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Biomedical subjects

Y Okamura

Publications and source records attributed to Y Okamura.

At least 127 records · Page 7Linked to original sources

Developmental changes in delayed rectifier K+ currents in the muscular- and neural-type blastomere of ascidian embryos.

1. Developmental changes in the amplitude, kinetic properties, tetraethyl-ammonium (TEA) sensitivity, and ion selectivity of the delayed rectifier K+ currents were investigated in differentiating muscular-type (M) and neural-type (N) blastomeres isolated from the early cleavage-arrested ascidian embryos, using conventional two-microelectrode voltage clamp techniques. 2. No voltage-sensitive outward K+ currents were found in either type of blastomere during the first 35 h of development at 9 degrees C. Thereafter the delayed rectifier K+ current became apparent. The peak amplitude of the K+ current in the M-blastomere increased abruptly from 50 to 60 h and tended to plateau after 60 h, while in the N-blastomere it continued to increase after initial emergence at around 35 h. 3. The threshold potential level of the K+ current in the M-blastomere was initially about -10 mV in a standard external solution (1 mM-K+ solution), but shifted towards the hyperpolarized direction until it reached a steady level at 45 h after fertilization. At the fully differentiated stages, the threshold was around -32 mV and -26 mV in the M- and N-blastomeres, respectively. 4. Throughout development, the reversal potential of the tail current changed with the external K+ concentration in both M- and N-blastomeres as expected for a K(+)-electrode. There was no significant difference in the selectivity ratios for the K+ channel between the two types of blastomeres. The relative selectivities were K+ (1.000): Rb+ (0.774): NH4+ (0.122): Na+ (0.074) and K+ (1.000): Rb+ (0.724): NH4+ (0.155): Na+ (0.074) in the M- and N-blastomeres, respectively. 5. Modified Scatchard plots of TEA-sensitivity data indicated a one-to-one reaction between TEA and the K+ channel. These plots revealed the presence of TEA-resistant K+ channels in addition to TEA-sensitive K+ channels in the M-blastomere, but revealed only TEA-sensitive K+ channels in the N-blastomere. The dissociation constant (Ki) values of these three types of K+ channel did not change during development. In the M-blastomere, the Ki of the TEA-sensitive K+ channel was 1.29 +/- 0.05 mM (mean +/- S.E.M., n = 31) and that of the TEA-resistant K+ channel was 1.4 +/- 0.1 M (mean +/- S.E.M., n = 31) at a test potential of 45 mV. The Ki value of the neural-type K+ current was 1.38 +/- 0.03 mM (mean +/- S.E.M., n = 20) at 45 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Expression of blood group A and B antigens in nuclear heterochromatin in mucous cells of human cervical glands.

Using a post-embedding immunogold labeling procedure, we found that monoclonal antibody against A (MAb-A) or B antigen (MAb-B) reacted with nuclear heterochromatin regions, as well as secretory granules, in mucous cells of human cervical glands. Systematic and critical observation of specimens from 24 individuals of different blood groups revealed that the labeling pattern with MAb with strictly dependent on the blood group (A,B, or O) of the donors, i.e., MAb-A reacted with the heterochromatin from blood group A and AB but not with B and O individuals. Labeling with MAb-B was also specific for the heterochromatin from blood group B donors. On the other hand, MAb against H antigen did not react with the heterochromatin from any individuals examined, despite the fact that H antigens were detected by the MAb in secretory granules. Such specific reactions provide evidence that certain types of blood group-related antigens exist in the nuclear heterochromatin in mucous cells of human cervical glands. In contrast to the secretory granules in which ABH antigens were recognized by blood group-specific lectin, heterochromatin regions had little or no affinity for these lectins. Furthermore, the secretory status of individuals affected the staining intensity with MAb in secretory granules but not in the heterochromatin. These results suggest that the blood group substances found in the heterochromatin may have different molecular properties from those in the secretory granules, although both have the same determinant structures of ABH antigens.

ABO Blood-Group System↗

[Disorder of serum electrolytes following CAP therapy].

Combination chemotherapy with Cyclophosphamide, Adriamycin and Cisplatin (CAP) is one of the most effective chemotherapies for ovarian cancer. Severe vomiting induced by this treatment may cause a disorder of the serum electrolytes. Severe hyponatremia was observed in one patient who complained of convulsions and unconsciousness. Accordingly we studied the disorder of serum electrolytes in 158 courses of CAP treatment (44 patients) during the five years from 1984 to 1988. The serum electrolytes were influenced by the amount of vomiting in this study. Consequently frequent examination of serum electrolytes is necessary during this treatment.

Antineoplastic Combined Chemotherapy Protocols↗

[Evaluation of chest wall resection in the patients with breast cancer involving chest wall].

Twenty-three patients with advanced or recurrent breast cancer involving bony chest wall were treated by extended full-thickness chest wall resection and immediate reconstruction. The results were as follows: 1) Distant metastases were found concurrently or subsequently in more than half of the patients. Therefore, we should regard chest wall lesions as a systemic disease. 2) Long term result was encouraging, with 73.9% local control rate. 3) Post-surgical prognosis of the patients with sternal metastasis and solitary chest wall lesions were favorable, in that order. 4) Both local control rate and survival of the patients with mediastinal invasion, however, were fairly poor. 5) Disease-free interval (D.F.I.) after mastectomy longer than 5 years correlated significantly with a long survival after chest wall resection. As a result, we confirmed that chest wall resection was the treatment of choice for the patients with long D.F.I. and solitary chest wall lesion without mediastinal invasion nor metastasis, but the postoperative systemic therapy was indispensable to improve the patient's survival.

Adult↗

[A case of successful surgical repair for congenital corrected transposition of the great arteries associated with Ebstein's malformation and diverticulum of atrialized ventricle].

Congenital corrected transposition of the great arteries (C-TGA) is frequently associated with VSD and PS. Systemic atrioventricular valve regurgitation is also sometimes present in patients with C-TGA. It is though that left-sided A-V valve regurgitation is caused by the deformities of the tricuspid valve (TV) or intolerance of TV and the right ventricle (RV) against systemic pressure load. We had a patient with C-TGA associated with Ebstein's malformation. The patient suffered from congestive heart failure due to left-sided A-V valve regurgitation. In this case, the septal and posterior leaflets were displaced below the atrioventricular annulus. The edges of all valves were thickened and partially calcified. Focal agenesis was found in the septal leaflet. There was a distinct atrialized ventricle which had a thin wall and no trabeculae. It shaped like a diverticulum of 3 cm in depth toward the diaphragm. Preoperative cardiac catheterization showed that the functional RV had an adequate size (RVEDVI 162% of normal) and ejection fraction was 53%. Left-sided valve replacement was performed using SJM 31M with preservation of TV. Left-sided atrioventricular annulus was so deformed due to the diverticulum that the prosthetic valve was sutured at the ventricular wall below the atrioventricular annulus to which TV had attached. Good clinical result was obtained after surgical treatment.

Diverticulum↗

[Clinical significance of a tumor marker NCC-ST-439 in breast cancer--a comparative study with CA 15-3, CEA and TPA].

We compared a new tumor marker NCC-ST-439 (ST-439) with CA 15-3, CEA and TPA for its clinical usefulness in 600 patients with breast cancer (81, primary; 49, recurrent; 470, non-recurrent), and confirmed the following results. The sensitivity of ST-439 (41.5%) was significantly higher (p less than 0.05) than that of CA 15-3 (26.2%), CEA (28.5%) and TPA (26.9%). The specificity of ST-439 (84.5%), however, was considerably lower (p less than 0.01) than these other three markers. In primary cases, the positive rate of ST 439 (34.6%) was significantly higher (p less than 0.05) than that of the other markers, and was remarkable in the early stage. As to the positive rate at the various metastatic sites, there were a few differences among these four markers. Because of no significant correlation among these markers, combination assay with ST-439, CA 15-3 and CEA showed an excellent sensitivity (57.7%). These results suggest that ST-439 is a useful tumor marker not only in monitoring the recurrence, but also in the diagnosis of primary cancer.

Antigens, Tumor-Associated, Carbohydrate↗

[A case of inflammatory breast cancer successfully treated with intra-arterial infusion of high-dose epirubicin].

A 56-year-old female with extensive inflammatory breast cancer was treated with intra-arterial infusion chemotherapy using a high dose of epirubicin. One cycle consisted of epirubicin; 150 mg (day 1, 4, 7) and daily administration of tamoxifen; 40 mg. After completion of 2 cycles of the regimen, both the main tumor and the extensive inflammatory skin lesion completely disappeared (CR). Hair loss, gastrointestinal disorders and leukopenia (nadir; 1,600) were the side effects encountered, but all of them were reversible. These findings suggested that dose-escalation of epirubicin was effective, and that cases with extensive skin involvement were also candidates for this modality.

Administration, Oral↗

[A study on hyperprolactinemia in female patients with alcoholics].

The clinical signs and symptoms of sexual dysfunction with amenorrhoea, loss of libido and infertility, are frequently found in chronic alcoholic women. But few investigations have been made concerning hormonal changes in fertile aged women experiencing sexual dysfunction. In order to assess prolactin levels of fertile-aged women with alcoholism under 40 years of age-excluding those with liver cirrhosis were surveyed. We found that many of them (82.6%) had moderate elevations of plasma prolactin. Hyperprolactinemia is commonly associated with amenorrhoea and hypogonadism. An acute alcohol loading experiment was conducted on 6 healthy female volunteers in luteal phases of their menstrual cycles in order to evaluate the effects of alcohol on the hypothalamo-pituitary-ovarian axis. Evidence was obtained that alcohol intake caused transient hyperprolactinemia. The present results indicated that hyperprolactinemia can occur with high frequency among alcoholic women and this causes sexual dysfunction and ovarian dysfunction. The etiology of hyperprolactinemia could not be explained solely by the direct action of alcohol, rather, liver dysfunction must be implicated.

Adult↗

Heterogeneity of the blood group ABH antigens and variation in the expression of these antigens of secretory granules in human cervical glands. An electron microscopic observation using lectins and monoclonal antibodies.

Cytochemical localization of blood group ABH antigens was examined in secretory cells of human cervical glands by application of a post-embedding lectin-gold as well as immuno-gold labeling procedure using monoclonal antibodies. Blood group specific lectins such as Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA), Griffonia simplicifolia agglutinin I-B4 (GSAI-B4) and Ulex europaeus agglutinin-I (UEA-I) reacted with secretory granules but not with other cytoplasmic organellae such as nucleus and cell membrane. The reactivity of secretory granules with these lectins showed strict dependence on the blood group and secretor status of tissue donors. The binding patterns with these lectins were not homogeneous, but exhibited marked cellular and subcellular heterogeneity. Thus, for example, in blood group A individuals, some granules were stained strongly with DBA and others were weakly or not at all with the lectin. Such a heterogenous labeling with the lectin was observed even in the same cells. Similar results were obtained with UEA-I and GSAI-B4 staining in blood group O and B secretor individuals, respectively. Monoclonal antibodies likewise reacted specifically with the granules but they occasionally bound to some nucleus. The labeling pattern of the antibodies with the granules was essentially the same as those of lectins.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗

Difference in the ability of blood group-specific lectins and monoclonal antibodies to recognize the ABH antigens in human tissues.

Twelve different kinds of blood group-specific lectins have been used along with monoclonal anti-A, -B and -H antibodies for detecting the corresponding antigens in selected human tissues. Although most of the lectins recognized the antigens in the tissue sections examined, they displayed marked differences in their recognition patterns in certain tissues. Helix asparsa agglutinin (HAA), Helix pomatia agglutinin (HPA) and monoclonal anti-A antibody recognized A antigens in the mucous cells of salivary glands from blood group A or AB nonsecretor as well as secretor individuals, whereas Dolichos biflorus agglutinin (DBA), Griffonia simplicifolia agglutinin-I (GSA-I), Sophora japonica agglutinin (SJA) and Vicia villosa agglutinin (VVA) did not bind to them from nonsecretors. A antigens in endothelial cells, lateral membrane of pancreatic acinar cells and small mucouslike cells of submandibular glands from some individuals were likewise recognized by HAA and HPA but not by other blood group A-specific lections. In contrast, both HAA and HPA did not recognize the A antigens in mucous cells of Brunner's glands while other A-specific lectins and monoclonal anti-A antibody reacted specifically with the antigens. Such a difference was not observed with lectins specific for blood group B. However, the B antigens in Brunner's glands were recognized by these lectins but not with monoclonal anti-B antibody. The difference in labelling ability was also noted among the blood group H-specific lectins and monoclonal anti-H antibody in endothelial cells of blood vessels. Ulex europaeus agglutinin-I reacted with these cells irrespective of ABO and the secretor status of the individuals, while Anguilla anguilla agglutinin and monoclonal anti-H antibody reacted only with those cells from blood group O individuals. No reaction was observed with Lotus tetragonolobus agglutinin in these tissue sites. These results suggest a great diversity of blood group antigens in different human tissues.

ABO Blood-Group System↗

Relationship between lectin binding properties and the expression of blood group ABH antigens in vascular endothelia and red blood cells from 18 primate species.

The reactivity was examined of horseradish peroxidase labelled Ulex europaeus agglutinin-I (UEA-I) and Griffonia simplicifolia agglutinin I-B4 (GSAI-B4) with red blood cells and vascular endothelium in formalin-fixed, paraffin embedded tissues from 18 primate species. The expression of blood group ABH antigens in these cells as well as secretions from other tissues was also examined by the indirect immunoperoxidase method using monoclonal anti-ABH antibodies as primary antibodies. In Prosimians and New World monkeys which lack ABH antigens on both red blood cells and endothelial cells, but produce these antigens in other tissue secretions, GSAI-B4 always reacted with both red blood cells and endothelial cells. In Old World monkeys, which express blood group antigens on endothelial cells but not on red blood cells, neither GSAI-B4 nor UEA-I reactivity were observed, except the endothelial cells from blood group B or O individuals occasionally reacted with GSAI-B4 or UEA-I, respectively. Although UEA-I reactivity was not observed in the endothelial cells of gibbon, it reacted with these cells from chimpanzees. In these two anthropoid apes, both endothelial cells and red blood cells expressed ABH antigens as in humans. These results suggest the close evolutionary relationship between the expression of blood group ABH antigens and lectin binding properties of red blood cells and endothelial cells in primate species.

ABO Blood-Group System↗

Coronary revascularization in a child with Kawasaki disease: use of right gastroepiploic artery.

In coronary insufficiency produced by Kawasaki disease, myocardial revascularization using saphenous vein, internal mammary arteries, and a combination of both grafts has been performed with considerable success. Recently, we successfully used a right gastroepiploic artery as another conduit in coronary revascularization of a 6-year-old boy with Kawasaki disease. Use of the gastroepiploic artery was feasible even in a small child, and this technique is expected to contribute to long-term graft patency as an arterial graft adjunct to internal mammary arteries.

Child↗

Development of the hypothalamic luteinizing hormone-releasing hormone-containing neuron system in the rat: in vivo and in transplantation studies.

The development of the hypothalamic LHRH-containing neuron system was immunohistochemically investigated in vivo and in tissue transplantation using rat embryos aged from 12.5 to 17.5 days of gestation. The sera used were generated against rat gonadotropic hormone-releasing hormone-associated peptide (28-56) (rGAP) and LHRH. Immunoreaction for rGAP was first found in cells migrated from and in the vomeronasal organ on Days 13.5 and 14.5 of gestation. Immunoreactive cells seem to ascend along the terminal nerves, reaching the medial surface of the forebrain vesicles. Subsequently the cells occurred in the septum and further into their final position in the septopreoptic-diagonal band area on Days 16.5-17.5 of gestation; during this traverse the cells become secretory neurons after changes in morphology and in behavior. Intraventricular transplantation revealed that nasal epithelia of Day 12.5 embryos raised only a few cells immunoreactive both for LHRH and rGAP, but a great number of immunoreactive cells and fibers in the presence of the medial basal hypothalamus (MBH). The fibers formed a median eminence-like structure together with dense capillary plexus that had grown in the cografted MBH. The same phenomenon was apparently observed in the grafts obtained from older embryos of gestation, but not in the combined grafts of the anterior septum and the nasal epithelium or the MBH. We conclude that hypothalamic LHRH neurons originate from the nasal placode and acquire secretory behavior in the presence of the MBH.

Animals↗

Changes in sodium channels during neural differentiation in the isolated blastomere of the ascidian embryo.

1. The current density and the kinetics of voltage-sensitive sodium channels during neural differentiation were examined in the isolated, cleavage-arrested blastomere of ascidian embryos which contains presumptive neural regions. The macroscopic sodium current were measured with the two-microelectrode voltage-clamp technique and the single sodium channel currents were recorded with the patch-clamp technique under the cell-attached configuration. 2. The entire time course of sodium channel development could be divided into three phases from the current density and channel gating properties. 3. In the first phase, from fertilization to about 40 h, the density of the sodium channel current was from 8 to 50 microA cm-2. The channel gating properties were similar to those of the sodium channel in the egg cell except for a negative shift in the voltage dependence of the peak inward current, the steady-state inactivation, and the decay time constant. The sodium channels in this phase were classified as 'type-I' channels. 4. In the second phase (40-60 h after fertilization), the density of the sodium channel current increased from 20 to 800 microA cm-2. The curves of the I-V relationship and of the steady-state inactivation shifted in the positive direction by 5-10 mV. 5. At 45-55 h, when the rate of increase in the sodium current was greatest, as much as 40 microA cm-2 h-1, the decay time course of the sodium current became slowest. The time for the current to decline from the peak to the one-tenth of the peak (t 1/10) increased to about five times that in the first phase. After 55 h t 1/10 gradually decreased. 6. In this phase, steady-state inactivation curves showed two inflexion points at different levels of membrane potential and were fitted with a sum of two Boltzmann distribution curves with distinct parameters. The relative contribution of the component with its voltage dependence shifted in the positive direction tended to decrease with development. 7. On examining single-channel recordings, two types of sodium channel were identified in this phase. One type (type-II) showed frequent repetitions of open-to-shut states throughout a voltage step. The ensemble current of the type-II channel showed a slow decay, suggesting that this type of channel may underlie the markedly slow decay of the macroscopic current in this phase. The second type (type-III) had more late openings than the type-I channel but fewer than the type-II channel.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Inactivation kinetics of the sodium channel in the egg and the isolated, neurally differentiated blastomere of the ascidian.

1. Inactivation kinetics of the sodium channel was compared between the egg-type channel in the egg cell and the differentiated-type channel in the cleavage-arrested, neurally differentiated blastomere of the ascidian. The techniques of the two-microelectrode voltage clamp and the cell-attached patch clamp were used. 2. In both types of channel, the time course of inactivation development obtained with a two-pulse protocol at potentials from -40 to -60 mV could be fitted with two exponentials with distinctive parameters. 3. The time course of recovery from inactivation at potentials more negative than -70 mV was compared between the two types of channel. At -80 to -120 mV, a delay of recovery was evident in the egg-type channel, whereas no delay was observed in the differentiated type. 4. In both types of channel, the two time constants of the inactivation of the macroscopic current, derived from the measurements of inward current, inactivation development and recovery from inactivation, had a bell-shaped voltage dependency. The fast time constants had a peak at -55 mV in the differentiated type and -70 mV in the egg type. The slow time constants had a peak around -60 mV in both types. 5. At the single-channel level, the averaged current from the differentiated-type channel showed both fast and slow decays. The frequency of late openings was higher in the differentiated-type channel than in the egg type. 6. The voltage dependence of the decay time constant and the carried charge in the summed current of the single-channel events was found to be shifted in the negative direction by 10-30 mV, compared with that of the macroscopic current. 7. The possibility that the higher frequency of late openings in the differentiated-type channel might be derived from delayed activation was excluded, since first-latency histograms of the single channel were not significantly different between the two types of channel.

Action Potentials↗

Histochemical localization and analysis of blood group-related antigens in human pancreas using immunostaining with monoclonal antibodies and exoglycosidase digestion.

We examined the distribution of blood group-related antigens using an indirect immunoperoxidase method with monoclonal antibodies (MAb) directed to A, B, H, Lewis a (Lea), Lewis b (Leb), Lewis x (Lex), and Lewis y (Ley) antigens and Type 1 precursor chain in human pancreas. Effects of prior digestion with exoglycosidases on MAb stainings were simultaneously investigated. A, B, H, Leb, and Ley antigens were detected in acinar cells and interlobular duct cells but not in centroacinar cells, intercalated duct cells, and islet of Langerhans cells. The expression of these antigens in acinar cells was not dependent on Lewis type and secretor status of the tissue donors, whereas that in interlobular duct cells was strictly dependent on secretor status. The distribution pattern of these antigens in acinar cells was not homogeneous, i.e., cells producing H antigens expressed both Leb and Ley antigens but not A or B antigens, whereas those producing A or B antigens did not secrete Leb and Ley as well as H antigens. Digestion with alpha-N-acetylgalactosaminidase or alpha-galactosidase resulted in the appearance of Leb and Ley antigens as well as H antigen in acinar cells producing A and/or B antigens. Type 1 precursor chain was not detected in pancreatic tissues from secretors but appeared in acinar cells producing H antigen after alpha-L-fucosidase digestion, which also disclosed Lex but not Lea antigen in acinar cells expressing both Leb and Ley. In some non-secretors, MAb against Type 1 precursor chain reacted with acinar cells without enzyme digestion. Although Lea antigen was not detected in acinar cells, it was found in centroacinar cells, intercalated duct cells, and interlobular duct cells from all individuals examined except two Le(a-b-) secretors. After sialidase digestion, Lex antigen appeared in centroacinar and intercalated duct cells from some individuals. Sialidase digestion also elicited reactivity with MAb against Type 1 precursor chain in islet of Langerhans cells from some individuals. These results demonstrate the complexity in the pattern of expression and regulation of blood group-related antigens in different cell types of human pancreas. Such complexity may largely be ascribed to differences in individual genotypes and in gene expression patterns of different cell types.

ABO Blood-Group System↗