RT significantly. This inhibition mode was very similar to those of nicorandil which increases K conductance. These data suggest that bradykinin plays a protective role in coronary vasospasm, and this antivasospasm effect may be mediated through the increase in K conductance.

Animals↗
PubMed1989

Reciprocal effects of Ca2+ and Mg-ATP on the 'run-down' of the K+ channels in opossum kidney cells.

Using the patch clamp technique, we identified an inwardly rectifying K+ channel in the membrane of opossum kidney cells. The single channel conductance was about 90 pS for inward currents and 30 pS for outward currents under a symmetrical high-K+ condition. The activity of the channel was found to decrease with time during recording from inside-out patches. In the solution with submicromolar Ca2+, the activity disappeared within 4-20 min. Intracellular Ca2+ promoted the run-down of the channel activity at 0.1-1 mM, whereas millimolar Mg-ATP restored the activity after run-down. The run-down channels could never be reactivated by ATP in the absence of Mg2+, or by a nonhydrolyzable ATP analog, AMPPNP, even in the presence of Mg2+.

Adenosine Triphosphate↗
PubMed1989

Plasma levels of atrial natriuretic peptide in patients with liver cirrhosis and its relation to ascites and renal function.

Plasma immunoreactive alpha-human atrial natriuretic polypeptide (Ir-alpha-hANP) was measured by radioimmunoassay in 21 cirrhotics and 10 normal subjects. Average of Ir-alpha-hANP level in cirrhotics was significantly higher than in normal subjects (125.8 +/- 79.6 versus 28.7 +/- 12.2 pg/ml, P less than 0.001). In cirrhotics without ascites, Ir-alpha-hANP levels were positively correlated with creatinine clearance (Ccr) and urinary sodium excretion, suggesting that alpha-hANP was closely related to renal circulation and sodium homeostasis. On the contrary, in cirrhotics with ascites Ir-alpha-hANP levels were negatively correlated with Ccr. Urinary sodium excretion in cirrhotics with ascites and Ccr more than 50 ml/min was positively correlated with Ir-alpha-hANP levels. However, cirrhotics with ascites and Ccr less than 50 ml/min excreted little sodium in spite of high Ir-alpha-hANP levels. On the basis of the Ir-alpha-hANP before and after treatment of ascites, cirrhotics with ascites were subdivided into 2 groups. In group I Ir-alpha-hANP decreased from high values and in group II it was further elevated from slightly high values by treatment. The difference in renal function and plasma volume may account for the difference in Ir-alpha-hANP changes in the 2 groups.

Adult↗
PubMed1989

High-affinity binding sites for PK 11195, but not for RO5-4864, in porcine aortic smooth muscle.

Peripheral benzodiazepine (BZ) binding sites were characterized in porcine aortic smooth muscle membrane preparation. [3H]PK11195 bound with high affinity to the membranes (Kd = 8.6 + 0.9 nM), whereas [3H]Ro5-4864 bound slightly to the membranes. The Ki value of Ro5-4864 obtained from the inhibition of [3H]PK 11195 binding was 1200 + 200 nM, which was 480 times weaker than that obtained in rat kidney. Furthermore, the Ro5-4864 effect was temperature-insensitive. When [3H]PK 11195 binding was examined in porcine, human and rat platelets, Ro5-4864 inhibited the binding in porcine and human platelets one order of magnitude less potently than that in rat platelets. These results suggest that low affinity for Ro5-4864 in porcine aorta smooth muscle originates in porcine tissue, but not in smooth muscle.

Animals↗
PubMed1989

A randomized controlled study of (2"R)-4'-O-tetrahydropyranyladriamycin and adriamycin in combination with cyclophosphamide and 5-fluorouracil in the treatment of advanced and recurrent breast cancer. Clinical Study Group of THP for Breast Cancer in Japan.

The chemotherapeutic treatment of advanced and recurrent breast cancer was examined in a randomized controlled comparison test. Group A received (2"R)-4'-O-tetrahydropyranyladriamycin (THP) in combination with 5-fluorouracil (5-FU) and cyclophosphamide (CPA), while Group B was administered adriamycin (ADR) together with 5-FU and CPA. These combined chemotherapies were administered in a dosage regimen that was repeated in a 28-d cycle. On d 1 and d 8, THP and ADR were given at a dose of 30 mg/m2 IV and 5-FU was administered at a dose of 500 mg/m2 IV. CPA was administered at a dose of 100 mg/body, PO on consecutive days from d 3 to d 16. Among 37 complete cases in Group A, a complete response (CR) was noted in one patient and a partial response (PR) in 12, to give a rate of 35.1%. CR was noted in one patient and PR was observed in 7 out of 27 complete cases in Group B, giving a response rate of 29.6%. The mean PR duration was 19 wk (range, 4+--63) in Group A, and 14 wk (range, 4+--51+) in Group B. The 50% survival duration was 20.6 mo and 14.3 mo in Groups A and B, respectively, while mean survival duration was 17.9 mo and 16.6 mo in Groups A and B, respectively. No significant between-group differences were found for any of these measures. There were fewer side effects in Group A than in Group B, with Group A showing significantly less alopecia (P less than 0.01) and a lower incidence of anorexia (P greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Loss of heterozygosity on chromosome 10 in human glioblastoma multiforme.

Recessive mutations, revealed by loss of the wild-type allele, have been associated with the development of a variety of cancers in children and adults. Polymorphic chromosome 10 markers were used to screen paired tumor and lymphocyte DNA samples in 13 patients with glioblastoma multiforme. Ten patients showed loss of constitutional heterozygosity in the tumor samples. This finding suggests that a recessive gene involved in the development of glioblastoma multiforme is present on chromosome 10.

Alleles↗
PubMed1989

Experimental induction of uterine cancer in rats by N-ethyl-N'-nitro-N-nitrosoguanidine dissolved in polyethylene glycol.

In the present experiment we attempted to experimentally induce uterine cancer in rats by injecting into the uterine cavity N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG). Fifty-nine female F-344 rats, 7-8 weeks old, were divided into three groups and each received in the left uterine cavity with laparotomy a single dose of ENNG dissolved in PEG according to the following schedule: Group 1 received 75 mg ENNG/kg body wt.; Group 2 had 20 mg ENNG/kg body wt.: and Group 3 was given only PEG. In Group 1 it was observed that adenocarcinoma and sarcoma were present in the uterine corpus while squamous cell carcinoma occurred in the uterine cervix. In Group 2, although tumors such as adenocarcinoma, adenoma and sarcoma were observed in the uterine corpus, no tumor was present in the uterine cervix. No tumor growth whatsoever was observed in Group 3. From the above results it is apparent that the present method is an efficient means for experimentally inducing uterine cancer and that the site of tumor generation varies according to the concentration of ENNG administered.

Animals↗
PubMed1989

Plasma active renin concentration in children.

In normal children aged one month to 16 years, the plasma active renin concentration (PARC) was measured with a renin immunoradiometricassay (IRMA) kit, and was compared with plasma renin activity (PRA). The IRMA for renin was found to be independent of the amount of renin substrate and not affected by the dilution of plasma samples, and was therefore proved to be a simple and reliable method. PRA measured in non-diluted plasma samples correlated well with PARC. In the age-related change, PARC in infants was significantly higher than that in older children. In infants, PARC was markedly higher in the crying state than that in the non-crying state. In normal children aged 7 to 11 years, PARC was significantly increased in the upright position compared to the supine position. These findings suggest that a hyperresponse of PARC to acute stress during blood sampling may cause an increase in active renin secretion in infants, and that stimulation by short-term standing may accelerate the activation of inactive renin or the release of active renin.

Adolescent↗
PubMed1989

Urinary prostaglandins and renal function in obstructive jaundice.

Changes in urinary prostaglandin E2 (PGE2), 6-keto PGF1 alpha, and thromboxane (TXB2) excretion in 12 patients with obstructive jaundice were observed in relation to renal function and the renin-angiotensin (R-A) system. In obstructive jaundice before percutaneous biliary drainage the creatinine clearance (CCr) was significantly lower (p less than 0.001) and the PGE2 and plasma angiotensin II (AII) concentrations were significantly higher (p less than 0.005 and p less than 0.005, respectively) than those in normal subjects. Both 6-keto PGF1 alpha and TXB2 were widely distributed. When CCr returned to normal after drainage, PGE2 and plasma AII also returned to normal, but when CCr decreased after drainage, PGE2 and plasma AII increased. Before drainage, PGE2 correlated negatively with CCr (r = -0.72, p less than 0.01) and positively with plasma AII(r = 0.69, p less than 0.02). 6-Keto PGF1 alpha correlated positively with serum total bilirubin (r = 0.66, p less than 0.02). The percentage change in PGE2 after drainage correlated negatively with that in CCr (r = -0.95, p less than 0.005). The percentage chang in plasma AII correlated positively with that in urine PGE2 (r = 0.94, p less than 0.005) and negatively with that in CCr (r = -0.85, p less than 0.02). These results suggest that PGE2 is closely related to the R-A system and might assist in the maintenance of renal circulation in obstructive jaundice.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Proto-oncogene analyses in brain tumors.

The present study determined which oncogenes (N-myc, c-myc, v-sis, or v-fos) were amplified and which messenger ribonucleic acids (mRNA's) accumulated in 10 primary human brain tumors of neuroectodermal origin. The tumors included four glioblastomas multiforme, one mixed glioma (astrocytoma grade I and ependymoma), one astrocytoma grade II, one cystic cerebellar astrocytoma, one ependymoma, one ganglioglioma, and one medulloblastoma. The relative amounts of polyadenylated (poly(A)+) RNA's homologous to these genes and their copy number were determined using the RNA and deoxyribonucleic acid blot hybridization techniques. The N-myc and v-sis probes hybridized strongly to the poly(A)+ RNA from the same recurrent glioblastoma with gene amplifications (N-myc 80 copies; v-sis three to four copies). The c-myc probe hybridized strongly to the recurrent medulloblastoma without gene amplification. The amplification or abundant accumulation of mRNA's homologous to their oncogenes may be involved in tumorigenesis or the aggressiveness of these malignant brain tumors of neuroectodermal origin and may be good molecular indicators of an extremely malignant state in these tumors.

Adolescent↗
PubMed1989

Effects of norepinephrine on the proximal tubular cells in perfused bullfrog kidney.

UNLABELLED: To study effects of norepinephrine (NE) on sodium and hydrogen ion transport, we used H(+)-, Ca2(+)-, or Na(+)-selective microelectrode and split-oil droplet techniques in doubly-perfused bullfrog proximal tubules. Peritubular membrane potential difference (EM), intracellular activities of Na+ ((Na)i) and Ca2+ ((Ca)i), and pH of the cytosol (pHi) and the lumen (pHTF) were monitored continuously during peritubular administration of NE (10(-6)-10(-7) M), phenylephrine (PHE, 10(-7) M), or dibutyryl cyclic AMP (db-cAMP, 10(-4) M). RESULTS: (1) The peritubular application of NE produced: a) an enhancement of proximal fluid reabsorption, b) a transient fall of pHTF by about 0.2, c) a gradual hyperpolarization of EM and a slight decrease of (Na)i with oscillation, d) a mild cell acidification by about 0.05 pH, and e) an increase of (Ca)i. (2) The peritubular perfusion of PHE (alpha 1-agonist) caused: a) a transient fall of pHTF by about 0.3, b) a transient depolarization of EM and an increase of (Na)i, followed by sustained hyperpolarization of EM and a decrease of (Na)i, c) cytosolic acidification by about 0.1 pH, and d) a slight decrease of (Ca)i, followed by a sustained increase of (Ca)i. (3) The peritubular application of db-cAMP produced: a) a reduction of proximal fluid reabsorption, b) a transient elevation of pHTF by about 0.15, c) a hyperpolarization of EM with a gradual decrease of (Na)i, d) cytosolic alkalinization by about 0.15 pH, and e) biphasic change of (Ca)i: i.e., a slight increase of (Ca)i followed by a sustained decrease of (Ca)i.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Intracellular pH of gastric surface epithelial cells exposed to HCl and ethanol.

Ultramicro-pH electrodes were used to determine intracellular pH changes induced by luminal perfusion of acid and alcohol in the gastric mucosa. In preparations of the bullfrog antral mucosa mounted on a horizontal type Ussing chamber, we determined intracellular pH (pHi) in situ of the surface epithelial cells exposed to HCl in the presence or absence of 10% ethanol in the luminal side. The pHi and apical membrane potential (LEM) of the surface epithelial cells were measured with double-barreled liquid ion-exchanger pH microelectrodes. In normal control conditions, the mucosal pHi was 7.43 +/- 0.01 and LEM was 29.5 +/- 0.7 mV (SE, n = 54). Acidification of luminal perfusate to pH 3.5 had no influence on pHi. Exposure to luminal 1 mM HCl (luminal pH: pHL = 3.1) lowered pHi to 7.31 +/- 0.01 (n = 6). Addition of 10% ethanol (EtOH) to luminal perfusate at pH 4.2 (0.1 mM HCl) led to immediate and progressive acidification of pHi (delta pHi = 0.12 +/- 0.02, n = 6). Hyperpolarization of LEM (by several mV) was also observed under such conditions, indicating an altered ion permeability of the apical membrane. These results suggest that even a low concentration of alcohol added to the gastric lumen causes a significant change in the surface epithelial cells, and this change becomes manifest when the luminal fluid is acidified to pH lower than 4.

Animals↗
PubMed1989

[Experimental study on the effect of various types of peritonitis and elevation of intra-abdominal pressure on endotoxin absorption].

The experimental studies were conducted in order to elucidate the effect of intra-abdominal chemical and bacterial inflammation and elevation of intraabdominal pressure on endotoxin (Et) absorption from the peritoneum. Sixty three adult mongrel dogs were subjected to this study by producing models by intra-abdominally administering only Et (0.5mg/kg) [Et only group], by intra-abdominally administering a same dose of Et after inducing peritonitis by bile, stool and acid [Peritonitis group], and by intra-abdominally administering a same dose of Et after elevating intraabdominal pressure [Elevated intraabdominal pressure group]. In comparison with the group in which only Et was intra-abdominally administered, Et absorption of the Peritonitis group was significantly inhibited and the response of the animals was minimal. It was suggested that peritonitis per se had a host defensive function with regard only to Et absorption. However, in the elevated intra-abdominal pressure group, Et absorption from the peritoneal cavity was significantly increased to bring rise to aggravation of the circulatory system such as decrease in not only blood pressure but also in its antecedent cardiac output and hepatic blood flow, which aggravated the severity of the disease.

Abdomen↗
PubMed1989

Methicillin-resistant Staphylococcus aureus in nosocomial infections in the surgical ward and operating room.

In this study 214 strains of Staphylococcus aureus were isolated from clinical specimens on the surgical ward from 1983 to 1988 and in addition, 62 airborne strains were collected in the operating room. Highly methicillin-resistant strains of S.aureus (H-MRSA, MIC greater than 100 micrograms/ml) not detected in 1983 showed a significant increase in frequency by 1987 accounting for about 60% of MRSA (MIC greater than or equal to 12.5 micrograms/ml). Countermeasures instituted in 1987 such as the use of disinfectant chlorhexidine alcohol significantly decreased the frequency of MRSA and H-MRSA isolates in 1988. In our study of coagulase type, MRSA type IV strains were predominant until 1984, whereas after 1986 type II was prevalent. All airborne strains collected in the operating room were methicillin-sensitive S.aureus, with type VII currently epidemic. We therefore concluded that cross infection with MRSA took place on the surgical ward rather than in the operating room.

Cross Infection↗
PubMed1989

[Correlation between coagulase typing and antibiotic susceptibility in methicillin resistant Staphylococcus aureus].

One hundred and fifty-two strains of Staphylococcus aureus isolated from clinical specimens from 1983 to 1987 were examined in their susceptibility against various antibiotics and in their coagulase typing. The isolation frequency of methicillin resistant strains (MRSA) was 61.6%, and highly methicillin resistant (MIC greater than 100 micrograms/ml) group occupied 81.3% of MRSA in 1987. From the study of coagulase type, it was found that current epidemic strains in our ward was type II. In MRSA, type IV strains were predominantly isolated until 1984, but after 1986 most of all MRSA strains belonged to type II. According to the coagulase type-classification of MRSA, the isolation frequency of type II was 97.5% of highly methicillin resistant group. Type II strains were more sensitive to MINO and OFLX than type IV, although in the susceptibility to DMPPC type II was less sensitive than type IV. In type IV, the percentage of beta-lactamase-producing strains was 79.3%, and type II, 33.3% with the high significance of statistical difference (p less than 0.01). In conclusion, a close correlation was suggested between beta-lactamase producing activity and the mechanism of resistance to non-beta-lactam antibiotics as to MINO, OFLX in type IV strains. On the other hand, in type II strains the mechanism of resistance seemed to be simply explained by changes of penicillin-binding-protein (PBP), and there was little concern with beta-lactamase, and other antibiotic-modifying enzymes.

Anti-Bacterial Agents↗