Re: Acute hemorrhagic conjunctivitis.
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Biomedical subjects
Publications and source records attributed to R Kono.
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Adenovirus 7 (Ad7) is the adenovirus species that most frequently has been associated with severe illness. Seven distinct genome types of adenovirus 7, Ad7p, Ad7a, Ad7b, Ad7c, Ad7d, Ad7e, and Ad7f, can be identified by using restriction endonucleases BamHI and SmaI. We analyzed the distribution of the different Ad7 genome types among 314 isolates from patients and healthy shedders. The Ad7b and Ad7c genome types accounted for 90% of the isolates from patients and appeared to be mutually exclusive. A shift from Ad7c to Ad7b genome types occurred in 1969 in Europe and in 1975 in Australia. During the last decade, Ad7b genome types predominated in Australia, Europe, and North America. Ad7c was detected in South Africa, Ad7d was detected in China, Ad7e was detected in Brazil, and Ad7f was detected in Australia. The Ad7p and Ad7a genome types dominated among isolates obtained from healthy shedders and appeared scattered through the years and the geographical areas. The prevalence of Ad7 infections is high in Japan as judged by the herd immunity. However, the low percentage (2%) of Ad7 isolates among all adenovirus isolates chiefly from patients, coupled with 30 to 50% antibody prevalence, argues for a high proportion of inapparent infections and, hence, Ad7 strain(s) of low pathogenicity.
Ultrasonic measurement (0.333-200 MHz) of melanosomes isolated from B16 and Harding Passey (HP) mouse melanomas indicates that the partial wave resonance and principal relaxation of the 2 kinds of melanosomes are similar, but that their stochastic resonance is markedly different. The structure of the melanosomes appears basically amorphous, but linearly ordered and copolymeric in the molecular dimension of a segment composed of 5-6 zigzag units, which are packed closely in B16 and more openly in HP.
Different isolates of enterovirus type 70 (EV70) taken between 1971 and 1981 were studied by molecular biological methods to elucidate their evolutional change. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that only a few isolates had a slight alteration in mobility in some viral proteins. On the contrary, oligonucleotide mapping of virion RNA could clearly delineate the molecular changes among isolates. The number of base changes of isolates became greater as the years elapsed. In addition, the number of base changes among recent isolates from different areas of the world was much greater than those among early isolates. Thus, when the isolates were arranged three-dimensionally according to the number of base changes between each other, the constellation of the strains gave rise to a conical shape. The central axis of the figure was the time of isolation of the strains. The early isolates clustered near the top of the conical figure and the recent isolates tended to disperse divergently at the bottom. The figure indicated that all EV70 strains were derived from a common ancestor, and its top would be the time of emergence of the original strain. It was estimated to be around 1966, 3 years prior to the first epidemic in Accra, Ghana. From the results, it was presumed that EV70 would have emerged at a single focus in Africa as a novel human virus. After having circulated there for a few years, the virus spread to the other parts of the world. Based on the difference in the oligonucleotide spots between the recent isolates and early isolates, the base changes of EV70 that occurred during 10 years was estimated to be 320, about 4% (0.4% a year on the average) of the bases of the total RNA genome.
The persistence of neutralizing antibody (NA) against three types of poliovirus acquired after two doses of trivalent live attenuated poliovirus vaccine (LPV) has been followed up for ten years in individual vaccinees. Sixty-seven children were bled once a year over a five year period following the primary vaccination. More than 80% of them retained NA against all three types of poliovirus. Thirty-two individuals whose NA titres were 1:16 or over for types 1 and 2 and 1:4 or over for type 3 at the fifth year were further followed up for a further five years and it was shown that during this period some of them had a naturally-acquired antibody rise, mostly against type 3 virus. At the sixth to eighth year after the primary vaccination, one further dose of the trivalent vaccine was administered to the children whose NA titres were down to 1:8 or less and the effect of booster vaccination on NA was followed. Other subjects were revaccinated with LPV and their fecal excretion of the vaccine virus was investigated. The results showed that a decrease in serum antibody level could be a good indicator of the local resistance of the alimentary tract and that reinfection could occur if serum NA had decreased to 1:8 or less, which allowed a virus excretion in the stools.
The genetic relationship between two enteroviruses causing the acute hemorrhagic conjunctivitis (AHC) syndrome was examined by the RNA-RNA hybridization technique. Nucleotide sequence homology between the J670/71 strain of enterovirus type 70 (EV70) and the EH 24/70 strain of Singapore epidemic conjunctivitis (SEC) virus was found to be only 2% or less of the total RNA genome, while more than 90% homology was detected between the prototype (J670/71) and other isolates of EV70. The results indicate that the SEC virus, an agent of conjunctivitis epidemics in limited areas of southeast Asia and India since 1970, was distinguished serologically and genetically from EV70, which caused pandemics of AHC over the African and Eurasian continents from 1969 to 1972.
Ultrasonic measurement of the two different forms of melanosomes was carried out at 20 to 300 MHz on B16 and Harding-Passey mouse melanomas which produce ellipsoidal-lamellar and spherical-granular melanosomes, respectively. We found that the structure of the two forms is basically amorphous and copolymeric in the molecular dimension of a segment composed of 5 to 6 zigzag units. A marked difference in particle wave resonance was found around 200 MHz in the two melanosomes. Based on the chemical structure of melanin proposed by Hempel, it was indicated that the physical structure of Harding-Passey melanosomes is a copolymer in which melanin and protein moieties run parallel to each other but may bind together at the sites of planar groups, while that of B16 melanosomes is a double-helix polymer of melanin and protein moieties with a screw symmetry of N = 6. This type of one-dimensional cyclic ordering, commonly known as the Born-Karman periodic boundary condition in semiconductive band theory, may be related to the formation of the lamellar structure seen in B16 melanosomes.
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The brains of 34 patients at the chronic stage of acute carbon monoxide poisoning (CO poisoning) were examined using computerized tomography (CT). Ventricular and sulcal dilatations were measured quantitatively, with picture analysis of CT for the measurement of ventricular dilatation. Significant ventricular and sulcal dilatations were found in all cases of the CO group compared with age-matched controls, and bilateral low density areas in the globus pallidus were seen in 9 of the patients. There were significant correlations between duration of initial unconsciousness and the ventricular dilatation or cortical atrophy. Such dilatations were considered to be due to the cerebral damage in the acute stage.
High and rising neutralizing antibody titers (NATs) to enterovirus type 70 (EV70) were detected in the serum and cerebrospinal fluid (CSF) of patients with polio-like motor paralysis accompanying acute hemorrhagic conjunctivitis (AHC) in an outbreak of AHC in 1981 in Bombay, India. Fifty-four (88.5%) of 61 patients with AHC with or without neurologic disease had serum NATs of greater than or equal to 1:16, and some paired sera from these patients showed significant increases in NAT. Serum from noninfected control subjects had no significant neutralizing antibody to EV70. Thirty-six (94.7%) of 38 CSF specimens from 30 patients with spinal or a combination of spinal and cranial motor paralysis associated with AHC had NATs ranging from 1:2 to 1:256. No neutralizing antibody was found in CSF specimens from patients with AHC alone or in those from non-infected control subjects, and a reduced ratio of serum NAT to CSF NAT was detected in patients with neurologic disease. Therefore, it is highly likely that intrathecal synthesis of antibody occurred in response to direct invasion of the central nervous system by EV70. The results represent strong laboratory evidence of the neurovirulence of EV70.
Antitoxic immunity against diphtheria was surveyed during the period from 1962 to 1980. The survey was done by Schick test in the first decade and then by antitoxin titration of sera by the cell culture method in the recent six years. The data show clearly that the successful control of diphtheria has been accomplished in Japan as the result of active immunization. Both single (D) and combined (DP or DPT) vaccines were effective to convert Schick reaction negative. In addition, immunity was greatly improved by the introduction of the combined vaccine and one additional booster injection. However, such subsequent changes in the immunization schedule introduced in 1976 that giving the primary vaccination at older age and the omission of one booster injection at the preschool, has resulted in appearance of a high risk group below three years of age as well as in the lower immunity levels among school children. The data indicate that the continuous surveillance for diphtheria is required in this country.
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Enterovirus type 70 (EV70) agglutinated human 'O' erythrocytes at 4 degrees C as well as 22 degrees C, but visible agglutination was lost when warmed at 37 degrees C although the virus remained attached to the surface of the erythrocyte. The receptor sites for the virus were neuraminidase-sensitive. A direct involvement of sialic acid on the cell surface in virus-cell interaction was confirmed by the fact that the presence of fetuin or free N-acetylneuraminic acid inhibited the haemagglutinating activity of EV70. Similar numbers of virus particles were required for 1 haemagglutinating unit (HAU) of EV70 and 1 HAU of mengovirus, whereas 2.6-fold or more of virus particles of echovirus type 7 and type 11 gave the same activity. On the other hand, the number of receptor sites on the cell surface for EV70 was found to be sevenfold more than for mengovirus. Therefore, the erythrocyte receptor for EV70 is different from that for common enteroviruses and similar, though not identical, to the cardiovirus receptor. However, serological tests such as neutralization, complement fixation or haemagglutination inhibition did not reveal any common antigen between EV70 and cardiovirus.
A one-year survey was conducted on the psychiatric consultation work at Kyushu University Hospital. It was found that an organic brain syndrome was the most frequent psychiatric diagnosis of the referred patients. The most frequent purpose of request for psychiatric consultations was for the management of the patient. The main consultant functions were diagnoses and to advise on the management of the patient. The consultant functions agreed with the purposes of request in many cases, but discrepancies between the two were found about the patient disposition. The nature of the consultant role was compared with some American studies. It was deemed necessary that consultation-liaison psychiatry based on Japan's present conditions, medical and social, should be developed.
A cultivable human rotavirus, Wa, was propagated in MA-104 cells and used as an antigen in immune adherence hemagglutination (IAHA) and complement fixation (CF) tests. IAHA antibody titers of sera from normal humans were found to be eightfold higher than CF antibody titers. The IAHA antibody determination with the Wa antigen is considered to be especially useful for the seroepidemiological studies of human rotavirus infections.
We succeeded in isolating human rotaviruses from the feces of gastroenteritis patients by using roller cultures of primary cynomolgus monkey kidney cells with trypsin in the maintenance medium but without concentration and trypsin treatment of the inocula at each passage level. These cells were found to be more sensitive than MA-104 cells (derived from fetal rhesus monkey kidney) for the propagation of human rotaviruses. Polyacrylamide gel electrophoresis of the genome RNA revealed that there were small differences in the migration pattern of the segments among all the strains isolated from 1976 to 1981. The cultivation of human rotaviruses in primary cell cultures might aid in developing a liver rotavirus vaccine.
The mechanism of the failure of enterovirus type 70 to replicate at a nonpermissive temperature (39 degrees C) was investigated, and the following results were obtained. (i) Viral RNA synthesis was not observed at 39 degrees C in LLC-MK2 cells, in accordance with our previous findings with primary monkey kidney cells (Miyamura et al., Intervirology 9:206-213, 1978). (ii) Shutoff of host cell macromolecular synthesis by virus infection was as efficient at 39 degrees C as at a permissive temperature (33 degrees C). This inhibitory effect similarly occurred even in the presence of guanidine hydrochloride. (iii) Viral protein synthesis proceeded in vivo at the nonpermissive temperature, and the rate of the protein synthesis was higher than that at the permissive temperature under the conditions in which sufficient viral mRNA had been accumulated. This was also confirmed by analyzing the intracellular proteins synthesized at the nonpermissive temperature by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which identified them as virus-specific proteins. (iv) When infected cells were incubated at 39 degrees C and then transferred to 33 degrees C, viral RNA synthesis took place even in the presence of cycloheximide. (v) Furthermore, in experiments performed with an in vitro cell-free assay system, viral polymerase activity was found in the membrane-bound preparation extracted from infected cells which had been incubated at 39 degrees C in the presence or absence of guanidine hydrochloride. These results indicate that early translation of mRNA proceeds normally at the nonpermissive temperature and that the temperature-sensitive defect resides in the transcriptional stage.