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Biomedical subjects

K Okajima

Publications and source records attributed to K Okajima.

At least 253 records · Page 14Linked to original sources

A mathematical model of the primary visual cortex and hypercolumn.

A mathematical model of the primary visual cortex is presented. Basically, the model comprises two features. Firstly, in analogy with the principle of the computerized tomography (CT), it assumes that simple cells in each hypercolumn are not merely detecting line segments in images as features, but rather that they are as a whole representing the local image with a certain representation. Secondly, it assumes that each hypercolumn is performing spatial frequency analyses of local images using that representation, and that the resultant spectra are represented by complex cells. The model is analyzed using numerical simulations and its advantages are discussed from the viewpoint of visual information processing. It is shown that 1) the proposed processing is tolerant to shifts in position of input images, and that 2) spatial frequency filtering operations can be easily performed in the model.

Depth Perception↗

[Surgical treatment of far-advanced gastric cancer].

Surgical treatment of far-advanced gastric cancer should be categorized as part of a multidisciplinary treatment. Its therapeutic principles may be summarized as follows: survival should be expected; operative death must be avoided; any operation promoting the growth of cancer should be avoided; oral intake should be made possible, pain should be eased; and the main focus must be removed as far as possible. In the cases with positive peritoneal dissemination, even at P3, a significant extension of life is recognized in the palliative gastrectomy group as compared with the non-resected group. However, considering the postoperative length of life, palliative gastrectomy seems applicable to cases of P1, H1, partly to H2, n3(+), and S3, but in more advanced cases, it was learned essential to determine the surgical method in consideration of the nature of the cancer in the individual cases.

Humans↗

[Intracranial lipoma of the temporal lobe--report of a case and review of the literature].

A 52-year-old female was admitted to our clinic with chief complaint of headache since 2 months ago. Plain computed tomography (CT) revealed low density mass in her right temporal lobe beneath the sylvian fissure with mean Hounsfield number of -52. On admission, no neurological deficit was found. This low density mass had no enhancement region. No abnormal finding was seen in plain skull roentgenogram and right carotid angiography. No epileptic pattern was found electroencephalographically. Right fronto-temporal craniotomy and total removal of tumor was performed to confirm the histological nature of this tumor. The tumor was elastic soft with yellowish color and totally removed. Histological examination revieled typical fatty cells and many capillaries. Her postoperative course was uneventful and was discharged with no neurological deficit. Intracranial lipoma is one of rare brain tumors with incidence of 0.03% or 0.046% in all brain tumor. These tumors are most frequently located in the midline structure, especially in the corpus callosum. After introduction of CT scan, however, lipomas of the extraaxial locations are also reported. From review of literature, location of the lipomas may be divided into 2 groups: the one is located in the midline or paramedian structures of the brain and the other is the extraaxial region such as the sylvian fissure or the cerebellopontine angle. The former group is often associated with anomalies of the central nervous system related to dysraphism. However, the latter group is seemed to have rare association with dysraphism.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗

Role of plasma albumin in renal elimination of a mercapturic acid. Analyses in normal and mutant analbuminemic rats.

Biosynthesis of N-acetylcysteine S-conjugates of xenobiotics (mercapturic acids) occurs via interorgan metabolism and the renal transtubular transport system plays an important role in elimination of the final metabolites from the organism. To assess the behavior of a mercapturic acid in the circulation, plasma clearance of radioactive S-benzyl-N-acetylcysteine and its interaction with plasma proteins were studied in normal and mutant analbuminemic rats (NAR). Intravenously injected S-benzyl-N-acetylcysteine rapidly disappeared from the circulation both in NAR and normal animals. However, its plasma clearance was significantly higher in NAR (45.7 ml kg-1 min-1) than in normal rats (25.2 ml kg-1 min-1). Ultrafiltration analysis revealed that 18.4% and 80.1% of the mercapturate bound to plasma protein(s) from NAR and normal rats, respectively, at 50 microM ligand concentration. The mercapturic acid bound to plasma albumin with an association constant of 2.24 X 10(5) M-1 and the number of binding sites was 1.18/mol albumin. The binding was competitively inhibited by probenecid and L-tryptophan. Concomitant administration of this mercapturic acid with equimolar amounts of albumin resulted in a marked decrease in the plasma clearance (26.2 ml kg-1 min-1) and an increase in the urinary secretion of this ligand in NAR. 30 min after injection of the mercapturic acid (10 mumol/kg body weight), 27.3% and 60.4% of the injected dose was recovered from urine and kidneys of NAR and normal rats respectively. About 41% of the dose was recovered in NAR urine when the ligand was injected bound to an equimolar amount of albumin. These results suggested that albumin is important for the renal accumulation and urinary elimination of the circulating mercapturic acid.

Acetylcysteine↗

[Phase II study of 5'-DFUR (5'-deoxy-5-fluorouridine) by the Cooperative Study Group].

Phase II study of 5'-DFUR was conducted in 195 patients with malignant tumors by the Osaka Chemotherapy Cooperative Study Group. Five CR and 20 PR cases were obtained out 133 evaluable cases and the total response rate was 18.8% (15.8% in gastric, 38.1% in breast) One PR was observed for each of head & neck and esophageal cancer. It was noteworthy that four CR were observed in breast cancer. Adverse reaction was observed in 61 out of 151 cases (40.4%), and major side effects were digestive symptoms such as diarrhea (22.5%), nausea-vomiting (11.9%) and anorexia (10.6%). These results suggest that 5'-DFUR can be useful for the treatment of malignant tumors.

Administration, Oral↗

Studies on the mechanism for renal elimination of N-acetylphenylalanine: its pathophysiologic significance in phenylketonuria.

To elucidate the mechanism and biologic significance of urinary occurrence of N-acetylphenylalanine in phenylketonuria, the metabolic fate of N-acetylphenylalanine was studied in rats. In vivo and in vitro analysis revealed that N-acetyl-14C(ul)-phenylalanine bound to plasma albumin with an association constant of 8.52 X 10(3) M-1 and that the number of binding sites was 0.98 per mole albumin. Intravenously administered N-acetylphenylalanine was rapidly extracted from the circulation predominantly by the kidney and excreted into urine. Plasma clearance of the injected ligand was markedly decreased by bilateral nephrectomy but not by bilateral ureter ligation. Probenecid, a potent inhibitor of the renal excretory system for organic anions, such as hippuric acid, sharply decreased the rate of disappearance from the circulation, renal accumulation, and urinary secretion of intravenously administered N-acetylphenylalanine. These results indicate that intravenously administered N-acetylphenylalanine undergoes renal peritubular transport via a probenecid-sensitive excretory system for organic anions. This renal transtubular excretory mechanism may possibly operate in elimination of N-acetylphenylalanine, a hazardous amphipathic metabolite of phenylalanine, from plasma into urine in phenylketonuric patients.

Animals↗

[Study on detection of metastatic lymph nodes from gastric cancer--use of hematoporphyrin-injection in submucosal layer of the stomach].

It is well known that hematoporphyrin (Hp) has the affinity for malignant tissue and the deposition of Hp can be visualized by ultraviolet (UV) irradiation as red fluorescence. This study was attempted to detect the metastatic lymph nodes from gastric cancer at the time of operation, utilizing Hp and UV irradiation. Forty eight hours before the operation, 2ml of Hp solution was endoscopically injected into the submucosal layer neighbouring the cancerous lesion of the stomach. Deposition of Hp in lymph nodes was detected as red fluorescence by UV irradiation during the operation. Resected lymph nodes were reexamined by the same procedure and the histological examination was also performed. The detection rate for metastatic lymph node by UV irradiation during the operation was 78.9%, which was confirmed by histological examination retrospectively. However, this procedure was accompanied by 8.6% of false negative. Postoperative evaluation of resected lymph nodes revealed that histological metastasis rate from lymph nodes which had the red fluorescence was 56.9% and that from lymph nodes which had no fluorescence was 13.2%. Present study suggested that endoscopic injection of Hp was of use in detecting the metastatic lymph nodes from gastric cancer at the time of operation.

Animals↗

[Recurrence of cerebral aneurysm after neck clipping--report of a case and review of literature].

A case of recurrent cerebral aneurysm after complete neck clipping is reported. A 38-year-old man was admitted to our service 14 days after attack of subarachnoid hemorrhage. On admission, ruptured left middle cerebral artery aneurysm with intercerebral hematoma and non-ruptured right anterior cerebral artery aneurysm were revealed by radiological examinations. Neck clipping was successfully performed to both of aneurysm and aneurysm was completely disappeard in the postoperative angiographical study. Postoperative course was also uneventful and he was discharged with slight right hemiparesis and motor aphasia. Thirteen months after the neck clipping, however, he was readmitted to our hospital with attack of subarachnoid hemorrhage. After admission, a new aneurysm was noted just under the clip at the right anterior cerebral artery. Neck clipping against this aneurysm was performed by reopening the craniotomy. For his postoperative normal pressure hydrocephalus, ventriculoperitoneal shunt was performed at one month after neck clipping. Postoperative course was uneventful and discharged. From review of literature, it was presumed that hemodynamic stress in the site of aneurysm and injury of arterial wall by the clip may be two major factors as a cause of recurrent aneurysm formation. In our case, possibility of the latter cause was suggested.

Adult↗

Topological aspects of microsomal N-acetyltransferase, an enzyme responsible for the acetylation of cysteine S-conjugates of xenobiotics.

Acetylation of cysteine S-conjugates of xenobiotics by microsomal N-acetyltransferase is the final step of detoxicative metabolism leading to mercapturic acid biosynthesis. To elucidate the subcellular site of N-acetylation and the effective mechanism by which the final metabolites are eliminated from the organisms, topological aspects and catalytic properties of microsomal N-acetyltransferase and mercapturic acid biosynthesis in vivo were investigated. Intravenous administration of radioactive S-benzyl-L-cysteine, a model compound of cysteine S-conjugates, resulted in rapid acetylation of the conjugate in liver and kidney to a similar extent. The acetylation was followed by a rapid excretion of the metabolite, a mercapturic acid, into the urine; about 60% of the injected dose appeared in urine within 60 min of administration. Limited proteolysis of microsomal vesicles obtained from liver and kidney by chymotrypsin or trypsin inactivated the transferase by 49-62% and 62-73%, respectively. Proteolytic inactivation of the transferase was not significantly affected by the presence of 0.04% sodium deoxycholate by which the vesicles became permeable to macromolecules due to its detergent action. To determine the sidedness of the active site of N-acetyltransferase on the microsomal membranes, two S-acetyldextran polymer derivatives (Mr 500 000) of cysteine and N-acetylcysteine which represent an nonpermeant substrate and product for this enzyme, respectively, were examined for their effects on the vesicle-associated enzyme activity. Both derivatives inhibited the transferase activity in a dose-dependent fashion; maximum inhibition of the enzyme activity was 40% by the former and 60% by the latter. Sulfobromophthalein strongly inhibited the enzyme activity and this inhibition was completely reversed by adding an equimolar amount of hepatic glutathione S-transferases (ligandins). In contrast to the strong inhibition by sulfobromophthalein itself, its glutathione S-conjugate did not inhibit the enzyme activity. These results indicate that the active site and the protease-sensitive domain(s) of the microsomal N-acetyltransferase are localized on the outer surface (cytoplasmic side) of endoplasmic reticulum and that the ligandin(s) might protect membranous N-acetyltransferase from inhibition by organic anions by binding them and catalyzing the conjugation with glutathione.

Acetylation↗

Hepato-renal cooperation in biotransformation, membrane transport, and elimination of cysteine S-conjugates of xenobiotics.

Biosynthesis of N-acetylcysteine S-conjugates of xenobiotics, mercapturic acids, occurs via inter-organ metabolism of the corresponding glutathione derivatives (Inoue, M., Okajima, K., & Morino, Y. (1982) Hepatology 2, 311-316). To elucidate the mechanism of mercapturate biosynthesis and its urinary elimination, hepato-renal cooperation in the enzymic processing and membrane transport of cysteine derivatives was studied in isolated hepatocytes, perfused liver and renal cortical tubules. Isolated hepatocytes rapidly accumulated S-benzylcysteine by a carrier-mediated mechanism and metabolized it to the N-acetylcysteine conjugate. Experiments in perfused rat liver revealed that, upon infusion of S-benzylcysteine, N-acetyl-S-benzylcysteine appeared in the effluent perfusate and hepatic excretion of this mercapturate was inhibited by simultaneous infusion of probenecid, an inhibitor of the organic anion transport system. Isolated renal cortical tubules actively accumulated N-acetyl-S-benzylcysteine by a dinitrophenol-sensitive, carrier-mediated mechanism which was competitively inhibited by probenecid and hippuric acid. These and other results indicate that a cysteine S-conjugate in plasma is rapidly taken up by the liver and converted to the N-acetyl derivative which is translocated into plasma via a probenecid-sensitive transport system in hepatic sinusoidal membranes. The mercapturic acid excreted in plasma is transferred to the kidney and finally excreted into urine by a probenecid sensitive transtubular transport system for organic anions in renal cortical tubules. Hepato-renal cooperation in metabolic conjugation and membrane transport of these intermediates appears to constitute an important process in mercapturate biosynthesis and urinary excretion of the final metabolites.

Acetylation↗