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Biomedical subjects

K Sakata

Publications and source records attributed to K Sakata.

At least 433 records · Page 24Linked to original sources

Studies on the distribution of lidocaine in tissue after spinal and intravenous application in rabbits: clinical and forensic toxicological aspects.

Distribution of lidocaine in tissue was investigated after spinal anesthesia and intravenous application in rabbits to examine aspects of forensic and clinical toxicology. Respiratory arrest occurred at 5-15 min after injection of 5 mg/kg hyper-baric lidocaine solution into the subarachnoid space followed by standing in the head down position. The minimum concentration of lidocaine in the middle part of the cervical spinal cord of the dead rabbits was 197 micrograms/g. On the other hand, maximum concentration in the same site at the critical state of almost complete respiratory arrest was 175 micrograms/g. The time at which the concentration of lidocaine reached a maximum in plasma and various tissues after subarachnoid administration was 10-15 min. The concentrations in the lumbar spinal cord, a site of administration, were 1200-1500 micrograms/g 5 min after the injection, which decreased gradually to about 180-250 micrograms/g at 60 min when paralysis of the hind legs began to recover. According to these data, the concentration of lidocaine in the spinal cord of rabbits required for neural blockade was presumed to be about 200 micrograms/g. Since the maximum concentrations of lidocaine in each tissue was already observed at 2.5 min after intravenous injection, transport of lidocaine from plasma to tissues was considered to be very rapid. Lidocaine accumulates most rapidly in the spleen and kidney, followed by the brain, lung, heart, spinal cord and plasma. The concentration in the liver was the least because of its hepatic metabolism. Distribution to adipose tissue was slower than that to other tissues, but the highest accumulation was observed at the late stage. Elimination rates of plasma and tissues other than adipose were almost the same.

Animals↗

[Triple primary malignancies (malignant melanoma, laryngeal cancer and hepatoma)].

A 61 year-old male patient, diagnosed to have a malignant melanoma in the left arm in April, 1981, was treated by chemotherapy (gamma-INF and DAVP) and a left axillary lymphadenectomy. In March, 1985, he had complained of hoarseness and an early laryngeal squamous cell carcinoma was found, and was subjected to laser treatment. On May 25, 1986, during his hospitalization for treatment of a multiple metastasis of a malignant melanoma, he suddenly suffered from a gastroduodenal perforation. During an emergency operation, a third cancer, a primary mixed hepatocellular and cholangiocellular carcinoma, was discovered.

Carcinoma, Hepatocellular↗

[Experience with CDDP therapy in advanced and recurrent gastric cancer cases].

For 3 years beginning in 1984, 14 advanced and recurrent gastric cancer cases with measurable lesions (8 unresected cases, 3 cases of recurrence, 2 cases with non-curative resection, 1 case of no operation) were treated by CDDP therapy alone or in combination with other chemotherapies. CR was obtained in 2 of the 8 non-resected cases, radical gastrectomy being feasible in these 2 cases by second-look operation. Five of the 8 cases showed PD, and in 1 case the effect was rather obscure. One of the 2 non-curative resection cases achieved PR, and the other case was MR. One of the 3 recurrent cases was NC, the remaining cases being PD. The one case given no operation showed PD. Overall effectiveness of CDDP therapy for advanced and recurrent gastric cancer cases was seen in 3 (21.4%) of the 14 cases. All of these 3 cases showing effective CDDP therapy was elevated serum CEA values before the therapy, which was markedly reduced after starting the therapy, the reduction rate being very remarkable.

Adult↗

[Neurogenic stress gastric ulceration--an experimental study in rats].

Experimental investigation was performed on pathogenesis of neurogenic stress gastric ulceration, i.e. the gastric ulceration occurring under stress in individuals having brain lesions. Male Wistar rats, weighing 250 to 300 g, were divided into the following 4 groups: a) the normal group, b) the subarachnoid hemorrhage (SAH) group, in which 0.2 ml of arterial blood had been injected into the cisterna magna 3 days before, c) the brain lesion group, in which various right hypothalamic nuclei had been coagulated stereotaxically 7 days before, and d) the brain lesion plus SAH group, in which hypothalamic lesions had been produced 7 days before, followed by SAH 3 days before experimentation. They were stressed by applying restraint plus water immersion for 3 hours, and measurements were done on relative ulcer lengths (RUL) in the glandular stomach, gastric acid secretion, gastric mucosal blood flow (MBF) and gastric emptying function. In the SAH group, stress gastric ulcerations, 18.2 +/- 1.4 mm (mean +/- SE) in RUL, were produced, being significantly larger than the value, 10.2 +/- 1.7 mm, in the normal group. Stress ulcerations were milder than the normal control in the rats having lesions at the preoptic area (POA) or the anterior hypothalamic area (AHA), while the rats having ventromedial hypothalamic (VMH) lesions showed marked ulcerations, 21.8 +/- 2.7 mm in RUL, which were significantly larger than those in the normal group. Addition of SAH to VMH lesions did not cause a further increase in RUL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Heterotopic gastric mucosa accompanied by aberrant pancreas in the duodenum.

An operated case of a heterotopic gastric mucosa, accompanied by an aberrant pancreas tissue, in the bulb of the duodenum was reported. A 40-yr-old man complained of epigastralgia and was diagnosed to have a protruding lesion in the duodenum by roentgenological and endoscopic examinations. Partial excision of the duodenal wall including the mass was performed. Cut surface of the specimen showed a yellowish-whitish mass in the submucosal through the subserosal layers, which was covered by a papillary elevated mucous membrane. Histologically the mass was an aberrant pancreas of the Heinrich I-type and the mucous membrane covering the mass was a heterotopic gastric mucosa, consisting of completely developed fundic glands.

Adult↗

Expression of c-myc oncogene in rat liver by a dietary manipulation.

After rats deprived of protein for several days are fed a meal containing protein, hepatic DNA replication is induced. When nuclear DNA synthesis is stimulated in the normally quiescent rat liver by a dietary manipulation, we examined the changes of the steady-state levels of messenger RNA for c-myc. Levels of c-myc mRNA are gradually elevated approximately 4 to 5-fold above normal in the livers of rats that are fed for several days a diet that lacks protein. After a nutritional shift from a protein-free diet to a diet containing 50% casein, the levels of c-myc mRNA decrease rapidly by 2 h and returned to approximately basal levels after 8 h. Our results suggest that c-myc expression during the prereplicative stage of liver is likely to reflect events associated with entry and progression of hepatocytes into the cell cycle.

Animals↗

The regulation of tissue eosinophilia. IV. Purification and properties of eosinophil-directed chemotactic inhibitory factors from complete Freund's adjuvant-treated guinea pigs.

Eosinophil-directed chemotactic inhibitory factors (ECIF) from T lymphocytes of complete Freund's adjuvant-treated guinea pigs were recovered in two separate molecular weight (MW) fractions: the one is eluted near bovine serum albumin (MW about 70,000), and in pH range between 7.0 and 7.5 by chromatofocusing column, whereas the other is near cytochrome c (MW 12,500), and in pH range between 5.0 and 5.5. It was, however, found by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoadsorption that the high molecular ECIF is probably an aggregated form of the low molecular ECIF. It was subsequently confirmed that both the ECIF had similar physicochemical properties: sensitive to heating at 56 or 80 degrees C sensitive to enzyme treatment with trypsin and neuraminidase, sensitive in acid but not alkaline condition, and bind to peanut agglutinin-or Limulus polyphemus agglutinin-coupled agarose beads. The inhibitory activity of ECIF was suppressed by previous treatment of eosinophils with D-galactose and sialic acid. ECIF activity was specifically absorbed by eosinophils; the absorption was inhibited by pretreatment of eosinophils with D-galactose and sialic acid. Previous treatment of eosinophils with beta-galactosidase and neuraminidase led the cells not to respond to both ECIF. It was thus suggested that the inhibition by ECIF is receptor-mediating phenomenon, and that ECIF and ECIF receptors on eosinophils contain galactose and sialic acid residues which may play an essential role for the biological activity.

Adsorption↗

Eosinophil chemotactic factors from granuloma of Kimura's disease, with special reference to T lymphocyte-derived factors.

The granuloma of patients with Kimura's disease characterized by tissue and peripheral blood eosinophilia was reviewed with respect to eosinophil infiltration. An infiltrate of inflammatory cells with histiocytes and a sprinkling of eosinophils were observed in the fibrous stroma surrounding the newly formed vessels. Mast cells were rarely seen in the areas where eosinophils were grouped together. Three different eosinophil chemotactic factors (ECF) were isolated from the granulomas of Kimura's disease. They were termed as low molecular weight (LMW), intermediate molecular weight (IMW), and high molecular weight (HMW)-ECF according to the profile on gel filtration (LMW-ECF, about 500; IMW-ECF, about 12,500; HMW-ECF, 45,000-70,000). In terms of their activity when extracted from the granuloma, LMW-ECF and HMW-ECF seemed to be major natural mediators for the tissue eosinophilia, whereas IMW-ECF was a minor one. In an in vitro system, it was shown that granuloma lymphoid cells produce spontaneously at least two ECF having similar properties to LMW- and HMW-ECF, respectively. By analysis with monoclonal antibodies, granuloma T cells, probably OKT4-positive cells, were shown to be responsible for the production of those two ECF. It was thus suggested that prolonged synthesis of LMW- and HMW-ECF by OKT4-positive T cells plays a crucial role in the local eosinophilia of Kimura's disease.

Angiolymphoid Hyperplasia with Eosinophilia↗

Clinical studies on serum immunosuppressive acidic protein (IAP) and ferritin in gastric cancer patients: with special reference to preoperative value and influence of surgical stress.

Serum IAP and ferritin values were measured preoperatively in 83 resectable gastric cancer patients. IAP was significantly higher in them than in normal subjects, and increased gradually with progression of cancer, and the values at stages III and IV were significantly higher than that at stage I. It was significantly higher in the cases of n(+) than in those of n(-), and in the cases of noncurative resection than in those of curative resection. Ferritin was significantly higher in them than in normal subjects and mammary cancer patients, and in males than in females, and the values at stages I and IV were significantly higher than that at stage III. OK-432 was serially administered pre- and postoperatively in 83 cases and only postoperatively in 33 cases. IAP increased markedly at 1 week postoperatively and was reduced gradually at 2 and 4 weeks. Ferritin increased markedly at 1 week after operation and reached the maximum value at 2 weeks and was reduced toward the value of 1 week at 4 weeks. However, these changes showed no significant difference between the both groups.

Breast Neoplasms↗

Immunological response of regional lymph nodes after tumor cryosurgery: experimental study in rats.

Seven days after inoculation of metastasizing rat mammary tumor No. 1 into the thigh of 5-week-old female Sprague-Dawley rats, the tumor was treated cryosurgically by two-cycle freezing and by contact methods at -170 degrees C. Weights of the thymus and the spleen, histological findings of the lumbar lymph nodes, phytohemagglutinin (PHA)-induced blastogenesis of lymphocytes obtained from the lumbar lymph nodes and peripheral blood, and resistance rate to tumor rechallenge were examined 1, 3, 6, 10, and 17 week(s) after cryosurgery, with the following results: Thymus weight gradually decreased by 3 weeks after cryosurgery, while spleen weight increased by 1 week, recovering the preoperative level at 6 weeks. Paracortical hyperplasia of the lumbar lymph nodes markedly increased in 1 week and sinus histiocytosis increased after 3 weeks, both remaining at high values until 10 weeks, while germinal center hyperplasia showed a high value at 3 weeks and thereafter decreased gradually. PHA-induced blastogenesis of the lumbar lymph nodes significantly increased 1 week after cryosurgery and remained at its high value until 10 weeks. PHA-induced blastogenesis of peripheral lymphocytes showed the lowest value at 3 weeks and then significantly increased at 6 weeks. Resistance rate to rechallenge showed the lowest value at 3 weeks, reaching the highest level 10 weeks after cryosurgery. From the above results, it was suggested that anti-tumor immunity (resistance to tumor rechallenge) induced by cryosurgery was at the lowest level at 3 weeks after cryosurgery, and gradually increased starting at 6 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Spontaneous production of eosinophil chemotactic factors by T lymphocytes from patients with subcutaneous angioblastic lymphoid hyperplasia with eosinophilia.

Subcutaneous angioblastic lymphoid hyperplasia with eosinophilia (SALH) was reviewed with respect to eosinophil chemotaxis. Lymphoid cells separated from the granuloma spontaneously released at least two different eosinophil chemotactic factors (ECF): low-molecular-weight and high-molecular-weight ECF according to the profile on gel filtration (LMW-ECF, about 500; HMW-ECF, 45,000 to 70,000). The cells, however, failed to produce chemotactic activity for macrophages and neutrophils. By analysis with monoclonal antibodies against lymphocyte subpopulations, the granuloma T cells, probably OKT4-positive cells, were shown to be responsible for spontaneous production of these two ECF. Furthermore, the blood mononuclear leukocytes were separated from the patients with SALH. An ECF closely resembling HMW-ECF was also spontaneously produced by the blood OKT4-positive T lymphocytes, whereas no LMW-ECF was released. Mononuclear leukocytes from healthy donors, however, could produce an ECF resembling HMW-ECF and chemotactic activities for macrophages and neutrophils by stimulation with concanavalin A (Con A). Protein synthesis appeared to be essential for spontaneous ECF and for Con A-induced ECF production. These results suggest that the granuloma OKT4-positive T lymphocytes of the patients with SALH are in activated condition to release LMW- and HMW-ECF, whereas the blood OKT4-positive T lymphocytes are in activated condition to release only HMW-ECF. Such spontaneous and prolonged production of HMW-ECF by the cells can be one of the diagnostic means of SALH.

Angiolymphoid Hyperplasia with Eosinophilia↗

Combined mutagenicity of cobalt(II) salt and heteroaromatic compounds in Salmonella typhimurium.

Mutagenic activities of 4-aminopyridine (4AP), 4-aminoquinoline (4AQ), 9-aminoacridine (9AA) and harman (HM) were examined by the Salmonella test system in the presence of cobalt(II) chloride (CoCl2), which itself is non-mutagenic in this system. Mutagenic activity of the mixture of 9AA and CoCl2 was found to be much higher than that of 9AA alone in strains TA1537 and TA2637. A similar enhancing phenomenon was observed in 4AQ-CoCl2 and HM-CoCl2 mixtures but not in that of 4AP-CoCl2. Judging from visible and nuclear magnetic resonance spectral data, this increased mutagenicity may be attributable to the formation of moderate to weak complexes between these chemicals and the Co(II) cation. A survey of the mutagenicity of several Co(II) complexes supported this interpretation.

Cobalt↗

Partial purification and characterization of exudate gelatinase in the acute phase of carrageenin-induced inflammation in rats.

Gelatinase has been partially purified from exudate in the acute phase of carrageenin-induced inflammation in rats. The enzyme occurs in a latent form that can be activated with 4-aminophenylmercuric acetate (APMA). The latent gelatinase was separated into an active gelatinase and a protein fraction by zinc-chelating Sepharose 6B column chromatography in the final step of purification, suggesting that the latent gelatinase is an enzyme-inhibitor complex. The pH optimum of the active gelatinase is about 7.5 and no reactivity toward native type I collagen or alpha-casein was detected. The molecular weights of the latent and active gelatinases were about 245,000 and about 185,000, respectively, as determined by gel filtration on Sephadex G-200. On the other hand, both latent and active gelatinases occurred in multiple forms in SDS-substrate polyacrylamide gel electrophoresis; the latent gelatinase showed two bands with molecular weights of 105,000 and 69,000, and two additional bands of 88,000 and 83,000 appeared when the latent gelatinase was activated with APMA, while the active gelatinase showed all four species. The active gelatinase was inhibited by metallo-proteinase inhibitors, but not by serine- or cysteine-proteinase inhibitors, suggesting that the exudate gelatinase is a metallo-proteinase. The active gelatinase was also inhibited by serum proteins such as albumin and gamma-globulin, suggesting that gelatinase does not remain in an active form in the inflammatory lesion, where the vascular permeability is increased.

Acute-Phase Reaction↗

Inhibition of calcium channels by harmaline and other harmala alkaloids in vascular and intestinal smooth muscles.

Effects of harmaline and other harmala alkaloids on the contractions induced in the vascular smooth muscle of rabbit aorta and intestinal smooth muscle of taenia isolated from guinea-pig caecum were examined. In rabbit isolated aorta, harmaline inhibited the sustained contraction induced by 65.4 mM K+ with an IC50 (concentration needed for 50% inhibition) of 4.6 X 10(-5) M. This inhibitory effect on high K+-induced contraction was antagonized by raising the concentration of external Ca2+ but not by Bay K 8644, a Ca2+ channel facilitator. Harmaline also inhibited the sustained contraction induced by noradrenaline (10(-6) M) with an IC50 of 7.6 X 10(-5) M. The inhibitory effects on noradrenaline-induced contractions were not antagonized by raising the external Ca2+ concentrations or by Bay K 8644. In guinea-pig taenia, harmaline inhibited the 45.4 mM K+-induced contraction with an IC50 of 6.8 X 10(-5) M and the carbachol (10(-6) M)-induced contraction with an IC50 of 7.0 X 10(-5) M. The inhibitory effects on both high K+- and carbachol-induced contractions were antagonized by raising the external Ca2+ concentrations but not by Bay K 8644. Harmaline, at the concentrations needed to inhibit the muscle contraction, inhibited the increase in 45Ca2+ uptake induced by high K+, noradrenaline and carbachol in aorta and taenia. Harmaline did not change the cellular Na+ and ATP contents in resting and high K+ stimulated taenia. Other harmala alkaloids also inhibited the contractions in these smooth muscles. The order of the inhibitory potency was 6-methoxyharman = harmine > harmaline = 2-methylharmine = harmane > 6-methoxyharmalan > harmalol = harmol for the contractions induced by high K+ in aorta and taenia and by carbachol in taenia, and 2-methylharmine >6-methoxyharman >6-methoxyharmalan = harmol = harmalol = harmane > harmine> harmaline for the contraction induced by noradrenaline in aorta. 7 These results suggest that harmaline inhibits the contractile response ofrabbit aorta and guinea-pig taenia by inhibiting different types of Ca2 channel. The structure-activity relationship indicates that the potency and selectivity of the inhibitory effects on these channels are varied by modification of the structure of this alkaloid.

Adenosine Triphosphate↗

[Experimental study on the absorption mechanism of cryo-necrotized tumor antigens].

On day 7 of MRMT-1 tumor inoculation at the thigh in 5 week-old female SD rats, the tumor was treated cryosurgically by contact method at -170 degrees C and 2 cycle freezing. Postoperative changes in local blood circulation were observed by colloidal carbon perfusion and hydrogen-clearance methods, and pathway and time course of tumor antigen absorption were observed by measuring 3H-thymidine (injected intra-tumorally) uptake in various organs. The observations were done at 0.5, 1, 2, 3, 6, 9, 12, 24, 48, 72, 120 and 168 hour(s) after cryosurgery. The following results were obtained. At 0.5 to 1 hour after cryosurgery: vascular stasis, dilatation and tortuosity were observed. There were no inflow of colloidal carbon and almost no uptake of 3H-thymidine. At 6 hours: vascular stasis and sludging became more marked. There was no inflow of carbon, while uptake of 3H-thymidine was markedly increased. At 24 hours: some carbon inflows in fine vessels and partial recovery of blood circulation in the peritumoral region were observed. Rate of 3H-thymidine uptake was more increased. At 72 hours: carbon inflow and blood circulation were further increased, while the cryo-necrotized tumor showed hyaline degeneration. At 168 hours: increase of newly formed vessels and recovery of blood circulation were remarkable, but uptake rate of 3H-thymidine was decreased according to increased demarcation of the cryo-necrotized tumor. From the above results, it was suggested that the absorption of cryo-necrotized tumor antigens was starting through lymphatic channels in the early period, then also through newly formed capillaries surrounding the tumor at 24 hours after cryosurgery and continued until 72 hours after cryosurgery.

Absorption↗