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Biomedical subjects

M Sakakibara

Publications and source records attributed to M Sakakibara.

At least 91 records · Page 5Linked to original sources

Hypercalcemia associated with all-trans-retinoic acid in the treatment of acute promyelocytic leukemia.

Recent reports have described clinical benefits of all-trans-retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL). This paper describes severe hypercalcemia (serum calcium: 18.7 mg/dl) in association with ATRA treatment in a 14 year old girl with APL. Serum parathyroid hormone (PTH) concentrations were normal (0.21 ng/ml), which precludes the possibility of primary hyperparathyroidism or ectopic PTH secretion as a cause of the hypercalcemia. As for the factors which can accelerate mineral resorption, there were no apparent increases in the levels of PTH-related protein (PTH-rP), prostaglandins and vitamin D metabolites. In our in vitro experiment, ATRA did not stimulate the leukemic cells to produce PTH-rP. We speculate that ATRA, like PTH, may increase osteoclastic activity and induce hypercalcemia.

Adolescent↗

Reconstruction of ionic currents in a molluscan photoreceptor.

Two-microelectrode voltage-clamp measurements were made to determine the kinetics and voltage dependence of ionic currents across the soma membrane of the Hermissenda type B photoreceptor. The voltage-dependent outward potassium currents, IA and ICa(2+)-K+, the inward voltage-dependent calcium current, ICa2+ and the light-induced current, IIgt, were then described with Hodgkin-Huxley-type equations. The fast-activating and inactivating potassium current, IA, was described by the equation; IA(t) = gA(max)(ma infinity[1-exp(-t/tau ma)])3 x (ha infinity [1-exp(-t/tau ha)] + exp(-t/tau ha)) (Vm-EK), where the parameters ma infinity, ha infinity, tau ma, and tau ha are functions of membrane potential, Vm, and ma infinity and ha infinity are steady-state activation and inactivation parameters. Similarly, the calcium-dependent outward potassium current, ICa(2+)-K+, was described by the equation, ICa(2+)-K+ (t) = gc(max)(mc infinity(VC)(1-exp[-t/tau mc (VC)]))pc (hc infinity(VC) [1-exp(-t/tau hc)] + exp(-t/tau hc(VC)])pc(VC-EK). In high external potassium, ICa(2+)-K+ could be measured in approximate isolation from other currents as a voltage-dependent inward tail current following a depolarizing command pulse from a holding potential of -60 mV. A voltage-dependent inward calcium current across the type B soma membrane, ICa2+, activated rapidly, showed little inactivation, and was described by the equation: ICa2+ = gCa(max) [1 + exp](-Vm-5)/7]-1 (Vm-ECa), where gCa(max) was 0.5 microS. The light-induced current with both fast and slow phases was described by: IIgt(t) = IIgt1 + IIgt2 + IIgt3, IIgti = gIgti [1-exp(- ton/tau mi)] exp(-ton/tau hi)(Vm-EIgti) (i = 1, 2). For i = 3, /Igt(t) = gigt3m33h3(Vm - Eigt3)exp(-ton/Ton) x exp(-tfoff/t Off). Based on these reconstructions of ionic currents, learning-induced enhancement of the long lasting depolarization (LLD) of the photoreceptor'slight response was shown to arise from progressive inactivation of /A, lca2+ -K+, and lCa2+.

Animals↗

[A case of intrathoracic dumb-bell ganglioneuroma and a surgical approach using spinal evoked potentials (SEP)].

A successfully treated case of a seven-year-old girl with a left intrathoracic Dumb-bell ganglioneuroma is reported. The tumor was 10 cm in diameter. Preoperative angiography revealed that the location of tumor was very close to the Adamkiewicz artery. In order to prevent the artery from damaging, spinal evoked potentials (SEP) was used during the surgery and was very useful for monitoring the spinal cord. Although SEP has often been employed in spine surgery, the literature on the use of it for posterior mediastinal tumor is scarce. It is considered that SEP is very useful for not damaging the feeding artery to the spinal cord, and for preventing the postoperative neurologic complications.

Child↗

Nucleotide sequence of aminoglycoside 6'-N-acetyltransferase [AAC(6')] determinant from Serratia sp. 45.

Gene for aminoglycoside 6'-N-acetyltransferase [AAC(6')] from Serratia sp. 45 was cloned into E. coli. The enzyme produced in E. coli carrying the recombinant plasmid was compared to the Serratia enzyme. Both enzymes acetylated the 6'-C position of amikacin, dibekacin, tobramycin, sisomicin, gentamicin C1a and kanamycin but effected gentamicin C1, gentamicin C2 and micronomycin minimally. No significant difference in optimal pH, isoelectric point or molecular weight was detected. The nucleotide sequence of the gene was determined. Initiating with a GTG codon for methionine, it was composed of 552 base pair coding for 184 amino acids. The molecular weight of the enzyme was about 20418. Comparison of the amino acid sequence of this AAC(6') with the amino acid sequence of aacA4 gene from Serratia marcescens (G. Tran Van Nhieu and E. Collatz, J. Bacteriol., 169, 5708(1987)) showed 98.3% homology.

Acetyltransferases↗

[Assessment of autonomic function by the spectral analysis of heart rate variability: an examination in a mirror drawing task].

The effect of an experimental task on autonomic function was investigated by spectral analysis of heart rate variability in 13 male college students. Power spectral density of heart rate variability has been said to contain two significant components: respiratory sinus arrhythmia (RSA) as an index of cardiac vagal activity, and Mayer wave related sinus arrhythmia (MWSA) as an index of sympathetic activity with vagal modulation. Those two components were examined during a task of mirror drawing on the CRT. In order to eliminate the effect of respiratory rate on RSA, the respiratory rate was controlled at 15 breaths/min. Furthermore, the coefficient of variance of R-R interval (CV-RR) and the fluctuation of plethysmograph (PTG) were calculated simultaneously. Results indicated that, while RSA decreased significantly, MWSA did not change during the task. On the other hand, neither CV-RR nor PTG showed any significant differences during the task. These findings indicated that cardiac parasympathetic activity was diminished in the mirror drawing task. The significance of spectral analysis of heart rate variability were discussed.

Adult↗

Synthesis and antitumor activity of 4'-O-acylanthracyclines.

4'-O-Acyl derivatives of doxorubicin, daunorubicin, 13-deoxocarminomycin, 13-deoxo-10-hydroxycarminomycin, 13-deoxo-11-deoxycarminomycin were synthesized through the formation and mild acid hydrolysis of 2-oxazoline intermediates. The antitumor activity of these 4'-O-acyl derivatives against P388 leukemia was similar to or more effective than the parent anthracyclines.

Animals↗

[Left ventricular trabeculae evaluated with MRI in dilated cardiomyopathy and old myocardial infarction].

The morphological examination of the left ventricular trabeculae was performed using MRI (0.5T) in 14 normal volunteers, 12 patients with dilated cardiomyopathy (DCM), and 9 patients with old myocardial infarction (OMI). Left ventricular trabeculae were observed at the free walls of the left ventricle in all subjects, but not at the septal wall. Left ventricular trabeculae were larger in DCM than in the normals. The trabeculae were scarce in OMI and inner sides of the infarcted myocardium were very smooth. The development of the left ventricular trabeculae was graded as diminished, ordinary, and marked. Ordinary trabeculae were seen in 86% of the normals, whereas; marked trabeculae in 75% of DCM, and diminished trabeculae in 78% of OMI. In patients with DCM, the mean area of the left ventricle with marked trabeculae was greater than that with ordinary trabeculae. The more dilated left ventricle, the thinner the anterior wall was and the lower the ejection fraction was in DCM and OMI, though there were no significant differences in values of these 3 items between DCM and OMI. The MRI findings on the development of the trabeculae were confirmed in patients with DCM at autopsy. Thus, the MRI findings were very useful in the differential diagnosis between DCM and OMI.

Adult↗

[Human lung cancer cell lines in our laboratory: establishment of three large cell carcinoma cell lines and their biological characterization].

Three large cell carcinoma cell lines were established from tumors of lung cancer patients. The cell lines were named NUTLC-2, NUTLC-4 and NUTLC-5 and they were found to have the following biological characterization. 1) By chromosomal analysis, the tumor cells of two of the cell lines (NUTLC-2 and NUTLC-5) were human-origin cells. Numbers of chromosomes of these cells ranged from 52 to 59 in NUTLC-2 and from 68 to 75 in NUTLC-5, with the modal numbers of 56 and 71, respectively. 2) Primary tumor resected from the patient with lung cancer was heterotransplanted into the subcutis of a nude mouse. NUTLC-4 cell line was established in vitro from the tumor in nude mouse and the tumor cells were found to be mouse-origin cells by chromosomal analysis. Human DNA was not detected by Alu analysis. 3) The tumor cells of three cell lines could be heterotransplanted subcutaneously into nude mice. However, no natural distant metastasis in nude mouse was observed. 4) Drug sensitivity to NUTLC-2, NUTLC-4 and NUTLC-5 tumor cells differed individually according to MTT colorimetric assay, and characteristic drug sensitivity was not noted in histological types of lung cancer.

Aged↗

[A clinical study of transfer of cefminox and piperacillin into pulmonary tissue].

Serum concentrations of cefminox (CMNX) and piperacillin (PIPC) and their transfer into pulmonary tissue during surgery were serially studied following 1-hour intravenous instillation of 1 g of CMNX or PIPC immediately before thoracotomy, and the following results were obtained. Maximum serum concentrations of CMNX and PIPC were observed 1 hour after the commencement of administration, and their levels gradually decreased thereafter. The mean peak level of CMNX was 72.21 micrograms/ml, and T 1/2 was 1.62 hours. The mean peak level of PIPC was 43.26 micrograms/ml, and T 1/2 was 1.54 hours. In the pulmonary tissue, mean concentrations of CMNX in the normal pulmonary (alveolar) tissue were 28.80, 26.50 and 17.80 micrograms/g at 2.5, 3 and 4 hours, respectively, after the commencement of administration, and the corresponding levels for bronchiolar tissue were 19.6, 18.40 and 20.53 micrograms/g, respectively. The mean concentrations of PIPC in the normal pulmonary (alveolar) tissue were 18.97, 7.34 and 5.0 micrograms/g at 2, 3 and 4 hours, respectively, after the commencement of administration, and the corresponding levels for bronchiolar tissue were 7.2, 9.20 and less than 0.2 micrograms/g, respectively. PIPC also showed favorable transfer into the hilar lymph node tissue and obstructive pneumonitic lesions. The transfer of both drugs into pulmonary tissue suggests that both drugs are useful for the treatment of respiratory infectious diseases and the prevention of postoperative infections.

Adult↗

Transfer of beta-lactam preparations created in Japan to lung tissue and the drug selection for chemotherapy of respiratory tract infections.

Intraoperative transfer of eight beta-lactam preparations to lung tissues was investigated by one-gram one-hour intravenous drip infusion immediately prior to operation. The Japanese drugs used were piperacillin, cefotiam, ceftizoxime, cefuzonam, latamoxef, flomoxef, cefotetan and cefbuperazone. The serum peak level was highest with cefotetan, 104.1 micrograms/ml, followed by cefbuperazone, latamoxef, ceftizoxime, cefotiam, piperacillin, flomoxef and cefuzonam, in decreasing order. Except for cefuzonam, there was a correlation between the serum peak level and the human serum protein binding rate (r = 0.89). There was a correlation (r = 0.98) between the Cmax of normal lung tissue (alveoli) level and the serum peak level (Cmax), but no correlation between the former and the human serum protein binding rate. The tumour level was lower than that in normal lung tissue (alveoli), but the tissue level at the obstructive pneumonia area was higher. The Cmax of bronchiolar tissue level was highest with cefuzonam, followed by latamoxef. There was no correlation between the Cmax of bronchiolar tissue level and the serum peak level, human serum protein binding rate or the Cmax of lung tissue (alveoli) level. It is therefore presumed that the drug level in tissue of the acute pneumonia area can be determined from the serum peak level of the respective drug. An appropriate drug for chemotherapy may be selected from beta-lactam preparations which are effective against main causative organisms in acute respiratory tract infections. Cefuzonam and latamoxef are especially useful for chemotherapy in patients with acute bronchiolitis.

Adult↗

[Daily activity evaluated from total energy consumption in the chronic stage of myocardial infarction and limiting factors in elder patients].

In chronic case of myocardial infarction (OMI), alternation of a daily total energy consumption (DTEC) between in OMI and in the pre-infarction stage was investigated. The limiting factors of DTEC, including functional classification according to New York Heart Association (NYHA) subset, Forrester's hemodynamic subset (FS) in the stage of acute myocardial infarction (AMI), numbers of significant coronary arterial stenosis (NCAG), cardiac function at rest in OMI, for example; cardiac index (CI), pulmonary capillary wedge pressure (PCW), left ventricle end-diastolic pressure (EDP) and exercise tolerance in OMI, were considered. Subjects, consisting of 191 OMI cases, were classified into the younger group less than 59 years old (79 males and 10 females) and the older group greater than 60 years old (102 males and 23 females). Daily physical activity was examined by questionnaires from these patients and DTEC was calculated based on daily physical activity. Results in the younger group and older group were investigated separately. Reduction of DTEC after myocardial infarction was recognized in all ages and both sexes, however, reduction of DTEC in the older group was less than in the younger group, especially in males. Concerning the limiting factors of the older group, exercise tolerance in OMI was related to reduction of DTEC. NYHA category, FS in the AMI stage, NCAG, CI, PCW and EDP had no significant relation to DTEC. In addition, the effects of social limiting factors, for instance retirement, and mental limiting factors were considered to be important.

Activities of Daily Living↗

[An inexpensive and flexible personal-computer-based system for controlling the multiple stimulus events in classical conditioning].

For the demand of biological discipline it is worth to develop a stimulus control system especially suitable for behavioral studies on learning and memory, in which the precise temporal control of the event sequence has been desired. We developed a flexible and inexpensive system based on IBM-PC for the classical conditioning of the marine mollusc. User can set a various temporal conditions with the data sheet on a display. It can be applicable in a wide range of conditions as well as in a lot of situations which require temporal control of multiple stimuli.

Animals↗

[A study of fibroblasts in the chemosensitivity testing on human lung cancer cell lines].

The purpose of this study is to assess effects of fibroblasts in the vitro chemosensitivity testing on human lung cancer cells and to remove them. Fourteen lung cancer cell lines and 14 fibroblasts derived from resected specimens of lung cancers were used, whose S.D (succinate dehydrogenase) activities were measured with MTT colorimetric assay. The chemosensitivity of a lung cancer cell alone was compared with that of mixed cancer cell and fibroblast. As results, S.D activities of fibroblasts were less 2-4 fold than those of lung cancer cells. Fibroblasts were as sensitive to CDDP, MMC and 5-FU as lung cancer cells, but more sensitive to ADM and VP-16 than them. When sensitivity testings were performed on mixed cancer cells and fibroblasts, or mixed cancer cells and conditioned media of fibroblasts to CDDP with 3 day's incubation times, the sensitivity was affected in 61%, or 10% of all the pairs, respectively. However, when these tests were done without any incubation times, the sensitivity was not affected. Therefore, it was suggested that anticancer drugs had to be simultaneously added when single cell suspensions were plated if resected specimens were used in a anticancer drug sensitivity test.

Antineoplastic Agents↗

[Interaction of lung cancer cells and fibroblasts].

Fibroblasts are found to secrete several factors, but complex interactions between cancer cells and fibroblasts are not well known. In this report, it was discussed how fibroblasts derived from lung cancer tissues affected lung cancer cells in vitro and in vivo. As results, the growth of 4 of eight cancer cells was promoted by any medium conditioned by fibroblasts (C.M) in vitro. Fifty percent of the 12 fibroblasts had some effect on promoting the growth of cancer cells, but had no effect on suppressing cancer cells. The C.Ms promoting the growth of cancer cells in vitro exerted the same effect in nude mice, too. Coinoculation of fibroblasts and cancer cells into nude mice gained higher tumorigenicity than cancer cells alone with no relation to their subclasses. It was suggested that to examine the effect on promoting the growth of cancer cells by fibroblasts derived from lung cancer tissues in vitro was able to prospect how fibroblasts affected cancer cells in vivo and fibroblasts made some good condition to transplanted cancer cells into nude mice by means different from growth factors.

Animals↗

[A clinical study on pulmonary tissue uptake of flomoxef].

Based on the results of a study on pulmonary tissue uptake of flomoxef (FMOX), a new antibiotic agent, in 45 patients undergoing thoracotomy, the following conclusions were drawn: 1. Immediately preoperative 1 hour-drug infusion of 1 g FMOX led to maximum serum concentration (averaging 42.4 micrograms/ml) 1 hour later, with a half-life of its beta phase of 1.26 hours. 2. Normal lung (alveolar) tissue concentration was Cmax 17.98 micrograms/g with its ratios to serum peak value being 31.8, 27.1, 22.2, 9.4, 5.9 and 5.0% at 1, 2, 3, 4, 5 and 6 hours later, respectively. 3. Bronchiolar tissue concentration was Cmax 31.91 micrograms/g, with its ratios to serum peak value being 27.8, 19.3 and 10.1% at 2, 3 and 4 hours later, respectively, indicating its good bronchiolar intra-tissue transition. The above results suggested the usefulness of FMOX for both the treatment of respiratory infections and the prevention of postoperative infections.

Adolescent↗

Early regulation of membrane excitability by ras oncogene proteins.

Two electrode voltage clamp conditions were used to study the early effects on ionic membrane channels of the intracellularly injected proto-oncogenic form of c-Ha-ras (c-ras) and its oncogenic counterpart v-Ha-ras (v-ras). These experiments were conducted on isolated somata of identified fully differentiated neurons of the sea snail Hermissenda. 20 min after c-ras, and 10 min after v-ras intracellular injections into type B medial photoreceptors of Hermissenda, the peak amplitude of two outward potassium currents (IA and IC), across the isolated Type B soma membrane begin to decrease. These two currents have been previously isolated by differences in activation and inactivation kinetics and their response to pharmacological blockers. c- or v-ras injections did not have any effect on a voltage-dependent inward calcium current. Reduction of IA preceded that of IC. Current reductions due to c-ras, but not to v-ras injection reversed spontaneously after 40 min. The voltage dependence of the steady state inactivation of IA shifted toward more negative potentials with ras injections. Ras-mediated cell transformations therefore, could involve, perhaps as initial events, prolonged modification of membrane currents.

Animals↗

An acute state of a daily physical activity in the chronic stage of myocardial infarction and a proposal of an optimal exercise therapy.

An optimal target of exercise therapy for the chronic stage of myocardial infarction (OMI) was proposed by investigating a daily total energy consumption (DTEC) in 172 outpatients (142 males and 30 females) with OMI. DTEC was significantly lower in OMI than in the preinfarction state: 2005.8 +/- 487.8 vs. 2451.6 +/- 631.7 Kcal (p less than 0.01) in the male, 1389.9 +/- 367.4 vs. 1626.2 +/- 426.0 Kcal (p less than 0.01) in the female. Limiting factors of a daily physical activity (DPA) in OMI were selected from various non-cardiac and cardiac factors by using multifactorial analysis (Hayashi III). Non-cardiac limiting factors included; age of greater than 60, house-wife, joblessness and female, sex, and cardiac limiting factors included; NYHA class II, III, low anaerobic threshold (AT), treadmill exercise tolerance of less than 6 min, Forrester subset III, IV, heart failure in OMI and the recurrence of MI. Eighty percent of patients without cardiac limiting factors restricted DPA by 25% of DTEC of the preinfarction state. Our optimal target of exercise therapy for OMI was set to resume DTEC up to the level before MI. For patients without exercise habits, activities requiring 100 to 150 Kcal a day were requested. Also, this regimen had an educational purpose to obtain self-confidence both mentally and physically and was expected to raise the level of DPA to that of preinfarction state.

Activities of Daily Living↗