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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 559 records · Page 31Linked to original sources
PubMed1993

Comparison of potentiality to induce graft-versus-host reaction with small bowel, pancreas/spleen, and liver transplantation in the rat.

Although small bowel transplantation (SBT), or pancreas-spleen transplantation (PST) often lead to lethal graft-versus-host reaction (GVHR) in experimental animals, fatal GVHR is rare after clinical liver transplantation. This study describes a modified model of SBT and PST in the rat using cuff techniques applied to the renal artery and vein of the recipient. The ability of LEW (RT1(1)) or BN (RT1n) lymphocytes accompanying intestinal, splenic, or hepatic grafts to induce lethal GVHR in (LEW x BN) F1 hybrid recipients was compared. SBT and PST experiments showed that lethal GVHR always occurred in LEW-into-F1 combination, but was much less frequent in BN-into-F1 SBT. In mixed lymphocyte reaction (MLR), LEW mesenteric or splenic T cells showed significantly higher proliferative responses against BN stimulators than did BN mesenteric or splenic T cells against LEW. Adoptive cell transfer experiments using mesenteric or splenic cells also showed that LEW cells were higher responders than BN. In contrast with SBT and PST results, a lethal GVHR was not induced after liver or pancreas grafting alone in either parent-to-F1 combination. In MLR, hepatic T cells from either parent failed to elicit a proliferative response against allostimulators. These results indicate that the occurrence of lethal GVHR is dependent upon the reactivity of parental lymphocytes against allo-antigenicity of F1 hybrids and also upon the lymphoid tissue transplanted. The lack of alloreactivity of hepatic T cells accounts for the absence of lethal GVHR after liver grafting.

Animals↗
PubMed1993

[In vivo effect of growth-inhibitor produced by Pseudomonas aeruginosa isolates and anti-pseudomonal drugs on model infection due to Pseudomonas aeruginosa].

Pseudomonas aeruginosa Nos. 1 and 5, each co-existing growth-inhibitor-producing and -nonproducing cells, were used in this study. An equal number of both cells (each 10(8) CFU/mouse) was challenged intraperitoneally to mice, and these cells in the heart blood and kidneys of mice were determined. Furthermore, the effect of piperacillin, ceftazidime and sisomicin on the cell distribution in mice was studied in the model infection due to P. aeruginosa Nos. 1 and 5. As a control experiment both cells of P. aeruginosa No. 1 were each challenged intraperitoneally at a dose of 10(8) CFU/mouse to mice of two groups, but there were no marked differences between the two types in cell counts of the heart blood or kidneys 9 hours after challenge. When a concomitant challenge of both cells (each 10(8) CFU/mouse) was performed in mice, the number of growth-inhibitor-producing cells of the heart blood and kidneys was about 100 times greater than that of the non-producing cells. These in vivo results were well comparable to the previous in vitro results and indicated that the inhibitor affected the invasion of the non-producing bacteria in the body in the model infection due to P. aeruginosa isolates consisting of the two types of cells. Similar results were obtained in mice with the model infection due to P. aeruginosa No. 5. Anti-pseudomonal drugs such as piperacillin (50 mg/mouse) and ceftazidime (50 mg/mouse) and sisomicin (1 mg/mouse) were given intramuscularly to mice infected concomitantly with both cells of P. aeruginosa No. 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

In vitro and in vivo antibacterial activities of E1077, a novel parenteral cephalosporin.

E1077, a new injectable cephalosporin with a broad antibacterial spectrum and potent antibacterial activity, was evaluated for its in vitro and in vivo antibacterial activities in comparison with those of cefpirome, cefuzonam, ceftazidime, and cefotaxime. E1077 showed broad in vitro antibacterial activity against gram-positive and gram-negative bacteria. Against methicillin-susceptible Staphylococcus aureus, E1077 was as active as cefpirome; the MIC for 90% of strains tested (MIC90) was 1.0 microgram/ml. Against methicillin-resistant S. aureus, E1077 was less active (MIC90, 64 micrograms/ml). For Enterobacter cloacae and Pseudomonas aeruginosa, E1077 was fourfold more active than cefpirome, with MIC90s of 1.0 and 16 micrograms/ml, respectively. For Proteus vulgaris, the MIC90 of E1077 was 32 micrograms/ml, which was fourfold greater than that of cefpirome. Against other gram-negative strains tested, the in vitro activity of E1077 was comparable to that of cefpirome. The broad antibacterial spectrum of E1077 was reflected by its in vivo efficacy against experimental septicemia caused by gram-positive and gram-negative bacteria. Against S. aureus 90 and P. aeruginosa E7, E1077 had activity superior to those of the reference compounds; against most other bacterial strains, the efficacy of E1077 was similar to that of cefpirome. Levels of E1077 in plasma and tissue of mice were studied. At 15 min after a single subcutaneous administration, E1077 displayed high peak levels (mean, 31.8 +/- 3.1 micrograms/ml). These results indicate that the in vitro and in vivo efficacies of E1077 are similar to those of cefpirome except against P. aeruginosa and P. vulgaris.

Animals↗
PubMed1993

Detection of Mycobacterium tuberculosis in clinical specimens by polymerase chain reaction and Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test.

The polymerase chain reaction (PCR) using oligonucleotides based on the repetitive sequence (IS986) of Mycobacterium tuberculosis as a primer and the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD), which combines an M. tuberculosis rRNA amplification method with the hybridization protection assay format, were evaluated for detection of M. tuberculosis in clinical samples. The detection limits of these two assay systems based on nucleic acid amplification for cultured M. tuberculosis were less than 10 cells per reaction. A total of 135 sputum specimens were examined by the two assay systems. The PCR and the MTD systems for detection of M. tuberculosis gave overall positivity rates of 84.2% (32 of 38) and 91.9% (34 of 37), respectively, as compared with 71.9% (23 of 32) by smear and 96.9% (31 of 32) by culture in the liquid medium MB-Check. Procedures for sample preparation used in the two methods were different. Although the sensitivities of the PCR and MTD appeared to be similar to that of culture with the MB-Check system, the two methods based on nucleic acid amplification should be very useful for rapid detection of M. tuberculosis infections without the long time required for culture of M. tuberculosis.

Bacteriological Techniques↗
PubMed1993

Latency of the Achilles tendon reflex for detection of reduced functions of the peripheral nervous system in workers exposed to lead.

The latency of the soleus muscle potential, evoked by a tap of the Achilles tendon, was used in the mass assessment of healthy male workers exposed to lead. Three groups were studied: a control, a low exposure, and a high exposure group. Mean blood lead concentrations were 9.3, 19.2, and 53.1 micrograms/100 ml respectively. Latencies were adjusted for age and height and then compared among the three groups. The mean corrected latency of the high exposure group showed a 4% increase compared with the other two groups (p < 0.01). The latencies of the other two groups showed no between group differences. These results were consistent with previous neurophysiological studies done by many researchers on workers exposed to lead. They suggested that nerve conduction velocities decreased from 3 to 13% among workers whose mean blood lead concentrations were more than 30 micrograms/100 ml. The method was simple, time conserving, non-invasive, and non-aversive, and provided a quantitative measure of the nerve conduction velocities of peripheral nerves. Thus it may be useful for early detection of occupationally related impairment of peripheral nerves.

Achilles Tendon↗
PubMed1993

Prolonged activation of fibrinolytic system induced by fibrin nonselective thrombolytic agent can contribute to preventing early reocclusion after coronary thrombolytic therapy.

The incidence of early reocclusion is reported to be higher in patients who receive fibrin-specific thrombolytic agents than nonspecific ones. The reason has yet to be clarified. In the present study, we focused on the difference in duration of fibrinolytic activity. The hemostatic parameters of 7 consecutive patients suffering from acute myocardial infarction treated with a fibrin-nonspecific thrombolytic agent (urokinase) were compared with 9 patients who received a fibrin-specific agent (tissue plasminogen activator, t-PA). The plasma concentrations of alpha 2-plasmin inhibitor (alpha 2-PI), plasmin alpha 2-PI complex (PLC), fibrin degradation products E fragment (FDP-E), and D-D dimer (D-dimer) were measured before, soon after, 1, 2, 3, 4, and 6 h and 2, 3, 4, and 7 days after thrombolytic therapy to estimate the hemostatic and fibrinolytic state. A significant decrease in alpha 2-PI (less than the lowest measurable level) with a simultaneous increase in FDP-E and D-dimer was induced soon after the administration of urokinase. FDP-E and D-dimer decreased, with a significant increase in alpha 2-PI, more than 6 h after thrombolytic therapy. In contrast, a less significant decrease in alpha 2-PI with a lesser amount and shorter duration of fibrinolysis were observed in patients who received t-PA. The amount of PIC soon after drug administration was not different between the two groups. Our data suggested that fibrinolytic activities induced by fibrin-nonspecific urokinase persisted longer than expected by its plasma half-life.The fibrinolytic activities might be terminated by the production of alpha 2-PI.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Serial changes in plasma concentration of plasminogen activator inhibitor-1 before and serially after thrombolytic therapy for acute myocardial infarction.

Plasminogen activator inhibitor-1 (PAI-1), which is secreted from vascular endothelial cells, plays an important role in regulating fibrinolysis. We measured the plasma concentrations of tissue-type plasminogen activator (t-PA), PAI-1 and t-PA PAI complex before and serially after thrombolytic therapy for acute myocardial infarction to clarify the relationship between thrombolytic therapy and PAI-1. Plasma concentrations of t-PA, PAI-1 and t-PA PAI complex before thrombolytic therapy were 11.6 +/- 5.5, 27.0 +/- 13.0 and 7.3 +/- 5.4 ng/ml, respectively. t-PA and t-PA PAI complex increased to 25.0 +/- 5.3 and 14.3 +/- 6.5 ng/ml immediately after drug administration; however, the level of PAI-1 decreased slightly immediately after thrombolytic therapy. The PAI-1 level increased again several hours after therapy, especially in patients showing apparently successful reperfusion. All values returned to normal 4-7 days after thrombolytic therapy. Not only augmented antifibrinolytic activity suggested by increased PAI-1 but also augmented fibrinolytic activity suggested by increased t-PA was observed in patients with acute myocardial infarction. These abnormal findings persisted several days after coronary thrombolytic therapy.

Aged↗
PubMed1993

Dissecting aneurysm of the posterior inferior cerebellar artery: case report.

A patient with a dissecting aneurysm of a posterior inferior cerebellar artery who presented with Wallenberg's syndrome is reported. A 31-year-old man suddenly experienced an occipital headache, vertigo, and vomiting, followed by dysphagia. A neurological examination revealed partial Wallenberg's syndrome. Vertebral angiography revealed aneurysmal dilatation at the origin of the left posterior inferior cerebellar artery, with distal luminal narrowing. T1-weighted magnetic resonance imaging demonstrated an area of high-signal intensity, indicating an intramural hemorrhage in the arterial wall of the narrowed lumen. The dissecting aneurysm with a typical intramural hematoma of the posterior inferior cerebellar artery was entrapped with clips after an anastomosis of the left occipital artery to the distal posterior inferior cerebellar artery. The diagnosis and the treatment of dissecting aneurysms of the posterior inferior cerebellar artery are discussed.

Adult↗
PubMed1993

Pharmacological modulation of antigen-induced airway hyperresponsiveness by thromboxane A2 inhibitors in guinea pigs.

The effects of OKY-046 (thromboxane A2 (TXA2) synthetase inhibitor) and ONO-3708 (TXA2 receptor antagonist) on antigen-induced airway hyperreactivity in guinea pigs were investigated. Ketotifen was used as a reference drug. Seven inhalations of an antigen into actively sensitized animals resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (macrophages, neutrophils, eosinophils and lymphocytes) and the quantity of mediators (thromboxane B2, leukotriene D4 and histamine) in bronchoalveolar lavage fluid increased. All examined drugs inhibited the antigen-induced airway hyperreactivity to acetylcholine. Whereas ketotifen inhibited an accumulation of inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid, OKY-046 and ONO-3708 had no effect on the accumulation of inflammatory cells. OKY-046, but not ketotifen and ONO-3708, inhibited an increase of thromboxane B2 in the bronchoalveolar lavage fluid after antigen provocation. These results suggest the participation of TXA2 in the onset of antigen-induced airway hyperresponsiveness in guinea pigs, and the efficacy of TXA2 inhibitors, without affecting the accumulation of inflammatory cells in bronchoalveolar lavage fluid.

Acetylcholine↗
PubMed1993

Evaluation of enteric coated tablet sensitive to pancreatic lipase. II. In vivo evaluation.

Plain tablets containing a model drug, sulfamethizole (SMZ), were coated with triolein (TO), trilaurin (TL) and ethylcellulose (EC). The biological behavior of the coated tablets (TOTL-Tab), which are pH independent and sensitive to pancreatic lipase, was investigated in humans. Results of the administration of the tablets with or without an antacid, under fasting and non-fasting conditions, and at 0.5 h before and 0.5 h after meals, were examined. A comparison of the in vivo behavior of SMZ after the administration of these tablets was done using the following data: the lag time of urinary excretion (Ulag), the total urinary recovery percentage (X infinity u), and the mean residence time after Ulag (MRTaf). A typical pH-sensitive tablet coated by cellulose acetate phthalate (CAP-Tab) was used as a reference. For the administration of a CAP-Tab alone, the Ulag obtained under both the non-fasting and fasting condition was longer than that of the plain tablet. However, Ulag after the administration of a CAP-Tab with an antacid became considerably shorter. This lag time was about the same as that obtained from the plain tablet, regardless of food ingestion. The obtained CAP-Tab MRTaf and X infinity u values were not significantly different in comparison to the plain tablets. Under the non-fasting condition, Ulag, MRTaf and X infinity u of TOTL-Tab were not affected by the co-administration of an antacid, and these values were virtually the same as those obtained from a CAP-Tab without an antacid. The urinary excretion data obtained after the administration of TOTL-Tab alone under fasting was analogues to the non-fasting case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of hydrophilic and lipophilic vehicles on skin permeation of tegafur, alclofenac and ibuprofen with or without permeation enhancers.

The effects of an ethanol/panasate 800 (tricaprylin) (40/60) system as a lipophilic vehicle, and an ethanol/water (60/40) system as a hydrophilic vehicle, with or without permeation enhancers for in vitro skin permeation and in vivo skin absorption of tegafur, alclofenac and ibuprofen with different lipophilicity, were evaluated. The in vitro and in vivo skin permeability of tegafur, alclofenac and ibuprofen was enhanced by the use of ethanol/panasate 800 (40/60) or ethanol/water (60/40) binary vehicles as a donor composition. However, the two vehicles showed contrastive properties in relation to the extent of permeation enhancement of the three drugs: tegafur > alclofenac > ibuprofen for the ethanol/panasate 800 (40/60) system, and ibuprofen > or = alclofenac > tegafur for the ethanol/water (60/40) system. When lauric acid, as a permeation enhancer, was added to both of the binary vehicles, the in vitro and in vivo skin permeability of three drugs further increased, and the in vivo absorption rate of the drugs from the ethanol/water (60/40) system was larger than that from the ethanol/panasate 800 (40/60) system. In conclusion, it was suggested that the ethanol/panasate 800 (40/60) lipophilic binary vehicle is useful for hydrophilic drugs, and conversely, the skin absorption of lipophilic drugs can be improved by the use of the ethanol/water (60/40) hydrophilic binary vehicle with or without lauric acid as a permeation enhancer.

Animals↗
PubMed1993

Transport of aspirin and its metabolites through human erythrocyte membrane.

The transport of aspirin (ASP) and its metabolites (salicylic acid (SA), salicyluric acid (SAU), gentisic acid (GA) and gentisuric acid (GAU)) through human erythrocyte membrane was investigated. ASP permeated rapidly into the erythrocytes and the concentration dwindled gradually after the maximum concentration was attained almost within one minute. It was suggested that SA is released from the erythrocytes after ASP transported into the erythrocytes is hydrolyzed in them. In both an inward and outward direction, the transport rates of SA and GA were rapid, while those of SAU and GAU were lower by conjugating glycine. It was suggested that GAU remains for a long time in a living body. The rate of transport of GA and GAU were markedly obstructed by the band 3 protein inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate, although the transport rates of SA and SAU were obstructed only slightly. It was suggested that the transport of GA and GAU are mediated through band 3 protein.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1993

Enhancement effect of an ethanol/Panasate 800 binary vehicle on anti-inflammatory drug permeation across excised hairless mouse skin.

The novel binary vehicle system consisting of ethanol (EtOH) and Panasate 800 as tricaprylin was applied to five types of nonsteroidal anti-inflammatory drugs, and its enhancing effect on drug permeation across hairless mouse skin in vitro was assessed. The permeability of all drugs was remarkably increased by the treatment of skin with EtOH/Panasate 800 binary systems compared with either EtOH or Panasate 800 alone, and the effect reached a maximum in EtOH/Panasate 800 (40/60) system. With regard to this binary system, the skin permeation ratio or flux of the drug increased in the following order: salicyluric acid (SU) > salicylic acid (SA) > alclofenac (ALC) > ketoprofen (KP) > ibuprofen (IBU). The one-layer skin model was applied concerning the above skin permeation profiles of the five drugs. Diffusion parameter (D'), partition parameter (K'), and permeation constant (Kp = D' x K') were calculated using the Laplace-transformed equations with the aid of MULTI (FILT). It was well demonstrated that the reduction of lag time and the increase of flux caused by EtOH/Panasate 800 binary vehicle systems was due to an increase of D' value by Panasate 800 and K' value by EtOH, respectively, in the skin. Especially, the EtOH/Panasate 800 (40/60) binary vehicle system produced the largest Kp value in each drug. In relation to all the EtOH/Panasate 800 binary vehicle systems, the logarithms of calculated Kp were found to be in inverse proportion to the logarithms of a n-octanol/water partition coefficient (P) of the drug which appeared in previous literature.

Animals↗
PubMed1993

In vivo release of water-soluble drugs from stabilized water-in-oil-in-water (W/O/W) type multiple emulsions following intravenous administrations using rats.

The in vivo release of four water-soluble drugs, cefadroxil, cephradine, antipyrine and 4-aminoantipyrine, from a stabilizing water-in-oil-in-water (W/O/W) type multiple emulsion was studied using rats. The W/O/W type multiple emulsion used in this study could be stabilized for 30 d after preparation at room temperature and also for 24 h in pH 7.4 isotonic phosphate buffer or in rat plasma at 37 degrees C. The cefadroxil and cephradine concentrations in rat plasma following intravenous administrations of their W/O/W type multiple emulsions containing drugs were considerably prolonged compared with those of respective aqueous solutions. Sustained-releasing properties of cefadroxil and cephradine from W/O/W type multiple emulsions could be explained by the mechanism underlying the long residence time of W/O/W type multiple emulsions and delay-release of drugs from the W/O/W type multiple emulsions circulated with rat blood stream. However, antipyrine and 4-aminoantipyrine decreased rapidly following W/O/W type multiple emulsions and these plasma profiles coincided precisely with those following intravenous administration of the aqueous solutions of drugs. These in vivo releasing data correlated with in vitro drug release observation stated in the previous papers.

Amino Acids↗
PubMed1993

[Anxiolytic activities of pentanthrene type heterocyclic compounds].

A series of pentanthrene type heterocyclic compounds were synthesized and evaluated for anxiolytic activities by three kinds of behavioral pharmacological tests. Several compounds showed anxiolytic activities. In particular, s-triazolo[3,4-a]phthalazine (Tri-P) and 3-propyl derivatives of Tri-P(PTP) showed remarkable activities, although the activities were slightly lower than those of diazepam. The results suggested that Tri-P or PTP is a useful lead compound for the development of the antianxietic agents. The relationship between the structure and anxiolytic activity, and the inducing mechanism of the activity was discussed.

Animals↗
PubMed1993

Further studies on the endogenous serotonin-uptake-inhibitor-like substances in the human cerebrospinal fluid.

The properties of endogenous substances that inhibit 5HT uptake in human cerebrospinal fluid (CSF) were investigated. Human CSF was loaded onto a Sephadex G-25 column, and each fraction was tested for its ability to inhibit [3H]paroxetine binding in monkey brain preparations. We found four different inhibitory peaks with respective molecular weights (M.W.) of > 12400, 2000 and two of < 1350. The third and fourth peaks (F-3, F-4: < 1350 M.W.) of inhibitory activity were determined to consist of some monoamines (5HT, etc.) or their metabolites (5HIAA, etc.) and other unidentified compounds by using an HPLC-electrochemical detector. The second peak (F-2, M.W. about 2000) displaced [3H]paroxetine binding noncompetitively (decreased Bmax and did not change Kd) and inhibited [3H]5HT uptake noncompetitively (decreased Vmax and did not change Km), but had no effect on either [3H]norepinephrine uptake or [3H]dopamine uptake. These results suggest that the endogenous substances that selectively inhibit 5HT uptake are present in human CSF as low molecular weight compounds.

Animals↗
PubMed1993

20 days bed-rest on insulin action in relation with body fat in young subjects.

It is well known that a daily positive physical activity is able to control body fat and to improve insulin action for intaking glucose in the muscles, especially under administration of nutrition in human. Conversely, when exposed prolonged inactive condition such as bed-rest in spite of control of nutrition, the insulin action may be declined due to less glucose intake in the muscles and thus the insulin secretion may be increased to maintain blood glucose level. If it is so, the increased insulin should accelerate intake of neutral fat and to lower fatty acid in the fat tissues. Further, if the prolonged inactivity would decrease plasma epinephrine and norepinephrine secretion, the breakdown of the stored fat should be declined due to declining hormone susceptible lipase secretion, resulting in increase in body fat, which may reflect the changes in lipo-proteins and apoproteins. In the present study, the hypothesis mentioned above were investigated in young persons exposed to prolonged horizontal bed-rest of 20 days.

Adipose Tissue↗