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Biomedical subjects

Y Yoshikawa

Publications and source records attributed to Y Yoshikawa.

At least 271 records · Page 15Linked to original sources
PubMed1991

Structural homology between hemagglutinin (HA) of measles virus and the active site of long neurotoxins.

The amino acid sequence of a carboxy terminal domain corresponding to the end of the outer envelope projection of the hemagglutinin glycoprotein (HA) of measles and subacute sclerosing panencephalitis viruses has a high degree of homology with the active domain of long neurotoxins, which specifically binds to the nicotinic acetylcholine receptor. The homology in amino acid sequence of HA to this domain of neurotoxin, as well as native alpha-bungarotoxin (BTx), was confirmed by the following evidence: a) rabbit anti-HA monospecific sera reacted with BTx in ELISA, b) HA dose-dependently blocked the binding of radio-labeled BTx in competitive radioimmunoassay, and c) antibody to a synthetic peptide of the active domain of BTx precipitated HA in radioimmunoprecipitation. In addition, SSPE patients had significantly high titers of antibody to BTx than healthy children who had been previously infected with measles. This epitope of HA may play an important role in the transsynaptic spreading of the virus in the brain.

Adolescent↗
PubMed1991

Immunological and virological characterization of improved construction of recombinant vaccinia virus expressing rinderpest virus hemagglutinin.

We constructed a recombinant vaccinia virus (RVV) expressing rinderpest virus (RPV) hemagglutinin (H) by modifying the promoter region of the original RVV. The promotor region was modified at three points, i.e., an outframe ATG was eliminated, the sequence between the promoter and initiation codon was shortened and the base sequence just upstream of the initiation codon was changed. As compared with the original RVV, the modified RVV was found to produce a remarkably large amount of H protein in infected rabbit kidney cells cultured in vitro and to induce high titers of anti-RPV-H antibodies in rabbits. The median protective doses in rabbits of the modified and of the original RVVs were 10(2) pfu and 10(3.5) pfu, respectively, indicating that the modified RVV was at least 10-times more effective in protection than the original. The neurovirulence of the modified RVV and the parental LC16mO strain was roughly at the same level, and was much lower than that of WR strain. The modified RVV was as heat-stable as the original one. These results indicate that the modified RVV could be a candidate rinderpest vaccine for further examinations including cattle.

Animals↗
PubMed1991

Protective effects of monoclonal antibodies against lethal canine distemper virus infection in mice.

Monoclonal antibodies (MAbs) against the haemagglutinin (H), fusion protein (F) and nucleoprotein of canine distemper virus (CDV) were examined for their ability to protect mice against lethal CDV infection. One MAb against H and two of six MAbs against F protected mice, the protective effect of the anti-H MAb being stronger than that of the anti-F MAbs. The anti-H MAb showed virus neutralizing activity, but the two anti-F MAbs, which recognized the same epitope, did not. Protection by the anti-F MAbs correlated with cell fusion inhibition, but not with complement-dependent neutralization, complement-dependent cytolysis or antibody-dependent cell-mediated cytotoxicity. These results suggest that neutralization by antibody against H and cell fusion inhibition by antibody against F play important roles in the protective mechanism against CDV infection.

Animals↗
PubMed1991

Antigenic and functional characterization of rinderpest virus envelope proteins using monoclonal antibodies.

A total of 24 monoclonal antibodies (MAbs) against the haemagglutinin (H) and the fusion protein (F) of rinderpest virus (RPV) were used to characterize their antigenic structure and biological properties, and to analyse natural variation in the envelope proteins of morbilliviruses. The anti-H and anti-F MAbs defined seven and three distinct antigenic sites, respectively. The MAbs to six sites on H were able to neutralize the infectivity of RPV. The addition of guinea-pig complement or anti-mouse immunoglobulin increased the virus-neutralizing antibody titre of most of the anti-H MAbs, including those lacking neutralizing activity. One of the antigenic sites on H was conserved among morbilliviruses and the MAbs to this site had haemagglutination inhibition activity against measles virus (MV). The remaining sites were specific for RPV and varied antigenically between strains of RPV. The anti-F MAbs lacked neutralizing activity, but two of the five MAbs did show activity in the presence of complement or anti-mouse immunoglobulin. On the whole, the antigenic sites on F were conserved in some strains of MV, but not in canine distemper virus. All of the sites on the surface proteins were sensitive to SDS and, although those on F were not affected by 2-mercaptoethanol, five of the seven sites on H were destroyed by it. These results suggest that the epitopes on the envelope proteins are conformation-dependent.

Animals↗
PubMed1991

Genetic studies on experimental autoimmune gastritis induced by neonatal thymectomy using recombinant inbred strains between a high-incidence strain, BALB/c, and a low-incidence strain, DBA/2.

Thymectomy on day 3 after birth induced autoimmune gastritis (AIG) at the age of 2 months in 51-73% of BALB/c mice, and in only 3-5% of DBA/2 mice. AIG was detected by histological and serological (immunofluorescence staining for detecting anti-parietal cell autoantibody) examination. However, autoantibody was weakly positive in almost all of these DBA/2 mice when measured by ELISA using extract of murine gastric mucosa as the antigen. To investigate genetically the mechanism controlling the incidence of AIG, II recombinant inbred strains established by brother-sister mating of (BALB/c x DBA/2) F2 mice (C x D2 strains) were used. Among 26 markers tested, the Mls-1 locus on BALB/c chromosome 1 and the Hc locus coding a complement component (C5) on BALB/c chromosome 2 were found to be associated with high susceptibility to AIG. However, if one or both of the loci were of DBA/2 origin, mice showed medium or low susceptibility to AIG. For further analysis, F1, F2 and back-cross generations of these two strains were tested, but segregation of a single susceptibility or insusceptibility gene was not obtained. Taken together, it seems probable that two or more genes are involved in the induction mechanism of AIG. We did not detect C5 deposition in AIG lesions, nor complement-dependent cytotoxic antibody to parietal cells in serum from AIG mice. However, injection of irradiated spleen cells of DBA/2 mice into BALB/c mice thymectomized on day 3 augmented the incidence of AIG from 71 to 100%, but not that of oophoritis (33%). A relationship between Mls-1a determinants and the pathogenesis of AIG was further suggested from the fact that V beta 6 TcR-expressing T cells increased in number in AIG-bearing compared with normal BALB/c mice.

Animals↗
PubMed1991

Renal lesions of hyperlipidemic Imai rats: a spontaneous animal model of focal glomerulosclerosis.

The hyperlipidemic Imai rat was originally developed as an animal model of spontaneous hyperlipidemia. We report the natural course of the Imai rat up to 32 weeks of age focusing on renal pathology. The degree of proteinuria, which first appeared at 8 weeks, increased with age, and all Imai rats developed heavy proteinuria (mean, 228 mg/24 h) with impaired renal function (mean BUN, 78.7 mg/dl) at 32 weeks. Histologic changes of the glomeruli were characterized by focal and segmental sclerosis and hyalinosis. Both the percentage of affected glomeruli and the severity of each affected glomerulus were progressively increased with age. The immunofluorescence and electron-microscopic findings were also comparable to those of focal glomerulosclerosis (FGS) in humans. The serum levels of total cholesterol, triglyceride, and phospholipid in Imai rats were significantly higher than those in normal Sprague-Dawley rats at 8 weeks of age, and progressively increased thereafter. The proteinuria, glomerular involvements, and hyperlipidemia were generally less severe in the females than in the males. We conclude that the hyperlipidemic Imai rat, a naturally occurring animal model of FGS, is useful in studying the pathogenesis of FGS and the renal effects of hyperlipidemia in humans.

Animals↗
PubMed1991

An ultrastructural study on vestibular sensory cells in a new-mutant mouse.

The ultrastructural characteristics of the vestibular epithelium and light microscopical study of the central nervous system of a strain of new-mutant mice were analyzed. For the vestibular study, we used 72 homozygotes with ages ranging from 10 days to 18 months. The most striking findings observed in these mice were the disarray of the stereocilia of the utricular and saccular maculae and disintegration of the saccular otoconia. Many hair cells displayed abnormality of the stereocilia such as reduced number, disorganized distribution, and giant cilia, although the hair cell cytoplasm, including the nerve terminals, became fully developed. Demineralization of the saccular otoconia was age dependent, and a complete loss of the saccular hair cells was demonstrated. In conjunction with the disarray of the outer hair cells of the cochlea, morphological manifestation of the gene abnormality of these mice was related to immaturation of the stereociliary tufts. Because no morphological abnormality was observed in the central nervous system, the abnormal behavior in these mice was primarily correlated with morphological abnormalities of the vestibule.

Animals↗
PubMed1991

Vestibular pathology in a new-mutant mouse.

The histological characteristics of the vestibule in a strain of new-mutant mice were studied under light microscopy. These new-mutant mice, manifesting drawing back, circling, head-tossing and hyperactive behavior arose as a spontaneous mutation in the C3H/He stock. For our study, 36 of these mice ranging in age from 10 days to 18 months were used. At 10 to 15 days after birth, the vestibular gross anatomy was well-developed and all three cristae and two maculae were morphologically normal. Age-dependent degeneration of the saccular maculae was found to begin at 21 days, and almost all hair cells were missing at 90 days. Further, morphological changes in the utricular maculae appeared at one year, and a severe loss of hair cells was observed at 18 months. In contrast, the cristae ampullaris remained well preserved until the age of 18 months. The phenotype of the abnormal gene in these mutant mice correlates to the morphological abnormalities seen in the vestibule.

Animals↗
PubMed1991

Morphological changes of cochlea in a strain of new-mutant mice.

The hearing ability and histological characteristics of the cochlea of a strain of new-mutant mice were analyzed. This new mutant arose as a spontaneous mutation in the C3H/He stock. The genetic mode is autosomal recessive and the animals show abnormal behavior such as circling, head-tossing and hyperactivity. The audiological findings exhibited no recordable auditory brain stem response (ABR) in any homozygotes at ages ranging from 11 days to 117 days. For morphological examination, we used 36 homozygote with ages ranging from 10 days to 18 months. The primary morphological abnormalities were observed in the organ of Corti. The stereocilia of the outer hair cells showed disarray throughout the whole cochlea, although outer hair cell cytoplasm became fully developed, including the nerve terminals. Age-dependent degeneration of the outer hair cells subsequently occurred from the basal to the apical part of the cochlea. The earliest change demonstrated in the outer hair cells was cuticular degeneration. Although the abnormalities of the inner hair cells occurred late, a complete loss of inner and outer hair cells was demonstrated. The stria vascularis was well preserved at a later age as were spiral ganglion cells. These histological findings confirm that this mouse is classified as a neuroepithelial-type mutant. As this animal was expected to have a single gene abnormality, molecular genetic studies on this animal can provide important information on the nature of histological changes of the hair cell from a mode of gene action.

Acoustic Stimulation↗
PubMed1991

Characterization of temperature-sensitive mutants of measles virus.

Ten temperature-sensitive (ts) mutants derived from the Edmonston strain of measles virus were characterized by the complementation test and were shown to have four defective sites (A, B, C, and D). Five ts mutants which were confirmed to have a defective site D, induced neither cytopathic effect (CPE) nor an infectious virus. Among the other five ts mutants which produced viral proteins with CPE and showed positive HAD at 39.5 degrees C, the three ts mutants (P253-505, P333, and F2-104) were studied in detail. P253-505 had a defective site C and both P333 and F2-104 had a defective site A. P253-505 and F2-104 produced neither a cell-free nor cell-associated infectious virus and P333 produced only a low level of cell-associated infectious virus. P253-505 and P333 produced virus particles at 39.5 degrees C, while F2-104 did not. The pulse-chase experiment showed a normal pattern of synthesis and processing of viral proteins, but immunofluorescence tests using monoclonal antibodies indicated that P253-505 lacked two epitopes of the M protein at 39.5 degrees C, and both P333 and F2-104 lacked one epitope of the P protein. The lack of these viral epitopes was shown to correlate with the temperature-sensitivity of the three ts mutants.

Animals↗
PubMed1991

Free, thinned, paraumbilical perforator-based flaps.

Free, thinned paraumbilical perforator-based flaps, fed by a muscle perforator from the inferior, deep epigastric artery and having no muscle and little fatty tissue components, were used in two cases. This flap provides great advantages in overcoming some of the problems of the conventional rectus abdominis musculocutaneous flap.

Abdominal Muscles↗
PubMed1991

[A case of juvenile vesical endometriosis with unilateral renal agenesis and bicornate uterus].

A case of vesical endometriosis with unilateral renal agenesis is reported. A 13-year-old girl complained of difficulty in urination and lower abdominal pain during the menstruation. Detail urological examinations revealed left renal agenesis and intravesical cystic mass. The mass was located in the left vesical lateral wall, obstructing the vesical outlet and containing dark-brown-coloured fluid in it. She finally suffered from urinary retention following the menstruation and underwent a resection of the mass together with a part of the vesical wall. During the operation, the uterus was found to be a bicornate one. The resected mass was diagnosed as an endometriosis based on the histological findings. Eighteen months after the operation she is free from any symptoms during the menstruation and recurrence of endometriosis.

Adolescent↗
PubMed1991

Electron microscopic study of an unusual posttransplant glomerular lesion.

Glomerular lesions are frequently seen in renal allografts and are usually classified into transplant glomerulopathy and posttransplant glomerulonephritis. The latter is subdivided into donor-related, de novo, and recurrent glomerulonephritis. We report a distinctive posttransplant glomerular lesion that does not fit into any diagnostic category mentioned above. This lesion was characterized by the presence of global, diffuse, subepithelial, electron-lucent deposits, in addition to the usual features of transplant glomerulopathy. This unusual usual lesion, to the best of our knowledge, has been reported only once and, indeed, was recognized in only one of 297 renal allograft biopsy specimens in our file. Although the classification, pathogenesis, and origin of this rare lesion remain to be elucidated, it can be associated with nephrotic syndrome, deterioration of renal function, and eventual graft loss.

Adult↗
PubMed1991

A comparative study of IgA nephropathy between two institutions in Japan and Korea.

As an approach to the geopathological evaluation of kidney disease, we conducted a comparative study on IgA nephropathy (IgANP) between Saga Medical School (SMS) in Japan and Kosin Medical College (KMC) in Korea for the period 1983-1987. The relative incidence of IgANP among primary glomerular diseases was significantly higher (P less than 0.05) at SMS (103 cases of IgANP among 250 cases of primary glomerular diseases, 41.2%) than at KMC (63 cases among 201 cases, 31.3%). Clinical and histological comparisons of the IgANP between the institutions revealed that the SMS series was generally milder than the KMC series. When the renal manifestations at the time of biopsy for all cases with primary glomerular diseases were compared, asymptomatic urinary abnormalities were more commonly found at SMS than at KMC. This suggests that certain differences in medical practice may exist between the two institutions, as follows: 1) the medical checkup system may be more efficient, 2) the accessibility to medical service may be easier, and 3) the biopsy criteria may be more liberal in Japan/SMS than in Korea/KMC. Thus, the real differences in incidence and severity of IgANP between the two institutions could be smaller than those reported here.

Adult↗
PubMed1990

Molecular analysis of structural protein genes of the Yamagata-1 strain of defective subacute sclerosing panencephalitis virus. I. Nucleotide sequence of the nucleoprotein gene.

The complete nucleotide sequence of cloned cDNAs corresponding to the full-length mRNA encoding the NP protein of the Yamagata-1 strain of subacute sclerosing panencephalitis (SSPE) virus was determined. The gene is composed of 1683 nucleotides and contains a single large open reading frame, which is capable of encoding 525 amino acids with a molecular weight of 58,399. Comparison of the nucleotide and predicted amino acid sequences with those of the Edmonston strain of measles virus (MV) showed that the gene and the protein were highly conserved. However, the antigenic sites on the NP protein of the Yamagata-1 strain were found to be changed by an epitope analysis using monoclonal antibodies against the NP protein of MV. Only 1 of 4 monoclonal antibodies reacted with the NP protein of SSPE virus, and the other three antibodies did not. Almost identical changes in nucleotides and amino acids were found to occur in the NP gene of the Yamagata-1 strain when compared with the IP-3-Ca strain of another SSPE virus. In addition, the deduced secondary structure of the NP protein of the IP-3-Ca strain was similar to that of the Yamagata-1 strain, but differed from the MV. These results suggest that the NP proteins of SSPE viruses have a common property that is different from MV.

Amino Acid Sequence↗
PubMed1990

Molecular analysis of structural protein genes of the Yamagata-1 strain of defective subacute sclerosing panencephalitis virus. II. Nucleotide sequence of a cDNA corresponding to the P plus M dicistronic mRNA.

The nucleotide sequence of a cloned cDNA corresponding to the P + M dicistronic mRNA of a subacute sclerosing panencephalitis (SSPE) virus was determined and compared with data of measles virus (MV). The dicistronic mRNA of the SSPE virus consisted of the 3' proximal 626 nucleotides of P mRNA, intercistronic trinucleotides, a full length of M mRNA, and 75 poly A nucleotides. The part encoding the P protein had a high homology to MV, except at the noncoding region. The terminating consensus sequence of the P gene and the intercistronic trinucleotides of the SSPE virus were CTAC(A)6 and CCT; in MV they are TTAT(A)6 and CTT, respectively. In the M gene, the starting consensus sequence was exactly the same as MV, but at the 5' proximal end, one third of this gene was different: The first ATG codon of the MV M gene signaling opening of the reading frame was changed to ACG in the SSPE virus and one long open reading frame started from the third ATG codon. The stop codon (TAG) of the MV M gene was also changed to CAG in the SSPE virus. Thus, the deduced SSPE-virus M protein lacked 50 amino acids at the amino terminal and had 15 extra amino acids at the carboxyl end when compared with the MV M protein.

Amino Acid Sequence↗