Biomedical subjects

M Inoue

Publications and source records attributed to M Inoue.

At least 55 records · Page 3Linked to original sources

PubMed1992

Predominant beta-adrenoceptor blocking effect of xamoterol averaged over the day in patients with mild to moderate heart failure: insight into the mechanism of its long-term clinical efficacy.

Xamoterol acts as a beta 1-adrenoceptor agonist at low sympathetic activity and as an antagonist at high activity. Although its long-term efficacy has been proven in patients with mild to moderate heart failure, it remains unclear which effect, agonism or antagonism, accounts for its long-term activity. To clarify the effect of xamoterol on cardiac sympathetic activity in daily life, 24-h R-R interval histograms were obtained during administration of xamoterol 100 mg b.d. for 1 week to 10 patients with mild to moderate heart failure. Eight normal subjects were also studied as controls. To examine the relation between the effect of xamoterol and sympathetic activity, plasma noradrenaline (NA) levels were measured under 5 graded conditions simulating daily living. Xamoterol administration significantly decreased the standard deviation of the R-R interval, both in patients with heart failure and in normal subjects. The mean R-R interval, however, was increased in patients with heart failure, relative to normal subjects. In both groups, the R-R interval histograms had two peaks, i.e. a short daytime peak and a long night-time peak. Xamoterol decreased the median of the night-time peak without changing the daytime peak in normal subjects. In contrast, it increased the median of the daytime peak without producing a significant change in the night-time peak in patients with heart failure. Levels of plasma NA were significantly higher in patients than in normal subjects under all conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1992

Temporal increase in resting coronary blood flow causes an impairment of coronary flow reserve after coronary angioplasty.

Impaired coronary flow reserve immediately after coronary angioplasty may be attributed to an increase in resting coronary blood flow. To test this hypothesis we measured great cardiac venous flow (GCVF) at rest and during rapid atrial pacing before and immediately after angioplasty in 22 patients with significant narrowing of the left anterior descending artery and 12 patients (control group) with minimal narrowing. A follow-up (6 months) study was also done in seven patients. Immediately after angioplasty the coronary flow reserve (peak GCVF during pacing/resting GCVF) was not fully restored (1.5 +/- 0.36 before angioplasty, 1.76 +/- 0.42 after angioplasty, and 2.13 +/- 0.33 in the control group). Resting coronary vascular resistance (2.4 +/- 0.9 mm Hg/ml/min) was significantly decreased after angioplasty (2.0 +/- 0.8 mm Hg/ml/min), whereas coronary vascular resistance during rapid pacing was fully restored to normal. Resting hyperemia was restored 6 months later, whereas coronary vascular resistance during pacing was unaltered. In five patients, however, slight ischemic ST-T changes were observed during rapid pacing, even after successful angioplasty associated with a decrease in the lactate extraction ratio. These results indicate that the impaired coronary flow reserve immediately after angioplasty may be attributed mainly to the temporal but significant increase in resting coronary flow, although impaired coronary vascular response to augmented myocardial oxygen demand may also be partially involved.

Aged↗

PubMed1992

Stimulus-specific enhancement of luminol chemiluminescence in neutrophils by phosphatidylserine liposomes.

When stimulated with different stimuli, neutrophils generate various active oxygen species. These active oxygen molecules can be analyzed by luminol chemiluminescence (LCL). Phosphatidylserine (PS)-liposomes increased the formylmethionyl-leucyl-phenylalanine-induced LCL of guinea pig peritoneal neutrophils without affecting their oxygen consumption and superoxide (O2.-) generation. Similar effects of PS-liposomes were also observed in LCL of neutrophils stimulated by phorbol myristate acetate or arachidonic acid but not by opsonized zymosan. Kinetic analysis revealed that the PS-liposome-induced increase in LCL depended on extracellulary generated O2.-. Moreover, the stimulatory effect of PS could be seen only when it formed liposomal membranes. The effect of PS-liposomes was also inhibited by superoxide dismutase, catalase, and deferoxamine, an iron chelator, but not by azide, an inhibitor of myeloperoxidase. Similar enhancement of stimulation-dependent LCL response was also observed with Fe3+ and ADP-Fe3+, but the degree of enhancement was much greater with PS-liposomes than with iron and its complex. The increase in hydroxyl radical generation by PS-liposome-treated neutrophils was confirmed by experiments with EPR spectrometry using spin-trapping agents. These results suggested that the interaction of neutrophils with PS-containing membrane surface might generate reactive oxygen species that enhance the stimulus-dependent LCL response of neutrophils.

Animals↗

PubMed1992

Detection of human papillomavirus types 16 and 18 in the exfoliated cervical cells using the polymerase chain reaction.

We applied the polymerase chain reaction (PCR) to detect HPV 16 and 18 in cytological samples obtained from the uterine cervices of Japanese women. HPV infection was detected in 17 (25%) of 67 with CIN and 11 (37%) of 30 with cervical carcinoma. It is notable that 11 (16%) of 69 women with normal cervices were infected with either HPV 16 or 18. The polymerase chain reaction is sensitive and useful for epidemiological studies.

Adolescent↗

PubMed1992

A synthetic analogue of vitamin D3, 22-oxa-1,25-dihydroxy-vitamin D3, stimulates the production of prostacyclin by vascular tissues.

We investigated the effect of 22-oxa-1,25-dihydroxyvitamin D3, a synthetic analogue of vitamin D3, on the production of prostacyclin by vascular tissues using rat aortic rings and A7r5 cells derived from fetal rat aortic smooth muscle. Prostacyclin synthesis by aortic rings of rats treated with 22-oxa-1,25-dihydroxyvitamin D3 was much higher than that of non-treated controls, but did not cause any significant hypercalcemia. Treatment with 22-oxa-1,25-dihydroxyvitamin D3 significantly increased the production of prostacyclin by A7r5 cells for 48 hours in a dose-dependent manner. In time-course studies, cells incubated with 22-oxa-1,25-dihydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 produced prostacyclin progressively over a period of 48 hours. The shortest period of incubation that produced a significant amount of prostacyclin compared with control cultures was 24 hours. We observed that treatment with 22-oxa-1,25-dihydroxyvitamin D3 induced cyclooxygenase mRNA in A7r5 cells. Our data suggest that 22-oxa-1,25-dihydroxyvitamin D3 may possibly be a protective substance against the development of atherosclerosis by modulating prostaglandin metabolism.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Antifertility effect of active immunization with ZP4 glycoprotein family of porcine zona pellucida in hamsters.

Female golden hamsters were immunized with solubilized porcine zona pellucida (s-PZP) or ZP4 glycoprotein family isolated from s-PZP by preparative SDS-PAGE. Both antigen preparations induced production of antibodies which reacted not only with porcine zona pellucida but also with the hamster zona pellucida. The hamsters immunized with solubilized porcine zona pellucida mainly produced antibodies reactive to ZP3, while the hamsters immunized with ZP4 mainly produced antibodies reactive to ZP4. The former animals became permanently infertile but the infertility in the latter animals was temporary and they became pregnant later. Histological studies revealed that the ovarian follicles in hamsters immunized with s-PZP were completely destroyed leaving only atrophic follicle-like cell clusters, while in the ovaries of hamsters immunized with ZP4 a number of small follicles with oocytes remained intact. These observations are encouraging for the further characterization of the ZP4 antigens as candidates for the development of a contraceptive vaccine.

Animals↗

PubMed1992

Modulation of ion channels by somatostatin and acetylcholine.

Somatostatin and muscarinic acetylcholine receptors are similar as far as modulation of voltage-gated Ca2+ channels and anomalously rectifying K+ channels are concerned. Activation of either type of receptors induces inhibition of Ca2+ channels and activation of anomalous K+ channels without depending on intracellular cAMP. Somatostatin appears to act on the same receptor subtype for these two actions since somatostatin receptors are homogenous in pituitary cells (Srikant and Patel, 1982; Tran et al., 1985) where the peptide produces these two effects as well as an inhibition of adenylate cyclase. In the case of muscarinic receptors, however, it remains unclear whether the same subtype of receptors is involved in both inhibition of Ca2+ channels and activation of K+ channels. Activation of muscarinic receptors in hippocampal neurones evidently produces a cAMP-independent suppression of Ca2+ channel. In cardiac cells, however, muscarinic stimulation does not cause a cAMP-independent suppression of Ca2+ channels but does activate an anomalous rectifier. These findings do not necessarily mean that the muscarinic receptor involved in the inhibition of Ca2+ channels in hippocampal neurones is not of m2 type which is assumed to mediate the activation of anomalous K+ channels in cardiac cells. There is no evidence that cardiac Ca2+ channels are identical to hippocampal Ca2+ channels susceptible to muscarinic inhibition. In addition, a similar argument could be applied to G proteins coupling muscarinic receptors to Ca2+ channels in neurones and cardiac myocytes. In this regard, it should be noted that activation of GABAB receptors or mu and delta opiate receptors, an event known to inhibit adenylate cyclase activity through a PTX-sensitive Gi protein, also produces both inhibition of Ca2+ channels and activation of anomalous K channels in a cAMP-independent manner. This close correlation between inhibition of adenylate cyclase activity and cAMP-independent modulation of Ca2+ and K+ channels suggests the possible involvement of m2 subtype in the inhibition of Ca2+ channels in hippocampal neurones. Circumstantial evidence indicates that anomalous K+ channels are directly activated by alpha subunits of Gi, but not Go, proteins. The alpha subunit of Go protein seems to mediate inhibition of the Ca2+ channel, probably in a direct manner. The most striking difference between somatostatin and muscarinic receptors would be their opposite actions on the M channel. All the inhibitory receptors on the M channel, including m1 and m3 receptors, are known to stimulate PI hydrolysis via a PTX-insensitive G protein.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

PubMed1992

The temporal relationship between the onset of rapid eye movement period and the first micturition thereafter in the human fetus with advance in gestation.

The objective of this study was to investigate whether micturition occurs, temporally related to the onset of the rapid eye movement (REM) period, in the human fetus. The study was made on 139 fetuses at 33-36 weeks and 153 at 37-41 weeks gestation. The discrepancies between the expected (F(exp)) and observed (F(obs)) frequencies of time lag between the onset of the REM period and the first micturition thereafter were assessed using the goodness-of-fit test. At 33-36 weeks gestation, there was no statistical difference between F(obs) and F(exp) (P greater than 0.05). At 37 weeks onwards, however, significant differences were noted between F(obs) and F(exp) (P less than 0.005). Seventy-two percent of all micturitions occurred within eight minutes after the onset of the REM period. This indicates that there is a temporal relationship between the onset of the REM period and the first micturition thereafter, at term, during 37-41 weeks of gestation.

Embryonic and Fetal Development↗

PubMed1992

Sex determination by discriminant function analysis of lateral cranial form.

To sex the cranium, morphological features of cranial specimens were quantified with a personal computer that automatically measures distance and gradient for 39 craniometric points in the lateral contour line of the skull, which were digitized by a tablet digitizer connected to the computer. Specimens used for discriminant analysis were 50 male and 50 female adult Japanese skulls. The lateral contour showed sex differences in the nasal bone, supraorbital ridge, forehead and vertex. The nasal bone and supraorbital ridge were more developed in male contour line, and the forehead was more rounded in female contour line. But compared with the supraorbital ridge and forehead, the vertex had a wide variety of contour lines in both sexes. The vertex seemed to be less reliable as the indicator of sex. The sex differences were better reflected by gradient than distance. From variables of the gradient and distance showing significant sex differences, the discriminant function was derived and tested in 21 other specimens (13 male and 8 female skulls). The mean ratio of correct sexing of the human skull by the discriminant function was 86%.

Adult↗

PubMed1992

Genetic models of absence epilepsy, with emphasis on the WAG/Rij strain of rats.

In this review, the main characteristics of genetic models of absence epilepsy, in particular with respect to WAG/Rij rats, are presented. Genetic models are important and relevant, since evidence exists that these models mimic spontaneously occurring human epilepsy more than models in which epilepsy is artificially induced. Genetic models can be divided into models in which seizures are elicited and into those in which epilepsy appears without any sensory stimulation. The majority of genetic models show that absence type of epilepsy; during the last few years, we and others have noticed that rats of various strains exhibit spontaneously occurring spike-wave discharges in the EEG. Among the strains highly affected is the WAG/Rij strain, which is a fully inbred strain. Individuals are homozygous and because of this property, genetic studies are meaningful. Electrophysiological studies have indicated that abnormal discharges in the cortical EEG are generalized and that the hippocampus is not involved. Parts of the thalamus, together with the thalamic reticular nucleus, apparently act as a pacemaker for the abnormal discharges. There is a circadian modulation in the number of spike-wave discharges. Discharges mainly occur during intermediate levels of vigilance such as passive wakefulness and light slow-wave sleep and at transitions of sleep states. Pharmacological studies with clinically effective antiepileptic drugs have shown a close agreement in seizure response between man and rat. Studies with new compounds have emphasized the role of the GABAergic and glutamatergic system in this type of epilepsy. Particularly striking is the role of the GABAergic system. GABA agonists enhance and GABA antagonists reduce the occurrence of spike-wave discharges, which deviates from the effects of GABAergic drugs in non-convulsive epilepsy. Even more striking is the role of the benzodiazepines, generally seen as GABA agonists; these drugs do not act as such in absence epilepsy since they reduce spike-wave discharges. Also good evidence for an involvement of other neurotransmitters such as noradrenaline, dopamine and opioid peptides exists in absence epilepsy. Genetic data obtained from the WAG/Rij model for absence epilepsy show a relatively simple pattern of inheritance with one gene determining whether an individual is epileptic or not, and with other genes regulating the number and duration of seizures. This is in good agreement with the more restricted human data. Cognitive studies have shown two important features of epilepsy in the WAG/Rij strain: modulation of the number of spike-wave discharges by mental or physical activity and on the other hand, the disruption of cognitive activity by spike-wave discharges.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

The impact of endometriosis on the reproductive outcome of infertile patients.

OBJECTIVE: We examined whether the presence and severity of endometriosis affect the reproductive outcome of infertile patients. STUDY DESIGN: The conception rates of 2080 infertile women, 1263 who had endometriosis and 817 who did not have endometriosis, were analyzed retrospectively by means of the chi 2 test. Depending on the stage of the disease patients who had endometriosis-associated infertility underwent expectant management, danazol therapy, or minor or major conservative surgery. The patients who failed to conceive after these conventional treatments were enrolled in the in vitro fertilization-embryo transfer program. RESULTS: The conception rates were virtually identical regardless of the presence or absence of endometriosis (30.7% vs 30.0%). The outcome of in vitro fertilization-embryo transfer was not affected either by the presence or the severity of the disease. CONCLUSION: Endometriosis had no impact on the reproductive outcome of infertile patients in this series unless the anatomy of the pelvic organs was heavily distorted, which can occur in the advanced stages of the disease.

Adult↗

PubMed1992

Expression of E-cadherin in normal, benign, and malignant tissues of female genital organs.

The expression of human E-cadherin in normal tissues and in benign and malignant tumors of female genital organs was examined immunohistochemically with a monoclonal antibody, HECD-1, specific for human E-cadherin. The normal tissues included the ovary, fallopian tube, uterine endometrium, uterine cervix, and vagina. E-cadherin was detected clearly in the cell-to-cell boundaries of both normal glandular and squamous epithelia obtained from those tissues. The tumor tissues consisted of 9 ovarian, 7 endometrial, and 4 cervical adenocarcinomas, 12 squamous cell carcinomas of the cervix, including 3 cervical intraepithelial neoplasms, and 5 mesenchymal tumors. E-cadherin also was detected in the cell-to-cell borders of all the epithelial tumors tested, with some reactivity in the cytoplasm of malignant cells, whereas mesenchymal tumors showed no expression. It is noteworthy that poorly differentiated areas of both the adenocarcinomas and squamous cell carcinomas showed less expression of E-cadherin. No difference in the expression of E-cadherin between the primary and metastatic lesions was detected in 10 sets of malignant tumors. E-cadherin may be an important factor among a variety of biologic events that occur during the process of metastasis. However, further studies are needed to clarify this.

Antibodies, Monoclonal↗

PubMed1992

Acute effects of doxorubicin on skinned cardiac muscle fibres of guinea pigs.

OBJECTIVE: The aim was to examine the effect of doxorubicin on spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum of skinned fibres, as measured by isometric tension development in EGTA free, Ca2+ free solution. METHODS: Experiments were done on fragments of papillary muscles from the right ventricles of guinea pigs. Skinned fibres were prepared by treatment with saponin. The effects of doxorubicin in concentrations of 2 x 10(-9) to 2 x 10(-5) M on cyclic contractions were evaluated in 20 muscles. The effects of doxorubicin in concentrations of 2 x 10(-7) and 2 x 10(-5) M on pCa-tension relation were examined in 14 muscles treated with Brij-58. RESULTS: Doxorubicin (2 x 10(-9) to 2 x 10(-5) M) increased the frequency of cyclic contractions and induced an incomplete muscle relaxation in a dose dependent manner. Doxorubicin 2 x 10(-7) M had no effect on pCa-tension relation. Doxorubicin 2 x 10(-5) M shifted the pCa-tension curve slightly to the left. CONCLUSIONS: An incomplete muscle relaxation is considered to be due to an increase in Ca2+ release from the sarcoplasmic reticulum and a slight increase in the sensitivity of the contractile proteins to Ca2+. These observations suggest that one cause of the intracellular Ca2+ overload induced by doxorubicin, a putative mechanism of the doxorubicin induced cardiomyopathy, is attributable to the direct effects of doxorubicin on the sarcoplasmic reticulum, impairing its ability to sequester Ca2+.

Animals↗

PubMed1992

Comparative in-vitro activity of RP 59500 against clinical bacterial isolates.

The activity of RP 59500 against Gram-positive cocci was determined by an agar dilution method and compared with that of erythromycin, cefotaxime and ampicillin. Of the 344 clinical isolates tested, none was resistant to RP 59500; this compound was active both against methicillin-resistant Staphylococcus aureus and against macrolide-resistant Gram-positive cocci. The bactericidal activity of RP 59500 was confirmed by killing curve determinations.

Ampicillin↗

PubMed1992

Intermittent intensive combination chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (cyclic PAC chemotherapy) for ovarian cancer.

Despite high primary response rates with cisplatin-based combination chemotherapy, the overall survival rate for advanced ovarian cancer remains unsatisfactory. This prompted us to design a new systematic approach using a combination chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide (PAC), namely, cyclic PAC chemotherapy. This is a 3-step chemotherapy with 3 courses of the PAC regimen in each step. It was administered for 18 months to patients with clinical Stage Ic-IV ovarian cancer, after cytoreductive surgery. In the present study, the cyclic PAC, brief PAC, and FAM (5-Fu, an alkylating agent, and mitomycin C) groups included 27 cases, 34 cases, and 38 cases, respectively. Treatment of Stage Ic-IV disease by cyclic PAC improved the outcome (57% estimated 5-year survival rate) compared to brief-PAC and FAM (20% and 32%, respectively). The outcome for patients with Stage III or IV ovarian cancer was also superior for the cyclic-PAC group compared to the brief-PAC and FAM groups (cyclic-PAC 44%, brief-PAC 9%, and FAM 0% estimated 5-year survival rates). Cyclic PAC chemotherapy was thus found to be capable of dramatically improving the long-term survival rate of ovarian cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Enflurane-induced release of an excitatory amino acid, glutamate, from mouse brain synaptosomes.

To clarify the mechanisms of enflurane-induced convulsions, we examined the effects of enflurane, halothane, and diethyl ether on the release of an excitatory neurotransmitter, glutamate, from isolated pinched-off nerve terminals (synaptosomes) of the mouse cerebral cortex. At concentrations corresponding to those used clinically (0.75 and 1.25 mM), enflurane released more glutamate than did halothane. Diethyl ether (10 and 58 mM) had no effect on glutamate release. Enflurane (0.75-15 mM) increased glutamate and aspartate release in a dose-dependent manner but had little effect on the release of the inhibitory neurotransmitters glycine and gamma-aminobutyric acid or on the release of glutamine. A glutamate uptake inhibitor, kainic acid (1 mM), did not affect enflurane-induced glutamate release. Replacement of the medium's Ca2+ by Co2+, or exposure to cold (about 2 degrees C), suppressed the enflurane-induced glutamate release. Depolarization caused by 40 mM K+ increased the basal level of glutamate released, and enflurane-induced glutamate release was lower after depolarization. Enflurane had no effect in synaptosomes prepared from the cerebellum, diencephalon and pons, or medulla oblongata. Thus, enflurane increased Ca(2+)- and temperature-dependent glutamate release, especially from synaptosomes of the cerebral cortex. These data provide a pathophysiologic explanation for enflurane-induced convulsions.

Animals↗

PubMed1992

Sialyl-Tn, sialyl-Lewis Xi, CA 19-9, CA 125, carcinoembryonic antigen, and tissue polypeptide antigen in differentiating ovarian cancer from benign tumors.

Serum sialyl-Tn, sialyl-Lewis Xi, CA 19-9, CA 125, carcinoembryonic antigen (CEA), and tissue polypeptide antigen were measured in 65 women with early-stage ovarian cancer (45 stage I and 20 stage II cases) and 317 with benign pelvic masses. As a single assay, sialyl-Tn showed the best sensitivity and specificity, 46 and 92%, respectively. CA 19-9 detected the greatest number of cancer patients but had the lowest specificity. The combination of sialyl-Tn, CA 125, tissue polypeptide antigen, and CEA seemed to perform the best, with a sensitivity and specificity of 71 and 76%, respectively. The combination of sialyl-Tn, CA 125, and tissue polypeptide antigen gave similar results and may be more cost-effective. However, one-fifth of the patients with early-stage cancer still showed up as false negatives even with use of the six markers in combination. Approaches other than serum assay alone will be needed to detect all malignant pelvic masses at an early stage.

Antigens, Neoplasm↗

PubMed1992

Intraoperative measurement of lumbar spinal instability.

To justify lumbar fusion or stabilization, a quantitative assessment and definition of spinal instability are essential. To quantify spinal instability, the tensile stiffness of a motion segment (vertebra-disc-vertebra) was measured with a spinal distractor during spinal decompression surgery. Stiffness was indicated by the relationship between load and displacement between the two adjacent spinous processes where a vertebral spreader was suspended. A load-displacement curve was recorded at each step of surgical decompression and fixation while the motion segment was being distracted at a constant speed. The device used for measuring stiffness of a spinal motion segment is a lumbar spinal spreader with a load strain gauge and a displacement transducer. The stiffness of a spinal motion segment was reduced as disc degeneration developed. Degenerative spondylolisthetic discs showed the least stiffness (lowest, 3.9 N/mm; average, 5.4 N/mm). The stiffness of herniated discs, however, was relatively greater (average, 11.8 N/mm). The stiffness of normal motion segments was greater than affected segments. If the stiffness of a motion segment before decompression was graded as 100, it was reduced to 82% after partial laminectomy and facetectomy and to 65% after discectomy on average. After interbody fusion by iliac bone graft, it increased to 133% and to 184%, after Luque fixation.

Female↗