Tissue distribution of heavy metals and their variations with age, sex, and habitat in Japanese serows (Capricornis crispus).
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to K Honda.
Explore the source record for details and available documents.
To clarify the origin of dystocia in bilaterally pelvic neurectomized (BPN) rats, the uterine activity during the periparturient period, and reflex straining movements in response to vaginal stimulation and cervical extensibility were monitored. The BPN rat displayed "stretching" movements and the regular continuous uterine activity with a similar onset and intensity to that in control rats (intact, sham-operated or unilateral pelvic neurectomized rats) on days 22 or 23 of gestation, but lacked the "straining" movements which precede each delivery of pups in controls so that parturition was prolonged. Dissection of rats revealed that an unborn fetus was retained in the expanded upper portion of the vaginal cavity. Vaginal distension induced contraction of the abdominal muscles and diaphragm and an inhibition of respiratory movements, resulting in an increase in intraabdominal pressure in urethane-anesthetized control rats. This reflex muscular contraction which reflects the straining movements in normal delivery may be called the fetus-expulsion reflex and does not occur in BPN rats. It differs from the fetus-ejection reflex (Ferguson reflex) which initiates oxytocin release. There was no difference in weight and distensibility of the uterine cervix between sham-operated and operated rats on day 22 of pregnancy. The results suggest that the main abnormality of delivery in BPN rats, a prolongation of the process of delivery, may be due to a lack of the fetus-expulsion reflex which plays a physiologic role in removing a fetus from the upper vaginal cavity against the resistance of the pelvic outlet.
A 10-h nocturnal intracerebroventricular infusion of 2 or 3 sleep substances such as 2.5 nmol delta-sleep-inducing peptide (DSIP), 2.0 nmol muramyl dipeptide (MDP) and 10 pmol uridine resulted in a significant, combination-dependent change in sleep-waking dynamics, which was quite different from the time-course sleep promotion induced by the single administration of each substance. The DSIP-MDP combination was characterized by a profound increase in SWS only at the middle infusion period. PS was little affected. The DSIP-uridine combination exerted a slight increase in SWS at the late infusion period with little change in PS parameters. The MDP-uridine combination caused a marked increase in both SWS and PS only at the early to middle infusion period. The DSIP-MDP-uridine combination induced an extremely large increase in SWS at the early to middle phase of the infusion period. PS significantly increased only at the early phase. These results may suggest that the sleep substances acted in tandem, either synergistically or antagonistically, on the sleep regulatory mechanism.
Rett syndrome is a distinct clinical entity with an unknown cause. In previous publications we stressed the age related sequential appearance of pathognomonic symptoms of Rett syndrome and suggested the early central monoaminergic deficiency disorder as the pathophysiology. In this report we present a series of cinefilms made of one patient at different ages which clearly show the age dependent changes of motor disturbances. Furthermore, the record of sleep-wakefulness rhythm and the series of polysomnography of another patient who was on L-DOPS are presented. The results of sleep studies again confirm the early involvement of the noradrenergic and serotonergic systems and relatively early development of postsynaptic supersensitivity of the dopaminergic system. The possibility of the involvement of the cholinergic system is also suggested. The summary of the sensory evoked potentials (SEP) performed on six patients is also presented and the pathomechanism of cortical involvement is discussed. Based on these new and past findings, we confirm our speculation on the pathophysiology. The basic mechanism is probably the deficient states of the monoaminergic systems occurring at a very early developmental stage. These derangements occurring at an early stage cause serious abnormality in the higher centers during development. The striking age dependent clinical manifestations and measurable physiological parameters are the reflexion of the underlying patho-physiology of Rett syndrome.
1. The effects of the intrahippocampal injection of ethylcholine mustard aziridinium ion (AF64A) on the following cholinergic markers were examined. 2. Bilateral injection of 10 nmol of AF64A into the dorsal hippocampus caused a loss of choline acetyltransferase (CAT) activity in the dorsal hippocampus, ventral hippocampus, cortex and striatum. 3. This treatment caused significant decreases in ACh contents in the dorsal hippocampus, ventral hippocampus and cortex, but not in the striatum. 4. The step-down latencies during the test trials of both 10 and 50 nmol AF64A-treated groups were significantly shorter than those of vehicle-treated groups. 5. None of the control animals stepped down to the large box where they had previously received a foot shock, but 40% of the 10 nmol and 60% of the 50 nmol AF64A-treated animals stepped down to the large box within 600 s. 6. These results indicate that AF64A treatment produces biochemical and functional deficits in the cholinergic neurons in the CNS.
The selectivity and specificity for alpha 1-adrenoceptor blocking activity of the optical isomers of YM-12617 have been examined in pithed, spontaneously hypertensive rats. R(-)-YM-12617 and prazosin (1 mg kg-1 p.o.) produced 360- and 88-fold rightward shifts, respectively, of the dose-response curve of control to phenylephrine, whereas S(+)-YM-12617 (1 mg kg-1 p.o.) failed to cause a shift. Based on dose ratio, R(-)-YM-12617 was 320 times more potent as an alpha 1-adrenoceptor antagonist than S(+)-YM-12617. This potency ratio corresponded to that formed in an in-vitro study. Both R(-)- and S(+)-YM-12617 hardly affected the UK-14304, angiotensin II, vasopressin and isoprenaline dose-response curves. These results suggest that R(-)-YM-12617 exerted selective alpha 1-adrenoceptor blocking activity and its activity was specific for alpha 1-adrenoceptors.
Extracellular action potentials of paraventricular neurosecretory cells were obtained from urethan-anesthetized rats during microinjection of a hyper- or hypotonic solution into the anteroventral third ventricle (AV3V), third ventricle, or the vicinity of the recording site. The injection of a 0.2-microliter NaCl solution with a concentration range from 0.16 to 0.8 M into the AV3V excited most of the neurons tested. However, the magnitude of the response was dose related. In most cases, arterial blood pressure recorded simultaneously with the excitatory response of the neuron did not change after the injection. Distilled water (0.2 microliter) was injected into the AV3V after the intraperitoneal injection of a 1.5 M NaCl solution (1 ml), which decreased the firing rate in 67% of the neurons tested. The small volume (0.2 microliter) of hypertonic saline, which was effective when injected into the AV3V, excited none of the neurons tested when injected into the third ventricle or the vicinity of the recording site. These results strongly suggest that the AV3V is sensitive to the osmotic stimulus within a physiological range and that the region plays an important role as an osmoreceptor site for the osmoregulation of paraventricular neurosecretory cells.
Prolonged stimulation of tissues by adrenergic agonists may lead to diminished responsiveness of the tissues to subsequent activation by catecholamines; this phenomenon has been termed desensitization or tachyphylaxis. We have examined the in vivo consequences of prolonged stimulation of vascular alpha-adrenergic receptors in rats harboring pheochromocytoma, a tumor that secretes catecholamines. In both early (3-4 weeks after implantation) and late (6-7 weeks after implantation) stages of tumor development, New England Deaconess Hospital rats with transplanted pheochromocytomas developed hypertension and tachycardia and had plasma dopamine and norepinephrine concentrations markedly greater than controls. In both these stages of pheochromocytoma, pressor responses to several vasoconstrictors were examined after pithing. Rats with the tumor were found to become progressively subsensitive to alpha-adrenergic agonists. In the early phase of pheochromocytoma, loss in sensitivity was found for both alpha 1- and alpha 2-adrenergic agonists, whereas responsiveness to the nonadrenergic vasoconstrictors Arg-vasopressin and angiotensin-II was intact (homologous desensitization). However, in the later stage of pheochromocytoma, pressor responses to all these vasoconstrictive agents and also to stimulation of the complex sympathetic outflow were found to be subsensitive (heterologous desensitization). In plasma membranes prepared from mesenteric arteries of early stage tumor-bearing rats, [3H]prazosin binding sites were significantly decreased to 150 +/- 12 fmol/mg vs. 234 +/- 19 fmol/mg in controls. [3H]Yohimbine binding sites were not significantly altered. Our results show that both postjunctional alpha 1- and alpha 2-adrenergic receptor-mediated vasopressor responses can be specifically attenuated in the presence of chronically elevated endogenous catecholamine levels produced by pheochromocytoma and that each alpha-receptor subtype may be differently regulated in the development of desensitization.
In the isolated detrusor smooth muscle of the rabbit urinary bladder, acetylcholine, prostaglandin (PG) F2 alpha, histamine and methoxamine produced dose-dependent contractions. The order of efficacy was acetylcholine greater than PGF2 alpha greater than histamine greater than methoxamine. Acetylcholine and oxotremorine increased tension remarkably in the rabbit detrusor muscle; and McN-A-343 also developed tension, but with weaker sensitivity and efficacy. The contractile response to acetylcholine was competitively antagonized by atropine (pA2 9.24) and pirenzepine (pA2 6.96), respectively. Histamine and 2-pyridylethylamine caused dose-dependent contractions. On the other hand, dimaprit caused no response in this tissue. Mepyramine (pA2 8.80) competitively antagonized the contraction induced by histamine, whereas cimetidine failed to antagonize the contraction even at a high concentration of 10(-5) M. Norepinephrine, phenylephrine and methoxamine have greater efficacies in the ability to contract than clonidine. R(-)- and S(+)-YM-12617 and YM-12617 (pA2 10.4, 8.31 and 9.75, respectively) and prazosin (pA2 8.13), phentolamine (pA2 7.55) and yohimbine (pA2 6.44) competitively antagonized the contraction elicited by methoxamine. These results suggest that the contraction of rabbit detrusor muscle can be mediated by alpha 1-adrenergic receptors as well as M2-muscarinic and H1-histaminergic receptors and suggest that the contractile force mediated by alpha 1-adrenergic receptor agonist is smaller than those stimulated by the other receptor agonists.
A case of lymphangiomyomatosis with marked chylous ascites and persistently elevated CA-125 levels is presented. A 30-year-old woman revealed milky urine, milky ascites and exertional dyspnea about one year after the normal delivery of her second child. The lungs showed bilateral diffuse reticular shadows. No pleural effusion was observed. Pulmonary function tests revealed hypoxemia and obstructive changes of the respiratory tract. The levels of CA-125 in blood and ascites were continuously more than 200 U/ml. The inguinal lymph node biopsy and open lung biopsy confirmed the diagnosis of lymphangiomyomatosis. The patient was first treated with progesterone without effect. Oophorectomy was then performed, resulting in the improvement of respiratory distress, although ascites continued. With addition of Le Veen's peritoneojugular shunt the patient improved with reduction of ascites.
Explore the source record for details and available documents.
Isolated strips of the human tracheal muscle had slow fluctuations of membrane potential (slow wave), essentially similar to those of guinea-pig trachea. The average amplitude and frequency of slow wave were 7.7 mV and 19.9/min (n = 9), respectively. There was clear correlation between the electrical activity and mechanical response during the excitation caused by tetraethylammonium (TEA), carbachol, and noradrenaline and also during the inhibition by isoprenaline. The slow wave seems to be related to the basal muscle tone, which is probably maintained by endogenous leukotrienes in human and by prostaglandins in guinea-pig.
Alpha-1 adrenoceptors in hypertrophied prostates of humans were characterized by a binding assay using [3H]prazosin as a radioligand. Specific [3H]prazosin binding in hypertrophied prostates of humans was saturable and of high affinity (Kd = 0.6 nM) with a maximal number of binding sites of 106 fmol/mg of protein, and it showed a pharmacological specificity as well as stereo-selectivity which characterized alpha-1 adrenoceptors. Adrenergic antagonists competed for the binding in order: R-(-)-YM-12617(5-[2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide HCl) greater than (+/-)-YM-12617 = prazosin greater than phentolamine greater than S-(+)-YM-12617 greater than idazoxan. R-(-)- and (+/-)-YM-12617, alpha-1 adrenoceptor antagonists, have been shown to exhibit an extremely high affinity for prostatic [3H]prazosin binding sites (Ki = 0.6 and 1.1 nM, respectively). In addition, R-(-)-YM-12617 was approximately 100 times as potent as the S-(+)-isomer. The affinities of prazosin and YM-12617 compounds for [3H]prazosin binding sites in hypertrophied prostates of humans correlated closely with their pharmacological potencies in prostates reported previously. The blockade of [3H]prazosin binding sites in hypertrophied prostates of humans induced by (+/-)-YM-12617 was easily reversed by washing. There was a significant 35% increase in the maximal number of binding sites for [3H] prazosin binding in hypertrophied prostates from benign prostatic hypertrophy compared to normal tissues, whereas the hypertrophy had little effect on the Kd value.(ABSTRACT TRUNCATED AT 250 WORDS)
A total of 452 cases of childhood malignant solid tumors were treated over the last twenty years at the National Children's Hospital. These included 175 cases of neuroblastoma, 64 cases of Wilms' tumor, 65 cases of malignant lymphoma, 45 cases of soft tissue sarcoma, 31 cases of hepatoma, 20 cases of malignant teratoma, 17 cases of testicular tumor, 7 cases of ovarian tumor and 28 cases of other forms of malignant solid tumor. Bone metastasis was observed in 62 of 175 cases of neuroblastoma, 3 of 64 cases of Wilms' tumor, one of 65 cases of malignant lymphoma, 4 of 45 cases of soft tissue sarcoma, one case of pulmonary blastoma and one case of osteogenic sarcoma, giving a total occurrence of bone metastasis in 72 of the 452 cases. The main sites of bone metastasis in neuroblastoma were the skull (61.4%), femur (56.8%), orbit (27.3%) and spine (22.7%). The average values of serum calcium and alkaline phosphatase activity showed no significant difference. The patients with bone metastasis were treated with a combination of radiation therapy and intensive chemotherapy, resulting in temporary improvement. The survival of patients with stage IV neuroblastoma with bone metastasis was worse than that of similar patients without bone metastasis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We report a case of intramural giant gallstone. Cholangiography revealed narrowing of the neck of the gallbladder due to a hemispherical prominence. At cholecystectomy, a giant gallstone 2.1 cm in diameter which was located in the submucosa of a hemispherical prominence at the neck of the gallbladder, was found. Although the usual sizes of intramural gallstones mentioned in previous reports have ranged from 2 to 5 mm in diameter, the stone found in our case is, as far as we know, the largest intramural gallstone yet reported.
Pharmacokinetic and clinical studies on cefotaxime (CTX) in plastic and reconstructive surgery field were carried out. The results obtained are summarized as follows. Two grams of CTX was administered intravenously by single bolus injection to each of 4 patients with burn blisters and mean levels of CTX concentration in blister exudates were investigated. Thirty minutes after administration, the mean level of CTX in the exudates was 3.90 micrograms/ml and it reached a peak of 9.81 micrograms/ml in 2 hours. The clinical efficacy rate for 30 patients with burn infections and postoperative infections was 73.3%, and the efficacy rate for 29 patients in prophylactic use was 72.4%. A side effect (eruption) and abnormal laboratory findings were observed in each one case out of 59. From the above results, CTX may be considered to be useful in plastic and reconstructive surgical treatments.