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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 775 records · Page 43Linked to original sources

Mapping of histamine H1 receptors in the human brain using [11C]pyrilamine and positron emission tomography.

We have studied the characteristics of carbon-11 labeled pyrilamine as a radioligand for investigating histamine H1 receptors in human brain with positron emission tomography (PET). [11C]Pyrilamine is distributed evenly in proportion to cerebral blood flow at initial PET images. Later (after 45-60 min), 11C radioactivity was observed at high concentrations in the frontal and temporal cortex, hippocampus, and thalamus, and at low concentrations in the cerebellum and pons. The regional distribution of the carbon-11 labeled compound in the brain corresponded well with that of the histamine H1 receptors determined in vitro in autopsied materials. In six controls, the frontal and temporal cortices/cerebellum ratio increased during the first 60 min to reach a value of 1.22 +/- 0.071. Intravenous administration of d-chlorpheniramine (5 mg) completely abolished the specific binding in vivo in the frontal cortex and temporal cortex (cortex/cerebellum ratio, 0.955 +/- 0.015). The availability of this method for measuring histamine H1 receptors in vivo in humans will facilitate studies on neurological and psychiatric disorders in which histamine H1 receptors are thought to be abnormal.

Adult↗

A method for identifying causative chemicals of allergic contact dermatitis using a combination of chemical analysis and patch testing in patients and animal groups: application to a case of rubber boot dermatitis.

A 63-year-old woman developed allergic contact dermatitis from rubber boots. Initial investigation, by patch testing in the patient and chemical analysis of the causative rubber boots, revealed that mercaptobenzothiazole (MBT) and dibenzothiazyl disulfide (MBTS) were the causative chemicals. Subsequent investigations were performed by patch testing in animal groups. An extract of the causative rubber boots, MBT and MBTS were used for sensitization of guinea pigs by the guinea pig maximization test (GPMT). 3 animal groups, A (with the boot extract), B (with MBT) and C (with MBTS) were successfully prepared. The boot extract was fractionated by column chromatography and thin-layer chromatography (TLC). Each fraction was subjected to patch testing in the animal groups. Positive reactions in all groups would show that the active fractions contained MBT-type compounds, whereas a positive reaction in group A but negative ones in group B and C would show that the active fractions did not contain any MBT-type compounds. Each fraction was then analyzed by gas chromatography (GC), GC-mass spectrometry (GC-MS), direct inlet-MS (DI-MS) and high-performance liquid chromatography (HPLC). By this investigation, we found not only known allergens (MBT, MBTS), but also unknown allergens: S-substituted MBT-type compounds and styrenated phenol (SP). Thus, SP was shown to be a candidate as a human sensitizer even though the patient did not react to it.

Allergens↗

Role of intracellular Ca2+ and the calmodulin messenger system in pepsinogen secretion from isolated rabbit gastric mucosa.

Both carbachol (10(-4)-10(-3) mol/l) and cholecystokinin octapeptide (CCK-8) (10(-8)-10(-6) mol/l) significantly stimulated the release of pepsinogen from rabbit gastric mucosa maintained in organ culture (213-216% and 143-261% of control, respectively, p less than 0.05-0.01). The secretion was not affected by removing Ca2+ from the culture medium with ethylene glycol tetra-acetic acid. Verapamil failed to inhibit the secretion of pepsinogen induced by the drugs in ordinary culture medium containing Ca2+. In contrast, nicorandil (10(-6)-10(-4) mol/l) attenuated the release of pepsinogen by the drugs in a dose dependent manner, regardless of the presence or absence of Ca2+ in the culture medium. W-7 (10(-6)-10(-4) mol/l) and W-5 (10(-5) and 10(-4), or 10(-6) mol/l) reduced significantly the secretion of pepsinogen induced by carbachol (53-71% and 63-81% of control, respectively, p less than 0.05-0.01) and that by CCK-8 (49-67% and 66-76% of control, respectively, p less than 0.01) in the Ca2+ containing medium. However, W-7 did not show significant inhibition of cyclic adenosine monophosphate (cAMP) and forskolin induced pepsinogen secretion. These findings indicate that the calmodulin messenger branch that is activated by a rise of intracellular Ca2+ mobilised in cytosol from its intracellular, but not extracellular, source plays a critical role in pepsinogen secretion induced by carbachol and CCK-8. It seems likely that an increase in cAMP in cytosol does not provoke any calmodulin mediated pepsinogen secretion.

Animals↗

Role of EDRF in splanchnic blood flow of normal and chronic portal hypertensive rats.

The role of endogenous endothelium-derived relaxing factor (EDRF) in splanchnic blood flow was assessed in normal and portal vein-stenosed rats (PSRs). Specific and maximal inhibition of EDRF was achieved by intravenous administration of NG-nitro-L-arginine (L-NOARG) as a 1.75 mumol/kg bolus, followed by constant infusion of 1.75 mumol/kg for 20 min. Pretreatment with L-arginine (175 mumol/kg iv) completely blocked both hypertension and the reduction in blood flow induced by L-NOARG. Pretreatment with D-arginine (175 mumol/kg iv) and prazosin (500 micrograms/kg iv) did not attenuate the pressor effect of L-NOARG. These results indicate that L-NOARG selectively blocks EDRF. The blood flow to the stomach, duodenum, jejunum, ileum, cecum, and colon in control rats was 81.1 +/- 8.7, 199.1 +/- 21.9, 153.3 +/- 20.0, 68.6 +/- 10.6, 79.4 +/- 11.8, and 59.3 +/- 7.8 ml.min-1.100 g-1, respectively, and in PSRs was 141.4 +/- 10.8, 244.0 +/- 10.4, 208.3 +/- 9.8, 126.8 +/- 13.0, 166.9 +/- 16.5, and 94.8 +/- 4.7 ml.min-1.100 g-1, respectively. Blood flow was measured using the radioactive microsphere method. L-NOARG significantly reduced blood flow to the stomach, duodenum, jejunum, ileum, cecum, and colon in control rats by 47, 44, 48, 55, 40, and 41%, respectively, and in PSRs by 30, 27, 36, 33, 28, and 23%, respectively. The magnitude of blood flow reduction in PSRs was lower than in normal rats. These results indicate that EDRF plays an important role in control of the splanchnic circulation, but its effect on the hyperdynamic circulation observed in PSRs is insignificant.

Animals↗

Further observations on serial serum immunoreactive inhibin levels in the luteal phase and early gestation after ovarian stimulation for in vitro fertilization and embryo transfer.

Serum immunoreactive inhibin of the luteal phase was measured by radioimmunoassay in 71 patients in vitro fertilization and embryo transfer (IVF-ET). The correlation between the pregnancy outcome and the serial inhibin pattern from the luteal phase to early gestation was studied. In nonconception cycles (n = 35), serum inhibin concentration rose and reached a peak level around 5 or 6 days after oocyte pick-up (OPU), then fell to the level of the early follicular phase. In conception cycles (n = 22), serum inhibin levels rose again 10-15 days after OPU. Serum inhibin levels were significantly higher from 10 days after OPU in multiple pregnancy (n = 5) than in single pregnancy (n = 17). In viable single pregnancy (n = 17), serum inhibin levels were significantly higher than in non-viable pregnancy (n = 14) from 15 days after OPU. Serum inhibin levels in early gestation correlated well with the pregnancy outcome of IVF-ET. These data suggest that inhibin is an important factor for the diagnosis of pregnancy outcome.

Abortion, Spontaneous↗

Multiple point mutation of N-ras and K-ras oncogenes in myelodysplastic syndrome and acute myelogenous leukemia.

We analyzed activating mutations of N-ras and K-ras by the polymerase chain reaction and oligonucleotide hybridization in hematological disorders. Activating mutations of these codons were detected in 4 of 20 cases of myelodysplastic syndrome (MDS) and 15 of 77 cases of acute myelogenous leukemia (AML). Our of 19 cases of MDS and AML who carried active mutations, 7 cases were found to have two or more distinct mutations in activating codons of N-ras and K-ras. Ras mutation was found preferentially in progressive disease such as refractory anemia with excess of blasts (RAEB) of RAEB in transformation (RAEB-t). A relatively high incidence of ras mutation was found in M5 AML (40%). No ras mutations were found in other hematological disorders, such as acute lymphoblastic leukemia and chronic myelogenous-leukemia. The most frequent amino acid substitution was that of an aspartate for glycine at codon 12 of N-ras resulting from G to A mutation (11/35). The survival of AML patients who carried ras mutations showed no significant differences from those without ras mutations calculated by Kaplan-Meier. Seven cases of MDS and 7 cases of AML patients could be investigated at various points during their clinical course. Among these 14 cases, we found 2 interesting cases of MDS. The first case lost multiple clones carrying ras mutations during disease progression, the second case acquired mutation of the ras gene during disease progression. These results suggested that multiple point mutations of ras genes may not be initiating events but may contribute to a clonal evolution of MDS and AML.

Adult↗

Increase of migration of cultured endothelial cells by angiotensin-converting enzyme inhibitor derived from tuna muscle.

The influence of angiotensin-converting enzyme (ACE) inhibitory octapeptide derived from tuna muscle (tuna AI) on the bovine aorta endothelial cell (BAEC) migration was investigated, as compared with captopril. BAEC migration was quantitated 6 d after release from contact inhibition by a teflon fence assay. The culture grown in the presence of tuna AI (1 and 10 microM) clearly exhibited an increase in migration, compared with the control. The media collected from tuna AI (1 and 10 microM)-stimulated BAECs significantly exhibited the interleukin (IL) -1 activity that was detected by the thymocyte costimulation assay with phytohemagglutinin. Although tuna AI was a weaker ACE inhibitor than captopril, the increasing effect of tuna AI on the migration and the IL-1 generation in BAECs was slightly greater than that of captopril. In quiescent BAECs, tuna AI (1 microM) apparently induced c-myc and platelet derived growth factor (PDGF) A-chain messenger ribonucleic acid (mRNA) expressions within 30 min, which persisted for 6 h. In contrast, captopril induced a very low expression of c-myc mRNA, and had no relation to PDGF A-chain mRNA expression. These results suggest that the increase of BAEC migration by tuna AI, unlike captopril, is likely related to the induction or activation of IL-1, and c-myc and PDGF mRNAs, in addition to the inhibition of the conversion of endogenous angiotensin I to angiotensin II.

Amino Acid Sequence↗

Inhibitory effect of bis(2-aminohexyl) disulfide and bis(2-amino-3-phenylpropyl) disulfide on several mouse inflammations.

The anti-inflammatory profile of the analogues of bis(2-aminopropyl) disulfide dihydrochloride with butyl (compd. II) and phenyl (compd. III) instead of the methyl group was studied in several mouse models related to phagocyte functions. The test samples were administered 2-3 h before the inflammatory stimulation or the peak of inflammation. Subcutaneously administered, compds. II and III significantly inhibited serotonin-induced paw edema in a dose-dependent manner (50% inhibitory dose values: 10 and 5 mg/kg, respectively), when orally administered at 25 mg/kg, these compounds were significantly effective, but their potencies were weaker. Neither compound had any irritant activity when administered at a dose of 12.5 micrograms/5 microliters/paw into the paw. In a sheep red blood cells (SRBC)-induced delayed-type hypersensitivity (DTH) reaction model, compd. II (25 mg/kg, s.c.) significantly inhibited the DTH responses when administered at two different times in relation to the time of challenge. However, there was only slight inhibition by compd. III (25 mg/kg, s.c.) on paw edema formation when administered 14 h after secondary immune response. In a model of experimental acute hepatic failure induced by successive injections of Propionibacterium acnes and lipopolysaccharide, both compounds increased mouse survived, compared with the control mice, and kept the serum levels of components involved in hepatic failure to nearly normal levels. These results demonstrate that compds. II and III possess an inhibitory effect on inflammation related to phagocytes.

Amines↗

Studies on thermophile products. V. Immunosuppressive profile in vitro of Bacillus stearothermophilus component, Fr.5-B.

The immunosuppressive profile of Bacillus stearothermophilus UK563 component, Fr.5-B, is presented in in vitro studies. Fr.5-B (0.1-1000 ng/ml), provided it was added at the initiation of mixed leukocyte reaction (MLR), inhibited dose-dependently the incorporation of tritiated thymidine ([3H]TdR) into mouse spleen cells and human peripheral blood lymphocytes. Even the addition of Fr.5-B 48 h after the onset of culture suppressed mouse MLR, unlike cyclosporin A (CYA). Fr.5-B significantly inhibited cytotoxic T lymphocyte generation determined by [3H]TdR-release micro-cytotoxicity assay by using mouse mastocytoma P815 as targets. Moreover, this component decreased dose-dependently the expression of class II major histocompatibility molecules (Ia) on mouse peritoneal macrophages induced by concanavalin A supernatant. The present results revealed the unique immunosuppressive property of Fr.5-B which was different from that of CYA.

Animals↗

Preparation of biologically active and site specifically radioiodinated recombinant human insulin-like growth factor-I.

Recombinant human insulin-like growth factor-I (rhIGF-I) was iodinated using a lactoperoxidase-catalyzed labeling method. The labeled products were separated into more than five fractions by ion-paired reverse-phase high performance liquid chromatography (HPLC). A fraction (peak 1), which showed the highest yield and radioactivity, was found to be biologically active in the BALB/c 3T3 cell proliferating system. The site of the iodination was investigated by S-pyridylethylation followed by trypsinization and separation with HPLC using reverse phase columns. From the amino acid analysis of the peaks which were radioactive, the iodination site of peak 1 was revealed to be Tyr-24 and Tyr-60. This is the first report of the biological activity of radioactive peptide hormone with a defined labeled site.

3T3 Cells↗

Acute myocardial infarction in a young adult as possible sequela of Kawasaki disease--a case report of successful intracoronary thrombolytic therapy and histological study of an aneurysm.

Emergency coronary angiography in a 28-year-old male suffering an acute anteroseptal myocardial infarction revealed complete obstruction of the left anterior descending artery in association with multiple aneurysms of the 3 major coronary arteries. Successful intracoronary thrombolytic treatment with urokinase infusion directly into the infarct-related artery was performed 2 h after the onset. Follow-up left ventriculogram showed preservation of left ventricular wall motion. Fifty days after the infarction, he underwent aorto-coronary bypass surgery. Histological examination of the biopsy specimen obtained from the aneurysm of the distal portion of the right coronary artery revealed that the 3-layer architecture of the arterial wall had been completely lost. The wall was replaced by fibrotic tissue, with slight mononuclear cell infiltration around the small vessels, but no acute inflammatory reaction or atheromatous change was seen. In spite of the presence of the coronary risk factors of hypertension and hyperlipidemia, angiography revealed no evidence of atherosclerosis of systemic arteries. It is suggested that the coronary aneurysms in this case are possible sequelae of Kawasaki disease in childhood.

Adult↗

N-(F-18)-fluoroacetyl-D-glucosamine: a new positron labeled pharmaceutical for cancer study.

In order to evaluate the role of hexosamine metabolism in tumor tissue, we studied the biodistribution of N-(F-18)-fluoroacetyl-D-glucosamine (FAGlu) in male Donryu rats bearing poorly differentiated hepatomas (AH109A and AH272). Compare with the former result of the high tumor uptake of FAGlu in C3H/He mice bearing well differentiated spontaneous hepatoma, the tumor uptakes of FAGlu in these tumors showed the lower values. This suggested that spontaneous hepatoma maintained a high activity of glucosamine metabolism, while poorly differentiated hepatoma had little activity. Metabolism of glucosamine in tumor tissue may be another marker for characterizing tumors. We also discuss the tissue distribution of new F-18 labeled hexosamines, N-(F-18)-fluoroacetyl-D-mannosamine and N-(F-18)-fluoroacetyl-D-galactosamine in tumor bearing rats.

Acetylgalactosamine↗

Wegener's granulomatosis in a patient with a rheumatoid arthritis.

A 38-year-old woman with rheumatoid arthritis who developed Wegener's granulomatosis is described. Wegener's granulomatosis appeared with saddle nose, perforation in her nasal septum, and granuloma in the nasal cavity. Laboratory evaluation showed a positive rheumatoid factor and circulating immune complex. Radiographic examination revealed ankylotic changes in both wrist and elbow joints. Bilateral anosmia and other disease manifestations completely responded to treatment with oral cyclophosphamide and prednisolone.

Adult↗

A variant serum cholinesterase and a confirmed point mutation at Gly-365 to Arg found in a patient with liver cirrhosis.

A 64-year-old man was admitted to our hospital because of possible liver cirrhosis. His serum cholinesterase was anomalously low with a delta pH of 0.1 (normal range; 0.8-1.1). His enzyme was more heat-labile than the normal controls. Km value of his enzyme for benzoylcholine was 1.1 x 10(-5) mol/l, while that for normal controls was 2.3 x 10(-6) mol/l. In addition, isozymic alteration of his enzyme was observed. Sequencing of the white blood cell DNA of the patient showed a point mutation at nucleotide 1093 (GGA to CGA), which changes codon 365 from glycine to arginine.

Amino Acid Sequence↗

[Guanidino compounds in the elderly].

To examine the metabolism of guanidino compounds in the elderly, we measured the serum concentrations of urea nitrogen, creatinine (Cr), guanidinoacetic acid (GAA) and creatine (CR) in middle-aged and elderly subjects. We also measured muscle mass in the elderly. The elderly subjects tended to have lower serum GAA concentrations than middle-aged subjects. On the contrary, CR concentrations of elderly subjects were higher than those of middle-aged subjects. Bedridden elderly subjects tended to have lower serum GAA concentrations and lighter muscle mass than ambulatory elderly subjects. On the contrary, serum CR concentrations of bedridden subjects were higher than those of ambulatory subjects. CR is an essential substance for muscle energy metabolism. These results indicate that high serum CR concentrations due to low CR metabolism in skeletal muscle might suppress glycine amidinotransferase (GAT) activity, resulting in decreased GAA production in the elderly.

Aged↗

Imaging of neurotransmitter receptors in the living human brain by positron emission tomography (PET).

More than 30 receptors or subtypes will be investigated in various neurological and psychiatric disorders using PET in the near future. However, the data obtained by PET should be carefully evaluated, because the PET method is based on the ligand-receptor binding in vivo. Extensive studies on animals and autopsied human brain samples are important to assess the significance of the findings revealed by PET technique to substantiate its validity.

Aging↗

Fibre type composition of the soleus muscle in hypoxia-acclimatised rats.

Fibre type composition in the soleus muscle was studied in second generation male and female Sprague-Dawley rats bred at 460 Torr (hypobaric hypoxia). In control male and female rats (bred at sea level atmospheric pressure) the percentage of slow twitch oxidative (SO) fibres increased, and the percentage of fast twitch oxidative glycolytic (FOG) fibres decreased over time. In male hypoxic rats fibre type composition did not change. However, in female hypoxic rats the percentage of SO fibres increased, and that of FOG fibres decreased over time. The female hypoxic rats had a higher percentage of FOG fibres and a lower percentage of SO fibres than age-matched control rats. These findings indicate that hypoxia-acclimatised rats have a relatively high percentage of FOG fibres, and that this is due to inhibition of the fibre type shift from FOG to SO, which occurs during normal development. Furthermore, there is a sex-related difference in the change in fibre type composition in hypoxia-acclimatised rats.

Acclimatization↗