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Biomedical subjects

T Ohashi

Publications and source records attributed to T Ohashi.

At least 343 records · Page 19Linked to original sources

Cortisol responsiveness to insulin-induced hypoglycemia in Cushing's syndrome with huge nodular adrenocortical hyperplasia.

A 51-yr-old male patient with a 3 yr history of Cushing's syndrome is described. The baseline plasma cortisol level was elevated, while the plasma ACTH levels remained at an undetectable level. Dynamic testing of pituitary-adrenal function revealed no suppression after 8 mg of dexamethasone, and there was no response to metyrapone or CRF, while plasma cortisol showed a hyperresponse to synthetic ACTH. Plasma cortisol responded to insulin-induced hypoglycemia without an obvious ACTH response. These and the computerized tomography data suggested a "huge" bilateral nodular adrenocortical hyperplasia which was later confirmed by surgery. The left and right adrenal glands weighed 55 and 76 g, respectively. In vitro experiments, using the adrenal tissue, showed that there was an adrenal cortisol response to 1-39 ACTH but not to regular insulin, arginine vasopressin, angiotensin II, norepinephrine or epinephrine. These results indicate that plasma cortisol responded to a slight hypoglycemia-induced plasma ACTH change which was not detected in the ACTH radioimmunoassay or to factors other than ACTH which might be induced by hypoglycemia.

Adrenal Cortex↗

Abnormal excretion of autofluorescent lipids in urine from patients with neuronal ceroid lipofuscinosis.

Two of our 5 patients with neuronal ceroid lipofuscinosis excreted a large amount of autofluorescent lipids in their urine. These autofluorescent lipids consisted of more than 5 bands in the thin-layer-chromatography. Excitation and emission spectra of these lipids showed that they had heterogeneous components. This finding was specific to neuronal ceroid lipofuscinosis, and never found in other neurological diseases. We also measured unesterified dolichol and dolichol fatty acid ester in urine, and 4 of our patients did not excrete a large amount of such compounds compared with control groups. This finding suggest that increased excretion of dolichol in urine of patient with neuronal ceroid lipofuscinosis may be the secondary effect, but there are some possibilities that certain abnormalities in glycoprotein metabolism exist in neuronal ceroid lipofuscinosis.

Chromatography, Thin Layer↗

Quantitative analysis of the oculocardiac reflex by traction on human extraocular muscle.

The oculocardiac reflex was quantitatively studied in 15 patients with strabismus. The reflex was observed in all patients when the medial rectus and inferior oblique muscles were stretched; the medial rectus muscle had a lower threshold than the inferior oblique. Bradycardia was evoked in 7 of the 15 patients when the lateral rectus was tractioned with tensions of 50 g and 600 g. The oculocardiac reflex was a graded phenomenon as a function of tension applied to the extraocular muscles. As tension was increased, bradycardia occurred rapidly and became deep. Systemic administration of atropine prevented completely the bradycardia from occurring. The results suggest that the response of the extraocular muscles to stretch are critically mediated through a polysynaptic path to the heart, resulting in suppression of the heart rate.

Arrhythmias, Cardiac↗

The platelet activation induced by wheat germ agglutinin.

In human platelets, wheat germ agglutinin (WGA) induced serotonin release without cell agglutination. WGA induced the phosphorylation of both 40-kDa and 20-kDa proteins in a parallel manner, and at least, the phosphorylation of 40-kDa protein was preceded by transient formation of endogenous diacylglycerol (DG) accompanied by a decrease in phosphatidylinositol (PI). Both phosphorylation of these two proteins and serotonin release were inhibited by prior treatment of platelets with dibutyryl cyclic AMP, W-7, or TMB-8. These results suggest that both phosphatidylinositol turnover and Ca2+ mobilization play an essential role in WGA-induced platelet activation.

Aminoquinolines↗

A monoclonal anti-human platelet antibody: a new platelet aggregating substance.

A monoclonal anti-human platelet antibody, TP82, is described, which caused irreversible aggregation of platelets in association with the release of adenosine triphosphate or [14C] serotonin, and which inhibited ristocetin-induced agglutination. Immunofluorescence assay showed that the antibody binds to platelets, megakaryocytes, and common acute lymphoblastic leukemia cells. The antibody (IgG1) immunoprecipitated a polypeptide of 23,000 daltons with an isoelectric point of about 7.0. The aggregation induced by the purified antibody and/or F(ab')2 fragments occurred in platelet-rich plasma and with washed platelets, but not with formalin-fixed washed platelets. TP82-induced aggregation was completely inhibited by disodium ethylendiaminotetraacetate, diltiazem, W-7, PGE1, and several metabolic inhibitors. At a concentration of apyrase or CP/CPK, which inhibited adenosine 5-diphosphate-induced aggregation. TP82-induced aggregation was only partially affected. Thrombin was not required for the antibody-mediated effects, since two thrombin inhibitors failed to block the reaction. The antibody, at least at a high concentration, induced platelet aggregation by a mechanism almost independent of thromboxane A2 formation, since cyclooxygenase inhibitors had little inhibitory effect on aggregation. TP82 monoclonal antibody is a new platelet-aggregating substance that interacts with a low-molecular-weight binding site on the platelet membrane.

Adenosine Triphosphate↗

Interaction of Solanum tuberosum agglutinin with human platelets.

Solanum tuberosum agglutinin (STA) binds to the surface of human platelets and leads to their agglutination. Lectin staining shows that 125I-STA most intensely labels a major platelet membrane glycoprotein identified as GPIIIa followed by GPIV . STA does not induce release reaction, TXB2 formation or platelet protein phosphorylation. Since STA-induced agglutination is independent of intracellular metabolism of platelets, STA may prove to be a useful tool to explore the clinical condition in which the composition of platelet membrane protein is altered.

Blood Platelets↗

Effects of histamine agonists and antagonists on luminol-dependent chemiluminescence of granulocytes.

Histamine inhibited luminol-dependent chemiluminescence (CL) of granulocytes in a dose-dependent manner, with an ID50 of about 3 X 10(-5) M. Dimaprit, a selective H2-agonist, produced a histamine-like effect. Furthermore, cimetidine, ranitidine, and TZU 0460, which are selective H2-antagonists, but not mepyramine, a selective H1-antagonist, blocked the inhibitory effect of histamine on CL. Thus it may be concluded that the inhibitory effect of histamine is mediated via histamine H2-receptors. H1- and H2-antagonists per se, except at extremely high concentrations, had no effect on CL of granulocytes.

Cimetidine↗

Co-storage of adrenaline and noradrenaline with Met-enkephalin-Arg6-Gly7-Leu8 and Met-enkephalin-Arg6-Phe7 in chromaffin cells of hamster adrenal medulla.

The co-existence of catecholamines with opioid peptides in adult hamster adrenal chromaffin cells was studied by Sternberger's peroxidase-antiperoxidase (PAP) method. Paraffin embedded serial sections (3-4 microns thick) of adrenal glands perfusion-fixed with either Bouin's fluid or 4% paraformaldehyde solution were immunostained using anti-adrenaline (AP16-2), -noradrenaline (NAP1-18), -Met-enkephalin-Arg6-Gly7-Leu8 (Met-Enk-Arg-Gly-Leu: R-0171, NE2-206) and -Met-enkephalin-Arg6-Phe7 (Met-Enk-Arg-Phe: AP3-311) sera. Selective and specific immunostaining for adrenaline and noradrenaline was obtained in tissues fixed in 4% paraformaldehyde solution. Bouin's fluid gave negative or unsatisfactory results. Immunostaining with two kinds of Met-Enk-Arg-Gly-Leu (R-0171, NE2-206) and one kind of Met-Enk-Arg-Phe sera (AP3-311) was dependent upon the method of fixation used. The immunostaining in the Bouin-fixed tissues was stronger than that in the 4% paraformaldehyde-fixed ones. Secretory granules in chromaffin cells were responsible for both adrenaline- and noradrenaline-like and Met-Enk-Arg-Gly-Leu- and Met-Enk-Arg-Phe-like immunoreactivities. All adrenaline-storing (A) and noradrenaline-storing (NA) cells showed intense Met-Enk-Arg-Gly-Leu- and Met-Enk-Arg-Phe-like immunoreactivities. In the Bouin-fixed adrenal medulla, immunostaining of A cells with the two kinds of anti-Met-Enk-Arg-Gly-Leu sera (R-0171, NE2-206) was deeper than that of the NA cells. Immunostaining of A cells with the anti-Met-Enk-Arg-Phe serum (AP3-311) was apparently of the same intensity as that of NA cells. In 4% paraformaldehyde-fixed tissues, no correlation was seen between the distribution of A and NA cells and that of intensely and slightly Met-Enk-Arg-Gly-Leu and Met-Enk-Arg-Phe immunopositive cells. The "masking" of immunoreactive residues in chromaffin granules by an aldehyde-noradrenaline complex may be one of the major causes of the decreased opioid peptide-like immunoreactivity in the 4% paraformaldehyde-fixed adrenal medulla.

Adrenal Medulla↗

Mechanism of neutrophil chemiluminescence induced by wheat germ agglutinin: partial characterization of the antigens recognized by wheat germ agglutinin.

Wheat germ agglutinin (WGA) stimulated neutrophils to produce significant levels of luminol-dependent chemiluminescence (CL). Since WGA is known to bind N-acetylglucosamine (GlcNAc) oligomers and N-acetylneuraminic acid (NANA), we attempted to determine which binding property of WGA is essential for induction of CL. The succinylated form of WGA (SuWGA), which is no longer able to bind NANA, was still able to induce CL. N-Acetylglucosamine at a concentration of 20 mmol/L almost completely inhibited WGA-induced CL production by neutrophils, whereas bovine submaxillary gland mucin, a potent blocker of NANA binding of WGA, failed to inhibit CL production. Lectins with the GlcNAc-binding property were examined for their ability to induce CL. Those that have higher valences and have a tendency to bind GlcNAc oligomers in the internal portion of glycoconjugates were able to induce CL, whereas those that have low valences and bind terminal GlcNAc of glycoconjugates failed to induce CL even at high concentrations. Attempts were made to characterize the neutrophil membrane proteins recognized by WGA. Glycoproteins with a molecular weight of 25,000 daltons were identified by a 50 mmol/L GlcNAc elution of WGA gels loaded with 125I-labeled neutrophil membrane proteins. Elution with 500 mumol/L GlcNAc trimer produced several glycoproteins of different molecular weights in addition to the glycoproteins of 25,000 daltons. 125I-labeled WGA and SuWGA were used for autoradiographic analysis of cell extracts of the neutrophils separated on sodium dodecyl sulfate polyacrylamide gels. WGA recognized multiple glycoproteins of different molecular weights, whereas SuWGA bound only a few of them. Glycoproteins of 25,000 daltons, probably corresponding to those identified by 50 mmol/L GlcNAc elution, were also recognized.

Antigens↗