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Biomedical subjects

K Kamiya

Publications and source records attributed to K Kamiya.

At least 19 recordsLinked to original sources

Effect of temporary pacing on patients with bradycardia in the acute stage following subarachnoid hemorrhage.

In nine cases of bradycardiac arrhythmia of less than 50 bpm that arose during cerebral vasospasm following aneurysmal rupture the patients were treated by temporary pacing. In patients with cerebral vasospasm, in whom autoregulation of the cerebral circulation is impaired, bradycardia aggravates the risk of decreased cerebral blood flow. This study demonstrated that temporary pacing is an effective and safe procedure in maintaining heart rate during vasospasm.

Bradycardia

Pulmonary surfactant apoprotein-A in neonates with different respiratory disorders.

A serial determination of pulmonary surfactant apoprotein-A (SP-A) was made on tracheal aspirates from seven intubated infants with different types of respiratory failure in the first week of life. A two-site immunoassay with monoclonal antibodies was adopted to determine the SP-A concentration. The concentrations of albumin in the same samples were also assayed, and these data were expressed as the ratio of SP-A to albumin (SP-A/albumin ratio), and evaluated against clinical data such as the arterial-alveolar oxygen tension ratio (a/APO2) or ventilatory index. In infants with respiratory distress syndrome, the SP-A/albumin ratio was initially low, and increased gradually in the first few days of life with the improvement of a/APO2 and ventilatory index. The complication of pulmonary hemorrhage due to patent ductus arteriosus (PDA) resulted in a temporary decrease in the ratio. The infant with transient tachypnea of the newborn showed higher concentration from the first day of life and, in the course of PDA without pulmonary hemorrhage, the ratio did not decrease. The cases of congenital pneumonia showed the SP-A/albumin ratio remaining low while the infection was evident. These data suggest that the SP-A/albumin ratio of the tracheal aspirate can be used for the quantitative and qualitative evaluation of endogenous pulmonary surfactant in newborn infants with different respiratory disorders.

Albumins

Effects of long-term oral administration of amiodarone on the electromechanical performance of rabbit ventricular muscle.

1. The effects of long-term administration of oral amiodarone on transmembrane action potential and contraction of ventricular muscle were investigated in rabbits. 2. ECGs of rabbits that received oral amiodarone 50 mg or 100 mg kg-1 daily for 4 weeks, showed a significant prolongation of RR, QT and corrected QT (QTc) intervals, whereas PQ and QRS were unaffected. Serum and myocardial tissue amiodarone concentrations were 0.14-0.18 micrograms ml-1 and 1.47-3.63 micrograms g-1 wet wt. respectively. 3. Right ventricular papillary muscles isolated from treated rabbits were characterized by a moderate prolongation of action potential duration (APD) compared with controls. A slight decrease of the maximum upstroke velocity (Vmax) was also observed at the higher dose. The APD prolongation by chronic amiodarone, unlike acute effects of sotalol, E-4031, Cs+ and 4-aminopyridine, did not show marked reverse use-dependence. 4. APD and Vmax restitution following slow basic stimuli (0.03 Hz) were unaffected by chronic treatment with amiodarone. 5. Acute application of amiodarone (10 microM) caused a significant decrease in APD and developed tension, as well as a marked use-dependent Vmax inhibition with fast recovery kinetics. 6. These findings suggest that a major and consistent electro-physiological effect of chronic amiodarone is repolarization delay (Class-III action) showing minimal frequency-dependence. However, when amiodarone above a certain concentration is present in the extracellular space, a fast kinetic Class-I action would be added as an acute effect.

Action Potentials

Protective action of iron-chelating agents (catechol, mimosine, deferoxamine, and kojic acid) against ischemia-reperfusion injury of isolated neonatal rabbit hearts.

Iron is suggested to play an important role in free radical generation during ischemia reperfusion. In the present study, the protective action of 4 iron-chelating agents, with different iron affinities, against reperfusion injury was examined in Langendorff-perfused hearts of neonatal rabbits. The chelators and their iron-binding constants (log Km) were as follows: catechol (43), mimosine (36), deferoxamine (31) and kojic acid (27). Following cardiac arrest, the hearts were subjected to global ischemia for 45 min at 37 degrees C, and then reperfused with modified Krebs-Henseleit solution for 30 min. In control, the left ventricular developed pressures (LVDP) after 30 min reperfusion recovered to 50.5 %/- 3.0% (mean +/- SEM; n = 5) of the preischemic level. In the hearts treated with catechol (30 microM), mimosine (30 microM) or deferoxamine (30 microM), the LVDP recovery was significantly improved up to 84.9 +/- 1.3, 88.2 +/- 2.9 or 87.4 +/- 1.5%, respectively (p < 0.01 vs. control). Creatine phosphokinase (CPK) leakage during the initial 5 min of reperfusion was significantly decreased to about half of control in the hearts treated with catechol, mimosine, or deferoxamine. However, the treatment with kojic acid (30 microM) showed no improvement in the LVDP recovery and CPK leakage. Free radical generation was measured with an electron spin resonance using a spin-trapping agent, 5,5-dimethyl-pyrroline-N-oxide (DMPO). The treatment with catechol, mimosine, or deferoxamine reduced the maximum intensity of DMPO-OH signal to about one third of control. However, the maximum intensity in the hearts treated with kojic acid showed a similar level to control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A model analysis for competitive binding of mexiletine and aprindine to the cardiac sodium channel.

A simulation model was developed to predict complex interaction between antiarrhythmic drugs and cardiac sodium channels. This model has four assumptions: (1) Vmax of the action potential is a linear indicator of available sodium channel conductance; (2) antiarrhythmic drugs block the channel by binding to a single common receptor site associated with the channel; (3) binding and dissociation rate constants differ for the three channel states: activated, inactivated and resting, and (4) both drug-free and drug-bound channels change states far more rapidly than binding and dissociation processes. Binding and dissociation rate constants for the three channel states were calculated from single cell experiments using guinea pig hearts. Vmax changes reflecting tonic and use-dependent sodium channel block in the presence of mexiletine and aprindine were simulated and compared with those obtained in the single cell experiments. The model predicted that 'tonic' Vmax inhibition would be enhanced, whereas 'use-dependent' ones would be attenuated after admixture of mexiletine with aprindine. The mechanisms would involve competitive interaction at the common receptor site. Single-cell experiments supported this prediction. We conclude that our simple two-drug binding model provides a useful tool to predict pharmacological interaction between class I antiarrhythmic drugs given in combination.

Action Potentials

Carcinogenic effect of in utero 252Cf and 60Co irradiation in C57BL/6N x C3H/He F1 (B6C3F1) mice.

C57BL/6N x C3H/He F1 mice were exposed in utero to 0, 1.0 and 2.7 Gy of 252Cf or 60Co at day 16.5th of gestation. Mice of both sexes were observed for 2 years. The females in the irradiated groups showed increases in the incidences of pituitary, mammary gland, liver and lung tumors. 252Cf was more effective in inducing tumors than was 60Co. Interestingly, the incidence of hematopoietic tumors decreased by irradiations with 252Cf but not with 60Co. The incidences of liver tumors in males increased by 252Cf-irradiation, whereas, the incidences of skin and soft tissue tumors increased by 60Co-irradiation. These results indicate that irradiation in utero during the late embryonic stage can induce tumors postnatally after a long latency. Moreover, females irradiated in utero had disfunction of the ovaries, evidence of impairment of the female's specific hormonal environment. This may be the cause of the low incidence of ovarian tumors and the high incidences of liver, lung and pituitary tumors in these female mice. Females with pituitary tumors had a high serum prolactin, which might be responsible for the concurrence of mammary gland tumors. These results indicate the importance of host factors in the development of radiation-induced tumors.

Animals

[Clinical assessment of urinary free L-fucose levels].

We measured urinary levels of free L-fucose in healthy subjects, patients with benign diseases, and patients with cancer using an automated analyzer and a newly isolated L-fucose dehydrogenase, and evaluated the clinical usefulness of the results. The values obtained were corrected for urinary creatinine as micromoles per gram of creatinine. The cutoff value, set at the mean + 2SD for the healthy subjects, was 250 mumol/g.Cr. Patients with gallbladder cancer, bile-duct cancer, liver cancer, pancreatic cancer, or cirrhosis of the liver had significantly higher levels of L-fucose than the healthy subjects. The diagnostic sensitivity for these five diseases, taken together, was 68% (144/213). Specificity for the detection of cancer was calculated by use of false positives for patients with cholelithiasis, hepatitis, and pancreatitis: it was 73% (76/104). Diagnostic accuracy for these seven diseases taken together was therefore 69% (220/317). We compared the positive ratio of the L-fucose level with that of the tumor markers AFD and CA19-9. The positive ratio of an L-fucose value above the cutoff was higher than the positive ratio of either marker in bile-duct cancer, gallbladder cancer, liver cancer, and pancreatic cancer. The results suggested that the urinary levels of free L-fucose reflected the metabolism of sugar chains of glycoconjugates, and may be usefully clinically as a tumor marker.

Biomarkers, Tumor

[Holoprosencephaly accompanied with dysgenesis of the cerebellum].

We have encountered 9 cases of holoprosencephaly, four of them with abnormalities of the posterior fossa. Three cases of semilobar type had severe cerebellar hypoplasia and a large cyst continuing to the fourth ventricle. They were diagnosed as Dandy-Walker syndrome. A case of lobar type had a relatively mild form of cerebellar hypoplasia and it was thought to be a Dandy-Walker variant. MRI was able to clarify the anatomical relationship of the intracranial construction, for example monoventricle, dorsal sac or large cyst in the posterior fossa, and it was very useful for the diagnosis of these congenital anomalies. All of them showed hydrocephalus and required treatment with ventriculoperitoneal or cyst-peritoneal shunt. With the availability of MRI, easy diagnosis of the mild forms of holoprosencephaly has been facilitated, and accompanying anomalies are also able to be diagnosed. Up to now, the structure of the posterior fossa in holoprosencephaly was thought to be normal. However, several cases of holoprosencephaly accompanied with cerebellar hypoplasia and cystic lesion of the posterior fossa, revealed by MRI or autopsy, have been reported. It was suggested that holoprosencephaly with anomalies of the posterior fossa may be less rare than has been thought, so far.

Cerebellum

Factor IX Amagasaki: a new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities.

Factor IX Amagasaki (AMG) is a naturally occurring mutant of factor IX having essentially no coagulant activity, even though normal levels of antigen are detected in plasma. Factor IX AMG was purified from the patient's plasma by immunoaffinity chromatography with an anti-factor IX monoclonal antibody column. Factor IX AMG was cleaved normally by factor VIIa-tissue factor complex, yielding a two-chain factor IXa. Amino acid composition and sequence analysis of one of the tryptic peptides isolated from factor IX AMG revealed that Gly-311 had been replaced by Glu. We identified a one-base substitution of guanine to adenine in exon VIII by amplifying exon VIII using the polymerase chain reaction method and sequencing the product. This base mutation also supported the replacement of Gly-311 by Glu. In the purified system, factor IXa AMG did not activate factor X in the presence of factor VIII, phospholipids, and Ca2+, and no esterase activity toward Z-Arg-p-nitrobenzyl ester was observed. The model building of the serine protease domain of factor IXa suggests that the Gly-311----Glu exchange would disrupt the specific conformational state in the active site environment, resulting in the substrate binding site not forming properly. This is the first report to show the experimental evidence for importance of a highly conserved Gly-142 (chymotrypsinogen numbering) located in the catalytic site of mammalian serine proteases so far known.

Amino Acid Sequence

CO2 reactivity and autoregulation in fetal brain.

Intraventricular hemorrhage (IVH) in preterm infants is well known to be associated with the high morbidity and mortality of this group. Previous studies have suggested altered cerebral blood flow (CBF) as an important pathologic factor. We measured the CBF in near-term rabbit fetuses using the hydrogen clearance technique. The local CBF of the rabbit fetuses was significantly low compared with that of the maternal rabbits. The response of CBF to changes in PaCO2 was observed in rabbit fetuses. The CO2 reactivity index of the fetal rabbit was lower than that of the maternal rabbit. This low CO2 reactivity might reflect the immaturity of the fetal brain and its low CBF. We were unable to monitor the fetal blood pressure, but the fetal CBF remained stable when the maternal blood pressure was altered. It is well known that IVH in preterm infants originates from the subependymal germinal matrix and that this has many fragile vessels. Our observation suggests that even a small increase of CBF during hypercapnia might have a large effect towards producing hemorrhage.

Animals

Effect of continuous cisternal drainage on cerebral vasospasm.

The effect of continuous cisternal drainage on cerebral vasospasm was studied under strict criteria in 140 patients with ruptured intracranial aneurysms. The degree of subarachnoid haemorrhage (SAH) on the computed tomography scan was graded from I to IV. The patients were classified according to the total amount of cisternal drainage into three groups, regardless of the duration of the drainage and whether or not it was accompanied by irrigation; i.e., those with less than 500 mL (group 1: 57 cases), those with 500-3000 mL (group 2: 44 cases), and those with 3000-9500 mL (group 3: 39 cases). While correlations could be found between both clinical and SAH grades with the severity of vasospasm, closer correlation could be found in the SAH grades. In analyzing the cases with subarachnoid haemorrhage grades III-IV (severe clots), the angiographic vasospasm was less severe in groups 2 and 3 than in group 1, and the incidences of permanent symptomatic vasospasm and low-density area on computed tomography were lower in groups 2 and 3 than in group 1. Regarding the surgical outcome in cases with SAH grades III-IV, the mortality rate was lower in groups 2 and 3 (22% and 19%) than in group 1 (33%). Further, the rate of good recovery was higher in groups 2 and 3 (61% and 57%) than in group 1 (28%). However, there were no differences between groups 2 and 3 in cerebral vasospasm or in surgical outcome. As a shortcoming of continuous cisternal drainage, the need for shunt operation was higher in groups 2 and 3 than in group 1.

Adult

Repair of potentially lethal damage in rat mammary clonogens following irradiation in organoid culture.

In the course of investigations of radiogenic neoplasia in mammary cells in vivo, post-irradiation repair of potentially lethal damage (PLDR) was previously observed in mammary epithelial clonogens when they were irradiated and left in their tissue environment for 4-24 h after exposure. This type of PLDR increases the initial shoulder of the survival curve without significantly affecting its terminal slope. It has since been described in similarly treated thyroid and hepatic clonogens, and significantly exceeds that generally seen in most mammalian cells in culture. In this study, a ten-fold increase in the concentration of mammary clonogens which could be assayed was achieved by the isolation and short term culture (2-4 days) of mammary organoids (ductal and end-bud fragments). Assays of clonogen concentrations were carried out with cell suspensions prepared immediately following irradiation of 4-day organoid cultures or 24 h after irradiation of such organoid cultures. A near four-fold increase in clonogen survival was observed with the delay in assay after irradiation; this is comparable to the PLDR seen in mammary clonogens irradiated and left in situ for 4-24 h after exposure.

Animals

A combination of inactivated sodium channel blockers causes competitive interaction on dV/dtmax of single ventricular myocytes.

STUDY OBJECTIVE: The aim was to study an interaction between class I antiarrhythmic drugs on the cardiac sodium channels. DESIGN: The single pipette, whole cell clamp method was employed to control and record membrane potential. The maximum upstroke velocity (dV/dtmax) was measured as an index of sodium channel availability during treatment of the preparations with aprindine (5 microM) in combination with mexiletine (40 microM), and lignocaine (40 microM). EXPERIMENTAL MATERIAL: Single ventricular myocytes (n = 6-8 per experiment) isolated from guinea pig hearts were used. MEASUREMENTS AND MAIN RESULTS: Trains of depolarisation to 0 mV (0.2-2.0 Hz) were applied from the resting membrane potential (-85 mV) following a long quiescent period to evaluate "tonic" and "use dependent" decrease (block) of dV/dtmax. Additional application of mexiletine or lignocaine to aprindine resulted in an increase of tonic block and a decrease of use dependent block. Because of such counteracting action, the steady state dV/dtmax during the train of depolarisation was unaffected for mexiletine, and even increased for lignocaine. Dual exponential components of dV/dtmax recovery following a 1 s conditioning depolarisation after admixture of mexiletine or lignocaine to aprindine suggest their competitive interaction on cardiac sodium channels. CONCLUSION: A combination of class I antiarrhythmic drugs having high affinity for the inactivated state of sodium channels may cause a reductive effect on dV/dtmax through competitive displacement from common receptors.

Animals

Induction of transplantable tumors by repeated subcutaneous injections of natural and synthetic vitamin E in mice and rats.

Natural vitamin E and synthetic vitamin E (dl-alpha-tocopheryl acetate) were tested for their tumorigenicity in rodents. Transplantable tumors, at the site of injection, were induced by repeated injections of these compounds in two strains of mice, NFS/N and C57BL/6N x C3H/He F1, and in a strain of rats, Fischer 344. Natural vitamin E was tumorigenic in both strains of female mice only when injected with soya oil. In contrast, dl-alpha-tocopheryl acetate alone was capable of inducing tumors in Fischer 344 rats. Only one out of 5 male NFS/N mice given dl-alpha-tocopheryl acetate developed a tumor. Therefore, Fischer 344 rats were more susceptible to tumor formation by dl-alpha-tocopheryl acetate than NFS/N mice. dl-alpha-Tocopheryl acetate with soya oil or with palm oil also resulted in the formation of transplantable tumors in NFS/N mice and Fischer 344 rats. There was no difference in the tumor incidence between mice treated with dl-alpha-tocopheryl acetate alone and dl-alpha-tocopheryl acetate plus soya oil or palm oil. However, in rats, the incidence was lower for a group treated with dl-alpha-tocopheryl acetate plus palm oil than for those with dl-alpha-tocopheryl acetate alone and with dl-alpha-tocopheryl acetate plus soya oil.

Animals