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Biomedical subjects

S Sakoda

Publications and source records attributed to S Sakoda.

At least 37 records · Page 2Linked to original sources

Monoclonal antibodies generated against an affinity-labeled immune complex of an anti-bile acid metabolite antibody: an approach to noncompetitive hapten immunoassays based on anti-idiotype or anti-metatype antibodies.

Conventional immunoassays for haptens such as steroids and synthetic drugs are dependent on the competitive reaction between an unlabeled antigen (analyte) and a labeled antigen against a limited amount of anti-hapten antibody. Although noncompetitive immunoassay procedures such as two-site immunometric assays offer a much higher sensitivity, direct application of this principle to haptens has been difficult due to their small molecular mass precluding simultaneous binding by two antibody molecules. Here, we have attempted to develop a noncompetitive immunoassay system based on anti-idiotype or anti-metatype antibodies. Ursodeoxycholic acid 7-N-acetylglucosaminide (UDCA 7-NAG), which is a bile acid metabolite (molecular weight, 595.8), was selected as the model hapten. A/J mice were immunized with a monoclonal antibody against UDCA 7-NAG, which had been affinity-labeled with a relevant hapten derivative. The fusion between the immune spleen cells and P3/NS1/1-Ag4-1 myeloma cells yielded four kinds of alpha-type and two kinds of beta-type monoclonal anti-idiotype antibodies, each recognizing the framework region and paratope of the anti-hapten antibody. The use of a selected combination between alpha-type and beta-type antibodies together with the anti-hapten antibody provided a noncompetitive assay system with a subfemtomole order sensitivity (detection limit, 118 amol) and a practical specificity.

Acetylglucosamine↗

Child and elderly victims in forensic autopsy during a recent 5 year period in the southern half of Osaka city and surrounding areas.

To outline the recent features of child and elderly victims from the medico-legal perspective with special reference to abuse and neglect, a retrospective investigation of forensic autopsy cases over a 5 year period (1994-1998) in the southern half of Osaka city and surrounding areas (a population of 1.57 million) was undertaken. Among 646 autopsy cases, there were 53 child cases (under the age of 15 years, about 80% below 6) and 121 elderly cases (65 years old and above). Nearly half of the child deaths and more than half of the elderly deaths were described as accidental. Fire and traffic victims were much more frequent in the elderly. Child victims included those of neonaticide/infanticide (n=6), physical abuse (n=10), unintentional fatal infliction (n=2), neglect (n=2), mutual suicide (n=2), suicide (n=1) and murder (n=3). Child abuse and neglect were domestic maltreatment by the parents. In this series, there was a comparable number of fatalities due to maltreatment in the elderly (n=13) and in children, and non-domestic violence was more frequent in the elderly than domestic violence. Elderly females tended to be battered by their sons or grandsons in domestic violence cases, whereas males were predominantly attacked by younger males in non-domestic violence. The other elderly victims included those of self-neglect (n=2), murder (n=7) and suicide (n=9). Non-domestic homicide of the elderly occurred mainly in the center of the city, whereas domestic maltreatment of children and the elderly was sporadic, although somewhat more frequent in the peripheral zone of the city and the surrounding areas. The above profile of child and elderly abuse suggests a substantial influence of social and familial backgrounds.

Accidents↗

Intrathecal administration of neutralizing antibody against Fas ligand suppresses the progression of experimental autoimmune encephalomyelitis.

A therapy aimed at blocking the Fas/Fas ligand (FasL) system was investigated using a relapsing form of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Intracisternal administration of neutralizing antibody against FasL during the progression phase of EAE significantly reduced the severity of the disease with milder inflammation and myelin breakdown in the central nervous system (CNS). These results raised the possibility that the Fas/FasL system might contribute to tissue destruction in the CNS in the acute phase of EAE and that the intrathecal administration of neutralizing antibody against FasL may be beneficial for suppression of the acute phase of MS.

Acute Disease↗

Successful generation of peripheral neuropathy with onion-bulb formation in the macrophage scavenger receptor classA knockout mouse treated with isoniazid.

We previously reported successful generation of many onion-bulbs (OBs) and formation of oxidized phosphatidylcholine after compression injury to the peripheral nerve of mice deficient of macrophage scavenger receptor classA (MSR-A). In the present study, we employed chemical injury with isoniazid to the peripheral nerve of the MSR-A knockout mice to investigate the role of the MSR-A in toxic neuropathy. Peripheral neuropathy has not previously been generated with isoniazid in mice. In the present study, we also noted little histological change after isoniazid administration not only to control littermates but also to the A/J strain mice known to be slow acetylators. Surprisingly, however, we were successful in generating peripheral neuropathy with isoniazid in the MSR-A knockout mice. Histologically, the predominant feature was the presence of many thinly myelinated fibers with some OBs, which have not been observed in rats with isoniazid neuropathy. Deficiency of the MSR-A appears to have played an important role in generation of peripheral neuropathy with isoniazid in mice.

Animals↗

HTLV-I-associated myelopathy manifested after renal transplantation.

We report a patient with HTLV-I-associated myelopathy (HAM), who developed symptoms of myelopathy 4 years after cadaveric renal transplantation. Since he was seronegative before the transplantation, it is suggested that HTLV-I infection was transmitted via renal graft transplantation. He has been treated with immunosuppressive agents such as cyclosporin A (CsA), mycophenolate mofetil (MMF), and prednisolone (PSL) to prevent graft rejection. This case suggested that these immunosuppressive agents are poorly effective in suppressing either the onset or progression of HAM/TSP.

Humans↗

Enhancement of Th2 response in IL-6-deficient mice immunized with myelin oligodendrocyte glycoprotein.

To investigate the mechanism for the resistance of IL-6-deficient mice to experimental autoimmune encephalomyelitis (EAE), we examined the production of cytokines in lymph nodes (LNs) of wild-type and IL-6-deficient mice immunized with myelin oligodendrocyte glycoprotein (MOG) by reverse transcriptase-polymerase chain reaction analysis. Significant up-regulation of IL-4 production and down-regulation of IFN-gamma production were found in LNs from IL-6-deficient mice as compared to LNs from wild-type mice. Administration of IL-6, which caused typical EAE in IL-6-deficient mice immunized with MOG, reduced IL-4 production but did not restore IFN-gamma production in LNs of IL-6-deficient mice. These results implied that the resistance of IL-6-deficient mice to EAE might be mainly due to enhancement of Th2 response.

Animals↗

Precise measurement of dp elastic scattering at 270 MeV and three-nucleon force effects

The cross section, the deuteron vector A(d)(y) and tensor analyzing powers A(ij), the polarization transfer coefficients K(y('))(ij), and the induced polarization P(y(')) were measured for the dp elastic scattering at 270 MeV. The cross section and A(d)(y) are well reproduced by Faddeev calculations with modern data-equivalent nucleon-nucleon forces plus the Tucson-Melbourne three-nucleon force. In contrast, A(ij), K(y('))(ij), or P(y(')) are not described by such calculations. These facts indicate the deficiencies in the spin dependence of the Tucson-Melbourne force and call for extended three-nucleon force models.

Journal Article↗

The effect of apoptosis inhibitors on experimental autoimmune encephalomyelitis: apoptosis as a regulatory factor.

The effect of apoptosis inhibitors on experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, was investigated by intraperitoneal or intracisternal administration of apoptosis inhibitors Ac-YVAD-cmk and zVAD-fmk. After onset of the disease, these agents had no suppressive effect on EAE and resulted in impaired recovery or earlier relapse. Histological examination revealed that administration of zVAD-fmk suppressed the apoptotic death of inflammatory cells in the central nervous system (CNS) of mice with EAE. The results indicated that the apoptotic elimination of infiltrated cells in the CNS might be one of the recovery mechanisms in EAE.

Amino Acid Chloromethyl Ketones↗

Onion-bulb formation after a single compression injury in the macrophage scavenger receptor knockout mice.

Onion-bulb (OB) formation is often encountered in acquired neuropathies such as chronic inflammatory demyelinating polyradiculoneuropathy and diabetic neuropathy and is believed to require repeated injuries to peripheral nerves. Although this suggests that remaining damaged cell membranes, including myelin debris, might trigger OB formation, the molecular mechanism remains unclear. In this study, we were successful in producing many small OBs after a single compression injury to peripheral nerves of the knockout mice deficient of macrophage scavenger receptor class A (MSR-A). Although morphometry showed no difference in the average densities of the remaining myelinating fibers between wild-type and MSR-A knockout mice after the compression injury, there were more macrophages and myelin debris positive for oxidized-phosphatidylcholine in the nerves from the MSR-A knockout mice. We believe that OB formation was induced after a single compression injury as the result of delayed phagocytosis of myelin debris possessing oxidized lipids by MSR-A deficient macrophages. The present work shed light on the molecular mechanism of OB formation seen in chronic neuropathies and provided a model for further investigation.

Animals↗

Morphometric analysis of the myelin-associated oligodendrocytic basic protein-deficient mouse reveals a possible role for myelin-associated oligodendrocytic basic protein in regulating axonal diameter.

Myelin-associated oligodendrocytic basic protein is a member of the proteins constituting the central nervous system myelin. By morphometric analysis, we demonstrated that axons of myelin-associated oligodendrocytic basic protein-deficient mice had larger diameters and more myelin lamellae as compared to those of wild-type mice at the same age. It is known that the number of myelin lamellae increases linearly with axonal diameter, and that the rate of radial axonal growth is the factor controlling the rate of myelin formation. In line with these observations, we found that the regression line for axonal diameter and the number of myelin lamellae in myelin-associated oligodendrocytic basic protein-deficient mice appeared to be identical to that in wild-type mice, indicating that the increase in the number of myelin lamellae was the result of the increase in axonal diameter. Furthermore, we generated myelin basic protein/myelin-associated oligodendrocytic basic protein-double-deficient mice through mating myelin-associated oligodendrocytic basic protein-deficient mice with shiverer mice, an autosomal recessive mutant characterized by a lack of all isoforms of myelin basic protein. With these knock-out mice, we showed that axons of the double-deficient mice had larger diameters and smaller form factor, an index of the deformation of the fiber contour, in ensheathed fibers than those of shiverer mice, although there was no difference in axonal diameter of unmyelinated fibers between them. Taken together, myelin-associated oligodendrocytic basic protein seemed to play a role in controlling axonal diameter and in keeping axons round.

Animals↗

Dental identification in routine forensic casework: clinical and postmortem investigations.

The aim of this study was to examine the factors which may disturb dental identification of unknown human remains and the practical value of dental evidence in routine forensic casework, including the changes due to dental treatment and postmortem interference. In the investigation of changes due to dental treatment on 696 patients' dental history at two clinics, increase of the number of dental restorations was the greatest in the initial 1-2 years. This finding suggests that dental treatments performed in early period after initial examination contributes more to forensic dental identification than those performed afterwards. The lower anterior teeth (incisors and canines) remained relatively unchanged for years compared with other teeth. The molars appeared to be more frequently restored at a relatively younger age and more frequently missing in the elderly. The investigation of 260 unknown remains in 971 forensic autopsy cases during a period of seven years (1992-1998) at our institute indicated the particular usefulness of dental evidence in cases where the candidates were identified from some other evidence, and usually in cases having a postmortem period corresponding to the obligatory preservation term for the clinical dental records and radiographic films. There were non-identity in the status of dental treatments between ante-mortem dental findings due to additional treatments received after the last day of examination recorded in the corresponding clinical dental records. Postmortem damage from decomposition and fire was more frequently observed in the anterior teeth. These observations indicate that precise documentation of dental evidence including postmortem deterioration and the establishment of a well-organized dental database of missing persons together with a suitable screening system is required to more effectively utilize dental evidence in routine forensic casework.

Journal Article↗

Significance of DNA analysis for determination of ABO blood groups from hair and nail of decomposed human remains: a comparison with phenotyping by the absorption-elution method.

Seventy samples from 35 decomposed human remains were investigated for ABO histo-blood group phenotypes and genotypes by the absorption-elution method and PCR-RFLP, respectively. Phenotypes could be determined by the absorption-elution method in all cases except for some failures to detect A and H antigens from scalp hair. Genotyping was also usually successfully performed using nails when intact samples were available. The findings using hairs appeared to depend on the postmortem interval. In this series, an inconsistency between ABO phenotyping and genotyping was observed in two cases, suggesting postmortem antigenic alteration in hair and nail. These findings suggested the usefulness of serial examinations by phenotyping and genotyping for reliable ABO blood grouping of badly decomposed remains.

Journal Article↗

Isaacs' syndrome successfully treated by immunoadsorption plasmapheresis.

We report a 70-year-old woman with Isaacs' syndrome (acquired neuromyotonia) who showed a marked improvement after immunoadsorption plasmapheresis (IAP). She developed hyperhidrosis in her teens, and slowly progressive symptoms of neuromyotonia for over 50 years. An in vitro investigation of her serum with patch-clamp technique suggested the presence of antibodies against potassium channels. She was treated with IAP, which brought disappearance of her symptoms. Though the symptoms started to recur in 3 weeks, moderate improvement has been maintained by immunosuppressive drug treatment.

Aged↗

Surface electromyographic evaluation of the asymptomatic human masseter muscle with turns and amplitude analysis.

Electromyographic turns, or reversals of direction, per second (TS) and mean amplitude per turn (AT) are variables that have been widely used to assist and support an electrodiagnosis in neuromuscular disorders. The purpose of this study was to explore the feasibility of utilizing the TS and AT in conjunction with surface electrodes as a method for assessing masticatory muscle function. Ten normal subjects were instructed to exert brief isometric contractions at various levels, and the TS and AT were calculated from the surface electromyographic signals of the masseter muscle. Our results showed that the AT increased with contraction at all contraction levels, demonstrating a linear relationship, while the TS showed a nonlinear increase characterized by an initial steep rise followed by a plateau, which was simulated with a third polynomial function. It is considered that the TS and AT may provide valuable physiological information about the underlying mechanisms of recruitment and the firing of motor units.

Adult↗

[A case of Gerstmann-Sträussler-Scheinker syndrome (P102L) accompanied by optic atrophy].

We report a patient with Gerstmann-Sträussler-Scheinker syndrome (GSS102) who developed optic atrophy. He had been complaining of slowly progressive postural unsteadiness and pain in both legs for 3 years. Visual acuity subacutely worsened in the last half year. His father and two aunts, who already died, had been diagnosed to have dementia. It is uncertain whether they had optic atrophy or not. He was alert but apathetic. Neurological examination revealed cerebellar ataxia, painful dysesthesia and loss of deep tendon reflexes in the lower limbs. Fundoscopic examination revealed bilateral optic atrophy without retinal degeneration, which has never been reported in GSS. A brain MRI showed mild atrophy of cerebellar hemispheres without signal abnormalities of optic nerves. DNA analysis of prion gene revealed point mutation at codon 102 (P102L), which was relatively common mutation in GSS. Other mutations were not found. Only two patients of Creutzfeldt-Jakob disease with optic atrophy have been reported. This case seems to be important to investigate why optic tracts are generally spared in prion disease.

Gerstmann-Straussler-Scheinker Disease↗

Wounding dynamics in distorted bitemarks: two case reports.

An essential factor involved in distortion of bitemarks on the skin is the dynamics of biting related to the location on the body. This study describes the comparison between the identification of bitemarks left on different regions of the victims' bodies in two homicide cases. The findings indicated that a stepwise dynamic comparison of serial adjacent marks with a part of the dentition in consideration of movement of the jaws and distortion of the skin was useful in identifying matching points. The identification process indicated possible wounding dynamics of biting.

Adult↗

IL-6 plays a crucial role in the induction phase of myelin oligodendrocyte glucoprotein 35-55 induced experimental autoimmune encephalomyelitis.

We investigated the role of IL-6 in myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE) using IL-6-deficient mice and found that IL-6-deficient mice were resistant to active induction of EAE, but that the treatment of those mice with IL-6 during the preclinical phase caused typical EAE. We also found that both wild-type and IL-6-deficient mice were resistant to passive transfer of EAE by lymphocytes from IL-6-deficient mice, but that passive transfer of lymphocytes from wild-type mice induced typical EAE in IL-6-deficient mice. Histological abnormalities of the central nervous system (CNS) in those IL-6-deficient mice with EAE were similar to those in wild-type mice with EAE. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed no difference in the production of inflammatory cytokines such as IL-1beta, IL-2, TNF-alpha, and IFN-gamma in the CNS of IL-6-deficient mice with EAE as compared to the CNS of wild-type mice with EAE. These results indicated that IL-6 might be an important factor in the induction phase, but might have little influence on the effector phase of EAE. We further estimated the production of cytokines in MOG-stimulated lymph node (LN) cells by enzyme-linked immunosorbent assay. Increased IL-4 and IL-10 production and reduced IL-2 and IFN-gamma production were observed in LN cells from IL-6-deficient mice as compared to LN cells from wild-type mice. These results suggested that a shift of T cell responses from Thl to Th2 might explain the resistance of IL-6-deficient mice to EAE. Taken together, IL-6 may play a crucial role in the induction phase of EAE by modulating Th1/Th2 balance.

Animals↗