[Diagnosis of varicella-zoster virus infection by immunological method].
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Biomedical subjects
Publications and source records attributed to T Kurata.
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Bolus intravenous cyclophosphamide therapy (IVCY) has recently been the subject of considerable attention because it is occasionally very effective in the treatment of severe lupus nephritis. However only a few reports on this form of therapy have been noted in Japan. Described here is a patient with lupus nephritis accompanied by multi-organ disorders resistant to various therapies including methylprednisolone pulse therapy which responded dramatically to IVCY. The patient, a 37-year-old woman with a history of systemic lupus erythematosus (SLE) starting in 1984, was admitted to our hospital with increasing generalized edema and malaise in January 1987. Evaluation revealed hypoalbuminemia, hypoxemia, ascites, hypocomplementemia and leukopenia. The patient was treated with high-dose oral prednisolone, however the lupus nephritis deteriorated and a high urinary protein level, massive ascites, and pericardial and pleural effusions were noted. Involvement of the central nervous system (CNS) was also observed. Subsequently, she was treated with intravenous methylprednisolone pulse therapy and low-dose oral cyclophosphamide. As her disease was refractory to these treatments IVCY was initiated in May 1987, at a dose 0.5-0.8 g/m2. A total of 3 doses were given, and treatment was discontinued in October 1987 because of marked clinical improvement. After the final IVCY treatment she was discharged, and her subsequent clinical course over a year with a maintenance dose of prednisolone has been uneventful. Thus, IVCY seemed to be useful in the treatment of severe lupus nephritis. More rigorous comparisons of IVCY with other therapies are necessary.
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A virus was isolated from the peripheral blood lymphocytes of patients with exanthem subitum, cultured successfully in cord blood lymphocytes, and shown to be antigenically related to human herpesvirus-6 (HHV-6). Morphological features, as studied by thin-section electronmicroscopy, resembled those of herpes group viruses. Convalescent-phase serum samples, tested against the new viral antigen and HHV-6 antigen, showed seroconversion. The results strongly suggest that the newly isolated virus is identical or closely related to HHV-6 and the causal agent for exanthem subitum.
Secretory IgA antibodies in mucosa are known to play an essential role in protection against various infectious agents. To enhance the induction of protective mucosal antibodies, influenza HA vaccine was inoculated intranasally into mice with the B subunit of cholera toxin (CTB), which is known to be an excellent mucosal self-adjuvanting molecule. This combination resulted in high levels of antiviral IgA antibodies in nasal secretions and enhanced serum haemagglutinin-inhibiting (HI) antibodies 4 weeks after inoculation, compared with the inoculation of vaccine alone which induced only a low level of HI serum antibodies and no local IgA antibodies. (Subcutaneous or intraperitoneal inoculation of the vaccine with CTB failed to induce detectable nasal antiviral IgA antibodies). Levels of nasal IgA and serum HI antibodies increased in a dose-dependent fashion with increasing nasal doses of both vaccine and CTB, and correlated with the degree of protection against viral challenge. A greater protective effect was seen with cholera toxin than with its B subunit. Moreover, a second administration of vaccine alone, 4 weeks after the inoculation of the vaccine with CTB, elevated the level of the antiviral IgA nasal antibodies to 10-100 times higher than that of the primary response. These results suggest that either CT or CTB could be used as a potent adjuvant to induce protective secretory antibodies by nasal vaccination against pathogens impinging on respiratory mucosa.
Four cases of acute retinal necrosis (ARN) syndrome were studied virologically. Varicella-zoster virus (VZV) antigen was demonstrated by immunofluorescence in cells from vitreous aspirates of two cases. No herpes simplex virus (HSV) or cytomegalovirus (CMV) antigens were detected by the same technique. Antibody to VZV in vitreous fluid was present in two cases; however, it was not detected in sera. Although virus isolation was unsuccessful, these findings strongly suggest that VZV may play an important role in the etiology of ARN syndrome.
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The effects of cholera toxin (CT) on delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) were studied in mice sensitized by intranasal administration of SRBC. CT (1 microgram/mouse), given intranasally together with SRBC (2 x 10(7)/mouse), induced a maximally enhanced DTH response, which reached its peak around 7 days after sensitization, and also induced an accelerated DTH response upon a second administration of SRBC 28 days later. The ability of CT to enhance the DTH to SRBC was lost, either when CT was administered via the intraperitoneal or subcutaneous route, or when CT was introduced into the nasal site from which a large proportion of the SRBC was discharged 2 days after SRBC administration. These results indicate that the cells that are located in the nasal site and participate in the earlier events of DTH response were most affected by CT. The following effects of CT on the earlier events, which occur within 24 hr after the intranasal administration of both CT and SRBC, appeared to be involved in the mechanisms by which CT enhances DTH to SRBC: (i) facilitation of the penetration of the antigen into the nasal tissue; (ii) reinforcement of the migration of immunocompetent cells from the blood to the nasal tissues; (iii) promotion of the ability of Ia-positive macrophages to present the antigenic determinants to T cells; (iv) facilitation of the differentiation of primed T cells to DTH-effector T cells.
A continuous cell line was established from a hepatocellular carcinoma obtained from a woodchuck that was sero-positive for woodchuck hepatitis virus (WHV). The cell line, designated WH44KA, grows as an adhering monolayer with a doubling time of 36 hr in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. The cells not only showed epithelial origin on light and electron microscopic examination but also possess biosynthetic markers of the latter, such as albumin and alpha-fetoprotein, which were demonstrated in cultured cells. When they were transplanted into athymic nude mice, tumors developed at the site of inoculation. These tumors were shown to be hepatocellular carcinoma, similar in morphology to the original tumor from which the WH44KA cells were derived. Chromosome analysis revealed a chromosome number ranging from 31 to 126, with a modal number of 35. Integration of WHV DNA was shown by Southern blot analysis. However, WHV surface antigen was not demonstrated in the cultured cells or supernatant medium. The WH44KA cell line appears to be a useful in vitro model for the study of virus-induced hepatocellular carcinoma.
The histochemical characteristics of liver cell foci in woodchucks were investigated. The foci appeared to be distributed throughout the liver and were observed only in the woodchuck hepatitis virus (WHV)-positive animals, including all 19 woodchucks with hepatocellular carcinoma(HCC), and 7 without HCC. No foci appeared in 11 WHV-negative animals. Histochemical studies revealed that liver cell foci and carcinoma cells were characterized by positive gamma-glutamyl transpeptidase (GGT) enzymatic reactions and decreased glucose-6-phosphatase enzyme activity compared to non-neoplastic liver. Furthermore, serum GGT was significantly elevated in almost all of the animals which had larger carcinomas. Ultrastructural findings of foci showed some resemblance to carcinoma cells, being characterized by abundant free ribosomes within the cytoplasm and undeveloped endoplasmic reticulum. These results suggest that the liver cell foci are potential precursors of HCC in WHV-infected animals, and that serum GGT may be a useful marker for indicating the development of carcinoma.
F1 cynomolgus monkeys bred in captivity and thought to be "SPF" had latent cytomegalovirus (CMV) infection although less frequently than in wild-born monkeys. Latent CMV could be activated under severe immunosuppression by inoculation with a certain strain of varicella-zoster virus (VZV) as shown in a previous study. We carried out further experiments using live and formalin-inactivated VZV in F1 monkeys which were sero-positive for CMV, but not for any other viruses. The results showed that both live and inactivated VZV were equivalent in permitting activation of latent CMV, suggesting that the VZV inoculum merely played an immunogenic, but not any virological, role in this case. Captive F1 monkeys, however, carried fewer CMV, and/or resisted CMV reactivation more than the wild monkeys in the previous studies, judging from the time required for generalized CMV infection to become expressed.
Ovarian involvement of cytomegalovirus (CMV) is rarely observed in autopsy and biopsy materials. Cortical necrosis of the ovaries was found in an autopsy case with generalized CMV infection. The patient was an 11-year-old girl in a remission state of acute lymphocytic leukemia. Autopsy revealed several areas showing necrotic change up to 2 mm in size in the cortex of both ovaries. Many cytomegalic cells were found in both the necrotic and intact areas of the cortex. CMV had infected the granulosa, thecal and stromal cells as well as vascular endothelial cells. Oocytes of neither primary nor graafian follicles showed cytomegalic changes, although they were destroyed due to the necrosis. CMV antigen was immunohistologically detected in these cytomegalic cells. Ultrastructurally, herpesvirus-type particles were revealed in the nuclei and cytoplasm of the cytomegalic cells. This case demonstrated that ovarian infection with CMV can potentially induce cortical necrosis and decrease the number of oocytes.
Effects of repeated oral administration of new quinolones, ofloxacin, enoxacin and norfloxacin, once daily for 7 days, on the drug-metabolizing enzyme system of rat hepatic microsomes were studied in comparison with that of phenobarbital, a potent inducer of cytochromes P-450. Treatment of phenobarbital at the oral dose of 120 mg/kg induced significant increases in the contents of cytochrome P-450, cytochrome b5 and NADPH-cytochrome P-450 reductase and in the activity of ethoxycoumarin O-deethylase, and significant decreases in the activities of benzphetamine N-demethylase and aniline hydroxylase. However, ofloxacin, enoxacin and norfloxacin at the oral dose levels of 80 and 320 mg/kg showed no significant effect on the content of each constituent of the drug-metabolizing enzyme system, and the three enzyme activities. Thus, it is concluded that new quinolones including ofloxacin have no ability to induce a cytochrome-P-450-dependent monooxygenase system.
As the pathogenesis of Bell's palsy, herpes simplex virus (HSV) infection has been suggested on the basis of several serological studies. To clarify and analyse the pathogenic mechanisms of this disease, guinea pigs were inoculated with type-1 HSV through natural infection routes into the peripheral areas innervated by facial nerve, and nervous tissues were examined by histopathological and immunohistochemical methods. HSV-I infection in the nasal mucosa, tongue, oral muscles and auricles brought about neither clinical facial palsy nor disturbed Preyer or corneal reflexes, but viral antigens in the inoculated peripheral areas, facial and trigeminal ganglia and pons with inflammatory cell response, hemorrhages and degeneration and necrosis. Cyclophosphamide treatment resulted in disturbed Preyer and corneal reflexes and enhanced the incidence of antigen appearance and histopathological changes.
A serosurvey for antibodies against type 1 and type 2 herpes simplex virus (HSV) was performed in consecutive sera collected from 61 patients with sudden deafness. A positive test for neutralizing antibody to type 1 HSV was found in 80% of patients and 77% of controls, a non-significant value. Almost all the patients possessing neutralizing antibody had complement-fixing antibody too, which some controls would have lost in the course of time. The kinetic survey of the antibody titers during the clinical course demonstrated constant levels of these antibodies. It is suggested that there may be some relationship of HSV to sudden deafness and that reactivation of a latent infection may play an important role in the etiology of this disease. We found some relationship between the serological data and the clinical findings with respect to hearing recovery.
The enzyme activities which depended on the ascorbic acid (AsA) tissue levels were assayed to investigate the effect of erythorbic acid (ErA) administration on the AsA availability in the guinea pigs administered 5 mg of AsA/day or 1 mg of AsA/day. The guinea pigs were given 5 mg of AsA and 1, 5, 20, 100 mg of ErA/day, or 1 mg of AsA and 1 or 20 mg of ErA/day for 16 days. The animals were sacrificed, blood was collected, and their livers were removed. The activities of liver aniline hydroxylase, liver acid phosphatase, and serum alkaline phosphatase, as well as the liver cytochrome P-450 content were measured. These enzyme activities and the liver cytochrome P-450 content of animals administered 5 mg of AsA seemed to show no change regardless of ErA supplement. Animals administered 1 mg of AsA showed different activities of liver aniline hydroxylase and liver acid phosphatase compared with those of animals administered 5 mg of AsA; however, the enzyme activities in animals administered 20 mg of ErA together with 1 mg of AsA were similar to those of the animals administered only 5 mg of AsA. These results indicated that ErA administration had no effect on the enzyme activities and the liver cytochrome P-450 content in the 5 mg AsA-supplemented animals, but administration of 20 mg of ErA was effective to maintain at normal levels the activities of liver aniline hydroxylase and liver acid phosphatase in the 1 mg AsA-supplemented animals.