[Statistical observation on bone tumors at the department of orthopedics, Kanazawa University].
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Biomedical subjects
Publications and source records attributed to N Takeda.
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Changes in myocardial contractility and ventricular myosin isoenzymes were examined during pressure-overloaded cardiac hypertrophy in rats. Effects of regression of cardiac hypertrophy were also examined. Cardiac hypertrophy was induced by abdominal aortic constriction in 7-week-old male Wistar rats. Regression of cardiac hypertrophy was obtained by opening the aortic band. Myocardial contractility was estimated by measuring isometrically developed tension and maximum rate of tension rise (+dT/dtmax) in isolated left-ventricular papillary muscles perfused with Tyrode solution (32 degrees C, pH 7.4, bubbled with 95% O2.5% CO2, stimulation frequency: 0.2 Hz). Left-ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis and the isoenzyme pattern was determined by densitometry. Isometrically developed tension (T) in hypertrophic myocardium remained unchanged, but +/-dT/dtmax decreased as compared with hearts of normal rats. Decreased +/-dT/dtmax recovered near to the level in normal rats by regression of cardiac hypertrophy. Left-ventricular myosin isoenzyme pattern shifted towards VM-3 in hypertrophied myocardium and shifted again toward VM-1 by regression of cardiac hypertrophy. In conclusion, myocardial contractility and ventricular myosin isoenzymes were changed in pressure-overloaded hypertrophy in rats and these changes were reversible to a normal level by regression of cardiac hypertrophy.
Effects of endurance swimming training on myocardial contractility and left ventricular myosin isoenzymes were examined in diabetic rats. A diabetic condition was induced in 15-week-old male Wistar rats, by intravenous injection of streptozotocin (50 mg/kg). Swimming training was carried out for five to six weeks (90 min/day, 6 days/week). In order to estimate myocardial contractility, the isometric developed tension of the isolated left ventricular papillary muscle was measured. Myosin isoenzymes were obtained by pyrophosphate gel electrophoresis. Fasting blood glucose of the trained group was significantly lower than that of the sedentary group (sedentary vs. trained = 409.6 +/- 25.9 vs. 266.3 +/- 20.5 mg/dl, p less than 0.001). There was no significant difference in isometric developed tension (T) between the two groups, and the dT/dtmax of the trained group showed a tendency to increase (sedentary vs. trained, T: 2.8 +/- 0.8 vs. 2.9 +/- 0.8 g/mm2, dT/dtmax: 23.1 +/- 3.6 vs. 26.2 +/- 3.5 g/mm2.s, p less than 0.1). Myocardial mechanical responses to isoproterenol and dibutyryl cAMP were increased in the trained group. Left ventricular myosin isoenzyme pattern was shifted towards VM-1 by endurance swimming (sedentary vs. trained, VM-1: 5.6 +/- 4.5 vs. 19.6 +/- 8.8%, p less than 0.001, VM-3: 75.1 +/- 10.0 vs. 54.9 +/- 14.7%, p less than 0.001). These results indicate that endurance swimming can improve disordered glucose metabolism and also influence myocardial contractility, myocardial catecholamine responsiveness, and energetics in myocardial contraction.
An investigation was carried out on the effects of 4 weeks' swimming training (2 X 90 min/day) on myocardial isometric tension development and rate of tension rise, and also on the changes induced therein by in vitro application of isoproterenol. This was done in 9 isolated papillary muscles of 9-week-old male Wistar rats and the results were compared with the data of age-matched sedentary controls. Ventricular beta-adrenoceptors [( 3H]-dihydroalprenolol binding) and the isoenzyme pattern of myosin (pyrophosphate gel electrophoresis) were examined in the same individuals. Isometric tension (T) and its first derivative (dT/dt) measured at the optimum of the length-tension diagram were moderately increased by long-term swimming training. Isoproterenol (10(-5) mol/l) induced a greater absolute and relative increase of both mechanical parameters in specimens of trained animals than in age-matched controls (delta T: 3.6 +/- 1.6 vs. 1.9 +/- 0.6 X 10(-2) N/mm2, p less than 0.05. delta dT/dt: 43.4 +/- 14.0 vs. 30.4 +/- 9.5 X 10(-2) N/mm2 X s, p less than 0.05). KD decreased significantly (4.23 +/- 1.0 vs. 2.44 +/- 0.3 nM, p less than 0.02), indicating an increase in receptor affinity, whereas receptor density revealed a tendency to decrease (98.8 +/- 22.6 vs. 67.1 +/- 18.0 fmol/mg protein, p less than 0.1). In addition, there was a shift in the isoenzyme pattern of myosin towards VM-1 after swimming training. Thus, under the conditions of the present experiments, the mechanical response to isoproterenol does not correlate to beta-adrenoceptor density. It is probable that, apart from the altered sensitivity of the receptors, other membrane or post-membrane processes, are responsible for the increased mechanical responsiveness to catecholamines. Although a relationship between myosin isoenzyme pattern and mechanical responsiveness to catecholamines is apparent taking into account our results and the findings on hypertensive rats as reported in the literature, it cannot be accounted for simply by altered beta-adrenoceptor density.
Pressure-overloaded cardiac hypertrophy was induced by abdominal aortic constriction in 10-week-old male Wistar rats. 24-26 weeks after aortic constriction, the hearts were excised and a myocardial mechanical study was performed using isolated left ventricular papillary muscles. There was no significant difference in isometric developed tension (T) between sham-operated control and aortic constriction (AC) rats (control vs AC rats = 2.9 +/- 0.6 vs 2.7 +/- 0.7 g/mm2). dT/dtmax of AC rats, on the other hand, was significantly lower than that of controls (controls vs AC rats = 32.8 +/- 7.5 vs 26.3 +/- 6.1 g/mm2s, p less than 0.05). Myocardial mechanical responses to isoproterenol (10(-7) mol/l) were depressed in the group with aortic constriction compared with the control group (delta T: 18.5 +/- 6.7 vs 12.1 +/- 4.9%, p less than 0.05, delta dT/dt: 25.2 +/- 6.2 vs 17.5 +/- 5.8%, p less than 0.02). Responses of the parameters to dibutyryl cyclic AMP (10(-5) mol/l) were also smaller in the AC group than in the control group (delta T: 18.0 +/- 5.6 vs 13.3 +/- 4.0%, p less than 0.05, delta dT/dt: 20.4 +/- 6.9 vs 14.7 +/- 4.1%, p less than 0.05). Left ventricular myosin isoenzyme pattern, revealed by pyrophosphate gel electrophoresis, shifted towards VM-3 under pressure overload. The present study demonstrates that post-membrane processes may be mainly responsible for the decreased myocardial mechanical catecholamine responsiveness in pressure-overloaded cardiac hypertrophy.
The extent to which conclusions about myocardial performance may be drawn from end-systolic pressure-volume relations was investigated. Left ventricular isovolumetric and end-systolic pressure-volume relationships were measured in the rat, under acute impairment of contractility (hexobarbital), at chronic pressure overload (spontaneously hypertensive rats), and at chronic volume overload (aorto-caval shunt). Our results confirm the classic conception of Otto Frank where the curves of the isovolumetric maxima and the curves of the end-systolic pressure-volume relations follow separate courses. Acute alterations in contractility can be detected from shifts in the end-systolic pressure-volume relations. In chronic pressure or volume overloaded hearts the end-systolic pressure-volume relations do not render conclusions about ventricular or myocardial performance since in chronically altered hearts, the course of the end-systolic pressure-volume relations is primarily influenced by geometric factors.
Alterations of myocardial mechanical catecholamine responsiveness by swimming training (2 X 90 min/day, 4 weeks) were examined in 13-week-old spontaneously hypertensive males rats (SHR). The relationships between myocardial mechanical catecholamine responsiveness and ventricular beta-adrenoceptors as well as myosin isoenzyme pattern were also examined. Compared with sedentary controls, trained rats showed a greater responsiveness to isoproterenol (10(-6) mol/l) on isometric tension (T) and its first derivative (dT/dt) (delta T: 0.45 +/- 0.55 vs. -0.15 +/- 0.11 10(-2) N/mm2, p less than 0.01, delta dT/dt: 17.1 +/- 10.1 vs. 8.3 +/- 3.6 10(-2) N/mm2 X s, p less than 0.05). In sedentary SHR, dT/dtmax increased significantly, whereas developed tension decreased slightly, coupled with a decrease of time to peak tension by high dose (10(-6) mol/l) isoproterenol. Therefore, it can be stated that dT/dt is a better indicator for catecholamine sensitivity than isometric tension. beta-adrenoceptor density [( 3H]-dihydroalprenolol binding) decreased significantly in trained rats (68.7 +/- 7.62 vs. 102.4 +/- 4.37 fmol/mg protein, p less than 0.01) with no significant difference in KD values (4.61 +/- 2.26 vs. 6.11 +/- 1.94 nM, ns). In addition, myosin isoenzyme pattern revealed by pyrophosphate gel electrophoresis shifted towards VM-1 after swimming training. The increased catecholamine sensitivity of fast contracting myocardium is, in principle, compatible with the assumption of cAMP-dependent regulation of myofibrillar ATPase activity (21) or cross bridge kinetics (9), although other postreceptor processes should also be taken into consideration for the increased catecholamine sensitivity.
Three kinds of neurotransmitters (histamine, acetylcholine, and catecholamine) are thought to be important in the neural processes of motion sickness because antihistaminics, scopolamine, and amphetamine are effective in preventing motion sickness. In this study, we examined the neurochemical and neuropharmacologic features of motion sickness in rats. Based on our results, we propose the following hypotheses for the neurochemical mechanisms of motion sickness: (1) the histaminergic neuron system is involved in the signs and symptoms of motion sickness, including vomiting; (2) the acetylcholinergic neuron system is involved in the processes of habituation to motion sickness, including neural store mechanisms; and (3) the catecholaminergic neuron system in the brain stem is not related to the development of motion sickness.
In addition to angular acceleration, eccentric rotation (ECR) imparts linear acceleration to the head positioned eccentric to the axis of rotation. Using ECR in squirrel monkeys, the effects of otolith organ stimulation by linear acceleration on vestibulo-ocular reflex (VOR) gain were investigated. With the animal's head facing away from the rotation axis, ECR significantly enhanced VOR gain over that seen in centric rotation (CR) at 1.0 Hz, but not at 0.5 Hz. However, no enhancement of VOR gain at 1.0 Hz was observed in eccentriclateral rotation when the animal faced tangentially. After bilateral ablation of the otolith organs (sacculectomy and utricular neurectomy), the ECR did not increase VOR gain, even at 1.0 Hz. In animals in which the lateral and posterior semicircular canals were plugged bilaterally, horizontal sinusoidal eye movements were induced by ECR at 1.0 Hz; no clear compensatory eye movement occurred during CR at 1.0 Hz. These findings demonstrate that during ECR, tangential acceleration along the interaural axis stimulates the utricular maculae, inducing horizontal eye movements in addition to those induced by the semicircular canal, thus resulting in an enhancement of VOR gain. Our results also suggest synergistic interactions of the otolith organs and semicircular canals. We conclude that ECR is a useful clinical test of the function of the otolith organs.
PURPOSE: This study seeks to evaluate the comparative role of alpha-fluoromethylhistidine and diphenhydramine in the prevention of motion sickness. METHOD: The role of histaminergic mechanisms in motion sickness were evaluated in a feline model. Twenty-six female cats were studied. A variety of doses of fluoromethylhistidine and diphenhydramine were administered before motion testing. RESULTS: Fluoromethylhistidine was effective in preventing motion sickness. The efficacy was dose dependent. In contrast, diphenhydramine failed to prevent motion sickness in any of the tested doses. CONCLUSIONS: The failure of diphenhydramine to prevent motion sickness was unexpected. This may reflect the route of administration or the animal model studied. Depletion of histamine with fluoromethylhistidine prevented motion sickness in cats. Our results suggest that this drug may provide a very long duration of protection in cats.
An epidemic of acute haemorrhagic conjunctivitis (AHC) caused by coxsackievirus A24 variant (CA24v) was reported in Accra, Ghana in May 1987. We studied 7 of the viral strains collected from May to November, 1987, by RNA genome fingerprinting. Pairwise comparisons of the oligonucleotide maps showed that genetic similarity among them ranged from between 60.0 to 84.7%. Using base sequence variations deduced from genetic similarity among the isolates, isolation time of the strains and the rate of nucleotide substitution (estimated in a previous paper, Miyamura et al., 1990), we calculated divergence times and constructed a phylogenetic tree. This tree indicated that all the 7 strains had diverged from each other from 11 to 26 months before the AHC epidemic in Accra. CA24v may have been introduced into the country or the neighbouring area, at least, more than two years earlier, i.e. in the early half of 1985.
In this study, PCDDs/DFs and co-planar PCBs concentrations in flue gases from 17 crematories and in fly ashes and bottom ashes (mainly bone) from several crematories were measured to grasp the present state of PCDDs/DFs emissions from crematories. The effects of several factors were discussed to prevent PCDDs/DFs emissions from crematories. Total concentration (normalized by 12% O2) of PCDDs/DFs was ranged from 4.9 to 1200 ng/m3 N, and toxic equivalent concentration was ranged from 0.064 to 24 ng TEQ/m3 N. As the results obtained in this research, the following measures to reduce PCDDs/DFs emission are recommended for existing crematories: (1) keeping the temperature at 800 degrees C in main/secondary chambers during a whole cremation, and (2) lowering the temperature in the dust collector. For newly installed crematories, following measures to prevent PCDDs/DFs emission including the measures for existing ones are recommended: (1) connecting one secondary chamber to one main chamber, (2) installing the high efficiency dust collector and reducing dust concentration to less than 0.01 g/m3 N, and (3) installing the sampling point for monitoring of PCDDs/DFs.
Simplified thermal formation experiments have been conducted using dioxin-free fly ash as a catalyst with many kinds of combustible samples such as newspaper, kerosene, paraffin, PE (polyethylene), PP (polypropylene) and PVC. Chlorine sources were PVC, NaCl and HCl. The combustion of samples containing chlorine in the absence of dioxin-free fly ash produced dioxins at a low level although HCl was present in the gas stream. On the other hand, the combustion of samples without chlorine with dioxin-free fly ash increased dioxins formation to a level around 10 times higher than that upon heating dioxin-free fly ash alone. This result is considered to be due to the presence of metal chloride in the fly ash and hydrocarbons in the gas stream. The combustion of samples containing either an organic or inorganic chlorine source or using a HCl stream with dioxin-free fly ash increased dioxin level dramatically.
Non-receptor-type tyrosine kinases of the Src family, such as Src, Yes and Fyn, are strongly expressed in the brain and have been suggested to have an important function in the central nervous system. We generated Fyn-deficient mice by inserting the beta-galactosidase gene (lacZ) into the fyn gene. The homozygous Fyn-mutant neonates from homozygous Fyn-deficient parents died because of a suckling problem. Neonates were, however, able to suckle milk normally when the homozygous mother's mammary glands had been activated by suckling of a heterozygous or wild-type pup. In these homozygous pups, the modified glomerular complex of the olfactory bulb, which had been suggested to play a role in perceiving pheromones, was abnormal in shape and reduced in size, and the hippocampal cell-layer was undulated. These results suggest that Fyn may be involved in the initial step of instinctive suckling behaviour in neonates.
The vitrification technique was applied to the preservation of human skin. This technique was simple, and no expensive equipment was needed. Split-thickness human skins from 8 patients were immersed in vitrification solution for 10 minutes at room temperature, immediately plunged into a liquid nitrogen tank, and cryopreserved for 3 weeks. The vitrification solution consisted of 40% ethylene glycol (vol/vol) and phosphate buffered saline solution that contained 30% Ficoll 70 (vol/vol; Wako Junyaku, Co, Tokyo, Japan) and 0.5 mol/L sucrose. The viability of vitrified and cryopreserved skin was evaluated with the trypan blue dye exclusion test, the methyl-thiazoldiphenyl-tetrazolium (MTT) colorimetric assay, and a culture test of the keratinocytes obtained from vitrified skin. The results of the trypan blue dye exclusion test showed 87.4% of viable cells, and MTT developed an average 0.817 absorbance. When vitrified skin was compared with 4 degrees C refrigerated skins after 3 weeks of storage, the difference of viability was significant both on the trypan blue dye exclusion test (P < .05) and on the MTT assay (P < .01). However, there was no significant difference in the viability of vitrified skins compared with fresh skin. Furthermore, keratinocytes from vitrified skin grew uneventfully in culture test. We used these vitrified skin allografts for patients with flame burns and electric burns. These allografts took well in both cases and promoted wound healing. We concluded that the vitrification method for skin preservation is simple and reliable, and this method could contribute to skin banking.
Cardiac dysfunction in animals with congestive heart failure due to myocardial infarction (MI) is known to be associated with a wide variety of defects in receptor and post-receptor mechanisms. Since the heart function have been shown to be improved by treatment with different angiotensin converting enzyme (ACE) inhibitors, we examined the effects of imidapril, an ACE inhibitor, on changes in post-receptor mechanisms involving adenylyl cyclase (AC) and G proteins in the failing heart. Heart failure in rats was induced by occluding the coronary artery and 3 weeks later the animals were treated daily with 1 mg/kg (orally) imidapril for 5 weeks. The animals were assessed for their left ventricular function and crude membranes were isolated from the viable left ventricle and examined for AC activities as well as G-protein activities and expression. Animals with heart failure exhibited depressions in ventricular function and AC activities in the absence or presence of forskolin, NaF and Gpp(NH)p. The AC activity in the presence of pertussis toxin was increased whereas that in the presence of cholera toxin was decreased in the failing heart. Protein contents and mRNA levels for G(i)-proteins were increased whereas those for G(s)-proteins were unaltered in the infarcted heart. All these changes due to MI were prevented by imidapril treatment. The results indicate that the depressed cardiac function in the failing heart may partly be due to the direct effects of changes in AC and G(i) proteins.
Eleven patients with high-grade osteosarcoma of an extremity were treated with neoadjuvant chemotherapy with NSH-7 protocol. NSH-7 is a refinement of the T-12 Rosen protocol. Preoperative chemotherapy is initiated with a doxorubicin (ADM) and high-dose methotrexate combination. If the primary tumor progresses after the first cycle, the preoperative chemotherapy is switched to a combination of cisplatin and ADM. Postoperative adjuvant chemotherapy was selected based on histological response of the primary tumor. In addition, recombinant human granulocyte colony-stimulating factor was used to prevent leukocytopenia and to increase the dose intensity of the chemotherapy. In 1 patient, preoperative chemotherapy was switched to salvage treatment. Of the 156 courses given, there were 10 delays and 4 dose reductions. Leukocytopenia accounted for only 1 delay. All 11 patients completed the chemotherapy and 5 patients were fully able to tolerate the protocol without delay or dose reduction. Nine patients remained alive and continuously free of disease at an average follow-up of 35 months. The rate of continuous disease-free survival at 3 years was 81%, which was significantly better than that of the T-12 study of our group. These observations suggest that the NSH-7 protocol is a safe and effective treatment regimen for osteosarcoma.