Biomedical subjects
Publications and source records attributed to M Oimomi.
Alfa-ketoaldehyde dehydrogenase, which was extracted and purified from human livers, may act on carbonyl compounds, such as 3-deoxyglucosone, and be involved in the control of glycation (Maillard reaction) in the body.
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There is increasing evidence that neuropeptide Y (NPY) affects the release of pituitary hormones, including adrenocorticotropic hormone (ACTH). The present study was designed to clarify the mechanism by which NPY activates the hypothalamic-pituitary-adrenal (HPA) axis in the dog. Mongrel dogs were equipped with a chronic cannula allowing intra-third (i.t.v.) or intra-lateral (i.l.v.) cerebroventricular administration. A 1.19 nmol, i.t.v. dose of NPY produced as great an ACTH and cortisol response as did equimolar ovine corticotropin releasing factor (CRF). This action of NPY was dose-dependent and shared by peptide YY (PYY) and pancreatic polypeptide (PP), other members of the PP family peptide. Intravenously (i.v.) administered NPY (1.19-11.9 nmol) was much less potent than i.v. CRF in stimulating ACTH and cortisol secretion. However, i.v. NPY significantly increased plasma ACTH and cortisol concentrations, raising the possibility that NPY may modulate the activity of corticotrophs. We have next investigated the possible relationship between NPY and CRF on the HPA axis. Pretreatment with a novel CRF antagonist, alpha-helical CRF9-41 (130.9 nmol i.t.v. or 261.8 nmol i.v.), partly but significantly attenuated the ACTH and cortisol responses to i.t.v. NPY (1.19 nmol). Furthermore, adding a subthreshold dose of i.t.v. NPY (0.119 nmol) to i.t.v. CRF (1.19 nmol) or i.v. NPY (2.38 nmol) to i.v. CRF (0.595 nmol) resulted in the potentiation of CRF-induced ACTH secretion. These results indicate that NPY may activate the HPA axis in concert with CRF probably at hypothalamic and/or pituitary levels. The present findings that NPY evokes ACTH secretion and potentiates the effectiveness of CRF as a secretagogue, together with high concentrations of NPY in the hypothalamus and pituitary portal blood, suggest that NPY is involved in the multihormonal control of ACTH release.
The extent of glycation in pieces of human aorta was estimated by determining the content of furosine, which is derived from fructose-lysine through acid hydrolysis. Glycation of human aorta was found to increase with advancing age. A significant positive correlation was found between the degree of atherosclerosis and the furosine level in the aorta in subjects over 60 years of age. Furthermore, the furosine level in the aortae of diabetic patients was significantly higher than that in normal subjects of the same age. These results suggest not only that glycation in the aorta may increase with aging and with the development of arteriosclerosis, but also that diabetes may be related as well to premature aging as to arteriosclerosis.
Cholecystokinin octapeptide, administered into the third cerebral ventricle (icv), suppresses feeding in sheep, pigs, chicken, rats, and dogs. Because of the species differences in the feeding response to cholecystokinin (CCK), we studied the pharmacological characterization of this peptide on feeding in 16-h-fasted dogs. We examined the effects of CCK-(26-33)-NH2 (CCK-8) and a variety of its analogues, nonsulfated CCK-(26-33)-NH2 (desulfated CCK-8), CCK-(26-33)-OH (deamidated CCK-8), (Nle28,31)-CCK-(26-33)-NH2 [(Nle28,31)-CCK-8], succinyl-CCK-(27-33)-NH2 (Suc-CCK-7) succinyl-Thr28, Leu29, MePhe33-CCK-(27-33)-NH2 [Suc-Thr28, Leu29, MePhe33)-CCK-7], CCK-(29-33)-NH2 (CCK-5), and CCK-(30-33)-NH2 (CCK-4) on food intake after iv injection. Systemic dose-response studies appeared to reveal the following rank order of potencies: Suc-CCK-7 = Suc-(Thr28, Leu29, MePhe33)-CCK-7 greater than CCK-8 = (Nle28,31)-CCK-8 greater than desulfated CCK-8 greater than deaminated CCK-8 greater than CCK-5 = CCK-4 = 0. Smaller COOH-terminal fragments acted as antagonists to the satiety effects of CCK-8. These data demonstrate in the dog that the structural requirements for the behavioral activity of CCK-8 are the COOH-terminal amide group, the sulfate ester of the tyrosine moiety, and the conformational constraints observed in CCK-7.
Porcine pancreastatin (1.19 nmol) was administered into the peripheral vein (i.v.) or the third cerebral ventricle (i.t.v.) of dogs and its effect on the secretion of insulin and pancreatic polypeptide (PP) studied. Neither means of administration had any effect on basal and glucose-induced insulin or PP secretion. However, i.v. pancreastatin did inhibit the i.v. CCK-8-induced insulin but not PP release. Pancreastatin may thus play a role in the regulation of insulin secretion in the canine pancreas.
Glycation of hair protein was assessed in diabetic patients by the measurement of furosine, which is derived from fructose-lysine, a glycated lysine residue in protein. The level of furosine in 12-cm-long hair which grew over the course of one year was significantly better correlated with the mean values of four determinations of fasting plasma glucose (FPG) and four determinations of hemoglobin A1c, respectively, at the time of hair sampling. The level of glycation in hair, which corresponds to the time taken for hair growth, may represent the mean level of blood glucose during the time corresponding to the growth period. The values of motor nerve conduction velocity and sensory nerve conduction velocity were better correlated with the level of furosine in hair corresponding in the length to 1 year's growth than the levels of FPG and hemoglobin A1c at the time of the determination of nerve conduction velocity. These results suggest that hair glycation may serve as a valuable indicator both of long-term blood glucose trends and of the relationship between diabetic complications and blood glucose.
The effect of fructose on the formation of advanced Maillard reaction products which have fluorescence and cross-links was investigated. Type I collagen was added to various concentrations of glucose and fructose which were then incubated at 37 C for 4 weeks. Both the level of furosine and the fluorescence intensity increased in direct proportion to glucose and fructose levels and to the duration of incubation. Incubation with fructose produced less furosine but more intense fluorescence than incubation with glucose. These results suggest that fructose in the polyol pathway plays an important role in the formation of advanced Maillard products.
We measured periflux blood flow (PBF) in people's fingers and its response to cold loading with a laser Doppler flowmeter. As an index in the cold loading test we used cold recovery time (CRT). Among normal people, CRT increased with age. Diabetics had significantly longer CRTs than did age-matched controls. CRT seems to be useful for evaluating the skin microcirculation in diabetics and the aged.
3-Deoxyglucosone, a carbonyl intermediate compound in the Maillard reaction, acts on bovine serum albumin to increase its fluorescence. Aminoguanidine inhibited the increase of fluorescence intensity formed by bovine serum albumin and 3-deoxyglucosone when 3-deoxyglucosone had been preincubated with aminoguanidine. These results suggested that aminoguanidine inhibits the action of 3-deoxyglucosone in the Maillard reaction.
The Maillard reactions between proteins and glucose or fructose, in 0.2M phosphate buffer (pH 7.4) at 37 degrees C, were investigated and the following results were obtained: 1) 3-deoxyglucosone (3DG) is formed as the major carbonyl intermediate; 2) fructose has a higher reactivity than glucose and 3DG is formed also from fructose without involvement of amino groups; 3) 3DG is a crosslinker responsible for polymerization of proteins; 4) 3DG is involved in the formation of a fluorescent advanced-stage product named "Peak L1" in vitro and in vivo.
Twenty eight cases out of 230 cases of early gastric cancer showed the superficial spreading type of early gastric cancer. Seventeen stomachs (60.7%) were compatible to the endoscopic finding of spreading cancerous regions, even to macroscopic and microscopic ones. Other 11 cases were not corresponded clinicopathologically to the infiltrated lesions. These 11 cases were studied on the superficial spreading lesions respectively. They were divided into three groups and compared each other micro- and macro-scopically and endoscopically. Group I contained 6 cases, compatible to micro- and macro-scopic findings but not to endoscopic ones. Endoscopic overdiagnosis may be redness and overflow of white fur and underestimate by a few cancer cells superficially in the mucosae, slight difference in height at the margin of II c and cancer without exposure. Group II was similar microscopic and endoscopic findings but not compatible macroscopically. Both cases in group II were overestimated macroscopically at the infiltrated edge because of color change in mucosae but endoscopically diagnosed by changes of color and gastric area. Group III contained 3 cases of microscopic characteristics and not compatible to macroscopic and endoscopic ones. Endoscopic underdiagnosis may be based on a few cancer cells superficially in normal mucosae and on less depressed lesions. These clinicopathological studies might be worthy to clarify the endoscopic and pathologic discrepancies of infiltrating areas by early gastric cancer, and might improve endoscopic techniques of the gastric mucosal observation.
A case of familial hypercholinesterasemia was presented. Cholinesterase isoenzyme study revealed the extra C5 band nearer to the cathode than C4 on the gradient polyacrylamide gel electrophoresis in 6 out of 8 subjects in the family. No significant difference in the effect of inhibitors and activator on serum cholinesterase activity of the family with hypercholinesterasemia was found compared to that of the normal control. It was considered to be clinically useful for differential diagnosis of patients with elevated serum cholinesterase to find subjects with familial hypercholinesterasemia.
We have assessed the effects of intravenous infusion of bovine pancreatic polypeptide (PP) (1 microgram kg-1 h-1) on the basal and postprandial secretion of gastrointestinal, pancreatic and adrenocortical hormones in normal dogs. Bovine PP within the physiological range increased plasma cortisol levels transiently but significantly. PP elicited an inhibition of insulin response to a protein-rich meal, and tended to reduce the gastrin response. There were, however, no significant changes in basal or postprandial plasma concentrations of motilin and pancreatic glucagon during PP infusion. These results suggest that PP may have a role in controlling insulin secretion from the pancreas. The possible mechanisms are discussed mainly on the basis of vagal innervation.
We used furosine, which is derived from fructose-lysine and is a glycation product, to measure the extent of hair protein glycation in diabetic patients. We took hair samples that were 12 cm long, corresponding roughly to 1 year's growth. While the furosine levels in these samples correlated poorly with fasting plasma glucose (FPG) and with hemoglobin A1c (HbA1c) levels at the time of sampling, better correlations were observed between glycation and the year-long average values of FPG, HbA1c, and the conduction velocities in two peripheral nerves. The glycation levels in these samples may thus reflect the year-long average of the patient's blood glucose. Hair glycation may serve as a valuable indicator both of long-term blood glucose trends and of the relationship between diabetic complications and blood glucose.
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