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Biomedical subjects

R Mori

Publications and source records attributed to R Mori.

At least 19 recordsLinked to original sources

Detection of human papillomavirus DNA in esophageal carcinoma in Japan by polymerase chain reaction.

BACKGROUND: Human papillomaviruses (HPV) have been implicated strongly in the pathogenesis of human squamous cell carcinomas, especially of anogenital carcinomas. Some pathologic changes of the esophagus may be one of the candidates for HPV etiology, but the role of HPV infections in the carcinogenesis of the esophagus remains to be clarified. METHODS: To elucidate the association of HPV with carcinogenesis of the esophagus, 45 biopsy samples of esophageal squamous cell carcinomas were examined for the presence of HPV DNA by polymerase chain reaction (PCR). Primers for PCR were (1) consensus primers (CP) for the simultaneous amplification of the E6-E7 regions of cancer-associated HPV types (HPV 16, 18, 31, 33, 52b, and 58), which have been shown to have transforming activities; (2) type-specific primers (SP16, SP18) for the E7 regions of HPV 16 and HPV 18, respectively; and (3) general primers (GP) for the simultaneous amplification of the L1 regions of HPV 6, 11, 16, 18, 31, and 33. RESULTS: PCR using CP first was done for screening and showed that 3 (6.7%) of 45 specimens contained HPV 16 or HPV 18 DNA, the oncogenic high-risk HPV types. This was confirmed by SP16 and SP18 PCR. However, no HPV DNA was detected by PCR using GP. These results suggested that the HPV DNA detected might be integrated into the cell genome with their transforming genes retained and their late regions deleted. CONCLUSIONS: Most oncogenic types of HPV (HPV 16 and HPV 18) were detected by PCR in carcinomas of the esophagus. Thus, HPV might play a role, although at a low frequency, in carcinogenesis of the esophagus.

Base Sequence

Reactivation of cytomegalovirus in patients with cirrhosis: analysis of 122 cases.

Human cytomegalovirus causes severe and often fatal infections in immunocompromised patients. After organ transplantation cytomegalovirus in peripheral blood mononuclear cells is thought to be activated by alloreaction and to spread because of immunosuppression, and it may cause endogenous cytomegalovirus diseases. Patients with cirrhosis, one group of candidates for liver transplantation, often show various grades of immunosuppression before transplantation. To evaluate the status of cytomegalovirus infection in cirrhotic patients and its relevance to the degree of immunosuppression, we examined the presence of cytomegalovirus in mononuclear cells by polymerase chain reaction and immunocytochemical analysis. We studied 122 patients with definite cirrhosis and 43 normal volunteers. All cirrhotic patients (100%) and 40 (93%) of 43 normal controls were seropositive for cytomegalovirus. Cytomegalovirus DNA was detected by polymerase chain reaction in 77 (63.1%) of 122 seropositive cirrhotic patients, but in only 1 (2.5%) of 40 seropositive normal controls (p < 0.01). Cytomegalovirus antigen could not be detected in mononuclear cells by immunocytochemical staining with monoclonal antibodies. Cytomegalovirus DNA-positive patients have a greater impairment of liver function than do cytomegalovirus DNA-negative patients; this fact is manifested by delayed indocyanine green retention rates and elevated serum bilirubin levels (p < 0.05). Lymphocyte proliferative response induced by phytohemagglutinin and natural killer cell activity were also significantly lower in cytomegalovirus DNA-positive patients as compared with cytomegalovirus DNA-negative patients (p < 0.01). Our data suggest that the reactivation of cytomegalovirus may have already occurred in patients with cirrhosis before transplantation.

Adult

Localization of herpes simplex virus type 1 in sebaceous glands of mice.

The distribution of HSV-1 during the development of zosteriform skin lesions in SCID mice was analyzed by immunofluorescence and electron microscopy. The virus initially appeared within certain keratinocytes, sometimes surrounded by keratinocytes whose surfaces were also positive for the antigens, in the lower epidermal layers including the hair follicles, and then extended upward to the entire epidermis and downward to the sebaceous glands 1-2 days later, when no macroscopic skin lesion was seen. The affected epidermal cells subsequently degenerated and lost their viral antigens within a day, when the zosteriform lesion then became evident. This was followed by a degeneration of the dermis. The sebaceous glands eventually degenerated in 10 days, but some glands in the necrotic skin areas preferentially retained HSV-1. The horizontal spread of the virus in the epidermis beyond the first invaded dermatome occurred much later. In mice passively immunized with specific immune serum, viral antigens were observed even 20 days after the infection in sebaceous glands in necrotized areas. Therefore, HSV-1 appears to spread first via the extracellular fluid among the keratinocytes after being shed from nerve endings, and then produces a successive degeneration of the affected keratinocytes which may prevent any further extension of horizontal viral spread. The pilosebaceous apparatus is possibly acting as a site not only for the replication of HSV-1 with a delayed cytopathic effect, but also as an area that is temporarily sheltered from host defense mechanisms.

Animals

Binding characteristics of naftopidil and alpha 1-adrenoceptor antagonists to prostatic alpha-adrenoceptors in benign prostatic hypertrophy.

Binding properties of naftopidil and alpha 1-adrenoceptor antagonists to alpha-adrenoceptors in prostates from benign prostatic hypertrophy (BPH) were characterized by radioreceptor assays using [3H]prazosin and [3H]rauwolscine. Specific binding of [3H]prazosin and [3H]rauwolscine in human prostatic membranes was saturable and of high affinity, and it showed a pharmacological specificity which characterized alpha 1 and alpha 2-adrenoceptors, respectively. Naftopidil and several alpha 1 antagonists competed for prostatic [3H]prazosin binding in order: R-(-)-YM-12617 greater than prazosin greater than bunazosin greater than terazosin greater than naftopidil greater than urapidil, and the inhibitory effect (Ki = 11.6 nM) of naftopidil was 10 to 45 times less potent than quinazoline derivatives such as prazosin, bunazosin and terazosin. The potencies of these antagonists in competing for [3H]prazosin binding sites in human prostates correlated well with their pharmacological potencies (pA2). Scatchard analysis indicated that the decrease of prostatic [3H]prazosin binding by naftopidil was due to a marked increase in the Kd value without a change in the Bmax value. The inhibition of prostatic [3H]prazosin binding by naftopidil was reversible. Naftopidil also inhibited prostatic [3H]rauwolscine binding (Ki = 70.0 nM). Thus, it is suggested that naftopidil antagonizes alpha 1-adrenoceptors in human prostates in a competitive and reversible manner.

Adrenergic alpha-Antagonists

Possible role of cytomegalovirus in the pathogenesis of inflammatory aortic diseases: a preliminary report.

To search for possible evidence of a relationship between human cytomegalovirus and aortic diseases, we examined 41 aortic lesions excised at surgery and 16 aortic tissues obtained at autopsy for the presence of cytomegalovirus DNA, by use of polymerase chain reaction. Cytomegalovirus DNA was present in seven (88%) of eight lesions of inflammatory aortic diseases with periaortic fibrosis, five of six inflammatory aneurysms, and all of two aortic occlusive lesions with inflammation. Cytomegalovirus DNA was detected in 20 (61%) of 33 atherosclerotic aneurysms, whereas it was detected in only five (31%) of 16 autopsy samples that showed neither inflammation nor atherosclerosis. Thus the possibility that cytomegalovirus may play a role in the pathogenesis of inflammatory aortic diseases warrants further attention.

Adult

Latent infection of SCID mice with herpes simplex virus 1 and lethal cutaneous lesions in pregnancy.

Some SCID mice survived primary infection with herpes simplex virus 1 without the development of peripheral lesions but established coculture-positive ganglionic latency when a low dose of a wild-type strain was inoculated intracutaneously. The latency was also evidenced by the development of the fatal zosteriform skin lesions and the isolation of the virus during pregnancy. We consider that the viral entry into neurons without successive replication, rather than the arrest of the lytic infection within the cells, is an important mechanism in the establishment of latency.

Animals

Neutralizing antibodies against HTLV-I in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and asymptomatic carriers.

We tested serum specimens from patients with HAM/TSP and asymptomatic HTLV-I carriers from endemic areas of Japan, Jamaica, Colombia, and Chile for neutralizing antibodies against HTLV-I. The data suggest a trend for neutralizing activity to be found more frequently in the sera from HAM/TSP patients than in sera from asymptomatic carriers. The result of this study emphasizes the importance of determining biologic properties of the envelope glycoprotein of HTLV-I.

Carrier State

[An unusual chronic microvasculitis: Goodpasture's syndrome with late myocardial involvement].

We describe a disease, started in a female young adult patient as an apparent pulmonary siderosis, followed nine years later by an extracapillary proliferative nephritis, which developed to uremia in a few months. Later an intra-myocardial vasculitis, responsible of heart failure, appeared. Immune-histochemistry and serological tests exclude a disease mediated by anti-GMB antibodies, and pathologic features suggest a vasculitis mainly affecting lungs and kidneys.

Adult

Rapid detection of a point mutation in thyroid-stimulating hormone beta-subunit gene causing congenital isolated thyroid-stimulating hormone deficiency.

Previous study showed that congenital isolated TSH deficiency in Japan is resulted exclusively from a G-A transition at nucleotide 145 in exon 2 of the TSH beta-subunit gene. All reported cases were from the inbred in Shikoku Island. We describe here a 10-year-old boy with hereditary TSH deficiency in the same area. The patient was born with a weight of 3,225 g to non-consanguineous parents. Evaluation at age 2 months revealed typical manifestations of cretinism without goiter. Serum T4, T3, and TSH values were 2.53 micrograms/dl, 107 ng/dl, and 0.5 microU/ml, respectively. A TRH stimulation test showed no increment of serum TSH value. Other anterior pituitary hormone levels were all within the normal range. Two oligonucleotide primers T1a and T1b were synthesized according to the sequence data. Amplified 169 bp nucleotides in exon 2 of the TSH beta gene with this primer set were digested with MaeI. Both the phenotypically normal brother and normal controls showed only the 169 bp fragment, whereas the proband showed 140 and 29 bp fragments and both parents showed three fragments; 169, 140, and 29 bp. These results were consistent with the point mutation of TSH beta gene in Japanese patients with congenital isolated TSH deficiency. Our PCR method with MaeI digestion contributes to the rapid detection of the homozygous patient and the heterozygous carrier.

Child

Glycoprotein C of herpes simplex virus type 1 is essential for the virus to evade antibody-independent complement-mediated virus inactivation and lysis of virus-infected cells.

Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) is a receptor for the complement component C3b. We have previously isolated HSV-1 gC- strains (TN1, TN2 and TN3) from a patient with recurrent keratitis at three different times. These are very rare isolates because gC was thought to be essential for the virus in vivo. To determine whether gC modifies the interaction of complement with cell-free virus or virus-infected cells, we constructed gC+ recombinant viruses in which the intact gC gene of strain KOS was inserted into the TN1 virus genome. TN1 virus was inactivated by complement and TN1 virus-infected cells were lysed by complement; however, gC+ recombinant viruses became resistant to these effects of complement. These results suggest a role for gC in protection of both the virion envelope and the infected cell surface against damage by complement. TN1 virus was inactivated by complement from rats (Wistar, WKA, F344 and SD), guinea-pigs (Hartley) and humans, but not by complement from mice (C3H, DDD and BALB/c), which indicates that mice seem to be inappropriate as an experimental model for the study of HSV infection in which complement factors need to be considered.

Animals

Characterization of glycoprotein C-negative mutants of herpes simplex virus type 1 isolated from a patient with keratitis.

Recently three strains of herpes simplex virus type 1 (HSV-1), which did not react with Micro Trak Herpes (Syva Co.), were isolated by us from a patient with recurrent herpetic keratitis. In this study we characterized these strains of HSV-1 and found them to be HSV-1 gC- mutants which are very rare isolates from humans. The properties of the HSV-1 strains regarding plaque morphology on Vero cells and chick embryo fibroblasts and viral DNA analysis were the same as those of the usual HSV-1 strains. An immunofluorescence study using anti-gC-1 monoclonal antibody and SDS-PAGE analysis of radiolabeled viral glycoproteins showed that these strains are deficient in gC-1. They were virulent for mice and sensitive to acyclovir and bromovinyldeoxyuridine. Furthermore the infectivity of the strains was inactivated by complement though the phenomenon was not observed in the usual HSV-1 strains. This finding suggests that protection from damages by complement is an important function of gC. In keratitis the effects of complement are thought to be minimal because of the scanty blood supply and this may be the reason why these strains were isolated from the cornea.

Adult

Seroepidemiology of herpes simplex virus type 1 in Yanji, Jilin, China.

Sera from 158 individuals in Yanji, Jilin, China, were tested for antibodies to herpes simplex virus type 1 (HSV-1) by the passive hemagglutination method. Age-specific incidence rates for antibodies to HSV-1 were calculated. For sera from persons in the age group 10 years or less, the positive rate was 54% but in the age group higher than 10 years, it was more than 91% (P less than 0.01). In the part of China surveyed, primary HSV-1 infection occurred in early generation before about age 10. In children, the positive rate in the Han race was significantly higher than that in the Korean race (P less than 0.05).

Adolescent

Recurrent herpetic keratitis: failure to detect herpes simplex virus infection using the Syva MicroTrak HSV1/HSV2 direct specimen identification/typing test.

A 35-year-old man had developed recurrent herpetic keratitis characterized by dendritic keratitis at intervals of a year. We were able to culture cytopathic agents repeatedly from his lesions by inoculating Vero cells. The cultures yielded definitive evidence of a virus that caused a cytopathic effect within 3 days. However, these virus strains could not be identified as herpes simplex virus (HSV) in immunofluorescence assays using the Syva MicroTrak HSV1/HSV2 direct specimen identification/typing test. Rather they were identified as strains of HSV type 1 (HSV-1) on the basis of plaque morphology, neutralization tests, electron-microscopic examination and DNA restriction endonuclease analysis. Our results allow us to assume the existence of HSV-1 strains isolated clinically that are negative to analysis using the Syva Micro-Trak HSV1/HSV2 direct specimen identification/typing test.

Adult

Immunological and molecular comparison of simian cytomegaloviruses isolated from African green monkey (Cercopithecus aethiops) and Japanese macaque (Macaca fuscata).

Simian cytomegaloviruses (CMV) isolated from African green monkeys and Japanese macaques were compared serologically and genetically. Twenty-three out of 31 sera from Japanese, Taiwan and rhesus macaques were positive for neutralizing antibodies to simian CMVs isolated from both African green monkeys and a Japanese macaque. The neutralizing antibody titers of those sera were slightly higher to the isolates of African green monkeys origin than to that of Japanese macaque origin. Studies with antisera prepared in guinea pigs revealed a partial antigenic cross-reaction between Japanese macaque CMV (JaM-CMV) and African green monkey CMV (AGM-CMV): the antiserum to JaM-CMV neutralized both homologous JaM-CMV and heterologous AGM-CMV, but the antisera to AGM-CMV neutralized only homologous AGM-CMV. DNAs of both AGM-CMV and JaM-CMV were compared by restriction endonuclease cleavage analysis. The individual simian CMV isolates showed unique restriction patterns when cleaved with EcoRI, BamHI, or HindIII. In addition, DNA of JaM-CMV was distinguishable from that of AGM-CMV when cleaved with EcoRI or BamHI.

Animals

Immunogenicity of herpes simplex virus glycoprotein gB-1-related protein produced in yeast.

A protein related to glycoprotein B of herpes simplex virus type 1 (HSV-1) produced in yeast (ygB-1) was purified with an immunoadsorbent. The molecular weight of the purified ygB-1 as determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis was 96,000. Mice injected twice with ygB-1 adsorbed to alum developed ELISA antibody to ygB-1, neutralizing antibody to HSV-1 and a lymphoproliferative response to ygB-1 and HSV-1. The immunized mice were protected against intraperitoneal and corneal challenge with HSV-1. Latent infection in the trigeminal ganglia after corneal challenge was also inhibited by immunization with ygB-1. Guinea-pigs pigs immunized with ygB-1 adsorbed to alum also developed ELISA antibody to to ygB-1 and neutralizing antibody to both types of HSV. After the second dose, strong lymphoproliferative responses were seen upon stimulation with HSV-2. Animals were protected against intravaginal challenge with HSV type 2.

Animals

Seroepidemiology of herpes simplex virus in Yogyakarta, Indonesia.

Sera from 487 individuals in Yogyakarta, Indonesia, were tested for antibodies to herpes simplex virus (HSV) by a passive hemagglutination method. Age-specific incidence rates for antibodies to HSV were calculated. For sera from persons other than prostitutes, in the age group from 10 to 19, the positive rate was 48% but in the age group higher than 20, it was more than 87%. Fifty of 59 pregnant women (85%) were positive. The positive rate and the distribution of antibody levels in prostitutes were higher than in the general population.

Adolescent