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Biomedical subjects

M Misaki

Publications and source records attributed to M Misaki.

At least 37 records · Page 2Linked to original sources

Effects of hexoses and their derivatives on glucagon secretion from isolated perfused rat pancreas.

Although it has been firmly established that D-glucose inhibits glucagon secretion from pancreatic A cells, the regulatory mechanism of glucagon secretion by D-glucose has not been elucidated. To study this regulatory mechanism by D-glucose, the effects of hexoses and their derivatives on glucagon secretion from the A cells of isolated perfused rat pancreas were investigated. When these cells were perfused with D-glucose, D-fructose, D-sorbitol, D-galactose, 2-deoxy-D-glucose, D-gluconic acid sodium salt and D-glucosamine HCl salt, glucagon secretion was significantly inhibited. None of the hexoses or their derivatives tested were found to stimulate glucagon secretion. The effects of these sugars on glucagon secretion were independent of their metabolism in the cells. From the findings that the sugars both metabolized and unmetabolized in the cells demonstrated comparable inhibition of glucagon secretion from the isolated perfused rat pancreas, it is speculated that the recognition system for these sugars may be probably present on the A cell membrane and responsible for mediating these inhibitory effects of glucagon secretion.

Animals↗

Antitumor activity of a medium-chain triglyceride solution of the angiogenesis inhibitor TNP-470 (AGM-1470) when administered via the hepatic artery to rats bearing Walker 256 carcinosarcoma in the liver.

The antitumor effect of an angiogenesis inhibitor, TNP-470 (AGM-1470, 6-0-(N-chloroacetylcarbamoyl)-fumagillol), administered via the hepatic artery in a medium-chain triglyceride (MCT) solution, in which TNP-470 is very stable, was examined in rats bearing Walker 256 carcinosarcoma in the liver. The MCT solution containing 0.1 mg of TNP-470 completely suppressed tumor growth after a single arterial injection, and the solutions containing 0.5 approximately 5 mg of TNP-470 caused tumor regression function. These antitumor effects lasted for at least 2 weeks. Moreover, the administration of the MCT solution containing 5 mg of TNP-470 also caused remarkable regression of well-developed enlarged tumors 2 weeks after inoculation, indicating potential in the treatment of unresectable hepatic cancer. When the MCT solution containing radiolabeled TNP-470 was injected via the hepatic artery, the initial radioactivity in the tumor was 22 times that in the normal part of the liver and 5.7 times that in the tumor when an aqueous solution of radiolabeled TNP-470 was injected. Also, in the case of the MCT solution, the radioactivity in the tumor was maintained at a relatively high level for over 2 weeks after injection. These results indicate that the remarkable antitumor effect resulted from the selective delivery and prolonged retention of TNP-470 at the tumor site.

Alanine Transaminase↗

Effect of absorption promoters on subcutaneous absorption of human epidermal growth factor in rats.

Subcutaneous administration of human epidermal growth factor (hEGF) to rats gave a significantly smaller value of area under the curve (AUC) of concentration in plasma of immunoreactive hEGF versus time than intravenous administration, probably because the slow entry rate into the blood circulation and consequently the enzymic degradation of hEGF at the injection site. In the present study, absorption promoters such as sodium caprate, N-acylamino acids, disodium ethylenediamine-tetraacetate (EDTA), and sodium glycocholate were used because they were expected to inhibit the enzymic degradation of hEGF at the injection site and to facilitate the entry of hEGF into the blood circulation. Coadministration of an absorption promoter with hEGF significantly increased the entry rate and AUC value of immunoreactive hEGF compared with the case without the absorption promoter. The enzymic degradation of hEGF in the supernatant of the rat subcutaneous tissue homogenates and in the buffer solution containing leucine aminopeptidase or protease was markedly inhibited by the presence of the absorption promoters except EDTA. On the other hand, only EDTA increased the initial entry rate of FITC-dextran (M(r), 4000), which is not metabolized at the injection site, although all absorption promoters including EDTA markedly increased the extravasation of Evans blue. Thus, the increased subcutaneous bioavailability of hEGF in the presence of absorption promoters (except EDTA) was mainly attributed to the inhibitory effect of absorption promoters against the enzymic degradation of hEGF at the subcutaneous tissues.

Adjuvants, Pharmaceutic↗

Wegener's granulomatosis with papillary adenocarcinoma of the thyroid.

A 59-year-old woman was admitted with scleritis, sinusitis, skin eruptions, nodular lesions of both lung fields in chest X-ray films and renal failure. Skin biopsy and elevation of the titer of anti-neutrophil cytoplasmic antibody confirmed Wegener's granulomatosis. A right nodular goiter was palpated and a diagnosis of thyroid cancer was made based on aspiration cytology. Although combined therapy with cyclophosphamide and corticosteroid was started and the Wegener's granulomatosis improved and disappeared except for the renal lesion, the renal failure worsened and she died. Apparently only 2 cases of Wegener's granulomatosis complicated with carcinoma as in this case have been reported.

Adenocarcinoma, Papillary↗

Increased concentrations of type IV (7 S) collagen in sera of hyperthyroid patients with Graves disease.

Serum concentrations of type IV collagen (7 S) were determined in 29 patients with untreated hyperthyroidism and 30 healthy subjects. Serum 7 S collagen was significantly higher (P less than 0.0001) in the hyperthyroid patients (6.3, SD 1.3, micrograms/L) than in the healthy control subjects (3.9, SD 0.6, micrograms/L). No difference in serum concentrations of 7 S collagen were observed between patients with normal liver function and those with abnormal liver function. Serum concentrations of 7 S collagen correlated positively with serum concentrations of free triiodothyronine (r = 0.41, P less than 0.05). In the hyperthyroid patients, 7 S collagen concentrations in serum gradually fell into the normal range as thyroid function became normalized. Thus, hyperthyroidism is one of the diseases in which serum concentrations of 7 S collagen are increased.

Adolescent↗

Serum erythropoietin concentrations and iron status in patients on chronic hemodialysis.

We studied the relationship between serum erythropoietin (EPO) concentration and iron status in 67 patients undergoing chronic hemodialysis. Serum concentrations of EPO were measured by RIA with recombinant human EPO. The geometric mean of the serum EPO concentration was 10.9 int. units/L (mean +/- SD range = 7.8 - 15.3 int. units/L) in hemodialysis patients, considerably lower than that in normal subjects (12.9 int. units/L). We found no significant correlation between concentrations of serum EPO and hemoglobin in hemodialysis patients, but found a significant negative correlation between serum concentrations of EPO and iron in hemodialysis patients. Moreover, we also found a significant positive correlation between the EPO concentration and the unsaturated iron-binding capacity (UIBC) in serum, and a significant negative correlation between the serum concentrations of EPO and ferritin in hemodialysis patients. Several patients who had relatively high EPO concentrations for hemodialysis patients also had low iron concentrations, high UIBC values, and low ferritin concentrations. These findings suggest that iron was utilized even at these EPO concentrations, which were very low for the degree of anemia observed in the hemodialysis patients.

Adult↗

Serum transferrin as a marker of bone growth in boys: correlation with serum alkaline phosphatase activity, plasma insulin-like growth factor 1 and rate of growth in height.

Transferrin (TF) has a growth promoting activity in cell culture. The aim of this work was to study possible relationships between serum TF, alkaline phosphatase activity (ALP), plasma insulin-like growth factor 1 (IGF-1) levels and rate of height increase in boys. 149 boys aged 13-15 yrs were studied. TF levels were measured using turbidimetric method. The serum levels of ALP could be used as a biochemical marker for bone formation. Significant correlation was found between serum TF levels and ALP levels (r = 0.31, P less than 0.0005). The TF levels are higher in iron-deficiency anemia. The hemoglobin (Hb) and serum ferritin were measured in all boys. Thirty-one of 149 boys had no iron-deficiency anemia (Hb 14.0 g/dl and serum ferritin 23 ng/ml). The rate of growth in height was estimated over a 5 month period. In these boys, the rate of growth in height was significantly correlated with serum TF levels (r = 0.37; P less than 0.05). A significant correlation was found between serum TF levels and plasma IGF-1 levels (r = 0.45; P less than 0.05). These data indicate that serum TF levels may be a marker of skeletal growth in normal boys.

Adolescent↗

Possible mechanism of gastric mucosal protection by epidermal growth factor in rats.

The mechanism of the protection by human epidermal growth factor (hEGF) against the gastric mucosal lesions induced by acidified ethanol was studied in rats. At different times following the subcutaneous administration of hEGF (30 micrograms/kg), intragastric acidified ethanol (EtOH: 0.125 M HC1 = 50:50 v/v%) was administered to induce an experimental gastric mucosal lesion. Mean length of the lesion in the gastric mucosa was used as a lesion index. Extravasation of intravenously injected Evans blue into the gastric wall and gastric contents was used as an indicator of vascular permeability. Pretreatment with hEGF decreased both the gastric mucosal lesions and the increase of vascular permeability caused by acidified ethanol with similar time profiles relative to pretreatment with hEGF. Maximal protective actions of hEGF occurred about 10 to 30 min after the observed peak plasma concentration of hEGF. Indomethacin and N-ethylmaleimide, but not iodoacetamide, blocked the protective action of hEGF, indicating that endogenous prostaglandins and/or sulfhydryls may participate in the protective action of hEGF. The content of endogenous nonprotein sulfhydryls in the gastric mucosa decreased markedly after acidified ethanol. However, pretreated hEGF did not restore the sulfhydryl contents. Thus, it seemed that endogenous prostaglandins, but not sulfhydryls, are the probable mediators for protection against gastric mucosal injury caused by acidified ethanol.

Animals↗

Protective effect of human epidermal growth factor against the experimental gastric mucosal lesions in rats.

The protective effect of human epidermal growth factor (hEGF) on the gastric mucosal lesions in rats was examined in relation to the immunoreactive concentration of plasma. Human EGF (30 micrograms/kg) was administered intravenously, intraperitoneally or subcutaneously. At different times following the administration of hEGF, rats received acidified ethanol solution to induce an experimental gastric mucosal lesion. Sum of lesion length in the gastric mucosa was used as a lesion index. Human EGF administered parenterally markedly decreased the gastric mucosal lesions in 10 min after administration of necrotizing solution, and 10 to 30 min delay was observed in the development of maximal protective action. Profiles of protective potency against the hEGF dose administered intraperitoneally or subcutaneously 30 min before administration of necrotizing solution revealed that the effective dose of hEGF (ED50) was about 5.2 and 2.6 micrograms/kg, for intraperitoneal and subcutaneous administrations, respectively.

Animals↗

Three-dimensional quantitative coronary angiography.

A method for reconstructing the three-dimensional coronary arterial tree structure from biplane two-dimensional angiographic images is presented. This method exploits the geometrical mathematics of X-ray imaging and the tracking of leading edges of injected contrast material into each vessel for identification of corresponding points on two images taken from orthogonal views. Accurate spatial position and dimension of each vessel in three-dimensional space can be obtained by this reconstruction procedure. The reconstructed arterial configuration is displayed as a shaded surface model, which can be viewed from various angles. Such three-dimensional vascular information provides accurate and reproducible measurements of vascular morphology and function. Flow measurements are obtained by tracking the leading edge of contrast material down the three-dimensional arterial tree. A quantitative analysis of coronary stenosis based on transverse area narrowing and regional blood flow, including the effect of vasoactive drugs, is described. Reconstruction experiments on actual angiographic images of the human coronary artery yield encouraging results toward a realization of computer-assisted three-dimensional quantitative angiography.

Algorithms↗

Basement membrane-related and type III procollagen-related antigens in serum of patients with chronic viral liver disease.

To assess the significance of serum basement membrane- and type III procollagen-related antigens in reflecting the degree of liver fibrosis, we measured radioimmunologically the concentrations of 7S collagen, laminin fragment P1, and the aminoterminal propeptide of type III procollagen (P-III-P) in serum from 48 patients with chronic viral liver disease: chronic persistent hepatitis (9), chronic active hepatitis (13), chronic active hepatitis with lobular disorganization (17), and liver cirrhosis (9). Concentrations of 7S collagen, laminin P1, and P-III-P in serum were increased in respectively 92%, 69%, and 77% of the patients with both chronic active hepatitis with lobular disorganization and liver cirrhosis. Concentrations of 7S collagen and laminin P1 in serum correlated well (r = 0.65, P less than 0.001, and r = 0.55, P less than 0.001, respectively) with the histological grade of liver fibrosis, whereas P-III-P correlated only weakly (r = 0.33, P less than 0.05). Evidently, measurement of serum 7S collagen is a reliable noninvasive test for detection of fibrosis in chronic viral liver disease.

Adult↗

Acromegaly and hyperthyroidism associated with McCune-Albright syndrome.

A 36-year-old man is described having McCune-Albright syndrome, acromegaly likely due to somatotroph hyperplasia and hyperthyroidism due to adenomatous goiter. Sexual precocity was not noted. The sella was narrow in size and no mass was seen. The decline of elevated GH by hyperglycemia and increase by GHRH-44(NH2) may support somatotroph hyperplasia, but plasma GHRH-44(NH2) levels were not elevated. A mass in the right lobe and enlargement of the left lobe of the thyroid were noted. Thyroid hormone levels in serum and thyroidal radioiodine uptake values were elevated, while TSH measurements in serum were low. The radioiodine scan showed a cold nodule in the right lobe and a hot area in the left of the thyroid. Thyroidal radioiodine was not suppressed following T3 given orally. These findings are compatible with functioning glands autonomously as the mechanism for the endocrinopathies associated with the McCune-Albright syndrome.

Acromegaly↗

A possible relationship between cord blood transferrin and birth length in infants.

Cord blood levels of transferrin (Tf) and insulin-like growth factor I (IGF-1) were measured in 33 normal and 12 preterm infants. Tf was measured by the single radial immunodiffusion technique, while IGF-1 was measured by specific RIA. Tf levels in normal term infants (195 +/- 27 mg/dl) were significantly below normal adult levels (261 +/- 12 mg/dl). Tf levels in preterm infants (159 +/- 30 mg/dl) were lower than those in normal term infants. Tf levels showed a positive correlation with birth length, weight, gestational age and albumin levels in all infants. There was no correlation between Tf and IGF-1 levels in term and preterm infants.

Birth Weight↗

Transferrin receptor on rat Kupffer cells in primary culture.

Kupffer cells may play a role in the turnover of iron in acute viral hepatitis. The transferrin receptor of rat Kupffer cells in primary culture was therefore investigated in this study. Daily specific bindings on 125I-diferric transferrin (Tf) to rat Kupffer cells in primary culture from day 3 to day 6 of culture were 1.64 +/- 0.08%, 4.16 +/- 0.05%, 4.34 +/- 0.07% and 2.63 +/- 0.07%, respectively. The specificity of the Tf binding sites was examined by competition studies showing that galactose (30 mmol x l-1) and ovalbumin (90 mumol x l-1) did not compete for the binding sites, but human lactoferrin (50 mumol x l-1) competed for the binding sites by about 30%. The affinity and capacity of Tf receptor on rat Kupffer cells in 5-day culture were analyzed according to the method of Scatchard. A single class of 125I-diferric Tf binding sites with an affinity constant of 1.65 x 10(7) l x l-1) and a capacity of 6.86 x 10(6) sites/cell was found. After zymosan (500 micrograms/ml) preincubation for 30 min, the binding capacity increased about 1.7-fold, and this increase depended upon the increase of the affinity of Tf receptor. These data suggest that Kupffer cells in the activated state accelerate the removal of elevated serum iron.

Animals↗

Ontogenesis of somatomedin and insulin receptors in the human fetus.

This study examines the ontogenesis of somatomedin and insulin receptors in man. Particulate plasma membranes were prepared by ultracentrifugation from various tissues removed from fetuses after abortion and classified as less than 17, 17-25, and greater than 25 cm in length. The binding of iodinated insulinlike growth factors 1 (IGF-1) and 2 (IGF-2), somatomedin A (SMA), multiplication-stimulating activity (MSA), and insulin was examined at the different ages. In the liver, cross-reaction studies revealed separate insulin and IGF-2 receptors. The Scatchard plots of insulin binding to liver membranes were curvilinear and showed an increase in the concentration of insulin receptors with advancing age. A single IGF-2 receptor was found on liver and no alteration was observed during development. The brain contained a lower concentration of insulin receptors. A change in the brain receptors for somatomedins occurred during development. Early in gestation, a high concentration of a low-affinity IGF-1 receptor was found. After approximately the 17th wk of gestation a higher affinity IGF-1 receptor appeared, which then increased in concentration. Cross-reaction studies also revealed changes in the specificity of these receptors during development. In the youngest fetal group IGF-2 was preferentially bound. Around midgestation a separate IGF-1 receptor, indicated by the preferential displacement of iodinated IGF-1 by IGF-1, appeared. In contrast, iodinated IGF-2 bound to a receptor where IGF-1 and IGF-2 were equipotent.

Brain↗