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Biomedical subjects

K Mikawa

Publications and source records attributed to K Mikawa.

At least 145 records · Page 8Linked to original sources

Effects of adenosine triphosphate on the cardiovascular response to tracheal intubation.

Laryngoscopy and tracheal intubation often cause hypertension and tachycardia, which may be exaggerated during rapid-sequence induction of anaesthesia. The efficacy of adenosine triphosphate (ATP) in attenuating this response was studied in patients receiving ATP 0.05 mg kg-1 or 0.1 mg kg-1 simultaneously with the start of laryngoscopy. These data were compared with those for a control group receiving saline. Each group consisted of 10 patients undergoing elective surgery. Anaesthesia was induced with thiopentone 5 mg kg-1 i.v. and tracheal intubation was facilitated with vecuronium 0.2 mg kg-1 i.v. During anaesthesia, ventilation was assisted or controlled with 1% enflurane and 50% nitrous oxide in oxygen. Patients receiving saline showed a significant increase in mean arterial pressure and rate-pressure product associated with tracheal intubation. These increase after tracheal intubation were reduced in ATP-treated patients compared with those of the control group (P less than 0.05). The data suggest that a bolus injection of ATP is a simple, practical and effective method for attenuating the hypertensive response to laryngoscopy and tracheal intubation.

Adenosine Triphosphate↗

Effects of pindolol on the cardiovascular response to tracheal intubation.

Laryngoscopy and tracheal intubation often cause hypertension, tachycardia and arrhythmias, which may be exaggerated during rapid-sequence induction of anaesthesia. We have studied the efficacy of pindolol in attenuating the cardiovascular responses to laryngoscopy and intubation in patients receiving pindolol 2 micrograms kg-1 or 4 micrograms kg-1 3 min before induction of anaesthesia in a double-blind design. The data were compared with those in a control group receiving saline. Each group consisted of 10 patients undergoing elective surgery. Anaesthesia was induced with thiopentone 5 mg kg-1 i.v. and tracheal intubation was facilitated with vecuronium 0.2 mg kg-1. Patients receiving saline showed a significant increase in mean arterial pressure and heart rate associated with tracheal intubation. These increases after tracheal intubation were reduced in pindolol 4 micrograms kg-1 treated patients compared with those in the control group (P less than 0.05). Pindolol 2 micrograms kg-1 attenuated tachycardia in response to intubation but did not affect hypertension. These data suggest that a bolus injection of pindolol 4 micrograms kg-1 is a simple, practical and effective method for attenuating cardiovascular responses to laryngoscopy and tracheal intubation.

Adult↗

H1 histone stimulates limited proteolysis of protein kinase C subspecies by calpain II.

Limited proteolysis of protein kinase C (PKC) subspecies with Ca2(+)-dependent neutral protease II (calpain II) was remarkably stimulated by basic polypeptides, such as H1 histone and poly-L-lysine. This stimulatory effect was observed for proteolysis of the active form of PKC, which was associated with phospholipid and diacylglycerol. The inactive form of PKC was far less susceptible to proteolysis, both in the presence and absence of the basic polypeptides. The basic polypeptides did not appear to interact with calpain II, but made the PKC molecule more susceptible to proteolysis. The relative rates of cleavage of type I (gamma), II (beta), and III (alpha) PKC were 2:2:1. The available evidence suggests that, like calpain I, calpain II may also contribute to the down-regulation or depletion of PKC.

Animals↗

Effects of exogenous intravenous glucose on plasma glucose and lipid homeostasis in anesthetized children.

Whether or not intravenous glucose administration during pediatric anesthesia is necessary remains a controversial issue. The current study was designed to investigate the effect of glucose infusion on concentrations of plasma glucose, nonesterified fatty acids (NEFA), triglycerides, ketone bodies, and insulin and to determine whether the use of solutions containing less than 5% glucose would maintain physiologic plasma glucose concentrations during tympanoplasty lasting about 6 h. Forty-five children aged between 1.5 and 9 yr were divided randomly into three groups of 15 patients each to receive the following intravenous solutions: LR groups, lactated Ringer's solution (LR) alone; D2LR group, 2% glucose in LR; and D5LR group, 5% glucose in LR. All fluids were infused at a rate of 6 ml.kg-1.h-1 until 1 h after anesthesia. In the LR group, the plasma glucose concentrations remained unchanged perioperatively compared with basal values, whereas in the D2LR group they showed a gradual increase during surgery but remained normoglycemic. On the other hand, in the D5LR group, the plasma glucose concentrations increased markedly both during and after the operation. Furthermore, 3 of 15 patients showed hyperglycemia of more than 300 mg.dl-1 during anesthesia. There was no evidence of lipid mobilization or impaired secretion of insulin, since plasma NEFA, triglycerides, ketone bodies, and insulin remained within normal concentration ranges throughout the sample period in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

[Protective effects of PGE1 on postoperative liver function after gastric cancer surgery].

The effects of PGE1 on liver function tests in patients who underwent gastric cancer surgery were studied. PGE1 was administered in 13 patients at a rate of 20-100 ng.kg-1.min-1 (PGE1 group) during surgery. Fourteen patients served as the control group. On the first postoperative day, SGOT and SGPT increased in both groups. But on the first and the third postoperative days, SGPT of the PGE1 group was significantly lower (P less than 0.05) than that of the control group. Five patients in the control group showed transaminase above 100 IU.l-1 in the postoperative period. In contrast, no patient showed this increase in the PGE1 group. These findings indicate that continuous infusion of PGE1 during surgery is beneficial in attenuating hepatic injury.

Aged↗

Protein kinase C during differentiation of human promyelocytic leukemia cell line, HL-60.

Protein kinase C (PKC) from human promyelocytic leukemia HL-60 cells can be resolved into three fractions (peak, a, b and c) by hydroxyapatite column chromatography. Peak a and c enzymes are indistinguishable from the brain type II PKC having beta (beta I and beta II)-sequence and type III having alpha-sequence, respectively. Peak b enzyme is a previously unidentified PKC subspecies that has enzymological properties subtly different from type I (having gamma-sequence), type II and type III PKC. Upon treatment of HL-60 cells with 1 microM retinoic acid, this peak b enzyme is decreased dramatically within 24 h, whilst peak a enzyme (beta-PKC) is increased, and peak c (alpha-PKC) enzyme is slightly decreased within 48 h. The result implies that the PKC subspecies in HL-60 cells have distinct functions during cell differentiation.

Amino Acid Sequence↗

Effect of nicardipine on the cardiovascular response to tracheal intubation.

We studied the cardiovascular responses to laryngoscopy and intubation in 30 patients who received nicardipine 15 micrograms kg-1 or 30 micrograms kg-1, or saline placebo 60 s before the start of laryngoscopy. Anaesthesia was induced with thiamylal 5 mg kg-1 i.v. and tracheal intubation was facilitated with vecuronium 0.2 mg kg-1. Patients receiving saline showed a significant increase in mean arterial pressure (MAP) and rate-pressure product (RPP) associated with tracheal intubation. The increases in MAP and RPP following tracheal intubation were reduced in both groups of patients who received nicardipine.

Anesthesia, Inhalation↗

The effect of diltiazem on the cardiovascular response to tracheal intubation.

The efficacy of diltiazem in the attenuation of the cardiovascular response to laryngoscopy and tracheal intubation was studied in patients who received 0.2 or 0.3 mg/kg diltiazem 60 seconds before the start of laryngoscopy. These data were compared with a control group who received saline. Each group consisted of 10 patients who had elective surgery. Patients who received saline showed a significant increase in mean arterial pressure and rate pressure product associated with tracheal intubation. These increases after tracheal intubation were reduced in diltiazem-treated patients compared with those of the control group (p less than 0.05). The data suggest that a bolus injection of diltiazem is a simple, practical and effective method to attenuate the hypertensive response to laryngoscopy and tracheal intubation.

Blood Pressure↗

Perioperative effect of methylprednisolone given during lung surgery on plasma concentrations of C3a and C5a.

Methylprednisolone or saline (placebo) solution was infused intravenously in 28 patients undergoing elective lobectomy for lung cancer. The state of the complement system during and after surgery and the effects of methylprednisolone on biologically active products of complement were studied by measurements of plasma C3a and C5a anaphylatoxins and leukocyte counts in peripheral blood perioperatively. In the placebo group plasma concentrations of C3a were significantly increased on postoperative days 1 and 2, whereas C5a had risen significantly 6 hours after surgery and on days 1 and 2. Methylprednisolone infusion during surgery eliminated the postoperative elevation of C3a and C5a. The postoperative leukocyte count in peripheral blood was higher in the methylprednisolone group than in the controls. The observations indicated that methylprednisolone may reduce the influx of leukocytes from peripheral blood into the airways by attenuating production of biologically active complements.

Complement Activation↗

Studies on proteolysis of protein kinase C with calpain I and II.

Earlier reports from this laboratory have shown that protein kinase C (PKC) is cleaved with Ca2(+)-dependent neutral protease (calpain) I or II to produce a catalytically active fragment, and that calpain I, which is active in the micromolar range of Ca2+, may react preferentially with the active form of PKC that is associated with membranes. Subsequently, PKC is shown to exist as a large family of multiple subspecies with subtle individual characteristics. Three types of PKC designated types I, II, and III are purified from rat brain cytosol, which are shown to correspond to the cDNA clones gamma, beta, and alpha, respectively. The aim of the present study was to characterize the proteolysis of each PKC subspecies with calpain I and II. All types of PKC (82 kDa) were converted to two major fragments: a 47-49-kDa catalytic and a 36-kDa regulatory fragments by the cleavage with either calpain I or II. Analysis of the NH2-terminal sequence of the resulting catalytic fragments indicated that both calpain I and II cleaved at one or two specific sites in the variable region (V3) of each PKC molecule of which structure was clearly different among PKC subspecies. From kinetic studies, the cleavage of PKC subspecies with calpain I, and to a lesser extent, with calpain II (active in the millimolar range of Ca2+), was remarkably enhanced by the simultaneous presence of phospholipid and diacylglycerol or phorbol ester, suggesting that the active forms of PKC subspecies were the preferred targets for proteolysis. Whereas, stimulatory abilities of the lipids were variable among PKC subspecies and inactive form of type I PKC was cleaved with calpain I at a significant rate. Quantitative analysis with a fixed amount of calpain under comparable conditions showed that the susceptibilities of the PKC subspecies were distinctly different one another; the relative rates of cleavage of types I, II, and III PKC with calpain I and II were approximately 100:16:2 and 100:48:23, respectively. These results indicated that within the cell various PKC subspecies might be cleaved at different rates under different physiological conditions.

Animals↗

The effect of hyperoxia on the lungs of rats deficient in essential fatty acids.

Morphological alterations in the lungs of rats deficient in either or both of vitamin E and essential fatty acids were investigated after exposure to hyperoxia for 48 h. In rats deficient in both vitamin E and essential fatty acids, there was damage to type-2 alveolar cells observed as swollen mitochondria and bleb formation in the cytoplasm. None of these changes was found in rats deficient in only one of these substances. Hyperoxia in rats deficient in both substance also caused destruction of the capillary endothelial cells and edema in the interstitium. The lungs of rats deficient in only one of the substances showed some edema in the capillary endothelial cells, but not destruction, and less interstitial edema. These findings suggest that simultaneous deficiency in vitamin E and essential fatty acids facilitates lung damage in rats exposed to hyperoxia.

Journal Article↗

Limited proteolysis of protein kinase C subspecies by calcium-dependent neutral protease (calpain).

Limited proteolysis of three distinct subspecies of protein kinase C (Ca2+/phospholipid-dependent enzyme, PKC), types I (gamma), II (beta I and beta II), and III (alpha), with Ca2+-dependent neutral proteases I and II (calpains I and II) was studied. All forms of PKC (82 kDa) were converted to two major fragments: a 45-49-kDa catalytic fragment and a 36-kDa regulatory fragment. The cleavage of these PKC subspecies by calpain I (active in the micromolar range Ca2+/ion concentration), and, to a lesser extent, by calpain II (active in the millimolar range), was enhanced by the simultaneous presence of phospholipid and diacylglycerol or phorbol ester, suggesting that the activated form of PKC is the preferred target for proteolysis. Analysis of the NH2-terminal sequence of the resulting catalytic fragments indicated that both calpains I and II cleave at one or two specific sites in the third variable region (V3) of each PKC molecule. Under comparable conditions with calpains I and II, the relative rates of cleavage of types I, II, and III PKC were approximately 100:16:2 and 100:48:23, respectively. The results imply that within the cell various PKC subspecies may be cleaved at different rates under different physiological conditions.

Amino Acid Sequence↗

Effect of dopamine on parathyroid hormone release during surgery.

There is much evidence that dopamine (DA) may play an important role in modulating parathyroid gland function. DA stimulates parathyroid hormone (PTH) secretion in cattle, which increases ionized calcium, but is without such effect on humans under normal physiological conditions. Ionized calcium plays a major role in muscle contraction including myocardial contractility. Therefore, we studied the PTH response to infusion of DA (4 micrograms/kg/min) under pathophysiological states during two different types of surgery; gastrectomy with halothane anesthetics and open heart surgery with high-dose fentanyl anesthetics. There was no change in PTH concentration, as measured by radioimmunoassay, in patients undergoing gastrectomy, although infusion of DA in these patients was effective in lowering the prolactin levels. However, plasma PTH concentration significantly increased where DA was applied (4 micrograms/kg/min) in patients undergoing open heart surgery. These results suggest that DA may stimulate PTH secretion by an indirect mechanism in humans under pathophysiological states, although details of the mechanism are unknown, and that there is the possibility that DA would indirectly regulate the levels of electrolytes such as ionized calcium and phosphate in patients undergoing open heart surgery mediated by elevation of PTH.

Calcium↗

Endothelium-dependent relaxation in isolated pulmonary arteries from rabbits exposed to hyperoxia.

The effects of hyperoxia and superoxide dismutase (SOD) administration on endothelium-dependent relaxation induced by acetylcholine in isolated rabbit pulmonary artery (PA) preparations were examined. Relaxation responses to papaverine, and contractile responses to KCl and norepinephrine were also assessed using a bioassay technique. Prolonged hyperoxia in rabbits for 3 days produced loss of endothelium-dependent relaxation of the PA, and significant attentuation of contractile response to KCl and relaxation response to papaverine. These changes were prevented by subcutaneous SOD administration. Histological examination using light and electron microscopy revealed focal edema, destruction, and detachment of the PA endothelium in the PA strip preparations from these rabbits. Thus, it is concluded that a high concentration of oxygen exposure in rabbits for 3 days produces not only histological damage in the PA endothelium, but also causes impairment of vascular reactivity to constricting and relaxing agents. Subcutaneous SOD administration prevented oxygen-induced PA damage.

Acetylcholine↗

Urinary sodium and potassium excretion, body mass index, alcohol intake and blood pressure in three Japanese populations.

Standardised data on blood pressure, 24 hour urinary electrolyte excretion and other lifestyle factors were obtained in three Japanese populations as part of the INTERSALT study. Urinary sodium excretion and sodium/potassium ratio were significantly (P less than 0.01) higher in Toyama (a semi-rural area in central Japan) than in Tochigi (a rural area 100 km north of Tokyo) and Osaka. There were also significant (P less than 0.01) differences between the centres in diastolic blood pressure (highest in Toyama), although systolic pressure was similar in all three centres. Average potassium excretion was low (46 mmol/day), and the prevalence of both heavy alcohol drinking (greater than or equal to 300 ml/week) and smoking was high in men (33% and 61% respectively); compared with other countries, there were favourable levels of body mass index (mean 22.4 kg/m2). Despite a recent decline in sodium consumption in Japan, which has been accompanied by a fall in blood pressure levels, in the prevalence of hypertension and also in stroke mortality, average sodium excretion in the three centres was high compared to other countries (187 mmol/day). Applying overall INTERSALT regression coefficients to the Japanese data, suggested that further falls in sodium intake together with a modest increase in potassium intake and a reduction (in men) in the prevalence of heavy alcohol drinking could have an important impact on average blood pressures and the prevalence of hypertension. It can be expected that these nonpharmacological approaches to improved blood pressure levels will be accompanied by continued reductions in mortality from stroke.

Adult↗