PubMed HealthSearch

Biomedical subjects

I Arita

Publications and source records attributed to I Arita.

At least 19 recordsLinked to original sources

Transition of phenotypic dimorphism with regard to spontaneous sister chromatid exchange in Epstein-Barr virus-transformed Bloom's syndrome lymphoblastoid cell lines.

We recently established four lymphoblastoid cell lines (LCLs) by infecting the peripheral blood of four Japanese patients suffering from Bloom's syndrome (BS) with Epstein-Barr virus (EBV). During the course of propagating these cell lines, two of them exhibited dimorphism regarding spontaneous sister chromatid exchange (SCE), i.e., a mixed population consisted of cells with extremely high SCE levels characteristic of BS and cells with low SCE levels indistinguishable from that of normal control cells. On the other hand, the other two cell lines maintained a monomorphic population with high SCE levels at least until 30 weeks after EBV infection. The proportion of the cells with high SCE levels in the cell lines with dual phenotype declined as the population doubling numbers (PDN) increased with time and they became ultimately undetectable. The proportion of cells with low SCE levels at the time of EBV infection was estimated in one of these LCLs as 0.075% by extrapolating the linear regression of the logit for the proportion plotted against PDN. In view of the well-known stability of the monomorphic phenotype in representative BS LCLs during extended cultivation, together with the present observations on the dual phenotype, we conclude that the frequent establishment of BS LCLs exclusively with low spontaneous SCE levels is attributable to the various proportions of low-SCE cells existing in vivo in the B-lymphocytes pool of BS individuals and to the selective pressure against the high-SCE cells in in vitro cultures.

Adolescent

Evidence for spontaneous conversion of Mex- to Mex+ in human lymphoblastoid cells.

A series of human lymphoblastoid cell lines (LCLs) called Mex- were defined by Sklar and Strauss on the basis of their inability to remove O6-methylguanine from DNA. Instability of Mex- has previously been shown as a population phenotype of LCLs. We examined whether Mex- as a cellular phenotype is spontaneously convertible or not. At the population doubling number (PDN) 23 after recloning, two out of 15 independent subcultures derived from a Mex- LCL, AT1-1, were found to contain a small fraction of Mex+ cells after treatment with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). Three Mex+ subclones were identified without exposure to ACNU among 486 subclones from replica plating of an expanded Mex- clone (PDN30). The rate of spontaneous conversion was estimated to be in the range of 10(-8)-10(-7) per cell per generation by the fluctuation analyses on two Mex- subclones. These results strongly support the hypothesis that Mex- as a cellular phenotype is spontaneously convertible to Mex+.

Cell Line

Tumorigenic conversion of xeroderma pigmentosum lymphoblastoid cells without karyotypic alteration.

In order to examine the process of malignant transformation of human somatic cells, we studied the tumorigenic conversion of an Epstein-Barr-virus-immortalized lymphoblastoid cell line (LCL) derived from a patient with xeroderma pigmentosum (XP) complementation group A. Repeated irradiation of the XP cells, XP7NI, with UV-light and subsequent treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in the acquisition of tumorigenicity in athymic nude mice. The tumorigenicity of XP7NI cells was also induced by TPA treatment alone. The tumors formed in athymic mice were of B-cell lymphoma with characteristic histology, cell surface immunoglobulins and an antigen as detected by a B-cell-specific monoclonal antibody (MAb), CD20. The surface immunoglobulins and the HLA type of these tumor cells were identical with those of the parental cells. These malignantly transformed cells retained the same UV sensitivity, serum requirement, colony-forming ability in soft agar, and normal human karyotype as the parental cells. Unlike other tumorigenic lymphoblastoid cell lines, this XP lymphoblastoid cell line provides a unique case in that process(es) leading to tumorigenicity may be induced by UV and TPA without apparent karyotypic changes.

Animals

Predominance of Mex+ cells in newly-established human lymphoblastoid cell lines.

Previous studies have demonstrated that approximately one-third of human lymphoblastoid cell lines (LCLs) are deficient in removing O6-methylguanine residues because of the lack of O6-alkylguanine-DNA alkyltransferase (O6-AGT) activity. Such LCLs have been designated Mex-, while the proficient LCLs are Mex+. Our determinations of O6-AGT activity as a function of cellular protein concentration on 37 previously-established LCLs disclosed that the expression of the enzyme was high in 14 (Mex+) and barely detectable in 16 (Mex-). The other seven LCLs showed intermediate activity of the enzyme. By contrast, all of the 28 LCLs that we newly established contained high enzyme activity, implying that they consisted of mainly Mex+ cells. Since the conventional O6-AGT assay on Mex+ cell populations was not capable of detecting the co-existence of Mex- cells as a minor component, we attempted to determine the proportion of Mex- phenotype in newly-immortalized lymphoblastoid cell clones which had been established directly on semisolid agar. All of the 15 independent clones derived from a single blood sample also showed high O6-AGT activity, rendering it unlikely that Epstein-Barr virus transformation per se was responsible for the generation of Mex- LCLs. These results collectively indicate that Mex+ cells predominate in LCLs shortly after establishment and also suggest that the possible growth advantage for Mex- cells should play an important role in the subsequent development of Mex- LCLs during the long-term culture in vitro.

Cell Line

Pseudohypoparathyroidism showing positive phosphaturic and negative cyclic AMP excretion response to parathyroid hormone.

We report a patient with pseudohypoparathyroidism (PHP) in whom parathyroid hormone (PTH) infusion failed to produce an increase in urinary adenosine 3', 5' monophosphate (cAMP) excretion in spite of the positive urinary phosphate excretion. The dbcAMP infusion test showed almost the same increase in phosphate as in the E-H test, although high urinary cAMP excretion was detected. Furthermore, a PTH infusion test in combination with calcium antagonist (diltiazem) administration markedly increased phosphate excretion, whereas the response of urinary cAMP excretion also remained negative. After treatment with 1 alpha(OH)D3, phosphaturic response increased by at least 14.3 mg/2 h compared with that in the pretreatment period. Therefore, intra and extra cellular calcium seem to affect the phosphaturic response induced by PTH.

Adult

Instability of Mex- phenotype in human lymphoblastoid cell lines.

Three lymphoblastoid cell lines (LCLs) had extremely low activities of O6-alkylguanine-DNA alkyltransferase (O6-AGT), and were classified as Mex-. They were highly sensitive to cell killing by 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoure a hydrochloride (ACNU), whereas NMO2, a Mex+ LCL with a high O6-AGT activity, was resistant to the agent. Small fractions of these Mex- LCLs survived the treatment with 10 micrograms/ml of ACNU for 24 h, and the surviving cells were found to be resistant to subsequent treatments with the agent. In addition, they contained O6-AGT activities comparable to that of NMO2 and were therefore regarded as Mex+. These results suggest that the Mex- phenotype in LCLs is unstable.

Cell Division

Serological survey for human monkeypox infections in a selected population in Zaire.

About 3460 persons living in Kole zone of East Kasai, in Zaire, were examined and their sera screened initially by a haemagglutination-inhibition test. Of these, 667 (19%) were positive. Radioimmunoassay adsorption tests for the presence of monkeypox- or vaccinia-specific antibodies gave unequivocal results in 300 of these sera; the remaining 47 were nonspecific. Monkeypox-specific antibodies were found in sera of 27 individuals, of all ages and both sexes, giving an overall prevalence rate of monkeypox virus-specific antibodies of 0.8%. The prevalence rate was four times higher in the 5 to 9 year age group (1.3%) than in children aged 0 to 4 years (0.3%), and was highest (2.4%) in the 15 to 19 year age group. There was no significant difference in the prevalence rates between the sexes. As might be expected, there are substantially higher prevalence rates in persons living in forest galleries than in those in savannah, and among those living in areas where human monkeypox cases had occurred in the past compared with those living in other localities. Nineteen children whose sera showed specific monkeypox antibodies were re-examined. Twelve showed facial and body skin changes suggesting the presence of vesiculo-pustular disease in the past; four of these had been known registered monkeypox cases. Seven children had neither signs nor history of past vesiculo-pustular disease, suggesting that they had suffered from subclinical infection with monkeypox virus.

Antibodies, Viral

Impact of population density on immunization programmes.

The eradication of smallpox was achieved by surveillance and containment vaccination after the failure of mass immunization campaigns. The reasons for this failure are considered in this paper. Comparison of population densities in the Indian subcontinent and Africa show that in highly populated areas even an 80% vaccine coverage will still leave a density of susceptibles high enough to maintain the disease, a finding with important implications for other vaccine campaigns.

Africa

Four generations of probable person-to-person transmission of human monkeypox.

This paper examines an outbreak of five cases of human monkeypox which occurred in children belonging to two families living in the West Kasai region of Zaire during May-July 1983. Epidemiologic investigations suggest that the first case was infected from an animal source, possibly a monkey, and that each of the other four cases was infected from a previous human case. Three of these cases of presumed person-to-person transmission occurred in close household contacts. The other case infection occurred either by casual contact within the hospital compound, or possibly because of infection due to use of the same syringe for injections. Human monkeypox is the most important orthopoxvirus infection in the post-smallpox eradication period. The disease is a zoonosis and person-to-person transmission is rather difficult. Thus, this episode is a rare event and special analysis of the circumstances is discussed. However, it supports the necessity to carry out surveillance and research on this disease as recently reported by Arita et al.

Animals

Human monkeypox: a newly emerged orthopoxvirus zoonosis in the tropical rain forests of Africa.

During the course of the recently concluded smallpox eradication program, a new human orthopoxvirus infection was discovered which is caused by monkeypox virus. The disease occurs sporadically in remote villages within tropical rain forests of West and Central Africa. The disease is rare; only 155 cases having been reported from 1970 to 1983. The symptoms and signs of human monkeypox resemble those of smallpox, differing significantly only in the occurrence of lymphadenopathy with human monkeypox disease. Of 155 cases, some 80% are believed to have resulted from infection from an as yet unknown animal reservoir; the rest occurred among unvaccinated close contacts among whom a secondary attack rate of 15% was observed. Although person-to-person spread appears to have occurred in some instances, few cases were observed in the third or fourth generation of transmission and none thereafter. Since 1982, the incidence of human monkeypox infections in Zaire has increased concomitant with an intensified surveillance program. Additional reasons which might explain the increased incidence are discussed. Further surveillance and research of this primarily zoonotic infection are warranted and are in progress.

Adolescent

[Monkey pox virus infection in humans in the Central African Republic].

A human monkeypox outbreak is reported which occurred in January 1984 in the extreme south-west areas of the Central African Republic. Six persons were found to be affected in a Pygmy camp with an estimated population of 50 residents. In the two affected families, out of 11 members, only unvaccinated children and a 22 year old unvaccinated woman contracted the disease. The disease was of moderate severity in two patients and very mild in the other four. The clinical diagnosis was confirmed by virus isolation from skin lesions of 4 patients and by sero-immunologic tests in all of them. The clinically apparent monkeypox case reported in the Central African Republic in 1983, the presently described outbreak, as well as information on the disease obtained from Pygmies and missionary paramedical staff who are in frequent contact with them, suggest that monkeypox is enzootic in the tropical rain forest in the south-west areas of the Central African Republic.

Central African Republic

Human monkeypox transmitted by a chimpanzee in a tropical rain-forest area of Zaire.

A case of monkeypox infection in a six-month-old baby girl who had been bitten by a wild chimpanzee in Kivu, Zaire, was investigated. The child had not been exposed to any monkeypox-like disease and no cases of such disease had occurred in the surrounding area during previous months. The time of onset of rash was consistent with the virus having been transmitted from the chimpanzee. However, it is still not known whether chimpanzees and other primates or lower mammals are the primary reservoir of monkeypox infection.

Accidents, Home

Surveillance of orthopoxvirus infections, and associated research, in the period after smallpox eradication.

In 1980, the World Health Assembly declared the global eradication of smallpox and recommended the universal discontinuation of smallpox vaccination; nevertheless, it recommended that surveillance and research on orthopoxvirus infections should continue. By early 1982, all except 8 countries in the world had stopped routine vaccination programmes and all except 1 no longer required an international certificate of smallpox vaccination for travellers. Since 1978, as a result of continuing active surveillance, 176 smallpox rumours have been investigated in 60 countries. Two of these concerned the two laboratory-associated cases that occurred in the United Kingdom in 1978; all the others were false alarms. Special surveillance programmes for human monkeypox have been developed in West and Central Africa. The number of laboratories retaining variola virus stocks has been reduced to four. Investigations to determine the identity and origin of the six known isolates of "whitepox" virus have continued. Research on mapping of variola DNA and on monoclonal antibodies against certain orthopoxvirus antigens is continuing. All these measures are aimed at ensuring that the achievement of smallpox eradication is permanent.

DNA, Viral

The confirmation and maintenance of smallpox eradication.

In December 1979, an independent scientific commission certified global eradication of smallpox. This conclusion was accepted at the 33d World Health Assembly of the World Health Organization (WHO) in May 1980. After WHO's intensified eradication program began in 1967, special certification procedures were used in 35 countries where the disease had been endemic and in 44 others at special risk. Six laboratories are known to retain variola virus; efforts have been made to ensure strict containment of these strains. There is no evidence that smallpox will recur as an endemic disease. Nevertheless, WHO will promote surveillance of smallpox-like disease and selected laboratory research on certain orthopoxviruses. These efforts will maintain confidence that smallpox has been eradicated and confirm that there are no animal reservoirs of variola virus. A more complete understanding of the orthopoxviruses, including monkeypox virus, should also be obtained.

Child

Human monkeypox, 1970-79.

Increasing attention has been given to human monkeypox since the achievement of global smallpox eradication. Monkeypox, which was first described in Central Africa in 1970, resembles smallpox clinically but differs from it epidemiologically. Forty-seven cases of human monkeypox have occurred since 1970 in 5 Central and West African countries; 38 of these cases have been reported from Zaire. The evolution of the illness and the sequelae of monkeypox and smallpox are the same; monkeypox has a case-fatality rate of about 17%. Children below 10 years of age comprise 83% of the cases. All cases have occurred in tropical rainforest areas and clustering of cases has been observed in certain zones within countries and within families. Person-to-person spread may have occurred in 4 cases; the secondary attack rate among susceptible, very close family members was 7.5% (3 cases/40 contacts) and among all susceptible contacts was 3.3% (4 cases/123 contacts)-much lower than the 25-40% secondary attack rate that occurs with smallpox. Although the low transmission rate and the low frequency of disease indicate that monkeypox is not a public health problem, more data are needed.Whilst many animals near human monkeypox cases have been demonstrated to have orthopoxvirus antibodies, the natural reservoir(s) and the vector(s) of monkeypox virus are unknown. Studies are in progress to identify the natural cycle of monkeypox virus and to define better the clinical and epidemiological features of this disease.

Adolescent