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Biomedical subjects

H Ohkubo

Publications and source records attributed to H Ohkubo.

At least 109 records · Page 6Linked to original sources

The serum pregnancy-specific beta 1-glycoprotein to beta-human chorionic gonadotrophin ratio as an index of prognosis in patients with choriocarcinoma.

The ratio of serum pregnancy-specific beta 1-glycoprotein (SP1) to the beta-subunit of human chorionic gonadotrophin (beta-hCG) before and after chemotherapy was measured in 12 patients with metastatic choriocarcinoma. The ratios before chemotherapy ranged between 0.03 and 0.75, with a mean value of 0.34 (SD 0.21). The ratio increased to over 1.0 (1.05-53.3) after one or two courses of chemotherapy in seven of the 12 patients. These women achieved complete remission. In the other five patients who died of the disease due to drug resistance of the tumour, the ratio after chemotherapy was low (0.04-0.74) and tended to decline. These data suggest that the serum SP1/beta-hCG ratio can be used to predict the prognosis of patients with choriocarcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Sodium balance effects on renin, angiotensinogen, and atrial natriuretic polypeptide mRNA levels.

The expressions of the renin, angiotensinogen, and atrial natriuretic polypeptide (ANP) genes were studied in rats with varying sodium intakes. mRNAs for angiotensinogen and renin were measured by a sensitive radiodensitometric hybridization assay. ANP mRNA was determined by a dot-blot hybridization assay. In the high-sodium state, plasma renin concentration (PRC), renal renin concentration (RRC), and renal renin mRNA decreased by 88, 90, and 75%, respectively. In the low-sodium state, PRC, RRC, and renin mRNA increased 17-fold, 2.5-fold, and 4.5-fold, respectively. With captopril treatment during sodium depletion, PRC and renin mRNA increased 144-fold and 17.1-fold, respectively, and RRC increased 4.2-fold. The angiotensinogen mRNA level in the liver and kidney decreased in the high-sodium and increased in the low-sodium state to similar extents. Captopril treatment decreased angiotensinogen mRNA in both organs by about half. Plasma ANP and ANP mRNA decreased in the low- compared with the high-sodium state, whereas atrial ANP content was unaltered in both low- and high-sodium states. These results demonstrate that sodium intake affects the expression of the renin and angiotensinogen genes and slightly alters the expression of ANP gene.

Aldosterone↗

Several functional and fluorescein fundus angiographic findings in Fabry's disease.

Fabry's disease has well-known characteristic morphological findings, i.e., the whorl-like corneal opacity and the posterior spoke-like cataract, etc. But its functional aspect has not been investigated fully. Thus, a 47-year-old male with Fabry's disease was examined with Cochet-Bonnet's esthesiometer, photokeratometry, ultrasonography, electropupillography, electroretinography, electro-oculography and fluorescein fundus angiography. Most of functional findings remained normal in spite of corneal opacity, cataract, retinal and conjunctival vascular tortuosity, choroidal vascular disturbance and delayed retinal circulation time. We discuss the reasons why significant functional disturbance has not developed.

Cornea↗

Augmented expression of atrial natriuretic polypeptide gene in ventricles of spontaneously hypertensive rats (SHR) and SHR-stroke prone.

Tissue levels of atrial natriuretic polypeptide (ANP) and ANP messenger RNA (mRNA) in the atrium and ventricle were measured simultaneously in spontaneously hypertensive rats (SHR) and its substrain, SHR-stroke prone (SHRSP), and these levels were compared with those in control Wistar-Kyoto rats (WKY). At 27 weeks of age with established hypertension and ventricular hypertrophy, ANPmRNA levels in ventricles from SHR and SHRSP were markedly increased, and total contents of ventricular ANPmRNA in SHR and SHRSP were approximately 50% and 250%, respectively, of the corresponding atrial contents. However, levels and total contents of atrial ANPmRNA in SHR and SHRSP were similar to those of WKY, and the total content of ventricular ANPmRNA in WKY was only 6% of the content of atrial ANPmRNA. ANP concentrations in ventricles of SHR and SHRSP were increased in association with the augmentation of ANPmRNA levels. During the prehypertensive stage at 6 weeks of age, slight increases in levels and total contents of ANPmRNA and ANP in the ventricle were observed only in SHRSP. These results demonstrate that the expression of the ANP gene is markedly augmented in ventricles of SHR and SHRSP, especially of SHRSP, at the stage of established hypertension and ventricular hypertrophy, and they also suggest that these genetically hypertensive rats are one of the best animal models to investigate the biosynthesis, storage, and secretion of ventricular ANP.

Aging↗

Regional differences of vascular sensitivities in canine long posterior ciliary arteries.

Information is needed with regard to the vascular reactivities of ophthalmic and ciliary arteries in order to provide rational medical treatment of ocular disease by systemic administration of drugs. In the present study, vascular reactions of isolated proximal and distal portions of dog long posterior ciliary arteries (LPCAs) to norepinephrine (NE), prostaglandin F2 alpha (PGF2 alpha) and KCl were examined using the arterial-perfusion method, in the presence and absence of 2 kinds of antagonists, bunazosin (a selective alpha-1 adrenoceptor antagonist) and diltiazem (a calcium antagonist). In the present study, the proximal LPCA is defined as the region of LPCA on the optic nerve, and the distal one the region along the sclera except the anterior uvea. Each drug was injected by a microinjector into the endothelial side of an artery through a cannulated rubber tubing. Responses were recorded as changes in perfusion pressure. Results were as follows: 1) Three agents produced temporal vasoconstrictions, and the rank order of potency for inducing a vasoconstriction was NE greater than PGF2 alpha greater than KCl in each portion. 2) In these two regions of LPCAs, the maximum increase in perfusion pressure and the threshold dose for KCl were almost the same. 3) The maximum increase in perfusion pressure by PGF2 alpha was the same in these regions, but the threshold dose on proximal vessels was significantly larger than that on distal ones, indicating that the distal LPCAs were more sensitive to PGF2 alpha than the proximal ones. 4) The threshold dose for NE in the distal LPCAs was significantly greater than that in the proximal ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vascular responsiveness to periarterial electrical nerve stimulation on canine ophthalmic arteries.

Both periarterial electrical stimulation (ES) and intraluminal application of norepinephrine (NE) produced a vasoconstriction in the isolated canine ophthalmic artery (OA). The ES-induced vasoconstrictor response was markedly inhibited by treatment with tetrodotoxin and slightly but significantly depressed by xylazine, a selective alpha-2 adrenoceptor agonist. Moreover, the ES-induced response was enhanced by either DG-5128, a selective alpha-2 adrenoceptor antagonist, or angiotensin II. The inhibitory effect of bunazosin on the ES-induced response was significant, but it was rather small compared with that on the NE-induced response. The NE-induced constriction was not affected by xylazine and DG-5128, but significantly enhanced by angiotensin II. These results indicate that (1) the ES-induced response is mediated via sympathetic nerve activation, (2) there are inhibitory prejunctional alpha-2 adrenoceptors, (3) there are more postjunctional alpha-1 than postjunctional alpha-2 adrenoceptors in canine OAs, and (4) prejunctional angiotensin II receptors may exist in isolated OA preparations.

Animals↗

Pre- and postsynaptic features of the central angiotensin systems. Indications for a role of angiotensin peptides in volume transmission and for interactions with central monoamine neurons.

The transmitter receptor matches and mismatches in the angiotensin (ANG) immunoreactive (IR) neuronal systems of the rat CNS have been characterized in various regions by means of ANG II immunocytochemistry and 125I-angiotensin II receptor autoradiography. By means of in situ hybridization the distribution of angiotensinogen mRNA has been mapped out and related to the distribution of ANG IR. In some areas, high densities of ANG IR nerve terminals and ANG II receptors (e.g. paraventricular hypothalamic nucleus, locus coeruleus and nucleus tractus solitarius) or high densities of ANG II receptors alone (e.g. medial geniculate body, subthalamic nucleus and superficial layer of the superior collicle) were often associated with high levels of angiotensinogen mRNA, suggesting the existence of an extracellular formation of ANG II, mediating biological responses. These results underline a role of ANG peptides in volume transmission in addition to transmitter function. Other areas, such as nuc. n. hypoglossi, practically lacking ANG IR terminals, pericarya and receptors, also contained high levels of angiotensinogen mRNA, suggesting a different role of angiotensinogen in these areas. Evidence for presynaptic (turnover changes) and post-synaptic (receptor-receptor crosstalk) interactions with CA neuronal systems has been obtained especially in cardiovascular centers. Thus, ANG II reduces in a concentration related way the affinity of 3H-paraminoclonidine binding sites in the dorsomedial medulla without influencing the Bmax value. These results indicate the existence of intramembrane interactions between ANG II and alpha 2 adrenergic receptors. Finally paraventricular but not perifornical ANG immunoreactive nerve cells costore nuclear glucocorticoid receptor IR, suggesting that some ANG neurons may be directly regulated by glucocorticoids.

Angiotensin II↗

Vascular reactivities of isolated and perfused human ciliary arteries.

The vascular responses to 8 agents, norepinephrine (NE), phenylephrine (PHE), xylazine (XYL), tyramine (TYR), dopamine (DA), 5-hydroxytryptamine (5-HT), prostaglandin F2 alpha (PGF2 alpha) and KCl were examined in human posterior ciliary arteries (HPCAs) which were isolated and perfused with Tyrode's solution gassed with 95% O2 and 5% CO2 under a constant flow rate at 37 degrees C. The rank order for potency of vasoconstrictions was 5-HT greater than NE greater than PHE = PGF2 much greater than DA greater than TYR much greater than KCl. Responses to XYL were various but not significant. DA frequently induced a vasodilatation at smaller doses but a vasoconstriction at larger doses. Although their antagonists were not used in this study, it was suggested that 1) there are rich alpha-1 adrenoceptors and 5-HT receptors, 2) dopaminergic receptors exist in these arteries and 3) there are rich tyramine-sensitive catecholamine stores in nerve terminals.

Adrenergic alpha-Agonists↗

Fluorescein angiographic findings in the detached and reattached retina.

Two cases with retinal detachment were treated with cryoretinopexy, scleral buckling and subretinal fluid-releasing procedures, and examined by pre- and postoperative fluorescein fundus angiography. Capillary dilatation was observed in a wide area of the detached retina. The capillary dilatation was improved in the reattached retina which was not indented by an exoplant, while it was observed in the reattached retina which was indented by an exoplant. After an encircling operation, a background mottling pattern was enhanced in the posterior pole which seemed to be choroidal vascular congestion. These findings suggest that retinal circulation in the detached retina was disturbed, but improved after surgery at least the area which was not indented by an exoplant. Choroidal circulation was disturbed after an encircling operation.

Female↗

[Preservation surgery of head and neck cancer. Results and postsurgical function].

The purpose of conservation surgery is to eradicate the cancerous lesion while preserving the morphology and function of the affected organ as much as possible. Many important functions including swallowing, phonation and articulation are carried out by the organs in the head and neck. This paper presents the short-term (2 years) results of conservation surgery for carcinomas of the tongue, oropharynx, hypopharynx and larynx. Long-term results await further follow-up because of the fact that we started full use of conservation surgery rather recently. Three types of conservation surgery were applied for cancer of the tongue in 36 cases:laser surgery alone, laser debulking surgery followed by (chemo) radiotherapy and induction chemotherapy followed by laser debulking surgery and radiotherapy. The local control rate and survival rate were 97% and 88%, respectively. The basic principles of conservation surgery for oropharyngeal cancer were the same as those for cancer of the tongue. A total of 23 patients were treated, yielding a 65% local control rate and a 63% survival rate. For hypopharyngeal cancer, two types of conservation surgery were applied:partial pharyngectomy and partial laryngopharyngectomy. A total of 10 patients underwent these procedures. The local control rate was 60% and the survival rate was 70%. Two major groups of conservation surgery were applied for cancer of the larynx:laser surgery with or without radiotherapy in 74 cases and partial laryngectomy in 94 cases. The local control rate was 69% for laser surgery and 87% for partial laryngectomy, while the survival rates were 100% and 91%, respectively.

Combined Modality Therapy↗

Simultaneous measurement of atrial natriuretic polypeptide (ANP) messenger RNA and ANP in rat heart--evidence for a preferentially increased synthesis and secretion of ANP in left atrium of spontaneously hypertensive rats (SHR).

Tissue levels of atrial natriuretic polypeptide (ANP) messenger RNA (ANPmRNA) and ANP in the rat heart were measured simultaneously. In Wistar rats, ANPmRNA of the same size (approximately 0.95 kbp) was detected in all four chambers of the rat heart. The ANPmRNA level was the highest in the right atrium, and the left atrial level was slightly lower than the right atrial level. Ventricular levels were more than two orders of magnitude lower than atrial levels. Tissue ANP concentrations of four chambers were roughly parallel to ANPmRNA levels. In spontaneously hypertensive rats (SHR) with the elevated plasma ANP level, the ANPmRNA level in the left atrium was substantially increased. The left/right ratio of atrial ANPmRNA level in SHR (150%) was higher than that in control Wistar Kyoto rats (WKY) (90%). In contrast, the left/right ratio of atrial ANP concentration was decreased in SHR (44%) compared with that in WKY (84%). The ratio of ANP to ANPmRNA levels in the left atrium of SHR was about three times smaller than that in the right atrium of SHR, and those in bilateral atria of WKY. These results indicate that the biosynthesis and secretion of ANP from the left atrium is preferentially increased in SHR. Thus, simultaneous determination of ANPmRNA and ANP levels is a refined strategy of investigation for the biosynthesis, storage and secretion of ANP.

Animals↗

Existence of multiple forms of cytochrome P-450scc purified from bovine adrenocortical mitochondria.

Three fractions of cytochrome P-450scc (denoted as fractions a, b, and c) were purified by a new procedure from bovine adrenocortical mitochondria. The amino-acid content analyses of these three fractions showed no difference. NH2-terminal amino-acid sequences of cytochrome P-450scc fractions, a and b agreed completely with the sequence deduced by nucleotide sequence of cDNA of cytochrome P-450scc mRNA (Morohashi, K., Fujii-Kuriyama, Y., Okada, Y., Sogawa, K., Hirose, T., Inayama, S. and Omura, T. (1984) Proc. Natl. Acad. Sci. USA 81, 4647-4651), whereas the sequence of fraction c showed a missing of isoleucine at the NH2-terminal. COOH-terminal ámino-acid sequences of fractions a, b and c were -Gln-Ala-COOH, identical with the deduced sequence from the cDNA. Measurements of the enzymatic activities of cholesterol side-chain cleavage reaction revealed no distinct difference among these three fractions. Although each of these fractions appeared as a single protein staining band upon SDS-polyacrylamide gel electrophoresis, these fractions showed heterogeneities upon two-dimensional electrophoresis and chromatofocusing. Fraction a contained the major form of cytochrome P-450scc, and its isoelectric point was estimated to be pH 7.8 by isoelectric focusing under both native and denatured conditions, and this value was confirmed by chromatofocusing. Neither of the carbohydrate-specific stainings (such as periodic acid-Schiff staining and lectin-peroxidase stainings using concanavalin A, wheat-germ agglutinin, and soybean agglutinin) of purified cytochrome P-450scc fractions after the electrophoretic resolution on SDS-polyacrylamide gel could show cytochrome P-450scc fractions as glycoproteins, suggesting that the heterogeneities were not due to the glycosylation state.

Adrenal Cortex↗

Differing utilization of homologous transcription initiation sites of rat K and T kininogen genes under inflammation condition.

Two types of rat kininogen mRNAs exhibit marked differences in the regulation of their expressions. The two T kininogen (T) mRNAs considerably increase under acute inflammation conditions, although no such increase occurs in the high molecular weight and low molecular weight K kininogen (K) mRNAs encoded by the same gene. This investigation examines the sequences of the 5' portions of the K and the two T genes and analyzes transcription initiation sites and their utilization at differently regulated conditions of the K and T genes. The sequence analysis indicates that the K and the two T genes are extremely homologous at the 5' portions as well as the 5'-flanking regions of at least 1.0 kilobase pairs. The S1 nuclease and primer extension analyses show that both T and K mRNAs start with three sets of the homologous initiation sites, and the utilization of the two 3'-side initiation sites of the T genes markedly increases under inflammation conditions. In contrast, no such elevation is observed for the three initiation sites of the K gene. Thus, although the sequences involved as transcription initiation sites are extremely homologous, their utilizations in the expressions of the K and T genes are regulated differently under inflammation conditions.

Amino Acid Sequence↗

Electrophysiological findings in familial exudative vitreoretinopathy.

Three patients in a family with familial exudative vitreoretinopathy (FEVR) were studied especially electrophysiologically. Two cases showed abnormal ERG, namely reduction of amplitude of oscillatory potentials, a and b wave of bright white flash ERG, scotopic and photopic b waves. One case showed reduced Light peak/Dark trough ratio of EOG. Next, the electrophysiological findings of cases with FEVR reported in the literature were analyzed. The result was that FEVR has electrophysiological varieties but a statistical significant relationship between electrophysiological findings and visual acuity. That is, cases with abnormal ERG or EOG have more impaired visual acuity than normal ones. Furthermore, there was a tendency that eyes with abnormal ERG or EOG showed more disturbed color vision and advanced fundus findings than normal ones. These results seemed to be understandable by anatomically characteristic fundus feature of FEVR.

Adult↗

Pharmacological analysis of vasoconstriction of isolated canine ophthalmic and ciliary arteries to alpha-adrenoceptor agonists.

Effects of five alpha-adrenoceptor agonists were investigated on the canine internal, external ophthalmic and ciliary arteries by the use of several kinds of antagonists. These arteries were isolated with the optic nerve and perfused with Tyrode solution under a constant flow rate at 37 degrees C. Control perfusion pressure was within 40-80 mmHg. Each drug solution except sodium nitroprusside (SNP) was administered by a microinjector into the endothelial side of the artery through a cannulated tubing, and SNP was administered by being dissolved into the perfusion solution. The response was obtained as changes in perfusion pressure. Results were as follows: (1) epinephrine (EPI), norepinephrine (NE), phenylephrine (PHE), and KCl induced a marked vasoconstriction in these arteries, although xylazine (XYL) and clonidine (CLO) did not produce any significant change; (2) bunazosin, a potent alpha-1 adrenoceptor blocker, antagonized the effects of NE and PHE in a dose-related manner, and did not affect the responses to KCl; (3) diltiazem reduced the KCl-induced vasoconstriction in a dose-related manner, and it did not significantly influence the vascular responses to NE; (4) SNP reduced the NE-induced vasoconstriction but the KCl-induced vasoconstriction was only suppressed by a large dose of SNP. From these results, it is suggested that; (1) these arteries contain alpha-1 but not alpha-2 adrenoceptors; (2) NE-induced vasoconstriction is independent of the Ca2+ inward current but probably involves intracellular Ca2+ ion movement; (3) SNP may influence intracellular Ca2+ movement in these arteries.

Adrenergic alpha-Agonists↗

Molecular biology of the angiotensinogen and kininogen genes.

In order to investigate the structures and expressions of the angiotensinogen and kininogen genes, we have isolated cDNA and genomic clones and characterized their structures. The following results were obtained. (a) The primary structures of rat and human angiotensinogens and bovine, human, and rat kininogens were determined, and they exhibit characteristic features. (b) Angiotensinogen and alpha 1-antitrypsin are related in not only protein structures but also gene organizations. (c) Angiotensinogen mRNA is synthesized not only in the liver but also in the brain, kidney, lung, adrenal gland, and ovary. (d) Angiotensinogen mRNA markedly increased in the liver but not in the brain after induction of acute inflammation. (e) Low molecular weight (LMW) and high molecular weight (HMW) kininogen mRNAs are generated from a single gene by alternative RNA processing events. (f) At least four types of kininogen mRNAs exist in rat liver. Two of them are LMW and HMW kininogen mRNAs, while the other two encode additional forms of kininogens (T-kininogens). (g) Two T-kininogen mRNAs but not LMW and HMW kininogen mRNAs dramatically increased after induction of acute inflammation, and T-kininogen turned out to be identical to alpha 1-major acute phase protein. (h) Kininogens have multifunctional domains; an amino-terminal domain for cystein proteinase inhibitor, a bradykinin moiety, and in the case of HMW kininogen a carboxyl-terminal domain for a cofactor of blood coagulation.

Angiotensinogen↗