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Biomedical subjects

M Aoyagi

Publications and source records attributed to M Aoyagi.

At least 217 records · Page 12Linked to original sources

Effect of simultaneous administration of leupeptin on induction of bladder tumors in rats by N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Male Wistar rats were given a diet containing 0.1% leupeptin, a microbial protease inhibitor, and drinking water containing 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 8 weeks. Leupeptin did not have any detectable effect on the induction of bladder tumors by BBN in week 40, in terms of the weight of the bladder including the tumor, the number of tumors per bladder, the extent of invasion, or the incidences of hyperplasia, papilloma, and cancer. This result is in marked contrast to the previous findings that leupeptin enhanced BBN-induced bladder carcinogenesis when administered continuously after BBN-treatment.

Animals↗

Chemotherapeutic study on canine gastric cancer induced by N-ethyl-N'-nitro-N-nitrosoguanidine.

Studies were made on the chemotherapy of gastric cancer in dogs induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Four male Beagle dogs were given a solution of ENNG at 100 approximately 150 microgram/ml with or without 0.4% Tween 60 to drink for 5 approximately 8 months. They all developed gastric adenocarcinomas, which were confirmed by histological examination of biopsy specimens taken in months 13 approximately 32 of the experiment. After confirming the presence of gastric cancer, 1-n-hexylcarbamoyl-5-fluorouracil (HCFU), a derivative of 5-fluorouracil, was given to the dogs orally as capsules at a daily dose of 5 or 10 mg/kg body weight. One dog died from adverse effects of HCFU 12 days after the beginning of chemotherapy. The other 3 dogs were treated with CHFU for 82 approximately 424 days. In these dogs, the tumor size, measured by X-ray examination, increased during chemotherapy. On autopsy, the tumors in the stomach were found to be restricted to the antrum, and metastases of the gastric adenocarcinomas to the regional lymph nodes and/or liver were found in 2 dogs. No degenerative changes of tumor cells were found in the stomach or metastasized organs, except for necrosis of cells in a perigastric regional lymph node of the dog. The value of using canine gastric cancer in studies on chemotherapy is discussed.

Adenocarcinoma↗

Alteration in the distribution of organ perfusion following profound hypothermia and circulatory arrest in the baboon.

The physiologic consequences of profound hypothermic circulatory arrest in infants are incompletely understood. Immature baboons underwent surface cooling, followed by core cooling using cardiopulmonary bypass, circulatory arrest for 30 min, and perfusion rewarming. Blood flow to and within organs was studied using the multiple-radionuclide-label microsphere technique. Marked redistribution of total and regional myocardial and cerebral flow occurred during cooling and rewarming.

Animals↗

Caloric pattern test with special reference to failure of fixation-suppression.

Fixation-suppression of caloric nystagmus was studied in 1230 consecutive cases. An analysis of caloric nystagmus with failure of fixation-suppression (FFS) made it possible to classify patterns of FFS into three types: Type I: FFS was observed bilaterally in caloric nystagmus; Type II: FFS was recognized unilaterally on either side; Type III: FFS was seen in either direction of nystagmus. On the basis of these three types, the underlying neuroanatomical substrate responsible for FFS is discussed.

Brain Diseases↗

Neurotological studies on Meniere's disease and sudden deafness.

During the period from January 1973 to June 1975, 60 cases with definite Meniere's disease and 30 cases with sudden deafness were listed according to such criteria for the diagnosis of both diseases as determined by the Research Committee of Japan. A neurootological assessment for both diseases were performed in our series. In patients with definite Meniere's disease, hearing impairment was characterized by deficiency in detecting low- and middle-pitched tones and fluctuation of auditory threshold in low frequency range. In sudden deafness, highly impaired hearing loss, i.e., total deafness, was frequently observed (45%). However, recruitment occurred at the same incidence (80%) in both diseases tested. The incidence of spontaneous nystagmus was almost the same regardless of associated vertigo and the course of both diseases. Moreover, it was also recognized that a reduction of caloric responses was a better indication for assessment of the affected ear in both diseases.

Audiometry↗

Regional cerebral blood flow changes after bilateral external carotid artery ligation in acute experimental infarction.

Regional cerebral blood flow (rCBF) was measured in baboons by intracarotid injection of 133Xe and a gamma camera after acute cerebral infarction was induced by occlusion of the middle cerebral artery (MCA). A steady state of rCBF was measured four hour after MCA occlusion and was followed by bilateral ligation of the external cartoid arteries (ECA). Subsequent rCBF measurements were obtained at 30, 60, and 120 minutes. After bilateral ECA ligation, flow in ischaemic and non-ischaemic areas was greatly enhanced and flow in the hyperaemic areas significantly reduced, presumably since they had provided collateral circulation to the ischaemic zone with a favourable redistribution.

Acute Disease↗

Neurotological studies upon intoxication by organic mercury compounds.

In 1965, a strange illness, which afterwards was diagnosed as the intoxication caused by organic mercury compounds, began to affect the inhabitants of the riverside areas of the Aganogawa River, Niigata, Japan. The authors have investigated the neurotological disturbances, which occurred in 144 cases intoxicated with organic mercurials. The results obtained are summarized as follows: (1) Recruitment (in SISI and other tests) was negative in all the cases except for 32 with inner ear deafness, and Békèsy's AUDIOMETRY (TTS) showed type II: unsettled wide amplitude in 17 cases and severe abnormal adaptation characterizing the type III pattern in nine cases. (2) Spontaneous and positional nystagmus were recorded with ENG in 94 of 144 cases. In 62 of 144 cases, pathological findings of horizontal optokinetic nystagmus were recorded, and those of vertical optokinetic nystagmus were frequently observed in 81 of the 118 cases tested (69 percent). Judging from the authors' observations, neurotological disturbances due to chronic mercurial intoxication may be considered mainly as lesions of the retrocochlea and of the oculomotor system in the brain stem and the cerebellum.

Adolescent↗

Neurogenic control of cerebral blood flow in the baboon.

Cerebral chemical vasomotor reactivity and autoregulation were tested in normal baboons before and after the intravenous or intravertebral infusion of atropine sulfate (0.02 mg/kg). Atropine did not appreciably effect autoregulatory response, but intravertebral injection suppressed the increase of cerebral blood flow (CBF) by inhalation of 5% CO2 and enhanced the decrease of CEF induced by hyperventilation. These changes produced by intravertebral injection of atropine were not observed after intravenous injection. Since the vertebrobasilar arterial system supplies the brain stem and diencephalon, this suggests that a central vasodilator tonus of the cerebral vessels is maintained by the innervation of the cerebral vessels by cholinegic neurons which have their central origin in the brain sterm and diencephalic area.

Acetylcholine↗

Central cholinergic control of cerebral blood flow in the baboon. Effect of cholinesterase inhibition with neostigmine on autoregulation and CO2 responsiveness.

Cerebral autoregulation and vastomotor responsiveness to carbon dioxide (CO2) were measured quantitatively by the use of the autoregulation index and chemical index, respectively, in normal baboons before and after intravertebral and intracarotid infusion of the anticholinesterase agent, neostigmine methylsufate (Prostigmin). Continuous measurements were made of cerebral blood flow (measured as bilateral internal jugular venous outflow), arterial and cerebral venous pO2 and pCO2, cerebral arteriovenous oxygen differences, and endotracheal CO2. The effect of intravertebral infusion of neostigmine (12.5 mug/kg body weight) was compared to intravertebral infusion of neostigmine (25 mug/kg body weight) for assessment of any specific action of the drug on a hypothetical cholinergic vasomotor center, presumed to be located in the territory of the vertebrobasilar supply. No significant or persistent changes in cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) followed either intravertebral or intracarotid infusion of neostigmine. Cerebral vascular resistance (CVR) and cerebral perfusion pressure (CPP), however, decreased significantly after intravertebral infusion. Cerebral autoregulatory vasoconstriction during increases of CCP was significantly reduced following both intravertebral and intracarotid infusion. Cerebral autoregulatory vasodilatation was not altered as CPP was lowered. Cerebral vasodilatory reactivity to CO2 inhalation was significantly enhanced following intravertebral neostigime but not following intracarotid neostigmine. Cerebral vasoconstrictive response to hyperventilation was not influenced by neostigmine. These results support the view that central cholinergic cerebrovascular influences exist, and are vasodilatory in nature.

Acetylcholine↗

Cerebral effects of profound hypothermia (18 degrees C) and circulatory arrest.

Clinical use of profound hypothermia and total circulatory arrest has been accompanied by occasional postoperative neurological abnormalities. In a series of infant baboons, surface cooling to 32 degrees C (brain) followed by perfusion cooling by cardiopulmonary bypass with a membrane oxygenator and heat exchanger to 18 degrees C was carried out, after which the circulation was stopped for 30 minutes. The animal was rewarmed to 35 degrees C. Marked alterations in the regional cerebral circulation were observed during perfusion cooling and rewarming. Regional cerebral ischemia was negatively correlated with jugular outflow (total cerebral blood flow) during rewarming, while regional hyperemia showed positive correlation both following perfusion cooling and after rewarming. A higher degree of ischemia in brain ischemic samples was found during rewarming than during cooling. These alterations in regional cerebral perfusion were associated with lactacidosis and hyperglycemia after rewarming, and may be considered potentially responsible for posthypothermic cerebral dysfunction.

Animals↗

[Double cholinergic and adrenergic regulation of cerebral blood flow].

Cerebral vascular tonus was measurably influenced by both alpha or beta adrenergic blockade and by inhibition of cerebrovascular acetylcholine or acetylcholinesterase. Cerebral autoregulatory response was significantly affected by intravenous injection of PBZ, intravertabral and intravenous injection of PPL and intravertebral and intracarotid injection of neostigmine. Cerebral vasomotor reactivity to changes in aPCO2 was altered significantly by intravertebral injection of PPL, atropine, and neostigmine. The doses of intravenous PBZ injections were large (1.5 mg/kg) so that PBZ not only blocked peripheral alpha adrenergic receptor sites in the cerebrovascular system but probably also those possibly located in the brain stem (vertebrobasilar territory). The functional significance of a double cholinergic and adrenergic neuronal system located in the brain stem influencing CBF appears to have been established.

Animals↗