Identification of dimeric structure of proteins by use of the glutathione S-transferase-fusion expression system.
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Electrophoresis, Polyacrylamide Gel↗
Biomedical subjects
M Kaneko
Publications and source records attributed to M Kaneko.
Gastric stump carcinoma occurring in a patient with Carney's triad 38 years after partial gastrectomy for epithelioid leiomyosarcoma.
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Adult↗
Differential requirements of CD45 for lymphocyte development and function.
CD45 exon 6-deficient mice show a profound block of thymocyte development at a transitional differentiation step from immature CD4+ CD8+ to mature single-positive cells. Only a few T lymphocytes are observed in the periphery of such animals, but B cell development is not affected. We investigated whether mature B lymphocytes in CD45 exon 6-deficient mice have normal functions in the absence of CD45 expression and show here that CD45-defective B lymphocytes from CD45 exon 6-deficient mice have intact B lymphocyte functions, including T-dependent and T-independent antigen-specific antibody production and class switching in vivo if normal CD4+ T lymphocytes were adoptively transferred into the mutant mice. From these results, we conclude that CD45 expression on B lymphocytes is not essential for B cell responses following antigen stimulation in vivo. However, CD4+ T helper function was severely diminished in CD45 exon 6-deficient mice, suggesting that the requirements of CD45 molecules in antigen-specific response and development are different between T and B lymphocytes.
Animals↗
Probable implication of mutations of the X open reading frame in the onset of fulminant hepatitis B.
A pathogenic role of precore-defective mutation in the onset of fulminant hepatitis B has been suggested. However, precore-defective mutants do not always cause fulminant hepatitis B and are not always isolated from affected patients. These findings strongly suggest the presence of some additional important mutations outside the precore region in fulminant hepatitis. In the present investigation an attempt was made to sequence the X open reading frame of hepatitis B virus DNA isolated from seven patients with fulminant hepatitis B and five patients with acute hepatitis B. The latter were used as controls. Since the X open reading frame encodes the X protein and contains the core promoter/enhancer II complex, some critical mutations may enhance or disrupt the replication and expression of hepatitis B virus DNA leading to fulminant hepatitis. A C-to-T substitution was found at nucleotide (nt) 1655, an A-to-T substitution at nt 1764 and a G-to-A substitution at nt 1766 in 4, 5 and 5 patients, respectively, out of the seven with fulminant hepatitis. These substitutions were not recognized in the patients with acute hepatitis. These mutations might change the function of the X protein and core promoter/enhancer II complex. It is suggested, therefore, that these mutations, as well as the precore-defective mutation, may play an important role in the pathogenesis of fulminant hepatitis.
Acute Disease↗
Treatment combined with bone marrow transplantation for advanced neuroblastoma: an analysis of patients who were pretreated intensively with the protocol of the Study Group of Japan.
One hundred and ten patients with advanced neuroblastoma were treated with the protocol of the Study Group of Japan between January 1985 and March 1991. Patients received six cyclic courses of regimen A1, consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (40 mg/m2), and cisplatin (90 mg/m2). Primary tumors and regional lymph node metastases were removed some time during the first six cycles of regimen A1. After six cycles of A1, the patients were divided into three groups. Patients in group 1 received alternating treatment with regimen B (cyclophosphamide and ACNU) and intensified A1, and those in group 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in group 3 were treated with supralethal therapy and bone marrow transplantation (BMT). Event-free survival rates at five years were 38.8% in the chemotherapy group (groups 1 and 2) and 50.0% in the transplant group (group 3). Because of the study design that was not in truly randomized fashion and because of the small number of patients in each risk group, it is indicated, though not concluded, that the transplant group had a better prognosis than the chemotherapy group in the cases with stage III disease or with amplified N-myc oncogene, based on the statistical calculations. Differences in survival rates for patients who underwent BMT when complete remission (CR) was achieved and for those who achieved CR but who did not undergo marrow transplant were statistically insignificant. BMT-related death occurred in 3 of 31 cases (9.7%) undergoing marrow transplant, and the causes of the death included hemorrhagic pneumonia, myocardial disturbance and hemorrhagic uremia.
Antineoplastic Combined Chemotherapy Protocols↗
Expression of neuron-specific enolase in the pineal organ of the domestic fowl during post-hatching development.
Immunohistochemistry for neuron-specific enolase (NSE) revealed that NSE is localized in both a limited number of pinealocytes and intrinsic afferent neurons in the pineal organ of the domestic fowl. Furthermore, a computer-assisted three-dimensional imaging technique allowed to clarify the reverse distributional pattern of both elements: NSE-positive pinealocytes displayed a dense distribution especially in the vesicular portion of the gland, whereas NSE-immunoreactive nerve cells were mainly found in the pineal stalk. The number of NSE-positive intrinsic neurons in the pineal organ of chickens decreased rapidly after hatching, with a concentration of these elements in the basal portion (stalk) of the pineal organ. On the other hand, immunoreactive pinealocytes increased remarkably in the end-vesicle of the organ with age, followed by a gradual expansion toward the proximal portion. Thus, the spectacular increase in NSE-positive pinealocytes and the progressive reduction of reactive neurons occurred in parallel during the course of post-hatching development. NSE-immunoreactive pinealocytes displayed morphological characteristics of bipolar elements, endowed with an apical protrusion into the pineal lumen and a short basal process at younger stages, whereas multipolar types of NSE-positive pinealocytes were predominantly found in the adult domestic fowl. These results indicate that in the pineal organ of the domestic fowl (1) the ontogenetic expansion of NSE-immunoreactive pinealocytes is paralleled by a regressive afferent innervation, (2) the NSE-positive pinealocytes transform from a bipolar (columnar) type to a multipolar type during post-hatching development, and (3) these ontogenetic changes in the NSE-immunoreactivity and morphology of pinealocytes may reflect the development of a neurosecretory-like capacity of the organ.
Animals↗
Concomitant coronary bypass grafting and curative surgery for cancer.
The surgical management of patients with concomitant critical coronary artery disease (CAD) and surgically resectable cancer is controversial. We evaluated 19 patients who underwent concomitant coronary artery bypass grafting (CABG) and curative operation for cancer of the stomach in 9 patients, the colon in 4, the lung in 4, and the breast in 2. Each cancer operation was performed under stable hemodynamics without any serious bleeding tendency, immediately after CABG with an average of 2.5 +/- 0.8 grafts. There were no operative deaths and no incidences of perioperative myocardial infarction. Postoperative complications developed in three of the patients with lung cancer: respiratory dysfunction caused by phrenic nerve paralysis in two and mediastinitis in one. During the mean follow-up period of 33 +/- 23 months, 5 patients died of recurrent cancer or non-cardiac disease; however, all 19 patients remained free from any postoperative cardiac events and their quality of life apparently improved. This experience suggests that such simultaneous correction would be safe and beneficial in carefully selected patients who have surgically correctable CAD and potentially curable cancer.
Adult↗
Cardio-pulmonary function of cyclists competing on an ascending mountain course between altitudes of 1400 m and 2800 m.
Physiological changes were investigated in the cardio-respiratory function of competitors in a bicycle race which involved not a flat course but ascending a mountain, from 1400 m to 2800 m. Heart rate throughout the race, arterial oxygen saturation and pulmonary function before and after the race of well trained competitors were measured. The individual's maximal heart rate during the race was designated as HRmax for the calculations. (1) There were significant correlations between the age and the mean %HRmax during the race, between mean %HRmax and time, and between age and time (n = 15); the mean %HRmax had a 3.90 times greater effect on time than did age. (2) The individuals who performed best had lower values of oxygen saturation just after finishing the race (n = 51). (3) At 1 min after reaching the finishing line, oxygen saturation levels had recovered to the value of 20 min after finishing the race, whereas the heart rate was still in the process of recovery (n = 18). (4) Maximum expiratory flow at 50% vital capacity measured 30 min after reaching the finishing line was significantly higher than at the starting point. The intensity of the load on the cardiac system produced by completion of this course was estimated to be almost the same as that of a full marathon on a flat course. The time depended on both the youth of the cyclist and on his ability to maintain a high value of %HRmax during the race.
Adolescent↗
Expression of intercellular adhesion molecule 1 (ICAM-1) on the cerebral artery following subarachnoid haemorrhage in rats.
In order to study how immune-inflammatory responses are involved in the pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH), the kinetics of expression of the intercellular adhesion molecule 1 (ICAM-1), a ligand for the leucocyte adhesion receptor, were studied on the cerebral arteries following SAH in rats. The SAH was induced by intracisternal injection of arterial blood. The rats were sacrificed at specified times: immediately after induction of SAH to seven days after SAH. Cryostat sections of the basilar artery (BA) were prepared and incubated with anti-rat ICAM-1 antibody. Morphometric analysis of the BA revealed a significant narrowing of the luminal diameter on Day 2 following SAH. While in the non-treated normal animals, no nor only weak expression of ICAM-1 was observed on the endothelial layer of the BA, there was greater expression of ICAM-1 on the endothelial layer of the BA in SAH rats, and the expression was observed also in the medial layer of the artery from Day 2 to Day 5 following SAH. The present results indicate that SAH really causes responses in the cellular immunity not only in the endothelial layer, but also in the medial layer of the artery as a target of immune damage, which is presumed to be one of the important steps in the development of cerebral vasospasm.
Animals↗
Pulse oximetry in an extensively burned patient.
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Bandages↗
Effects of Antidepressants and antipsychotics on the 5HT2 receptor-mediated signal transducing system in human platelets.
The IC50 values of the antidepressants amoxapine, mianserin, desipramine, clomipramine and imipramine, and the antipsychotics spiroperidol, chlorpromazine, levomepromazine and haloperidol for 3H-ketanserin binding, 5HT-induced intracellular Ca2+ increase, 5HT-induced shape change and 3H-paroxetine binding in human platelets were measured and the correlations of each parameter were examined. Results were as follows. Both the antidepressants and the antipsychotics had inhibitory effects on 3H-ketanserin binding, 5HT-induced intracellular Ca2+ increase and 5HT-induced shape change and there were significant positive correlations between the IC50 values of these three parameters. On the other hand, there were no significant correlations between the IC50 values in 3H-paroxetine binding and those in the other three parameters. These results suggest that 3H-ketanserin binding, 5HT-induced intracellular Ca2+ increase and 5HT-induced shape change are useful and reliable tools for the assessment of the effects of the antidepressants and the antipsychotics on the 5HT2 receptor-mediated signal transducing system in human platelets.
Adult↗
Effect of biotin on ammonia intoxication in rats and mice.
The effects of biotin on ammonia concentration in blood and brain were evaluated in hyperammonemic rats and mice. Rats were injected with 5 mmol/kg BW of ammonium acetate, and mice were injected with 10 mmol/kg BW. Increases in blood ammonia levels in rats 15-30 min after ammonia loading were prevented by treatment with 0.2 ml/100 g BW of biotin or 0.04 ml/100 g BW of arginine-glutamate with statistical significance. Blood ammonia levels after ammonia loading were lower, although not significantly, in the arginine glutamate-treated rats than in the biotin-treated animals. In mice also, increases in blood and brain ammonia levels after ammonia loading were prevented by the administration of biotin. The decrease in brain glutamate and aspartate after ammonia loading was lower and the brain glutamine level was higher in biotin-treated mice than in the controls. These findings indicate the protective effect of biotin against ammonia intoxication.
Acetates↗
Overseas transport of a patient with an extracorporeal left ventricular assist device.
An 18-year-old boy with end-stage cardiomyopathy who was undergoing support with an extracorporeal pneumatic left ventricular assist device was transported from Japan to the United States. During the 17-hour flight, the patient's condition was stable, and the pneumatic assist device worked well under low atmospheric pressure in the cabin. Subsequently, he had a successful heart transplantation after 119 days of left ventricular assist device support.
Adolescent↗
Experimental assessment of newly devised transcatheter stent-graft for aortic dissection.
Despite recent advances, surgical results for Stanford type B dissection are not yet satisfactory because the procedure is so highly invasive. The aim of this study was to devise a new intraaortic (IA) graft that would offer less invasive treatment for type B dissection. To close the entry of type B dissections using transcatheter placement, we devised an IA graft (inner diameter, 15-20 mm; length, 40 to 60 mm) in which a self-expandable stent was covered with a thin, open-cell-structured polyurethane jacket. In acute animal experiments in which type B aortic dissections were prepared in 4 mongrel dogs, IA grafts were implanted to close the entry using a transfemoral catheter sheath, and closure of all the entries was confirmed by aortography. In chronic experiments, five IA grafts for normal descending aortas and one IA graft for an experimentally dissected aorta were implanted to observe histologic biocompatibility for up to 8 months. Histopathologic examination conducted at the projected sacrifice periods revealed that endothelialization of the luminal surface of the IA graft had begun as early as 1 month after implantation and was completed within 4 months. The prototype device that we developed may be promising as an effective, minimally invasive therapeutic intervention for closure of the entry site of type B dissection.
Aortic Dissection↗
Influences of beta-blocking agents on cardiovascular actions induced by endothelin-3 administered intracerebroventricularly in anesthetized rats.
Possible involvement that the pressor and positive chronotropic effects of endothelin-3 (ET-3) administered intracerebroventricularly (i.c.v.) participate in the central beta-adrenoceptor has been studied in urethane anesthetized rats. ET-3 administered i.c.v. at dose of 50 pmol elicited the increase in blood pressure and heart rate over a long duration, but a dose of 30 pmol had a minimal effect. These cardiovascular responses to ET-3 were significantly reduced by intravenous pretreatment with pentolinium, ganglionic blocking agent, and phentolamine, alpha-blocker. Also pressor responses to ET-3 were abolished dose-dependently by i.c.v. pretreatment with propranolol at a dose of 1 mumol, nonselective beta-blocker and ICI 118551, beta 2-selective adrenoceptor blocker, but not by i.c.v. pretreatment with metoprolol, atenolol, beta 1-selective blocker, procaine and phentolamine. These results suggest that ET-3 may play a role in cardiovascular regulation through the activation of the sympathetic nervous system involved in the central beta 2-adrenoceptor system.
Adrenergic beta-Antagonists↗
Intrathecal prostaglandin E1 produces a long-lasting allodynic state.
The existence of prostaglandin (PG) receptors in the spinal cord has been demonstrated, but their role in sensory processing is not yet well defined. PGE1 is widely used clinically as a vasodilator. The present study was designed to investigate the effects of intrathecally administered PGE1 on the transmission of different types to sensory information, including that associated with noxious somatic, noxious visceral, and non-noxious somatic stimulation. The tail-flick (TF) test was employed to measure responses to noxious somatic stimuli, and the colorectal distension test was used to examine responses to noxious visceral stimuli. Withdrawal response to mechanical pressure produced by Semmes-Weinstein mono-filaments (SWMs) was measured as an assessment of sensitivity to non-noxious mechanical somatic stimulation. TF latencies and colorectal distension thresholds decreased for a short time (10-20 min) following the intrathecal (i.t.) administration of both 100 ng or 500 ng of PGE1. In sharp contrast to these short duration effects, there was a long-lasting increase in agitation scores (allodynia) produced by 3 different intensities of SWMs (0.217, 0.745 and 2.35 g) after administration of PGE1. The changes in agitation scores to SWMs were dependent on the dose of PGE1 and the intensity of stimulation. This increase of agitation score was seen when PGE1 was administered through the i.t. catheter or by direct i.t. puncture and the increase lasted for at least 2 days after drug administration. Intrathecal administration of saline, however, did not produce any changes in TF latencies, colorectal distension thresholds, or agitation scores produced by SWMs. No significant histological difference was seen between spinal cords exposed to 500 ng PGE1 and saline 48 h after drug administration. These results demonstrate that PGE1 may trigger a hypersensitive (allodynic and/or hyperalgesic) state in sensory processing pathways at the spinal level. They also indicate that long-lasting changes in processing of non-noxious, but not noxious, information produced by PGE1 continues after the disappearance of the direct action of PGE1.
Akathisia, Drug-Induced↗
The localization of DMPO spin adducts of OH in endothelial cells exposed to hydrogen peroxide.
Examination by electron spin resonance (ESR) spectroscopy revealed the localization of 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) spin adducts of hydroxyl radicals (.OH) produced by bovine endothelial cells exposed to hydrogen peroxide. Addition of 10 mM chromium oxalate, a line-broadening agent, to the reaction mixture virtually abolished the signal of DMPO-OH spin adducts. Moreover, the spin adducts were recovered in the filtrated fraction of the cell suspension. We, therefore, concluded that the location of DMPO-OH due to .OH radicals produced by endothelial cells was extracellular. Contrastingly, the site of formation of DMPO-OH was confirmed to be intracellular by the effect of Desferal, an iron chelator, and the effect of poly(ethylene glycol), an extracellular scavenger of OH radicals, as previously reported. The DMPO-OH adducts in the cell suspension mixture were degraded by a cyanide sensitive pathway and they were apparently more unstable than in the extracellular fraction. The initial amount of DMPO-OH adducts formed in endothelial cells could potentially be monitored by the DMPO-OH signals in the extracellular reaction mixture better than those in the cell suspension mixture.
Animals↗
Acute hemodynamic effects of intravenous bolus injection of ionic and nonionic magnetic resonance contrast media.
RATIONALE AND OBJECTIVES: With the development of fast magnetic resonance (MR) imaging, bolus injection of contrast media is often required. We evaluated the acute hemodynamic effects of intravenous (i.v.) bolus injection of two MR contrast media: ionic gadopentetate dimeglumine and nonionic gadoteridol. METHODS: Twenty normal rats were anesthetized, and the left ventricular pressure (LVP), right atrial pressure (RAP), peripheral arterial pressure (PAP), positive rate pressure development (dP/dt) of the left ventricle, and heart rate were continuously monitored up to 10 min after bolus injections of 0.1, 0.3, and 0.5 mmol/kg of either media. RESULTS: Bolus injections of gadopentetate dimeglumine induced temporal reduction of the blood pressure (the peak LVP was -25.0% at 0.5 mmol/kg and -13.2% at 0.3 mmol/kg). At the injected doses of 0.5 and 0.3 mmol/kg, the systolic PAP, mean PAP, and dP/dt were reduced. The lowest peak systolic LVP was observed at around 20 sec after injection. Those suppressed values returned to the control values within 120 sec. Injection of high doses of gadoteridol caused a temporal increase in the peak systolic LVP (9.2% at 0.5 mmol/kg and 7.4% at 0.3 mmol/kg), systolic PAP, and dP/dt. Approximately 15 sec after injection, the highest peak systolic LVP was observed, and within 30 sec the value normalized. With both ionic and nonionic contrast media, a dose of 0.1 mmol/kg did not cause significant changes in hemodynamics. CONCLUSION: In normal rats, bolus i.v. injection of high-dose gadopentetate dimeglumine has negative hemodynamic effects; gadoteridol produces mild positive effects.
Analysis of Variance↗