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Biomedical subjects

K Bando

Publications and source records attributed to K Bando.

At least 37 records · Page 2Linked to original sources

Activity and stability of recombinant human superoxide dismutase in buffer solutions and hypothermic perfusates.

The stability of recombinant human superoxide dismutase (r-hSOD) in buffer solutions was studied in solutions at various pH and temperatures. Additionally, we studied the effects of incubation with proteases, serum and two types of hypothermic perfusates. R-hSOD was stable in the pH range of 6-11 and at temperatures up to 80 degrees C for 30 min. R-hSOD activity was not affected by incubation with trypsin, aminopeptidase M or serum for 2 h. R-hSOD activity determined at various temperatures (4-37 degrees C) did not vary remarkably. R-hSOD in hypothermic perfusates was stable at 4-37 degrees C for 24 h.

Buffers

The evaluation of glucagon infusion algorithms for a counterregulatory system in artificial endocrine pancreas.

As counterregulatory system of artificial endocrine pancreas, glucagon infusion algorithm has been developed and its usefulness has been examined in pancreatectomized dogs and a pancreatectomized diabetic patient. Glucagon infusion rate (G1nIR(t)) was determined depending on proportional plus derivative action to blood glucose concentration (BG(t] with the time delay (tau) to start infusion as follows. G1nIR(t) = Gp(BGp- BG(t-tau)) + Gd(-dBG(t-tau)) + Gc where BGp is the projected value of blood glucose concentration, Gp, and Gd are the coefficients and Gc is the constant for basal glucagon supplement. Glucagon infusions based only on proportional action (Gp/Gd/Gc/tau) = (0.2/0/0.4/10 or 0.4/0/0.4/10) failed in simulating the pattern of blood glucose or glucagon response seen in normal dogs. Glucagon infusion based on proportional plus derivative action (Gp/Gd/Gc/tau = 0.2/0.4/0.4/10) successfully mimicked the pattern of blood glucose concentration and plasma glucagon profile seen in normal dogs. This glucagon infusion algorithm has been applied to control insulin-induced hypoglycemia in a pancreatectomized patient with the same infusion parameters. Hypoglycemia was recovered to normoglycemia in 80 min and the plasma glucagon patterns showed no significant difference from those in healthy volunteers. These data indicate that glucagon infusion algorithm thus developed is effective to render hypoglycemia to normoglycemia and mimic plasma glucagon response seen in normal subjects.

Algorithms

Oxygenated perfluorocarbon, recombinant human superoxide dismutase, and catalase ameliorate free radical induced myocardial injury during heart preservation and transplantation.

The effect of free radical scavengers on free radical-induced myocardial injury during heart preservation and transplantation was examined. Four groups of nine hearts each were harvested from mongrel dogs (12.5 to 16.5 kg) and orthotopically transplanted to size-matched recipients. All hearts received a continuous perfusion of oxygenated modified Collins' solution (group A). In addition, groups B, C, and D received Fluosol DA and albumin. Preservation perfusion was performed for 18 hours, at 4 degrees C, pH = 7.4, and 20 mm Hg. In group C, recombinant human superoxide dismutase (4,080 U/mg, 20 mg/kg) and bovine catalase (46,200 U/mg, 20 mg/kg) were administered only during preservation perfusion. In group D, these scavengers were administered just before and during reperfusion for 1 hour. Hemodynamic studies were performed before excision of the donor hearts and 1 hour after the termination of cardiopulmonary bypass. Creatinine kinase MB isoenzyme and thiobarbituric acid reactive substance levels in the coronary effluent were determined during preservation perfusion and reperfusion. Only group A showed a significant heart weight gain (p less than 0.05) and a decline in passive compliance (p less than 0.05) during preservation. Lactate release was higher in group A than in the groups receiving Fluosol DA. In contrast, pyruvate levels in group A were lower than in other groups. The generation of free radicals stayed at a low level during preservation, but significantly increased during reperfusion and was associated with a corresponding increase in creatinine kinase MB isoenzyme. Perfusion with a perfluorochemical solution (group B) inhibited the sharp rise in levels of thiobarbituric acid reactive substances and of creatinine kinase MB isoenzyme and improved cardiac function during reperfusion (versus group A). Exogeneous free radical scavengers administered just before and during reperfusion (group D) significantly ameliorated thiobarbituric acid reactive substances and creatinine kinase MB isoenzyme levels and also induced a significant hemodynamic improvement during reperfusion. However, administration of scavengers during preservation did not. This study demonstrates that the generation of free radicals is primarily significant during reperfusion and reoxygenation after ischemia. Thus the best time for administration of scavengers is just before and just after the onset of reperfusion. Furthermore, perfusion with perfluorochemicals effectively maintains aerobic metabolism and ameliorates free radical damage during this period.

Animals

Prevention of free radical-induced myocardial injury by allopurinol. Experimental study in cardiac preservation and transplantation.

To determine the role of free radical-induced injury during heart preservation and transplantation, we harvested hearts from 28 mongrel dogs (12.5 to 16.5 kg), divided them into four groups, and orthotopically transplanted them. A group of seven hearts were orthotopically transplanted immediately after excision (group A). A second group of seven animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours, and the hearts were orthotopically transplanted immediately after excision (group B). A third group of seven hearts were transplanted after continuous perfusion with oxygenated modified Collins solutions at 4 degrees C, pH 7.4, and a pressure of 20 mm Hg for 18 hours (group C). A fourth group of seven animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours, and the hearts were orthotopically transplanted after perfusion with modified Collins solutions in the same manner as group C hearts (group D). The generation of free radicals, estimated by measurement of thiobarbituric acid reactive substances (malondialdehyde) in the coronary effluent, stayed at low levels during perfusion in groups C and D and also remained at low levels during operational ischemia in group A and B. During reperfusion, their levels abruptly and significantly increased and were associated with a corresponding increase in creatinine kinase MB isoenzyme (malondialdehyde levels at 30 minutes' reperfusion: A, 2.25 +/- 0.43; B, 1.55 +/- 0.25 nmol/ml/100 gm wet weight [p less than 0.05 versus group A]; C, 2.67 +/- 0.28; D, 1.77 +/- 0.27 nmol/ml/100 gm wet weight [p less than 0.05 versus group C]). In the allopurinol pretreatment groups, allopurinol significantly slowed the appearance of malondialdehyde and the release of creatinine kinase MB isoenzyme during reperfusion. Furthermore, cardiac functions during reperfusion, expressed as percent of control (mean +/- standard deviation), were significantly better in the allopurinol pretreatment groups than in the untreated groups: maximum first derivative of left ventricular pressure: A, 76.4 +/- 9.5; B, 99.7 +/- 14.3 [p less than 0.05 versus group A]; C, 25.2 +/- 2.6; D, 42.7 +/- 7.9 [p less than 0.05 versus group C]). These results indicate that (1) the generation of oxygen free radical is not significant during perfusion with modified Collins solutions nor during operational ischemia, but only during reperfusion, and (2) allopurinol reduces free radical-induced injury during reperfusion. Allopurinol has potential application in the prevention of reperfusion injury during heart transplantation.

Allopurinol

cDNA cloning of IL-1 alpha and IL-1 beta from mRNA of U937 cell line.

Clones of cDNAs encoding growth inhibitory factors for human melanoma cell line A375 were isolated from cDNA library prepared by using mRNA derived from human histiocytic lymphoma cell line U937 induced with PMA and further stimulated with LPS. Cloning was achieved using Okayama-Berg cDNA expression vector system that permits expression of the inserted cDNA segments in mammalian cells. By assaying the transfected COS-1 cells supernatants and cell extracts, we isolated two distinct cDNA clones encoding growth inhibitory factors. It was determined by the nucleotide sequences of the inserts, the cDNAs corresponded to IL-1 alpha and -1 beta. Our results indicate U937 cells can be induced to produce both interleukin-1s.

Amino Acid Sequence

[Effects of ifenprodil tartrate on erythrocyte deformability and cerebral blood flow].

Effects of ifenprodil tartrate on whole blood filtrability ex vivo in rats was investigated by a standard technique for measuring whole blood filtration time passed through a filter (5 micron). Ifenprodil tartrate was observed to reduce the filtration time dose-responsively. This effect was especially evident at 20 mg/kg (P less than 0.05). On the other hand, no effect on the hematocrit value, plasma concentration of fibrinogen, erythrocyte count or mean cellular volume of erythrocytes was observed. These results indicated the increasing effects ex vivo of ifenprodil tartrate on erythrocyte deformability. The ex vivo effects on erythrocyte deformability was manifested without changing the ATP contents, ATP/ADP ratio or adenylate energy charge in erythrocytes; and a phenothiazine-like amelioration in the shape of crenated erythrocytes was observed. These results suggested that the effect of ifenprodil tartrate on erythrocyte deformability ex vivo might be due to direct action on the erythrocyte membrane. At 0.3 mg/kg, i.v., ifenprodil tartrate significantly (P less than 0.05) increased the blood flow in the hypothalamus of conscious rats. Thus, it was indicated that ifenprodil tartrate, which increases the erythrocyte deformability and the cerebral blood flow, is useful for the therapeutic treatment of cerebrovascular accidents.

Adenine Nucleotides

[A case of metastatic malignant melanoma mimicking pancreatic pseudocyst].

A 74-year-old male was admitted to our hospital complaining of an abdominal mass. Abdominal US and ERCP disclosed a cyst in the pancreas, communicating with a crater in the stomach. Spontaneous rupture of a pancreatic pseudocyst into the stomach was considered. Laparotomy demonstrated an irregular black pancreatic cyst, and histological examination showed atypical spindle shaped cells with brown to black pigmentation, compatible with malignant melanoma. Autopsy confirmed the diagnosis of malignant melanoma involving the pancreas, stomach and other organs. Efforts to elucidate the primary site were unsuccessful, Metastatic melanoma without a primary site is well known and has been reported to occur in from 2.4% to 8.7% of all cases. This case suggests that malignant melanoma must be considered in cases of tumors with various symptoms and multiple metastases without a definite primary site.

Aged

Reduced serum carnosinase activity in hypothyroidism.

Carnosinase hydrolyses carnosine in muscle, and its deficiency is associated with extensive neuromuscular abnormalities. We measured serum carnosinase activity in patients with thyroid dysfunction which often involves neuromuscular systems. In hyperthyroidism, the carnosinase activity was not significantly different from that in normal subjects. In hypothyroidism, however, it was significantly lower than that in normal subjects. The activity examined in five patients with hypothyroidism returned to normal after replacement therapy. In hypothyroidism, the carnosinase activity showed significant correlation with concentration of serum thyroxine and negative correlation with serum creatine kinase activity. This finding may be of practical importance in the differential diagnosis of disorders causing carnosinase deficiency.

Clinical Enzyme Tests

Regulatory effects of gastrin and secretin on carcinomas of the stomach and colon.

Gastrin (10 micrograms/ml) enhanced 14C-leucine uptake in cultured tissue of stomach and colon carcinomas and content of 14C-labelled protein in the medium was increased. One of 2 stomach and one of 3 colon carcinomas transplanted into nude mice were enhanced in growth by pentagastrin injected in a dose of 250 micrograms/kg every day. On the other hand, secretin (100 U/kg) inhibited the trophic action of pentagastrin.

Adenocarcinoma

Decreased activity of carnosinase in serum of patients with chronic liver disorders.

We measured the activity of carnosinase, a prominent hepatic peptidase, in sera from 69 patients with liver disorders. Mean values (and SDs) for those with liver cirrhosis (17 cases) and hepatoma (seven cases) were 0.51 (0.28) and 0.68 (0.21) mumol/mL per hour, respectively--clearly less than for normal adults: 4.19 (0.95) mumol/mL per hour. Samples from 17 cases of chronic hepatitis also showed moderately decreased activity, 1.41 (0.97) mumol/mL per hour. In contrast, 14 cases of acute hepatitis generally showed values falling within the normal limits: 3.41 (1.97) mumol/mL per hour. Our results for carnosinase correlated with those for cholinesterase (r = 0.70) and with the concentration of albumin in serum (r = 0.59), but not with the activity of either creatine kinase, aspartate aminotransferase, or alanine aminotransferase in serum. Carnosinase values differed more among groups of disorders than did the values for cholinesterase or albumin. Measurement of serum carnosinase activity may be of clinical value in assessing the severity of chronic liver-cell damage, but not in differentiating liver disease from nutritional, muscle, or endocrine disorders.

Adult

[Pharmacological actions of iprazochrome on the vascular system].

The pharmacological actions of iprazochrome (IC) on the vascular system were studied, and the following results were obtained: No death nor abnormal behaviors were observed in acute toxicity tests conducted on male and female mice and rats despite the administration of large doses of IC (10,000 mg/kg, p.o. and 80 mg/kg, i.v., respectively). IC inhibited dose-dependently platelet aggregation in vitro induced by arachidonate and ADP, whereas no effect was observed on ADP-induced respiratory depression in mice, which is closely related to platelet aggregation in vivo. The antiserotonergic actions of IC on the isolated external carotid arteries and femoral arteries in dogs observed in a noncompetitive manner were found to be 1/24 to 1/65 that of methysergide. On the other hand, IC showed no inhibitory effect on the paw edema of rats in vivo induced by serotonin. The inhibitory effect of IC on peritoneal dye leakage in mice was less than half that of phenylbutazone. IC prevented apoplexy in stroke-prone SHR (SHRSP) without lowering the blood pressure. Histological changes in the cerebrum of SHRSP were ischemic changes such as swelling of the neurons and shrinkage of the nuclei, mainly in the cerebral cortex and corpus striatum area.

Adrenochrome

[The study of developmental pharmacology (II). Histological observations of central nervous tissue in rats of dams given pentazocine HCl during perinatal and postnatal periods (author's transl)].

In previous literature, we reported that the rats whose dams had been administerd pentazocine HCl 200 mg/kg/day during the perinatal and postnatal periods, showed no differences between control rats in the physiological function and psychotic activity tests. Brain tissues of the rats were observed histologically herein to confirm the result of previous tests. Abnormal findings such as deficits, undevelopment and metamorphosis, in the shape, size and configuration of nerve cells, myelin sheaths and vessels in consecutive transverse sections stained by Nissl and Klüver-Barrera method were not evident on examination under light microscope, and in cell bodies, dendrites, axons, myelin sheaths, synaptic complexes of nerve cell, neuroglia and vessels in the cerebral cortex, under electron microscope. The lack of abnormal findings in the histological observation of brain tissues supports the result of previously conducted physiological function and psychotic activity tests in which no significant differences were found between treated and control rats. Pentazocine HCl had no effect on the brain tissues of rat offspring from dams administered the drug during perinatal and postnatal periods.

Animals