Factors affecting left-right heart output differences in artificial heart implanted animals.
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Biomedical subjects
Publications and source records attributed to M Umezu.
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The complete amino acid sequence of the coagulogen from hemocyte lysates of Limulus polyphemus has been determined by sequencing the peptides obtained from tryptic, chymotryptic, staphylococcal protease V8 and lysyl endopeptidase digestions. These results established the following sequence: (formula; see text) Limulus coagulogen consists of a single chain with a total of 175 amino acid residues and the molecular weight is calculated to be 19,675. It contains 16 half-cystines in disulfide linkages, with 5 half-cystines located in a cluster in the COOH-terminal 14 residues. The sequence of Limulus coagulogen is very close to that for the coagulogen of Tachypleus tridentatus (Japanese horseshoe crab), having 69% sequence homology. The 16 half-cystines of these coagulogens are in the same positions, suggesting a very similar conformation. Moreover, the COOH-terminal tripeptide regions of the A chain (from the NH2-terminal end to Arg-18) and peptide C (from Lys-19 to Arg-46), both of which seem to interact with a Limulus clotting enzyme to liberate peptide C, are completely conserved. From secondary structure predictions by the method of Chou and Fasman (Chow, P.Y., and Fasman, G. D. (1974) Biochemistry 13, 211-222), the coagulogen appears to contain an alpha-helical region in the peptide C segment, released by the clotting enzyme, suggesting a marked conformational change in the transformation of the coagulogen to the coagulin gel. beta-sheet and reverse turn regions are distributed in the B chain segment (from Gly-47 to the COOH-terminal end). It is likely that the 16 half-cystines and abundant beta-sheet structure make the coagulogen molecule compact.
Tensile and fatigue properties were studied on three kinds of segmented polyether polyurethanes developed for blood pump applications. To study the effects of plasma constituents, specimens were immersed in a cholesterol-lipid solution whose composition is similar to that of plasma. The results obtained were compared with those observed in a saline solution which had been reported previously. Immersion in the cholesterol-lipid solution has influence on the mechanical properties of Toyobo TM5 polyurethane and Avcothane 51: Its effect is enhanced by cyclic deformation. Cholesterol-lipids change the mechanical characteristics of Avcothane 51 more remarkably than those of Toyobo TM5 polyurethane possibly because the former contains about 10% silicone. On the other hand, there is little effect of the constituents of the cholesterol-lipid solution on the static and dynamic mechanical properties of Biomer, although moisture and cyclic deformation have some influence on the mechanical characteristics.
A permanently implantable left ventricular assist device (LVAD) pump of the pusher-plate type was designed based on mechanical analyses. A series of three different segmented polyether polyurethanes was utilized for the diaphragm, cannulae, and their blood-contacting surfaces, considering each material's characteristics. The span and thickness of the pump diaphragm were determined so as to minimize the stress developed by the bending and blood pressure forces. The inflow and outflow cannulae were designed using fundamental equations that describe the operation of a piston-type reciprocating pump. The pump diameter was determined considering the required flow for the average Japanese person. In vitro and in vivo experiments showed good pump performance, which satisfied the design specifications. No failure was observed in the designed diaphragm. The Hall effect sensor incorporated in the pump was very useful in monitoring the cardiac output of the pump.
One of the major causes of postoperative morbidity and mortality after valve replacement surgery is the prosthetic valve substitute itself. In this discussion, therefore, we make a fundamental evaluation of hydrodynamic valve function and present our clinical results following valve replacement with the Björk-Shiley valve prosthesis, the Hancock porcine xenograft and the Ionescu-Shiley bovine pericardial xenograft. In an experimental study using a mechanical simulator system, the pericardial xenograft displayed superior hydrodynamic characteristics compared to other two valve substitutes. Postoperative hemodynamic evaluation further indicated that the pericardial xenograft performed significantly better than the porcine xenograft regarding transvalvular pressure gradient, effective valve area and cusp opening. In addition, data from 387 patients with aortic, mitral or both types of valve replacement who had received one of the three kinds of valve substitute were analyzed. Systemic thromboembolic complications occurred in one patient with an aortic Björk-Shiley valve (0.6% per patient-year), six with mitral Hancock xenografts (2.8% per patient-year) and one with an aortic and mitral Hancock xenograft (2.2% per patient-year). The incidence of prosthetic valve endocarditis was 0.84% per patient-year for the Hancock xenograft and 1.84% per patient-year for the Ionescu-Shiley xenograft. It was concluded that the hemodynamic and antithrombogenic advantages of the pericardial xenograft proven by our mid-term follow-up study make it the valve substitute of choice. However, careful attention is required regarding prosthetic valve endocarditis tissue heart valves, which are more susceptible to infection than mechanical ones, and the long-term durability of the pericardial xenograft remains to be confirmed.
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Plasma gastric inhibitory polypeptide (GIP) concentrations following an oral glucose load were measured in 27 diabetics and 10 normal subjects. Plasma GIP concentrations increased significantly from the mean basal value following an oral glucose load in both groups. Diabetics showed significantly higher levels of plasma GIP in association with delayed and diminished peak increases in plasma insulin levels. When diabetics were divided into two groups according to their basal levels of blood glucose, moderate and severe diabetics exhibited more exaggerated increments of plasma GIP than mild diabetics. This exaggerated GIP response to an oral glucose load in proportion to the glucose intolerance indicates a relative failure of the beta cell response to GIP in diabetics and that the mechanism involved in hypersecretion of GIP would be diminution of the inhibition of GIP release caused by insulin in diabetics.
Many skin lesions are specific for diabetes mellitus. Necrobiosis lipoidica, lipoatrophy and idiopathic bullae (bullosis diabeticorum) are usually associated with diabetes. However, diabetic scleredema has not been noticed by internists, although dermatologists have paid attention to such a cutaneous manifestation. We reported a clinical case of a female diabetic patient aged 15 who had been afflicted with diabetic scleredema. She had been treated with insulin since 5 years of age. She noticed stiffness of the skin in April 1980. Skin biopsy showed thickness of the dermis and accumulation of acid mucopolysaccharide. After control of blood glucose with continuous subcutaneous insulin infusion (CSII) and administration of tocopherol acetate and hyaluronidase, the skin lesion improved. Etiology of diabetic scleredema is unknown. Such skin lesion which is observed frequently in insulin dependent obese patients is different from a category of scleredema of Buschke.
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Plasma gastric inhibitory polypeptide (GIP), insulin, glucagon concentrations and blood glucose levels in response to the ingestion of 100 g glucose were measured in 5 patients with hyperparathyroidism in order to elucidate the effect of hypercalcemia on the release of these hormones. In addition, the effect of acute hypercalcemia on the release of these hormones in response to glucose ingestion was investigated in normal subjects. Fasting plasma GIP concentration in patients with hyperparathyroidism was significantly greater than the value in seventeen normal subjects. Significantly higher responses of plasma GIP and insulin were observed after the glucose ingestion in the patients with hyperparathyroidism as compared with the values in the normal subjects, and integrated GIP and insulin responses to the glucose ingestion for 120 min in the patients with hyperparathyroidism were significantly greater than the values in the normal subjects. On the other hand, plasma glucagon concentration after the glucose ingestion in the patients with hyperparathyroidism remained unchanged, although plasma glucagon concentrations after the glucose ingestion decreased significantly from the basal value in the normal subjects. Blood glucose levels after the glucose ingestion in two groups increased significantly from the basal value in the same manner. In nine normal subjects calcium infusion (4 mg/kg bolus injection followed by continuous infusion of 4 mg/kg/hr for 3 hr) caused a significantly high concentration of plasma calcium (11.5 approximately 13.0 mg/dl) from the basal value. Significantly higher responses of plasma GIP and insulin to the glucose ingestion were observed during calcium infusion as compared with the values during saline infusion. On the other hand, plasma glucagon concentration after the glucose ingestion was not significantly changed during calcium infusion in contrast with a significant decrease of plasma glucagon after the glucose ingestion during saline infusion. Consequently, calcium was considered to play a major part in the release of GIP and insulin. The characteristic response of plasma glucagon during calcium infusion was considered, at least in part, to protect the hypoglycemia caused by hyperinsulinemia.
Gastric inhibitory polypeptide (GIP) is a candidate hormone for an incretin which stimulates or potentiates insulin secretion. We elucidated that, in five patients with hyperparathyroidism, GIP and insulin responded remarkably to glucose ingestion, and that hypercalcaemia appeared to have a stimulatory effect on glucose-induced GIP release as well as on insulin release. In nine healthy subjects a 2% calcium solution was continuously infused intravenously and a hypercalcaemic state was maintained. This caused GIP to respond significantly more to glucose ingestion. In spite of GIP being considered an incretin in the normoglycaemic state, GIP does not markedly stimulate insulin secretion. However, in the hypercalcaemic state in healthy subjects, glucose-induced GIP and insulin secretion is significantly greater than in the normocalcaemic state. The potentiated response of insulin to glucose may be caused, in part, by GIP.
Since Kahn et al. reported in 1976 insulin resistant diabetes due to anti-insulin receptor antibodies, an unusual form of diabetes mellitus (type B) has been found in many countries. We had two diabetic patients with anti-insulin receptor antibodies, associated with either acanthosis nigricans or systemic lupus erythematosus. Remission occurred 15 months after the onset of insulin resistant diabetes. One patient unfortunately died of acute pneumonia and the other has been followed up. The anti-insulin receptor antibodies were measured according to the method of Omori and Hirata by using the pellet of human placental membrane. The anti-insulin receptor antibodies in both cases diminished as remission occurred. Reverse hemolytic plaque assay (PFG) detected immunoglobulin-producing cells. In Case 2, the plaque forming cells were twenty times as many as the normal value. Immunosuppressive therapy with cyclophosphamide reduced the immunoglobulin secreting cells as remission occurred. The patients with insulin resistance (type B) should be treated with enough insulin inspite of the presence of insulin resistance. Besides, cyclophosphamide, 6-mercaptopurine and prednisolone should be used with caution. Plasma exchange is a treatment to be tried. It is important to note that spontaneous remission may occur more than half a year after the onset of insulin resistant diabetes.
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A PGF-2 alpha analogue (cloprostenol) was injected into 9 cows to synchronize oestrus. The cows were placed with or without a bull in a free-stall in groups of 3 at 46 h after the injection. Sexual behaviour was observed and serum LH concentrations were measured during the next 34 h. The bull ejaculated with the cows in regular sequence and did not return to cows after an ejaculatory series was completed. The mating behaviour of the bull was closely related to the LH surge of the cows.