Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 487 records · Page 27Linked to original sources

PubMed1994

Case report: nonsurgical treatment of an adult with severe anterior open bite.

A malocclusion characterized by open bite and vertical maxillary excess can be one of the most difficult problems to correct through orthodontic treatment because of the difficulty in permanently changing the morphological disharmony and/or functional disorder associated with open bite. However, in some patients with less severe skeletal impairment it may be possible to orthodontically correct the occlusal disharmony so that the new relationship of the dental arches becomes compatible with normal function of the oral environment. Stability may be enhanced if mechanics are used which do not extrude posterior teeth.

Activator Appliances↗

PubMed1994

Human monoclonal antibody [1-1-2D] against cancer of the uterine cervix.

To obtain a human monoclonal antibody (h-MAb) against cancer of the uterine cervix, lymphocytes from the regional lymph nodes of 14 patients with cervical cancer were fused with a mouse-human heterohybridoma [II]. Of 6,419 hybridomas, 1,295 produced human immunoglobulins (IgG 670, IgM 737). We isolated clone [1-1-2D], which has produced human IgM with stability for more than a year. This antibody reacted with three of five cell lines of cervical cancer but not with normal fibroblasts. Histoimmunostaining showed positive responses to 9/15 specimens of cervical cancer and in 2/7 specimens from cases of cervical dysplasia. Most of the normal human and fetal tissues showed no positive immune response. The positive immune response of [1-1-2D] to the cell membrane observed by the fluorescence antibody method disappeared after periodate treatment and was weakened by trypsin. Neuraminidase did not affect immune reactivity. This antibody showed a positive response by the thin-layer chromatography immunostaining method and precipitated a glycoprotein having a molecular weight of 38 kD. These results suggested that the epitope of the [1-1-2D] antibody is present on a carbohydrate moiety not containing sialic acid that is carried on protein and lipid moieties.

Animals↗

PubMed1994

Different cytoplasmic structure of the CD3 zeta family dimer modulates the activation signal and function of T cells.

The TCR complex transduces the antigen recognition signal through common activation motifs present in both CD3 gamma delta epsilon chains and zeta dimers within the complex. We have investigated functional roles of the cytoplasmic domain in zeta and CD3 gamma delta epsilon for T cell activation in early and late responses by comparing the signaling capability of the TCR complexes containing mutant zeta lacking some or all motifs, or eta chain, another zeta family molecule. The results with the mutant zeta lacking all motifs indicated that CD3 gamma delta epsilon can transduce signals to cause early activation events and production of IL-2 upon antigen stimulation in the absence of zeta motifs. However, any one of the zeta motifs was required to respond to Thy-1 stimulation and this requirement cannot be replaced by other CD3 chains. Such zeta motif-dependent responses were also observed in tyrosine phosphorylation of a 90 kDa protein upon TCR stimulation. Furthermore, we found that the C-terminal unique region of the eta chain exhibits inhibitory function in phosphorylation and Ca2+ response upon TCR stimulation as well as IL-2 production upon Thy-1 stimulation. Collectively, the present analyses suggest that two types of signals are induced through the TCR-CD3 complex: (i) the common motif-dependent signals which are mediated equally through zeta dimers and CD3 gamma delta epsilon, and (ii) zeta specific motif-dependent signals. Differences in the cytoplasmic domain of zeta family molecules may modulate the cooperation of these two signals, resulting in alteration of T cell functions.

Animals↗

PubMed1994

Amniotic fluid enhances allogeneic cytotoxic T cell responses, whereas it suppresses mitogen-stimulated lymphocyte proliferation.

Mouse amniotic fluid has been shown to suppress T lymphocyte proliferation and suggested to be important in regulating immunity during pregnancy. In allogeneic pregnancy, cytotoxic T cells in pregnant lymphocytes against paternal transplantation antigen are impaired. We examined the effect of amniotic fluid to the alloreactive CTL responses. Although the amniotic fluid suppressed Con A or LPS stimulated lymphocyte proliferation as previously reported, the amniotic fluid taken from syngeneic C57BL/6 pregnant mice or allogeneic C57BL/6 x BALB/c pregnant mice enhanced the anti-H-2d or anti-H-2k CTL responses dose-dependently. We speculate that amniotic fluid contains not only immunosuppressive factors but also immunoenhancing factors which upregulate the allogeneic CTL responses.

Amniotic Fluid↗

PubMed1994

Expression of aminopeptidase N on human choriocarcinoma cells and cell growth suppression by the inhibition of aminopeptidase N activity.

We previously found that an aminopeptidase inhibitor, ubenimex (bestatin), had a growth-suppressive effect on choriocarcinoma cell lines in vitro. To clarify the mechanism of this action, we investigated the expression of aminopeptidase N (AP-N/CD13) on choriocarcinoma cells and other human tumor cells. Two choriocarcinoma cell lines, NaUCC-4 and BeWo, had higher AP-N activity than other cell lines (358.8 and 340.2 nmol/h/10(6) cells, respectively), as did human myeloid leukemia cell line, HL-60 (373.8 nmol/h/10(6) cells). These choriocarcinoma and leukemia cell lines with abundant AP-N activity showed much higher sensitivity to bestatin (IC50 = 0.5, 2.1 and 1.0 micrograms/ml, respectively) than the other cell lines. By immunoblotting and immunocytochemical staining, AP-N was detected as an approximately 165-kDa protein and localized on the cell membrane in choriocarcinoma cells. We also examined the effects of two other aminopeptidase inhibitors and three anti-CD13 monoclonal antibodies (MAbs) (WM15, MCS2 and MY7) on the growth of NaUCC-4 cells. Cell growth was markedly suppressed by the AP-N inhibitor actinonin as well as bestatin, but not by the AP-B inhibitor arphamenine. Of the three MAbs, only WM15, which is able to inhibit AP-N activity, suppressed cell growth in a dose-dependent manner. These results indicate that AP-N inhibitors show a growth-suppressive effect, presumably through inhibition of the enzymatic activity of AP-N on tumor cells, and suggest that AP-N may play important roles in the growth of certain tumors, such as choriocarcinoma and leukemia.

Antibodies, Monoclonal↗

PubMed1994

Efficacy of prostacyclin analogue (OP-2507) in viable hepatic grafts from pigs with non-beating hearts.

We investigated whether the stable prostacyclin analogue (OP-2507; OP) would ameliorate warm ischemia-related injury of the liver graft under conditions of a nonbeating heart. Thirty-six mongrel pigs were arranged into 3 groups of 6 pairs. Group 1 pigs underwent orthotopic liver transplantation from heart-beating donors (HBD). In group 2, animals received liver grafts from nonheart-beating donors (NHBD), defined as 30 min of cardiac arrest. Group 3 pigs received grafts from NHBD, but the donor had been pretreated with OP by intraportal infusion (2 microg/kg x min for 30 min immediately before the induction of cardiac arrest). The grafts were preserved at 4 degrees C in Euro-Collins solution in which OP was dissolved at 200 microg/l. Five-day survival rates after transplantation improved significantly in OP-treated animals (3/6, for group 3), compared with 0/6 for group 2 (P < 0.05, generalized Wilcoxon test). Five of 6 animals survived more than 5 days in the HBD group (group 1). Although the serum transaminase activities and bile production did not differ in the early phase of recirculation among the groups, there was a significant improvement in the hepatic microcirculatory environment in the surviving groups (groups 1 and 3). Analysis of arterial prostanoid levels showed a substantial suppression of PGE2 release by OP treatment following reperfusion. Our data indicate that a stable prostacyclin analogue can be clinically useful for expanding the donor pool by improving the quality of the liver graft.

Animals↗

PubMed1994

Successful methods of pancreas transplantation in the rat using a cuff technique.

Two models of pancreas transplantation were examined in the rat with a view to choosing one for regular use in functional experiments. A cuff technique applied to the renal vessels of the recipient was used. The histology and endocrine functioning of whole pancreas-duodenal transplant (Tx) plus bladder drainage (drainage model), and the pancreatic duct ligated segmental pancreas Tx (ligated model) were examined. Syngeneic operations were performed using either Lewis or Wistar rats. Streptozotocin (STZ) 60 mg/kg intravenously (i.v.) was used to render the recipient rats diabetic. A cuff technique was used with both models to anastomose the grafts to the renal vessels instead of the conventional technique of hand suturing to the abdominal vessels. This allows a shorter warm ischaemia time for the donor pancreas and leaves the systemic circulation intact leading to a high success rate for both techniques. Operation survival rates were 93% (n = 30) and 90% (n = 10) in the ligated and drainage models, respectively. The recipients in both groups were normoglycaemic for > 100 days. Histological examination revealed atrophic exocrine tissue early in the ligated group but only two from the drainage group showed exocrine atrophy at > 100 days. There was no statistical difference in i.v. glucose tolerance tests with both models showing a normal pattern. Thus, endocrine function remained independent of exocrine function. Both models are quicker than the conventional techniques. The duct ligation model was a simpler transplant to perform, suggesting that this should be the technique of choice in future experiments.

Anastomosis, Surgical↗

PubMed1994

In vitro and in vivo antibacterial activities of KRM-1648 and KRM-1657, new rifamycin derivatives.

The in vitro and in vivo antibacterial activities of the new rifamycin derivatives KRM-1648 and KRM-1657 were compared with those of rifampin. Rifabutin, ciprofloxacin, and clarithromycin were also tested for reference. The respective MICs of KRM-1648 and KRM-1657 for 90% of the strains tested (MIC90S) were 0.016 and 0.0078 microgram/ml, respectively, for methicillin-susceptible Staphylococcus aureus, 0.016 and 0.0039 microgram/ml, respectively, for methicillin-resistant S. aureus, and 0.0625 and 0.016 microgram/ml, respectively, for methicillin- and quinolone-resistant S. aureus. These MIC90S of KRM-1657 were equal to or 2- to 64-fold lower than those of rifampin. KRM-1648 and KRM-1657 with MIC90S of between 0.002 and 0.078 microgram/ml were 2- to 128-fold more active than rifampin against Staphylococcus epidermidis and Streptococcus species, including Streptococcus pneumoniae and Streptococcus pyogenes. The MIC90S of KRM-1657 for Haemophilus influenzae and Neisseria gonorrhoeae were 0.25 and 0.1 microgram/ml, respectively; KRM-1657 was almost as active as rifampin and was 8- to 16-fold more active than KRM-1648 against these strains. The frequency of occurrence of spontaneous mutations to resistance to KRM-1648 and KRM-1657 was equal to that to rifampin. Against systemic infection with S. aureus in mice, the efficacies of KRM-1648 and KRM-1657 were comparable to that of rifampin.

Animals↗

PubMed1994

Serial changes in coagulant activities after thrombolytic therapy for acute myocardial infarction.

Early reocclusion and bleeding complications are still unresolved problems in thrombolytic therapy for acute myocardial infarction (AMI). In the present study, 16 patients treated with either fibrin-specific tissue-type plasminogen activator (t-PA) or nonspecific urokinase (UK) were studied to determine the effects of thrombolytic therapy on serial hemostatic states. Hemostatic states of each patient were estimated by measuring various plasma markers at one- to two-hour intervals during the first six hours of therapy, daily during the next three days, and subsequently on day 7. Two markers of plasma thrombin generation, thrombin antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F 1 + 2), showed an activated coagulant state immediately after thrombolytic therapy. The amount of thrombin generation indicated by these markers showed significant positive correlation with direct markers of fibrinolysis such as fibrin degradation products (FDP), while it did not show any correlation with the markers for plasmin generation. The potential for coagulation as indicated by prothrombin time (%) decreased with thrombolysis using fibrin nonselective agents, owing perhaps to destruction of coagulant factors by free plasmin. Fibrinolytic activity induced by thrombolytic therapy for AMI caused transient activation of the coagulant system, which could contribute to early reocclusion. Fibrin nonselective agents decreased the potential for coagulation by destroying clotting factor through the generation of free plasmin. These data provide theoretical support for simultaneous administration of anticoagulant therapy with fibrin-specific thrombolytic agents.

Aged↗

PubMed1994

Pharmacokinetics of RK-28 (a new radiosensitizer) and pharmaceutical design of a suppository form using rats.

The pharmacokinetics of RK-28, a new hypoxic cell radiosensitizer, was studied in rats following its intravenous, intraportal, oral, and rectal administration. The pharmaceutical design of an RK-28 suppository form was also examined. After intravenous injection, RK-28 was rapidly removed from the plasma (biological half-life of 17 min) and its area under the curve (AUC) was proportional to the amount of RK-28 administered. The absolute bioavailability of RK-28 was 59.7% for intraportal administration and 36.9% for oral administration. Following oral administration of RK-28, it seems likely that specific acid-catalyzed decomposition of RK-28 takes place in the stomach and then the absorbed RK-28 undergoes first-pass metabolism in the liver. When "solidified RK-28 suppository," made by solidifying molten RK-28, was inserted into the rectum, hepatic first-pass metabolism could be avoided substantially. The resulting absolute bioavailability of RK-28 increased to 75%. Furthermore, "RK-28 emulsion suppository," prepared by emulsifying RK-28 with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80 degrees C, showed a plasma concentration-time curve very suitable for radiation therapy; the maximum plasma concentration was attained 30 min after rectal administration and then decreased within a short period. Administration of "RK-28 emulsion suppository," resulted in an absolute bioavailability of 76%.

Administration, Oral↗

PubMed1994

Oral delivery of poly(lactide-co-glycolide) microspheres containing ovalbumin as vaccine formulation: particle size study.

The objective of the present study was to produce ovalbumin (OVA) loaded poly(lactide-co-glycolide) (PLGA) microspheres with different diameters and to evaluate their possibilities as vaccine formulation in mice following oral inoculation. Four kinds of OVA loaded PLGA microspheres with different mean average volume diameters (1.3, 4.0, 7.5, and 14.0 microns) were manufactured using a w/o/w emulsion/solvent evaporation method. Low loading efficiencies (8-20% w/w) were observed in all batches although smooth spherical particles were obtained. Single oral administrations of OVA loaded PLGA microspheres with different diameters to mice produced immune responses (serum IgG levels by ELISA) which were statistically higher than OVA solution as negative control (Fisher's paired t-test). A dose-response was observed, and single and double inoculation orally produced similar serum antibody levels. The rank of immune response was as follows: 4.0 microns- > 1.3 microns- = 7.5 microns- > 14.0 microns-microspheres. The oral inoculation with 0.13% OVA loaded PLGA microspheres having a mean volume diameter of 4.0 microns exhibited the best immune responses with values greater than those obtained after subcutaneous inoculation with complete Freund's adjuvant (CFA) as positive control, and not significantly different from those obtained after subcutaneous inoculation with the same microspheres.

Adjuvants, Immunologic↗

PubMed1994

In vivo microdialysis for the transdermal absorption of valproate in rats.

The suitability of sampling via microdialysis for a lipophilic drug, valproate (VPA), was evaluated by the elimination rate constant of VPA solution in an in vitro experimental first-order elimination system. The elimination rate constant of VPA in dialysate was found to be 0.43 +/- 0.05h-1, which was in good agreement with the real elimination rate constant (0.46 +/- 0.02h-1). A change in VPA concentration in the solution surrounding a microdialysis probe was well maintained by the microdialysis method, suggesting no adsorption between the membrane of the microdialysis probe and VPA. On the basis of the in vitro experiment, the effect of a penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), on the transdermal absorption of VPA was examined in rats by the use of microdialysis in vivo. An intradermal microdialysis was performed at a flow rate of 1.0 microliter/min for 7h after the dermal application of 50 mM VPA solution with or without 3% (w/v) HPE-101. HPE-101 increased the transdermal absorption rate of VPA by 80 times compared with the control. The microdialysis system was found to be quite useful for assessing the in vivo transdermal absorption of a lipophilic VPA.

Animals↗

PubMed1994

Relationship between lipophilicity and skin permeability of various drugs from an ethanol/water/lauric acid system.

The in vitro skin permeability of 16 drugs with a wide range of lipophilicity (log P; -0.95-4.40) was evaluated by the use of an ethanol/water (60/40) binary vehicle with or without lauric acid as a permeation enhancer. The enhancing effect by the addition of lauric acid to the ethanol/water (60/40) binary vehicle could be observed from the aspect of both permeation rate and lag time. The permeation rate increased with an increase in the hydrophilicity of the drugs. It was considered that lauric acid exerts an effect on both the polar and nonpolar regions of lipids of the stratum corneum, and the cooperative interaction of ethanol and lauric acid increases the participation of the polar pathway of drugs. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/water (60/40) binary vehicle with lauric acid showed a parabolic shape, with its peak at a more hydrophilic range (log P; 0.19) compared with other past references (log P; 2-3). The ethanol/water (60/40) binary vehicle with lauric acid appears to be a good candidate as a vehicle for transdermal therapeutic systems for hydrophilic drugs.

1-Octanol↗

PubMed1994

In vivo microdialysis for pharmacokinetic investigations: a plasma protein binding study of valproate in rabbits.

The use of microdialysis to study the binding of valproate (VPA) to plasma proteins was evaluated in rabbits. Prior to an in vivo microdialysis, in vitro relative recovery of VPA respectively from Ringer's solution, 5% (w/v) of albumin solution and plasma sample via a microdialysis probe was examined. The in vitro relative recovery was defined as a ratio of the VPA concentration determined in the dialysate to the free VPA concentration in the sample solution surrounding the membrane of the microdialysis probe. When the sample solution was well stirred at 700 rpm and maintained at 37 degrees C, the in vitro relative recovery of VPA was significantly different among them. It increased in the order of Ringer's solution (34.3 +/- 2.6%) > 5% (w/v) of albumin solution (25.7 +/- 4.6%) > rabbit plasma sample (15.8 +/- 1.2%). Thereafter, pharmacokinetics of VPA was determined using both microdialysis sampling via the rabbit femoral vein and collection of whole blood via the rabbit ear vein after intravenous administration of VPA at a dose of 43 mg/kg. Free concentrations of VPA in plasma were determined by ultrafiltration method as opposed to microdialysis method. There was no difference in the elimination half-life of VPA determined by microdialysis, 1.09 +/- 0.22 h, or ultrafiltration, 1.22 +/- 0.21 h. The AUC of VPA in dialysate was 15 +/- 4 micrograms.h/ml, which corresponded to 15% of that in ultrafiltrate (103 +/- 17 micrograms.h/ml). The value was in good agreement with the in vitro relative recovery of VPA from plasma sample (15.8 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Preparation and evaluation of suppositories for RK-28 (a new radiosensitizer) using rabbits.

The pharmacokinetics of RK-28 [1-(4-hydroxy-2-butenoxy)methyl-2-nitroimidazole], a new hypoxic cell radiosensitizer, was studied following intravenous, oral, and rectal administration to rabbits. After an oral administration of RK-28 solution, the plasma concentration of RK-28 was considerably lower than that after intravenous administration through all time periods, and the absolute bioavailability was a mere 4.2%. It was presumed that a specific acid-catalized decomposition of RK-28 progressed in the stomach, and also, the absorbed RK-28 suffered first-pass effects in the liver. In contrast, the absolute bioavailability following the rectal administration of a solidified RK-28 suppository preparation was significantly increased in comparison with that obtained by other administration routes. Also, RK-28 emulsion suppositories were prepared by emulsifying various amounts of the drug with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80 degrees C, and these were administered into the rabbit rectum. The resulting absolute bioavailability was 91% for the RK-28 emulsion suppository and 86.9% for an RK-28 emulsion suppository containing small amounts of Eudispert hv. These values were better than those in rats. The rectal administration of the RK-28 emulsion suppository containing small amounts of Eudispert hv showed a preferable plasma concentration-time pattern that reflects on radiation therapy.

Administration, Oral↗

PubMed1994

Familial arteriovenous malformations of the brain--two case reports.

Familial arteriovenous malformation (AVM) of the brain is an uncommon entity. A 24-year-old female presented with sudden onset of left hemiparesis due to an AVM with a hematoma in the right frontal lobe, which was surgically removed. Her 23-year-old younger sister presented with motor aphasia and right hemiparesis due to an AVM with a hematoma in the left frontoparietal lobes, which was surgically removed. Thirty-two patients in 15 families have been described in total. The mean age of these patients was 28 years, with 15 males and 17 females. Multiple AVMs occurred in four patients (12.5%), more frequently than in non-familial cases.

Adult↗

PubMed1994

Sequential changes in ischemic edema following transient focal cerebral ischemia in rats: magnetic resonance imaging study.

Sequential and regional changes in ischemic edema following various durations of focal cerebral ischemia were studied by magnetic resonance (MR) imaging in a rat unilateral intraluminal middle cerebral artery occlusion model. Occlusion was performed from 5 minutes to 5 hours. T2-weighted images were obtained chronologically 6 hours after onset of ischemia, on day 1 and day 7. An immunohistochemical study using antibodies to calcineurin and glial fibrillary acidic protein was performed to observe histological changes in the ischemic brain. The T2 high-signal-intensity areas representing ischemic edema were observed in the lateral striatum and/or the cerebral cortex by day 1 in all rats with 1- to 5-hour ischemia, and the areas were larger and detected earlier with longer durations of ischemia. In three of six rats with 15-minute ischemia and five of six rats with 30-minute ischemia, the T2 high-signal-intensity areas appeared transiently on day 1 in the dorsolateral striatum where loss of neurons expressing calcineurin immunoreactivity and associated gliosis were found. MR imaging in animal models of reversible focal ischemia can achieve sequential and noninvasive evaluation of dynamic regional changes in ischemic edema.

Animals↗

PubMed1994

[Treatment results of radical nephrectomy for relatively confined small renal cell carcinoma--translumbar versus transabdominal approach].

We performed radical nephrectomy for 166 patients with renal cell carcinoma over 25 years period between 1967 and 1991. Among them, 49 patients had stage T1-3 NOMOVO tumors less than 6 cm in maximum diameter. Twenty-seven of them received radical nephrectomy by a modified translumbar approach whereas the conventional transabdominal approach was applied to the remaining 22 patients. We retrospectively studied treatment results of the 49 patients to evaluate the current translumbar approach. There was no significant difference in the age and sex distribution of the patients, and the size, stage, grade and histological subtype of the tumor between translumbar and transabdominal groups, although the incidence of venous invasion (pVla) was significantly greater in translumbar group. Statistical analysis revealed shortened operating time, decreased blood loss and quickened postoperative recovery (resuming oral intake or walking) in translumbar group as compared to those in transabdominal group. No major complication was observed in both groups. There was no significant difference in actuarial survival rate or disease-free survival period between the two groups. Actuarial three-year survival rate was 96% for translumbar and 89% for transabdominal group, respectively. Sites of metastasis were lung (2 patients) or bone (1 patient) in translumbar group and bone (1 patient) or unknown (1 patient) in transabdominal group. With the favorable prognosis comparable to that of transabdominal radical nephrectomy and the relatively small invasiveness, the current translumbar radical nephrectomy appears to be the choice for the patients with relatively confined small renal cell carcinoma.

Adult↗