Biomedical subjects
Publications and source records attributed to S Okuyama.
Cajucarinolide and isocajucarinolide, two new clerodane diterpenes, have been isolated from the cortices of Croton cajucara (Euphorbiaceae). These compounds possess anti-inflammatory activity and inhibit bee venom phospholipase A2 in vitro.
Experiments were designed to investigate the effects of aging and hyperglycemia on relaxation of the aorta for both endothelium-dependent and -independent agents in Wistar (control) and WBN/Kob (genetically diabetic) rats. The concentration of glucose in serum was elevated significantly in aged (90-92 wk) but not young (13-15 wk) WBN/Kob rats. Endothelium-dependent relaxations of both control and WBN/Kob rats to acetylcholine were reduced by aging. The relaxations induced by acetylcholine in aortic strips were significantly attenuated in both young (nondiabetic) and aged (diabetic) WBN/Kob rats, compared with those from age-matched control vessels, respectively. The concentration-response curves for sodium nitroprusside in aortic strips from both aged control and aged WBN/Kob rats were shifted to the left when compared with those from young rats, respectively. However, the maximal relaxation responses to sodium nitroprusside showed no difference among all vessels studied. The relaxations induced by sodium nitroprusside in aortic strips from both young and aged WBN/Kob rats were similar to those from age-matched control rats, respectively. The relaxations induced by atrial natriuretic peptide showed no difference among all vessels studied. In genetically diabetic rats, functional changes in endothelium occurred before elevation of the levels of glucose in the serum. Thus impaired endothelium-dependent relaxation may play an important role in the high incidence of vascular complications in diabetes mellitus.
Evolutionary concepts of cancer (Okuyama and Mishina 1984; 1990) have already been found useful in understanding carcinogenesis and anti-cancer defense lines in the body and various cancer attributes. The concept of endosymbiotic disorders gave an impact upon the science of internal medicine leading to discovery of amitosis in Reed-Sternberg cells, a primitive eukaryotism (Okuyama 1991a). A novel concept of vasogenic necrosis was also developed for such diseases of Perthes' disease, cerebral vascular diseases and myocardial infarction: costs of bipedalitic evolution in man.
In a series of studies to investigate the structural features and the characteristics of the tooth, a detailed observation was made on the enamel surface and the enamel composing the fissure and pit of the freshly extracted human permanent molars, using scanning electron microscopy and transmission electron microscopy. The materials employed in this observation were taken from the noncarious surface of molars. The following results were obtained: The hypocalcified zone was observed more or less in the enamel composing the fissure and pit. In many cases, the dental cuticle can be seen on the enamel surface. A rodless enamel was present, in greater or lesser degree, in the enamel surface layer. Retzius's line was observed clearly in the enamel composing the fissure and pit. In many cases, perikyamata was found on the enamel surface. In some cases, tubular pits invaginated secondarily from the fissure and pit were observed. In some, a dental calculus can be observed in the fissure and pit. By the observation of the inner structure of the dental calculus, mineralization occurred around and within the bacteria and in the interbacterial matrix composing the dental caluculus. Bacteria of the same degree of calcification appear in the microcolonies.
The distribution of selective alpha 1-adrenoceptor agonist 1-(2',5'-dimethoxyphenyl)-2-glycinamidoethanol hydrochloride, midodrine, and its active metabolite 1-(2',5'-dimethoxyphenyl)-2-aminoethanol, DMAE, was evaluated on bladder and urethra of 8-weeks and 52-weeks old female rats. Prior to the intravenous injection of 14C-labeled midodrine and DMAE, bilateral ureters were ligated to prevent drug uptake from the urinary tract. In 8-weeks rats, 14C-midodrine activity was significantly (p less than 0.01) higher in the bladder than in the femoral muscle, which served as a control for drug distribution. Similarly, higher uptake of 14C-DMAE was observed in the bladder than in the femoral muscle (p less than 0.01) and the urethra (p less than 0.05). In 52-weeks rats, there was no significant difference of midodrine uptake among these tissues. However, significantly higher uptake of 14C-DMAE was observed in the urethra than in the femoral muscle (p less than 0.05). Compared with midodrine, the concentration of DMAE was significantly increased in the bladder of 8-weeks rat and in the urethra of 52-weeks rats (respectively, p less than 0.05). In autoradiogram, the grains corresponding to midodrine and DMAE were diffusely distributed on the smooth muscles of bladder (mainly bladder neck and trigone) and urethra. The grains were also recognized on the vessels and perivascular areas of these tissues. These findings support that midodrine and DMAE could be effective for stress incontinence, because these drugs are known to bind specifically to alpha 1-adrenoceptor.
The 4'-N-alkyl(1 approximately 10) and 4'-N-acyl derivatives (11 approximately 21) of pradimicins (PRMs) were synthesized by trimethylsilylation of PRMs A, C and FA-1 followed by condensation with appropriate alkylating and acylating agents. The 4'-hydroxy derivatives (23 and 24) were synthesized from PRM FA-2 in a 3-step sequence. Among these compounds, the 4'-N-carboxyl substituted alkyl (1, 5, 8 and 10), 4'-N-formyl (11) and 4'-axial-hydroxy (23) derivatives retained the antifungal activity of the parent compounds and showed great improvement in water solubility.
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1. We examined the effects of minaprine on cerebral infarction produced by occluding of unilateral middle cerebral artery (MCA) above the rhinal fissure in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Oral administration of minaprine (60 mg/kg/day) and vehicle were started 30 min after the occlusion of MCA, and continued for 6 days. 3. The brain was dissected out and 36 coronal multiple sections of the whole brain were histologically prepared to determine the location and extension of infarction. 4. The infarcted area produced by the occlusion of MCA was limited to the cerebral cortex. 5. Body weight of the minaprine-treated rats gradually decreased within 4 days after the occlusion of MCA and thereafter increased, whereas in the vehicle-treated rats, there was a gradual decrease during the experimental period. 6. Size of the infarcted area was serially measured, in each section, using a microcomputer imaging device. In all animals with an occluded MCA, there was a typical pattern of ischemic damage. 7. Post-treatment of MCA occluded SHRSP with minaprine resulted in reduction in infarct size, as compared to findings in the vehicle-treated controls. 8. The pharmacological and histopathological effects of minaprine on the progress of cerebral infarction produced by the occlusion of MCA in SHRSP are discussed.
A Reed-Sternberg cell in binary fission was observed in a case of Hodgkin's disease of nodular sclerosis type. This was thought to possibly represent a primitive eukaryotic manifestation or a retrograde replay of the endosymbiotic evolution of the modern eukaryotes as a part of devolution of malignancy (Okuyama and Mishina 1990).
It has been known that alpha 1-adrenoceptors play an important role in urethral contraction. The incompetence of the urethral contraction is a cause of stress incontinence. We studied the urodynamic effects of a selective alpha 1-adrenoceptor agonist (midodrine hydrochloride) on the bladder and urethra of female dogs. Under anesthesia with intravenous chloralose, four doses (0.03, 0.1, 0.3 and 1.0 mg/kg) of midodrine were administered intravenously and urodynamic studies including cystometry, urethral pressure profilometry and electromyography (EMG) of the external urethral sphincter were performed. The administration of midodrine induced a significant increase of the maximum closing pressure in the proximal portion of the urethra (p less than 0.05 at 0.03 mg/kg and p less than 0.01 at 0.1, 0.3, 1.0 mg/kg). There were no significant changes in the functional profile length, the closing pressure at the external sphincters, the maximum bladder pressure, bladder capacity and bladder compliance. The administration of 0.3 mg/kg or more of midodrine produced a significant increase in the mean arterial blood pressure. After midodrine administration, transient increases in the external sphincter EMG activities were recognized. The activities showed the synergistic pattern during the bladder contractions. In conclusion, lower dose administration of a selective alpha 1-adrenoceptor agonist (midodrine) specifically produced an increase of the closing pressure in the proximal portion of the urethra without affecting blood pressure. These results suggest that midodrine is useful for the treatment of stress incontinence in humans.
Syntheses of melanostatin and feldamycin have been completed from L-serine and L-threonine, respectively, and the configuration of unknown asymmetric carbons determined. Feldamycin analogs have also been prepared and the L-tryptophyl analog was the most potent in the depigmentation of Streptomyces bikiniensis and B16 melanoma cells.
Random samples of middle-aged (35-64) male residents of two different areas in Tokyo, Bunkyo-ku, a low-mortality area (n = 767) and Koto-ku a high mortality area (n = 790) were interviewed between March and April in 1988, concerning health and life style. The two populations were compared regarding, 1) health status which was examined from the view point of fatigue, symptoms and self-rated health, 2) factors related to the three health indices. The main results were as follows: 1. No significant differences were seen between the two populations in the gross means for health indices. However when the health indices were stratified by age group, mental fatigue and minor symptoms were more prevalent in Bunkyo-ku than Koto-ku among young people, while prevalence of physical fatigue and major symptoms was higher in Koto-ku among old people. 2. The relationship between the health indices and job type, income, education and marital status was examined. In Bunkyo-ku, no relationship was seen after controlling for age, working conditions and life style. On the other hand, in Koto-ku, significant relationships were seen with age, job type and marital status, and health problems were prevalent not only among those with low socioeconomic status but also in other socioeconomic groups. These results were maintained even after controlling for age, working conditions and life style, similar to the analysis for Bunkyo-ku, indicating that health problems in this population do not appear to be solely the result of working conditions or life style.
Cancer of the gallbladder is radioresistant. When a case of such was found inoperable, she was subjected to radiotherapy combined with aclarubicin and neocarzinostatin. Therapeutic effectiveness was confirmed at autopsy as she later succumbed to uterine cervical cancer. Thus, the present radiochemotherapeutic regimen would probably provide a means of overcoming those radioresistant inoperable malignancies. Intravenous administrations of appropriate antibiotics such as azthreonam and reniran may probably be helpful in the prevent ion and treatment of septic peritonitis possible during the course of reinforced radiotherapy of the abdomen.
We used the morphine-induced Straub tail to examine the actions of a 5-HT3 receptor antagonist and kappa opioid receptor agonist. The kappa opioid receptor agonist, U-50,488H (4-16 mg/kg i.p.), produced a dose-related inhibition of the tail elevation induced by morphine (10 mg/kg s.c.) in ICR male mice. ICS-205-930 (3 and 10 mg/kg i.p.) and zacopride (0.3 and 1 mg/kg i.p.), 5-HT3 receptor antagonists, attenuated the inhibitory effect of U-50,488H in a dose-dependent manner. ICS-205-930 and zacopride did not inhibit the morphine-induced Straub tail. These observations suggest that the actions of kappa opioid receptors may be modulated by 5-HT3 receptors in the morphine-induced Straub tail.
Acetylcholine (ACh) and choline (Ch) in cerebrospinal fluid from 29 normal volunteers and 7 patients with Alzheimer-type dementia (DAT) were examined using high-performance liquid chromatography with electrochemical detector coupled with liquid cation-exchange method. In normal volunteers, ACh concentration was decreased significantly from 40-50 years and Ch concentration was increased significantly from 50-60 years. CSF from patients with DAT revealed high Ch concentration and the increase was statistically significant while ACh concentration in CSF of DAT did not show a significant difference with that of normal volunteers. This Ch augmentation may suggest a disturbance in utilization of Ch for ACh synthesis and may become an useful indicator for organic changes in central cholinergic system.
The effects of stable PGI analogue TTC-909 on CBF and glucose metabolism was studied in the chronic stage of cerebral ischaemia produced by occluding the distal MCA in SHRSP. Administration of TTC-909 (100 ng/kg/day during 7 days) prevented the development of ischaemic oedema and improved secondary metabolic derangement coupled to flow in postischaemic tissues, particularly in the ischaemic rim.
A cataract classification and grading system for the main purpose of cataract epidemiological studies is proposed by the Japanese Cooperative Cataract Epidemiology Study Group. Cataractous types are classified principally into cortical, nuclear and subcapsular opacities. Stages of cataract advancement are classified into grade I (early stage), grade II (moderate stage) and grade III (advanced stage). Regarding cortical opacities an opacified area obtained from red-reflex images is utilized for grading judgment. Nuclear opacity grading is based on the intensity of scattering at the nucleus. Grading of subcapsular opacities is judged from their extension in the three different pupillary areas. To help grading judgments, standard pictures of cortical and nuclear cataracts are provided. Gradings of lens coloration are divided into pale yellow (grade I), yellow (II), brownish yellow (III) and brown including reddish and black brown (IV). A recording chart is also provided.
We examined the characteristics of cerebral ischemia-induced behavioral deficit in the passive avoidance task and the effect of minaprine and other cytoprotective drugs on passive avoidance deficit induced by cerebral ischemia in Mongolian gerbils. Severe impairment of passive avoidance was apparent when the duration of the ischemia exceeded 2 min. Histopathological ischemic neuronal damage in CA1 neurons at 7 days after occlusion was also induced when the ischemia was over 2 min. Otherwise, although cerebral ischemia was carried out at 5 min, 2 hr, 5 hr or 24 hr after the training session, the passive avoidance deficit was produced 24 hr after the training session. When the training session was carried out 24 hr before the occlusion, minaprine, which was administered 30 min before the occlusion, led to a recovery of the response latency. Pentobarbital, diazepam and ethylapovincamine improved the passive avoidance deficit induced by 5-min bilateral carotid artery occlusion. On the other hand, the passive avoidance deficit was not ameliorated by Ca(++)-hopantenate, nicardipine and idebenone. The hippocampal damage at 7 days after occlusion was prevented by the drugs that ameliorated the passive avoidance deficit. The relationship between passive avoidance deficit and CA1 neuronal death in the hippocampus induced by cerebral ischemia warrants further attention.