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Biomedical subjects

F Goto

Publications and source records attributed to F Goto.

At least 127 records · Page 7Linked to original sources
PubMed1992

Effect of platelet-activating factor antagonist and leukotriene antagonist on endotoxin shock in the rat: role of the leukocyte.

The effects of platelet-activating factor (PAF) antagonist (CV-3988) and leukotrienes (LTs) antagonist (ONO-1078) on endotoxin-induced sequelae in the rat were assessed. Pretreatment with either CV-3988 (6 mg/kg, i.v.) or ONO-1078 (150 mg/kg, p.o.) did not improve survival rate following the administration of Escherichia coli lipopolysaccharide (LPS) compared with that of control rats pretreated with solvents of the drugs. Rats pretreated with both CV-3988 and ONO-1078 exhibited significantly (P less than 0.01) enhanced survival following lipopolysaccharide (LPS) administration. Percentage survivals 48 hr after the administration of LPS were 20%, 32%, 24%, and 68% in the pretreatment with solvents, CV-3988, ONO-1078, and CV-3988 combined with ONO-1078 groups, respectively. Pretreatment with CV-3988 combined with ONO-1078 inhibited the change of plasma transaminase 3 hr after LPS administration. The neutropenia, due to the administration of vinblastine (1 mg/kg, i.v.), increased the survival rate following the administration of LPS without pretreatment with PAF and LT antagonists. Antishock action of CV-3988 and ONO-1078 could not be seen in neutropenic rats. These data suggest that combined pretreatment with PAF antagonist and LT antagonist inhibited leukocyte-mediated tissue injury in LPS-induced endotoxemia.

Animals↗
PubMed1992

Interleukin-1 receptor antagonist in inflammatory exudate cells of rabbits. Production, purification and determination of primary structure.

A rabbit interleukin-1 (IL-1) inhibitor in inflammatory peritoneal exudate cells was purified to apparent homogeneity. This inhibitor was extracted from exudate cells of the 24-hr stage of casein-induced peritoneal inflammation and purified using isoelectrofocusing (IEF), gel filtration, followed in this order by high-performance liquid chromatography (HPLC) steps with hydroxylapatite and anionic ion exchanger. The purified factor showed a single band on silver-stained SDS-PAGE. This molecule of MW 19,000 and pI 5.5 inhibited the binding of both IL-1 alpha and beta to receptors on a thymoma cell line, EL-4 and a B-cell line, 70Z/3. We determined its primary structure by a combination of peptide chemistry and molecular cloning. The inhibitor was synthesized as a precursor composed of 177 amino acids and was processed to a mature molecule of 143 amino acids. The N-terminal amino acid of the mature inhibitor was N-acetyl-methionine residue. The deduced amino acid sequence of the inhibitor showed a 77% homology to the human IL-1 receptor antagonist (IL-1Ra) and essentially the same mode of action as seen with human IL-1Ra. We consider that this inhibitor is a rabbit counterpart of human IL-1Ra, although there are differences with respect to the molecular structure; the N-terminus of the mature rabbit IL-1Ra at a position of nine amino acids downstream from that of human IL-1Ra.

Amino Acid Sequence↗
PubMed1991

Action site of circulating interleukin-1 on the rabbit brain.

Interleukin-1 (IL-1) is now generally accepted as an endogenous pyrogenic mediator of fever induction. IL-1 induces fever by means of activation of arachidonate metabolism in the brain. However, whether circulating IL-1 enters the brain or not, further, the question of where is the action site of circulating IL-1 on the brain, have not been clearly demonstrated. In the present study, to investigate the site of action of circulating IL-1 on the brain, recombinant rabbit interleukin-1 beta (IL-1 beta) was labeled with colloidal gold, injected into the carotid artery of anesthetized rabbits and traced in the brain tissue by means of electron microscopy. Dose-dependent increase in colonic temperature was induced by intravenous injection of used IL-1 in rabbits, while heated IL-1 beta lost the pyrogenicity. Injection of solution of colloidal gold per se did not affect the colonic temperature of afebrile conscious rabbits. However, the IL-1/gold conjugates induced fever; IL-1 beta retained its pyrogenic potency even after labeling with gold. By electron microscopy, the IL-1/gold conjugates were observed on the surface and in the vesicle of endothelial cells of the capillary in the region of the anteroventral third ventricle. This implies that circulating IL-1 acts, as the initial step to induce fever, on the endothelium in that region.

Animals↗
PubMed1990

Cerebrospinal norepinephrine concentrations and the duration of epidural analgesia.

This study was performed to determine whether the addition of norepinephrine to local anaesthetics prolongs epidural analgesia in man. In addition, cerebrospinal fluid norepinephrine (NE) concentrations were measured. In the first part of the study, epidural catheters were inserted in 14 patients before herniotomy. Mepivacaine, 1.5 per cent (0.35 ml.kg-1), was administered and norepinephrine (5 micrograms.ml-1) was added in seven patients. The duration of anaesthesia was prolonged from 54 +/- 11 min to 83 +/- 12 min (P less than 0.05) and CSF NE concentrations increased from 68 +/- 12 pg.ml-1 to 336 +/- 85 pg.ml-1 in the NE group (P less than 0.01). In the second part, eight patients with herpetic neuralgia received epidural analgesia at the fourth to eighth thoracic interspace, using bupivacaine 0.25 per cent, with and without NE. The CSF NE concentrations in this group were greater than in the surgical patients before operation and increased from 254 +/- 58 to 406 +/- 58 pg.ml-1 30 min after administration of bupivacaine with NE. The duration of pain relief was prolonged with NE. These results suggest that adding NE to local anaesthetics prolongs epidural analgesia. Moreover, NE concentrations in surgical patients increased to levels similar to those found in patients suffering from herpetic analgesia. This suggests that the increase of CSF NE in chronic pain states has an antinociceptive effect.

Analgesia, Epidural↗
PubMed1990

A limited role of IL-1 in immune-enhancement by adjuvants.

Generation of interleukin-1 (IL-1) in the draining lymph nodes after injection of complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA) and alum was studied in line with IL-1 mRNA expression (cytoplasmic slot blot analysis) and IL-1 beta antigen detection (ELISA and immunohistochemistry) in rabbits. The expression of IL-1 beta mRNA was marked from 6 to 96 hr, with a maximum at around 24 hr post-injection of CFA, while injection of the other two adjuvants elicited only a moderate or negligible response. On the other hand, IL-1 alpha mRNA expression was almost negligible during the entire 8-week observation period after injection of the above three adjuvants. Generation of IL-1 beta antigen in the draining lymph nodes after CFA injection paralleled the expression of IL-1 beta mRNA. Immunohistochemistry revealed that cells containing IL-1 beta resided in the medullary sinuses, marginal sinuses and para-cortical area, but not in the follicles. Despite marked generation of IL-1 beta in CFA-treated draining lymph nodes, the primary antibody response (IgG) to ovalbumin differed only slightly between the three animal groups that were immunized with the antigen incorporated in CFA, IFA and alum. Further, rIL-1 beta did not significantly enhance the immune response when it was entrapped together with the antigen in IFA and alum. IL-1 beta enhanced the immune response only when it was injected with antigen without adjuvant. Thus, IL-1 seemed to play only a limited role, if any, in the augmentation of the primary immune response by the above-mentioned adjuvants.

Adjuvants, Immunologic↗
PubMed1989

The behavior of 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) in blood and brain.

99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) is a reagent for scanning cerebral blood flow. We investigated how 99mTc-HMPAO changed in the blood and brain. The 99mTc-HMPAO, which was prepared by adding of 99mTcO4- to HMPAO and Sn(II), consisted of primary and secondary complexes, reduced hydrolyzed 99mTc, and 99mTc-pertechnetate. The percentage of the primary complex in 99mTc-HMPAO decreased with time after preparation. The primary complex converted to the secondary one very rapidly in the presence of plasma. When 99mTc-HMPAO was injected into patients, 99mTc activity was immediately partitioned in the plasma fraction, with approximately 60% in whole blood. In plasma, 99mTc was found to be associated with proteins such as albumin and globulin. 99mTc trapped in red cells was not washed out with either plasma or saline. Biodistribution studies showed that the less lipophilic compounds of 99mTc-HMPAO could not pass through the blood brain barrier (BBB), and therefore did not accumulate in the brain. The results of gel chromatography and equilibrium dialysis indicated that no specific 99mTc binding protein was present in the brain. Considering the instability of 99mTc-HMPAO in vivo, we proposed that the speed at which the primary complex converted to the less lipophilic compounds was important in allowing 99mTc-HMPAO to pass through the BBB and to be fixed in the brain.

Animals↗
PubMed1989

Comparative clinical study of induction and emergence time in sevoflurane and enflurane anaesthesia.

The induction and emergence times in patients who received minor oral surgery under sevoflurane with nitrous oxide or enflurane with nitrous oxide were compared. The induction time required for the loss of eyelid reflex when using sevoflurane (1.6 +/- 0.2 min) was significantly shorter than that in the enflurane group (2.9 +/- 0.4 min). There was no significant difference in the recovery time in the two groups.

Adult↗
PubMed1989

Interleukin-1 production by polymorphonuclear leukocytes during the course of acute inflammation in rabbits.

Inflammation-induced immune enhancement was observed when an antigen was introduced during an early period of casein-induced inflammation. An immune potentiation factor was detected at the early inflammatory site of mice and rabbits. This immune potentiation factor of rabbits was identified as interleukin-1 (IL-1) in respect of either its biologic activities or its molecular structure. Expression of IL-1 mRNA was observed only in peritoneal exudate cells from the early inflammatory site in parallel with the generation of the immune potentiation activity. The inflammation-induced immune potentiation was assumed to be mediated by newly synthesized IL-1 at the early inflammatory site. By using immunocytochemical staining, it was definitely proved with respect to a single cell level that the polymorphonuclear leukocytes were the major cells in synthesizing IL-1 at the casein-induced inflammation in rabbits.

Acute Disease↗
PubMed1989

Prevention of the toxic action of tumor necrosis factor by cyclooxygenase inhibitor and leukopenia.

The interactions between leukopenia induced by vinblastine and the cyclooxygenase inhibitor indomethacin on the toxicity of tumor necrosis factor (TNF) were studied. When indomethacin was injected 60 min before the administration of recombinant TNF, it provided significant protection against rapid killing by TNF; leukopenia also prevented the toxic action of TNF. However, their inhibition of the activity of TNF was not sufficient, and 17-25% of the rats died within 48 hr following TNF administration. Every rat that received peritoneal polymorphonuclear leukocytes (PMNLs) died within 24 hr following the administration of TNF. On the other hand, administration of indomethacin to the rats in leukopenia prevented the toxic action of TNF completely, and all rats lived for 48 hr and showed no changes, compared to normal rats, in hematocrit, plasma transaminase, and body temperature. From these findings, the toxic action of TNF seems to result from increases in synthesis of prostaglandins (PGs) and activation of PMNLs.

Animals↗
PubMed1989

Biosynthesis of interleukin-I beta at inflammatory site in rabbits: kinetics and producing cells.

Biosynthesis of interleukin-I beta (IL-I beta) by inflammatory peritoneal exudate cells (PEC) was studied in terms of biological activity (thymocyte co-mitogenic assay), IL-I beta mRNA expression (cytoplasmic slot blot analysis) and detection of immunoreactive IL-I beta molecule (immunocytochemistry). Our findings were taken to conclude that IL-I beta expression was observed only in PEC harvested from early inflammatory site and the kinetic profile of the IL-I activity during the course of the inflammation was explained by IL-I beta mRNA expression, namely de-novo synthesis by inflammatory exudate cells. With respect to a single cell level, it was definitely proved that polymorphonuclear leucocytes were the major producer of IL-I beta during the casein-induced acute inflammation in rabbits.

Animals↗
PubMed1988

Cloning and sequence analysis of a cDNA for lymphocyte proliferation potentiating factor of rabbit polymorphonuclear leukocytes: identification rabbit interleukin 1 beta.

Complementary DNA for a rabbit PMN-derived lymphocyte proliferation potentiating factor (PMN factor) was cloned from a cDNA library constructed from poly(A)+RNA of early inflammatory exudate PMN. Oligodeoxyribonucleotides as probes for cloning were synthesized according to the previously reported amino acid sequence of the purified PMN factor. This cDNA encodes a 268-residue protein which is homologous to the established structures of human IL 1 beta (74%0 or murine IL 1 beta (71%). The NH2-terminal amino acid sequence of the endogenously produced PMN factor indicates that the mature molecule is made up of carboxy terminal 152 amino acids of the precursor molecule. Taking into consideration the previous studies on biological activities, this cloned PMN factor is therefore considered to be rabbit IL 1 beta.

Amino Acid Sequence↗
PubMed1988

Purification and partial sequence of rabbit polymorphonuclear leukocyte-derived lymphocyte proliferation potentiating factor resembling IL-1 beta.

A rabbit polymorphonuclear leukocytes (PMN)-derived lymphocyte proliferation-potentiating factor (PMN factor) was finally purified to homogeneity. PMN factor was released from early inflammatory peritoneal exudate cells (98% of PMN) stimulated with kaolin under roller bottle culture conditions. PMN factor was purified by large sequential scale steps, using membrane-type ion exchangers and gel filtration, followed in this order by HPLC steps with cationic ion exchangers and a hydroxylapatite column. Homogeneity was manifested based on the criteria of a single m.w. 18, 500 band on silver-stained polyacrylamide gel, a superimposable activity on a UV absorbance peak in analytic HPLC gel filtration, and detection of a single amino-terminal sequence. The homogeneous PMN factor had an isoelectric value of 7.2 and an activity of 1.9 x 10(7) U/mg in the thymocyte comitogenic assay. PMN factor stimulated one-half of the maximal response of thymocyte proliferation at 2.8 x 10(-12) M. Because of similarities in the physicochemical properties, specific activity, and amino-terminal sequence between rabbit PMN factor and human IL-1 beta, this PMN factor is therefore considered to be a rabbit IL-1 beta.

Amino Acid Sequence↗
PubMed1988

Effects of thromboxane synthase inhibitors on renal function.

In general the effects of thromboxane A2(TXA2) on renal function are opposite those produced by other prostanoids. TXA2 synthase inhibitors decrease the biosynthesis of TXA2 and may increase the production of other prostanoids by causing endoperoxide shunting. Therefore, in situations of increased kidney arachidonate mobilization, inhibition of renal TXA2 synthase might alter renal function by reducing TXA2 production and/or increasing prostaglandin (PG) biosynthesis. This hypothesis was tested by comparing the changes in renal function induced by suprarenal aortic constriction in anesthetized dogs pretreated with either a TXA2 synthase inhibitor (UK38,485; n = 7 or OKY1581; n = 7) or vehicle (0.1 M Na2CO3; n = 9). Several renal function parameters were compared in control versus treated animals by analysis of variance. Neither UK38,485 (1 mg/kg, i.v.) nor OKY1581 (10 mg/kg, i.v.) significantly altered renal artery hypotension-induced changes in mean arterial blood pressure, heart rate, renal blood flow, renal vascular resistance, glomerular filtration, filtration fraction, urine flow rate, sodium excretion rate, fractional sodium excretion, potassium excretion, or fractional potassium excretion. However, both UK38,485 and OKY1581 seemed to attenuate the increase in renal renin secretion rate induced by suprarenal aortic constriction. We conclude that acute administration of TXA2 synthase inhibitors does not modify acute renal artery hypotension-induced changes in either electrolyte excretion or renal hemodynamics. However, acute administration of TXA2 inhibitors attenuates suprarenal aortic constriction-induced increases in renin release in anesthetized dogs by unknown mechanisms.

Acrylates↗
PubMed1988

Cerebrospinal fluid catecholamine levels and duration of spinal anaesthesia.

The effects of catecholamines added to dibucaine on the duration of spinal anaesthesia and cerebrospinal fluid catecholamine levels were studied. Free norepinephrine levels increased from 0.107 ng.ml-1 before anaesthesia to 5.8 ng.ml-1 and 1,238 ng.ml-1 after 1.0 microgram or 100 micrograms norepinephrine had been added to the local anaesthetic. The effects of 2.5 micrograms of either norepinephrine or epinephrine added to dibucaine on the duration of motor blockade and sensory regression time were compared. The duration of both were significantly prolonged by added norepinephrine from 96 +/- 17 min to 193 +/- 20 min (sensory blockade) and from 116 +/- 14 min to 204 +/- 34 min (motor blockade), but were not changed by addition of epinephrine. These data suggest that a 2.5 micrograms dose of norepinephrine is sufficient to prolong the duration of spinal anaesthesia and more effective than the same dose of epinephrine.

Adult↗