Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 361 records · Page 20Linked to original sources

PubMed1996

Intradermal administration of lipopolysaccharide in treatment of human cancer.

Lipopolysaccharide (LPS) has been recognized as a potent antitumor agent in animal tumor models; however, its use in human cancer therapy has been limited to only one trial, in which LPS from Salmonella was given intravenously. It was not very successful because of poor tumor response and was also toxic. We originally developed LPS prepared from Pantoea agglomerans (LPSp), and this was a well-purified, small-molecular-mass (5 kDa) agent. We chose intradermal rather than intravenous administration in the hope that the former would release LPS slowly into the bloodstream, and thus be less toxic while preserving antitumor activity. In our animal tumor models, intradermal administration was indeed less toxic and more beneficial for tumor regression than intravenous administration. We made a pilot study with intradermal administration of LPSp on the treatment of ten advanced cancer patients. Five of them had evaluable tumor, which had failed earlier to respond to conventional chemotherapy. Cyclophosphamide was also administered in this trial, in anticipation of its synergistic effect with LPSp. In this study LPSp was injected intradermally into each patient twice a week, starting with an initial dose of 0.4 ng/kg, and raising it to 600 or 1800 ng/kg. A 400-mg/m2 dose of cyclophosphamide was given intravenously every 2 weeks. After completion of the dose escalation, the treatment was continued for at least 4 months, and it was found that 1800 ng/kg LPSp was well tolerated. A significant level of cytokines was observed in the sera for at least 8 h. These results indicate higher tolerable doses and remarkably more continuous induction of the cytokines than were reported in a previous study by others using intravenous administration. Three of the five evaluable tumors showed a significant response to our combined therapy. Intradermally administered, LPS was less toxic and elicited a tumor response in combination with cyclophosphamide; it can thus can be applied to cancer treatment even in humans.

Administration, Cutaneous↗

PubMed1996

Promotion of proliferation of murine hematopoietic stem cells by growth factors in murine amniotic fluid.

It has been shown that murine amniotic fluid (MAF) displays immunosuppressive activities. We examined the effect of MAF obtained from normal mice on a murine fetal liver cell (FLC) primary culture in vitro for the detection of the possible existence of cytokines that affect hematopoiesis. MAF promoted proliferation of murine FLC and adult bone marrow cells. Proliferation-promoting activity of MAF was observed throughout the period between days 12 and 15 of pregnancy, peaking at day 12. Pooled MAF was subjected to purification procedures to isolate the active molecule(s). After ion exchange and size exclusion chromatography, one of the active molecules was shown to react with anti-mouse stem cell growth factor (SCF) antibody and the molecular weight was determined as 40-45 kDa by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. The proliferation-promoting activity of MAF was partially neutralised by the anti-SCF antibody. These results provide evidence that MAF may contain multiple growth factors for FLC, one of which may be a unique molecule related to SCF.

Amniotic Fluid↗

PubMed1996

Gabaergic transmission and tyrosine hydroxylase expression in the nigral dopaminergic neurons: an in vivo study using a reversible ischemia model of rats.

The authors conducted an in vivo study, using a rat striatal ischemic model, of the effect of GABAergic transmission upon the dopamine synthesizing enzyme tyrosine hydroxylase in the neurons of the substantia nigra pars compacta. Two hours transient middle cerebral artery occlusion produced massive striatal ischemic damage resulting in a marked decrease of GABAergic projection to the ipsilateral substantia nigra. Histological examinations were conducted in rats killed at three, seven, 15, 30 and 94 days after ischemia. The immunoreactivity for tyrosine hydroxylase in the ipsilateral pars compacta was unaltered up to three days after the ischemic insult, but it was markedly decreased at seven days post-ischemia. At this stage, the number of neurons positive for tyrosine hydroxylase was significantly decreased in the ipsilateral pars compacta, whereas there was no significant reduction in the number of pars compacta neurons containing Nissl substance. By 30 days post-ischemia, the tyrosine hydroxylase-positive cell number in the ipsilateral pars compacta appeared to be equivalent to that of the contralateral side. It was also noted that continuous intraventricular administration of a GABAA receptor agonist muscimol, initiated from 24 h post-ischemia, effectively prevented the transient reduction of immunoreactivity for tyrosine hydroxylase in the ipsilateral pars compacta at seven and 15 days after ischemic insult. The present study revealed that the striatal ischemic lesion induced a transient down-regulation of tyrosine hydroxylase synthesis in the pars compacta neurons, which could be prevented by administration of GABA agonist, suggesting that GABAergic transmission greatly affects dopamine metabolism in these cells.

Animals↗

PubMed1996

The hemagglutination inhibition antibody responses to an inactivated influenza vaccine among healthy adults: with special reference to the prevaccination antibody and its interaction with age.

The immunogenicity of the trivalent split-virus influenza vaccine was investigated among 70 healthy adults (mean age: 48.5, range: 36-68). The vaccine antigens were: A/Yamagata/32/89 (H1N1); A/Beijing/352/89 (H3N2); and B/Bangkok/163/90. Regarding the entire sample, the vaccine induced a tenfold or more rise on the average in the hemagglutination inhibition (HAI) antibody to each antigen. The response rates (greater than or equal to a fourfold rise) were about 90% or more among those with a prevaccination titer < or = 1:64 (equivalent to < or = 1:16 on the Western scale; in Japan, the HAI titers are expressed by the final, and not the initial, dilution of the serum; from hereon our findings will be expressed using the Japanese scale), whereas they were 0-50% at > or = 1:128. Thus, the prevaccination titer was negatively associated with antibody induction. The achievement rates (postvaccination titer > or = 1:128) among those with a prevaccination titer < 1:16 remained at 48-68%. Regarding the analysis of variance, a significant effect on antibody induction was indicated for the prevaccination titer (P < or = 0.002), but not for age (P > or = 0.425). The interaction between the prevaccination titer and age was significant for A/Yamagata (P = 0.030), while it was also suggestive for A/Beijing (P = 0.054): as age increased, those with no preexisting antibody (< 1:16) showed greater titer rises, in contrast to the smaller rises among those with a titer > or = 1:16. Based on the attack survey conducted separately, the vaccine efficacy on influenza-like illnesses with fever < or = 37 degrees C and > or = 37.5 degrees C was calculated to be 16% (95% confidence interval: -66% to 57%) and 37% (-55% to 74%), respectively.

Adult↗

PubMed1996

Ossification of the distal phalanx of the first digit as a maturity indicator for initiation of orthodontic treatment of Class III malocclusion in Japanese women.

The influence of mandibular growth on the stability of orthodontic treatment has been well established. A particular problem is late mandibular growth in patients with Class III malocclusions, because of skeletal jaw discrepancies that may influence the timing and course of treatment, as well as the stability of posttreatment. We have used the ossification of the distal phalanx of the first digit as an indicator of the skeletal maturity of the patient and of their potential for further growth. Our previous studies have shown that fusion of the epiphysis and the diaphysis of the distal phalanx of the first digit occurs from 1 to 3 years after the pubertal growth maximum in Japanese women. In these case reports, the orthodontic treatment of two female patients with mild Class III skeletal malocclusions is presented to show the possible clinical application of the ossification of the first digit as an indicator of the completion or near cessation of mandibular growth in the timing of treatment of Class III malocclusions. The case reports show that, although both patients experienced some mild degree of mandibular growth after treatment, this method can be helpful in determining residual mandibular growth potential in Japanese female patients with Class III malocclusions and mild skeletal discrepancies.

Age Determination by Skeleton↗

PubMed1996

Allograft acceptance and rejection, mediated by a liver suppressor factor, LSF-1, purified from serum of liver transplanted rats.

In certain rat strain combinations liver allografts are spontaneously accepted without immunosuppression and induce donor-specific tolerance to further skin and heart graft in the recipient. Such an effect is also transferrable using serum from orthotopically liver transplanted rats (OLT serum). In the OLT serum of one such combination, DA (RT1a) donor into PVG (RT1c) recipient, a 40 kDa protein (liver suppressor factor, LSF-1) has been identified and shown to be immunosuppressive in vitro. The aim of the present study is to investigate the immunological effect of LSF-1 and a polyclonal antibody (anti-LSF-1) against this molecule, in a rat heterotopic heart transplant (HHT) model and OLT model, respectively. Intramuscular injection of 300 micrograms of LSF-1, 1 h postoperatively, into a PVG recipient of either a DA or BN (RT1n) cardiac allograft caused significant prolongation of graft survival. Intravenous injection of polyclonal rabbit sera raised against an N-terminal peptide of LSF-1 (anti-LSF-1), within 1 h postoperatively, had variable effects on the survival of DA liver grafts in PVG recipients. In 5/6 cases injection of between 1 and 2 ml of anti-LSF-1 resulted in death of the recipient. Histological examination of the liver showed severe rejection with lymphoid cell infiltration of the portal tract and sinusoids and extensive damage to the parenchyma. All control rats survived for more than 60 days without any signs of rejection. The anti-LSF-1 polyclonal antibody prevented the injection of tolerance in the normally tolerogenic model (DA into PVG). This, together with the in vivo results, suggests a role for LSF-1 in the induction of tolerance.

Animals↗

PubMed1996

Electromyographic and kinesiographic study in patients with nonreducing disk displacement of the temporomandibular joint.

OBJECTIVE: The purpose of this study was to clarify electromyographic and mandibular kinesiographic properties of the chewing movements in patients with unilaterally painful nonreducing disk displacement of the temporomandibular joint. STUDY DESIGN: Chewing movement in 50 female patients was evaluated by electromyograph and mandibular kinesiograph, and the results were compared with those in 31 normal controls. RESULTS: In the analysis by electromyograph, some differences between patients and controls were found. In the analysis by mandibular kinesiograph, chewing movement showed deviation to the chewing side in the TMJ-affected-side chewing but did not show deviation in the TMJ-unaffected-side chewing in the horizontal plane. The maximal anteroposterior width between opening and closing paths in the sagittal plane was smaller in the experimental subjects. CONCLUSION: These differences between patients and controls may be helpful to diagnosis for painful nonreducing disk displacement of the temporomandibular joint.

Adolescent↗

PubMed1996

Cobalt exposure level and variability in the hard metal industry of Japan.

Cobalt, used as a binder for tungsten carbide, has been demonstrated to be toxic to the lung and to be a sensitizer of the bronchial airways among hard metal workers. To determine cobalt exposure levels in 9 job groups at a hard metal factory, 935 samples were collected from 356 workers. The arithmetic means of 8-hr time-weighted averages were more than 50 micrograms/m3 (American Conference of Governmental Industrial Hygienists' threshold limit value) in the powder preparation, rubber press, and shaping groups. The within-worker and between-worker components of exposure variation were estimated for each job group using the random effects analysis-of-variance model. The geometric standard deviations indicating the within-worker and between-worker components ranged from 1.88 to 2.77 and 1.00 to 2.31, respectively.

Air Pollutants, Occupational↗

PubMed1996

Analysis of protein carbonyls with 2,4-dinitrophenyl hydrazine and its antibodies by immunoblot in two-dimensional gel electrophoresis.

Protein carbonyls are reported to increase in aging and in pathologies such as Alzheimer's disease and ischemic injury. Detailed study of this important issue has, however, been hampered by lack of an appropriate method to identify individual carbonylated proteins. We describe here an immunoblot method to identify individual carbonylated proteins. We describe here an immunoblot method to investigate protein carbonyls reactive to 2,4-dinitrophenyl hydrazine. Rabbit polyclonal antibodies against 2,4-dinitrophenyl hydrazine were used to study the proteins derivatized by the reagent in one- or two-dimensional polyacrylamide gel electrophoresis followed by immunoblotting. More than 25 proteins with high carbonyl contents were clearly demonstrated in two-dimensional immunoblot of rat tissue soluble proteins. The method could detect concentrations as low as 1 pmol of carbonyls. The signals were mostly abolished by prior treatment of tissue proteins with sodium borohydride to reduce carbonyls. Fragments generated by V8 protease digestion of a single protein exhibited signal intensities of varying degrees, indicating that carbonylation is not uniform in different amino acid sequences. Proteins treated with glucose or aldehydes gave rise to positive signals, suggesting that the finding of carbonyls in tissue proteins is not necessarily an indication of direct oxidation of side chains of amino acid residues.

Acetaldehyde↗

PubMed1996

Characterization of the growth factor activity of amniotic fluid on cells from hematopoietic and lymphoid organs of different life stages.

We investigated the proliferation-promoting effects of murine amniotic fluid (MAF) on in vitro cultured cells originally obtained from murine hematopoietic and lymphoid organs at different life stages. MAF promoted proliferation of the fetal liver cells (FLC), newborn spleen cells and adult bone marrow cells. The proliferation-promoting activity of MAF was extended to liver cells and spleen cells from mice younger than 2 weeks old. MAF did not, however, promote the proliferation of newborn or adult thymocytes, or of spleen cells, liver cells or peritoneal cells, liver cells or peritoneal cells from 2-week-old or older mice. Rather, it partially inhibited the proliferation of spleen cells, thymocytes and peritoneal cells from 1-year-old mice. These results suggest that MAF contains growth factors for hematopoietic stem cells but not for either mature or immature T lymphocytes. Supporting this view, the MAF activity was partially neutralized by a polyclonal anti-mouse stem cell factor (SCF) antibody. Moreover, the immunoblotting of MAF against anti-mouse SCF antibody revealed a band at 30-32 kDa corresponding to the previously reported SCF. Interestingly, MAF was able to maintain FLC and adult bone marrow cells alive in culture for a relatively long time (2 weeks). The MAF activity was further shown to be partially and cell type-dependently antagonized by TNF-alpha and TGF-beta. These results provided evidence that MAF contains potentially multiple growth factors preferentially affecting the early stage of hematopoiesis, one of which is SCF.

Age Factors↗

PubMed1996

Species specificity in the blood cholesterol-lowering effect of YM-16638.

1. The compound YM-16638, [[5-[[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl] thio]-1,3,4-thiadiazol-2-yl]thio] acetic acid was developed in a series of in vitro and in vivo studies as a leukotriene D4 receptor antagonist. 2. In a clinical trial as a leukotriene antagonist drug, this compound was found to have a potent serum cholesterol lowering effect in normolipidaemic healthy male volunteers. 3. In the present study, we investigated the serum cholesterol lower effect of this compound in various species of experimental animals. 4. Administration of YM-16638 did not cause a significant decrease in serum total cholesterol (TC) in mice (up to 200 mg kg-1, body weight per day for 28 days), rats (200 mg kg-1 for 15 days) or rabbits (90 mg kg-1 for 18 days). In hamsters, administration of YM-16638 orally or by peritoneal injection at 50 mg kg-1 or more daily for 7 days caused a significant decrease in serum TC and the rate of body weight gain. In monkeys, serum TC did not change in YM-16638-administered squirrel monkeys (50 mg kg-1 daily for 3 weeks), but a significant decrease in serum TC was observed in cynomolgus monkeys (33% decrease at 30 mg kg-1 for 4 weeks) and rhesus monkeys (27% decrease at 30 mg kg-1 for 3 weeks) without any serious decrease in body weight. These results were consistent with those in a phase I study with human subjects. In contrast, serum alanine aminotransferase (ALT) level decreased in all animals after YM-16638 treatment. 5. From these results, we conclude that YM-16638 has a potent hypocholesterolaemic effect, but that this effect if species-specific and is only recognized clearly in human subjects and old-world monkeys.

Alanine Transaminase↗

PubMed1996

Epidemiological study of hard metal asthma.

OBJECTIVES: To elucidate factors contributing to hard metal asthma, the entire workforce of a corporation producing hard metal tools (n = 703) was examined. METHODS: The variables evaluated were the atopy reflected by immunoglobulin E (IgE) antibody against mite allergen, history of exposure to hard metal, smoking, concentration of airborne cobalt, specific IgE antibody reaction against cobalt, and the respiratory symptom of attacks of reversible dyspnoea with wheeze (asthmatic symptoms). RESULTS: Univariate analysis showed that the prevalence of the asthmatic symptoms was significantly higher in formerly and currently exposed male workers than in non-exposed male workers. Positive IgE reaction against cobalt was found in seven men (2.0%), all of whom had asthmatic symptoms. Furthermore, it was found that atopy, positive IgE antibody against cobalt, and age of 40 or older were significantly correlated with asthmatic symptoms. Multilogistic analysis on the same factors and smoking in all of the workers showed that the age, experience of hard metal exposure, and atopy were significant risk factors associated with the asthmatic symptoms. Multilogistic analysis of data for currently exposed and non-exposed workers also showed that age and atopy were risk factors, and that the exposure to cobalt at the low concentration (at or below 50 micrograms/m3) but not at the higher concentration was a significant risk factor. Exposure to mist of coolants containing ionic cobalt, used during grinding, was not found to be any more hazardous in terms of onset of asthmatic symptoms than exposure to hard metal dust containing metallic cobalt. CONCLUSIONS: Accordingly, it is concluded that both environmental factors and individual susceptibility should be taken into consideration in efforts to reduce the prevalence of hard metal asthma.

Adolescent↗

PubMed1996

Decreased ventilatory function in hard metal workers.

OBJECTIVES: To study individual effects on pulmonary function of exposure to hard metal including cobalt. METHODS: All of the workers in a hard metal company (583 men and 120 women) were examined for smoking, respiratory symptoms, ventilatory function, occupational history of exposure to hard metal, and present exposure to airborne cobalt. The ventilatory function indices (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory volume in one second per cent (FEV1%), peak expiratory flow (PEF), mid-maximal flow (MMF), forced expiratory flow at 50% vital capacity (V50), forced expiratory flow at 25% vital capacity (V25)) were standardised for height and age and expressed as a percentage of predicted values. RESULTS: Two way analysis of variance of indices of ventilatory function showed that an interaction of hard metal exposure and smoking decreased %V50 for both men and women. Among the currently exposed men, those with asthmatic symptoms (defined as reversible dispnoea with wheeze) had significantly lower %FVC, %FEV1%, %PEF, %MMF, %V50, and %V25 than did workers without asthma. The ventilatory disfunction did not differ between exposed and non-exposed workers with asthmatic symptoms. Even among the men without asthmatic symptoms, %V50 was significantly lowered by the interaction of hard metal exposure and smoking. The multilinear regression analysis of indices of ventilatory function for all of the subjects on sex, smoking (Brinkman index), exposure to hard metal, and asthmatic symptoms showed that asthmatic symptoms and smoking had significant effects on all variables and that the decrease in %V25 was associated with hard metal exposure. In the currently exposed and non-exposed workers, multilinear regression analysis applying indices for cobalt exposure (mean cobalt concentration, duration of exposure, and cumulative dose) showed that not only asthmatic symptoms or smoking but also duration of exposure had significant decreasing effects on %FVC, %MMF, and %V25. CONCLUSIONS: Occupational exposure to hard metal probably causes impairment of ventilatory function in a dose dependent manner.

Adolescent↗

PubMed1996

Subregional loss of putaminal efferents to the basal ganglia output nuclei may cause parkinsonism in striatonigral degeneration.

In this study, we examined the topographic involvement of the putaminal projection neurons and their axons in the globus pallidus and substantia nigra, which we visualized by calcineurin immunostaining, in the basal ganglia of patients with striatonigral degeneration (SND). In all cases examined, there was a marked decrease in number of calcineurin-immunopositive neurons in the caudal and lateral portion of the putamen. Also, marked depletion of calcineurin-immunoreactive putaminal efferents was consistently present in the posteroventrolateral portions of the globus pallidus interna (GPi) and externa, and in the ventrolateral portion of the substantia nigra pars reticulata (SNr) topographically corresponding to the putaminal lesion. In view of the functional model of the basal ganglia "motor" circuit, these findings suggest that subregional deafferentation of the GPi/SNr (i.e., basal ganglia output nuclei) from putaminal inputs may be responsible for parkinsonism in patients with SND.

Aged↗

PubMed1996

Instability of bovine insulin in poly(lactide-co-glycolide) (PLGA) microspheres.

Biodegradable poly(lactide-co-glycolide) (PLGA; 50/50) microspheres containing bovine insulin as a model protein was prepared by an oil-in-oil (o/o) emulsion solvent evaporation process. When aluminum tristearate (0.15% (w/v)) was employed as a dispersing agent, the loading efficiency of insulin was almost 100% and the yield was over 80%. The average diameter of the PLGA microspheres always ranged between 100 and 200 microns. Morphology study using a scanning electron micrograph showed smooth, spherical, fairly monodispersed PLGA microspheres containing insulin. In relation to release profile, the very low release rate of insulin was demonstrated (only 1% of insulin released after 7 d release test in pH 7.4 Tris buffer) for the PLGA microspheres. Nevertheless, the degradation of bovine insulin in PLGA microspheres was confirmed by high performance liquid chromatography. This degradation seemed to be caused by an acidic condition caused by poly(lactide-co-glycolide) polymer.

Animals↗

PubMed1996

Effect of fluvoxamine on 5-hydroxytryptamine uptake, paroxetine binding sites and ketanserin binding sites in the Japanese monkey brain and platelets, in vivo and in vitro.

We investigated the in vitro effects of fluvoxamine on 3H-paroxetine binding and 3H-monoamine uptake in monkey cerebral cortex in comparison with those of other antidepressants. Fluvoxamine selectively inhibited 3H-5-hydroxytryptamine (5-HT) uptake and 3H-paroxetine binding. However, it did not alter 3H-norepinephrine or 3H-dopamine uptake. In addition, we examined the effects of chronic treatment with fluvoxamine (5 mg/kg per day, p.o.) on 5-HT uptake sites that bind 3H-paroxetine and 5-HT2 receptors that bind 3H-ketanserin, in monkey brains and platelets. Chronic treatment with fluvoxamine affected neither the paroxetine binding sites nor the kentanserin binding sites of the brains and platelets. These results suggest that long-term treatment with fluvoxamine does not affect either the 5-HT uptake sites or 5-HT2-receptors of 5-HT neurons in monkey brain in spite of its strong inhibitory effect on 5-HT uptake in vitro.

Animals↗

PubMed1996

Chitinous component of the cell wall of Fusarium oxysporum, its structure deduced from chitosanase digestion.

The cell of Fusarium oxysporum was digested with commercial Bacillus chitosanase. The chitosanase produced low molecular weight heterooligosaccharides consisting of GlcN and GlcNAc from the cell wall. A main component of the digestion products was identified as 2-amino-2-deoxy-beta-D-glucopyranosyl- (1-->4)-2-acetamido-2-deoxy-D-glucopyranose. The chitosanase appeared to be more effective than Streptomyces griseus chitinase for cell wall digestion. Moreover, maltose was unexpectedly found in the digestion products, indicating that the cell wall contains alpha-1,4-linked glucan chain as a polysaccharide component.

Acetylglucosamine↗

PubMed1996

Skeletal malformations caused by the Dh (Dominant hemimelia) gene in mice.

Morphological characterization of the skeletal malformations caused by the Dh gene was carried out. Skeletal preparations from newborn mice of Dh/Dh, Dh/+ and +/+ genotypes, and adult Dh/+ mice were examined. The Dh gene induced skeletal deformities at the axial regions from the thorax to the tail. Attachment of the ribs to the sternum was sometimes irregular, and normal segmentation of the sternum was also disrupted. Abnormal fusion of the ventral part of the rib was observed in some cases. Lumbar vertebrae were fewer in number and abnormal in shape. Although it was rare, a curled tail was also observed due to distortion of the caudal vertebrae.

Abnormalities, Multiple↗