Biomedical subjects

A Adachi

Publications and source records attributed to A Adachi.

At least 127 records · Page 7Linked to original sources

PubMed1998

Suppression of HIV-1 replication in peripheral blood mononuclear cells by fasudil.

Fasudil is a potent inhibitor for various protein kinases such as myosin light chain kinase and protein kinase C. It has been used as a drug for improvement of intracranial vasospasm and following ischaemic diseases. In this report, we demonstrate that fasudil suppressed the replication of human immunodeficiency virus type 1 (HIV-1) in mitogen-activated peripheral blood mononuclear cells. Our finding shows that fasudil may be useful as a new and distinct chemotherapeutic agent against HIV-1 infection.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

[Successful treatment of pseudomyxoma peritonei using combination chemotherapy of intraperitoneal low-dose CDDP and oral 5'-DFUR administration].

We report a case of pseudomyxoma peritonei treated with combination chemotherapy. A 73-year-old woman was diagnosed as having psuedomyxoma peritonei originated from the vermiform appendix. Appendectomy was performed, and 10 mg of MMC was administered intraperitoneally. From day 7, 600 mg/day of 5'-DFUR was orally given for 2 years, and 20 mg of CDDP once a month was intraperitoneally administered seven times. The patient has been doing well with no evidence of tumor recurrence for two years after operation. Combination chemotherapy with CDDP and 5'-DFUR, as a biochemical modulation therapy, has fewer side effects and leads to better quality of life of patients. We recommend a combination chemotherapy with low-dose CDDP and 5'-DFUR for patients in poor general condition.

Administration, Oral↗

PubMed1998

Investigation of morphological changes in absorptive cells in young adult and infant mice fed different amounts of iron for a long-term.

The changes in fine structure of the intestinal tract in young adult (4 week-old) and infant (2 week-old) mice fed a diet containing different amounts of iron salt (Fe-0, Fe-2.5, Fe-25: 0, 2.5 and 25 mg Fe/100 g diet, respectively) for a long-term (1 or 2 weeks) were investigated. The hepatic iron levels in infant mice fed Fe-25 for 2 weeks were significantly higher than those observed after 1 week of feeding, but there was no such increase in young adult mice during the feeding period. Observations of fine structure indicated typical signs of impairment of enterocytes due to excess iron such as the opening of intercellular junctions between adjacent epithelial cells and the marked appearance of eosinophilic leukocytes outside the basement membrane in young adult and infant mice fed Fe-25. The frequency of the opening in intercellular junctions increased in young adult mice fed Fe-25 for 2 weeks, but decreased in infant mice. On the contrary, under iron-deficient conditions, the frequency in infant mice was higher than that in young adult mice. The appearance of eosinophilic leukocytes indicated that some immunological reaction was elicited in both groups of mice fed Fe-25 for 2 weeks.

Animal Feed↗

PubMed1998

Role of virus-induced apoptosis in a host defense mechanism against virus infection.

Many animal viruses are known to induce apoptosis in infected cells. This virus-induced apoptosis has been often described as a mechanism of host defense against virus infection, based on the finding that mutants of an insect virus with the ability to induce extensive apoptosis in some cells cannot grow in the same cells. In animal virus infection, we have shown that (1) viruses can somehow overcome this defense mechanism and that (2) virus multiplication in the apoptotic cells is not as completely suppressed as in the insect virus infection. These results suggest that, in the case of animal viruses, the virus-induced apoptosis does not play the same role in the host defense system as in insect cells. However, by examining the virus infection under the conditions comparable to the infection in vivo, we demonstrated the defensive role of apoptosis in animal virus infection.

Animals↗

PubMed1997

Functional domain mapping of HIV-1 Gag proteins.

A series of human immunodeficiency virus type 1 (HIV-1) proviral gag gene mutants carrying bacterial CAT gene were constructed and monitored for the expression of reverse transcriptase and CAT in a highly sensitive single-round replication assay system to determine the defective replication phase in lymphocytic cells. All the mutants displayed no abnormality in the process of transcription and translation at late replication stage. In contrast, some matrix, capsid, and p6 mutants were defective at final phase, that is, assembly and virion release. Most of the mutants including nucleocapsid mutants, which showed normal phenotype at late stage, were defective at early replication phase. From the functional domain map thus obtained, it is evident that HIV-1 Gag proteins are required for both early and late replication phases.

CD4-Positive T-Lymphocytes↗

PubMed1997

Immunocytochemical identification of pinopsin in pineal glands of chicken and pigeon.

Pinopsin is a blue-sensitive photoreceptive molecule possibly involved in photic entrainment of the circadian pacemaker in the chicken pineal gland. To characterize pinopsin as a circadian photoreceptor, antibodies were raised against the C-terminal portion of pinopsin. As expected from the divergence of the amino acid sequence of this region, the resultant antibody cross-reacted with neither chicken rhodopsin nor red-sensitive cone pigment (chicken red). In Western blot analysis, the antibody stained a single band of 42-kDa protein in a detergent-extract of chicken pineal membranes, suggesting that pinopsin (calculated molecular weight, 38187) might be glycosylated and/or palmitoylated. Immunocytochemical examination of pineal sections of the chicken and the pigeon with this antibody revealed strong positive images for most of the membrane structures in the lumen of the follicles. This antibody also stained string- and bulb-shaped structures of the chicken parafollicular cells, the morphology of which resembles those of retinal photoreceptor cells. In contrast to the predominant distribution of pinopsin, a monoclonal antibody specific for chicken red stained a smaller number of membrane structures in the lumen of chicken pineal follicles. These results strongly suggest that the chicken pineal gland contains at least two types of photoreceptive molecules, pinopsin (major) and chicken red (minor). We show that the former molecule is localized in parafollicular pinealocytes and in the outer segments of pinealocytes that make contact with the follicular lumen.

Amino Acid Sequence↗

PubMed1997

Cleavage of Gag precursor is required for early replication phase of HIV-1.

A mutant of human immunodeficiency virus type 1 (HIV-1), which is deficient for Gag precursor cleavage and noninfectious, was characterized with respect to its defective step in the viral replication phase. Upon transfection, the mutant produced a normal level of progeny virions as monitored by electron microscopy and RNA hybridization. Single-round replication assay demonstrated, in contrast, that the mutant was defective at the early phase of the replication cycle. Furthermore, no viral DNA was detected in the cells infected with the mutant. Taken together, it is concluded that maturation of Gag precursor protein of HIV-1 is required for an early event(s) before or during a coupled process of uncoating/reverse transcription.

Blotting, Southern↗

PubMed1997

HIV-1 capsid mutants inhibit the replication of wild-type virus at both early and late infection phases.

In-frame mutations were introduced into various portions of the human immunodeficiency virus type 1 (HIV-1) gag gene, and potentials of the mutants to suppress the replication of wild-type HIV-1 were monitored. In contrast to results obtained with matrix and nucleocapsid mutants, almost all capsid mutants blocked HIV-1 replication completely in single-round replication assays. A capsid mutant designated C6b was demonstrated to be one of the most efficient inhibitors for HIV-1 reported to date, and to be effective at both early and late viral replication phases. T-cells, which are engineered to express the C6b Gag in response to HIV-1 infection, were perfectly resistant to HIV-1.

Blotting, Western↗

PubMed1997

Immunolocalization of hCDC47 protein in normal and neoplastic human tissues and its relation to growth.

hCDC47 is a human member of the MCM family, which has been implicated in the regulatory machinery causing DNA to replicate once per cell cycle. We examined its protein expression and localization in normal human tissues, using immunostaining with polyclonal antibodies. Positive nuclei were found in the proliferative components of lymph nodes, bone marrow, epidermis and mucosa. Immunohistochemical analysis was also performed for 3 types of cutaneous keratinocytic tumor originating from same cell type but showing different grades of malignancy. In seborrheic keratosis, a benign condition, cells with hCDC47-positive nuclei were located in the outermost layers of the tumor lobules, while in Bowen's disease, carcinomas in situ and squamous-cell carcinomas, they were present throughout the lesions. The percentages of hCDC47-positive cells were 65.4% in squamous-cell carcinomas, 60.9% in Bowen's disease, 12.6% in seborrheic keratosis and 3.9% in normal epidermis (n = 5 in all cases). Further expansion of the analysis to include malignant tumors from several other organs revealed that all malignant lesions tested contained more nuclear hCDC47-positive cells than their normal counterparts. Our findings indicate that hCDC47 plays a role in normal and neoplastic cell growth in vivo and that hCDC47 immunolocalization could be used as an index of cell proliferation in tissue sections.

Carcinoma in Situ↗

PubMed1997

Growth ability of auxiliary gene mutants of human immunodeficiency virus types 1 and 2 in unstimulated peripheral blood mononuclear cells.

Mutational studies on the Vif, Vpr, Vpu, Vpx, and Nef genes of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) were performed to evaluate their biological functions in natural target cells. For this purpose, replication properties of mutant viruses derived from HIV-1 NL strain and HIV-2 GH strain in unstimulated peripheral blood mononuclear cells were determined. Vif- viruses of both HIV-1 and HIV-2 did not grow at all in these cells. Similarly, no replication of HIV-2 Vpx- mutant was detected. In contrast, both of Vpr- and Nef- viruses of HIV-1 and HIV-2, and Vpu- virus of HIV-1 grew quite well in the cells. These results show, together with the data previously reported, that only Vif and Vpx are essential for HIV replication in primary blood cell cultures.

Cells, Cultured↗

PubMed1997

Exaggerated C-fiber activation prevents peripheral nerve injury-induced hyperinducibility of c-Fos in partially deafferented spinal dorsal horn.

Dorsal horn neurons chronically deafferented by peripheral nerve injuries acquire hypersensitivity to noxious input from outside the original receptive field. This study examines the effect of electrical nerve stimulation at the time of injury on such injury-induced hypersensitivity. The medial 3/8 of the dorsal horn laminae I/II around the junction of 4th and 5th lumbar segments (the tibial territory) was deafferented by transection of the ipsilateral tibial nerve in rats. At 2 days or 3 weeks postinjury, the hindpaw was injected with formalin to induce c-fos. At 2 days, neurons with induced c-Fos protein-like immunoreactivity (fos-neurons) were largely confined in the lateral 5/8 of laminae I/II (the peroneal and hip, thus P and H territory). At 3 weeks, fos-neurons significantly increased in the deafferented tibial territory. A similar increase was also noted in the P and H territory. Thus the dorsal horn neurons exhibited c-fos hyperinducibility, an indication of hypersensitivity. Electrical stimulation with a train of 150 shocks (10 V, 2 ms) of the proximal nerve stump immediately after transection prevented the c-fos hyperinducibility. The effect was greater with the stimulation frequency of 0.5 Hz than 0.1 Hz or 10 Hz. The stimulation had no effect on the c-fos inducibility at 2 days postinjury.

Animals↗

PubMed1997

Functional analysis of vif genes derived from various primate immunodeficiency viruses.

Replication property in cells of human and simian immunodeficiency viruses (HIVs and SIVs) lacking intact vif gene was evaluated. Of 10 vif mutants constructed in vitro of the major four HIV/SIV groups, only those derived from HIV-1 and HIV-2/SIVmac displayed replication defect. The cell lines non-permissive for the vif mutants of HIV-1 and SIVmac were found to be different. To determine whether Vif is exchangeable between HIV-1 and SIVmac, chimeric virus clones with respect to the vi gene were constructed and virus replication in the cells non-permissive for the vif mutant viruses was monitored. Productive infection in these cells of chimeric viruses clearly indicated that Vif is functionally exchangeable, and that Vifs of different virus origin act through a similar mechanism.

Animals↗

PubMed1997

Induction of apoptosis by herpes simplex virus type 1.

Although herpes simplex virus type 1 (HSV-1) does not induce apoptosis in infected HEp-2 cells, in the presence of cycloheximide infection induced apoptosis with characteristic morphological changes as well as endonucleosomal DNA cleavage. The induction of apoptosis without de novo protein synthesis suggests that a structural protein of the HSV-1 virion is responsible for the observed apoptosis.

Apoptosis↗

PubMed1997

Protection of monkeys vaccinated with vpr- and/or nef-defective simian immunodeficiency virus strain mac/human immunodeficiency virus type 1 chimeric viruses: a potential candidate live-attenuated human AIDS vaccine.

Two simian immunodeficiency virus strain mac (SIVmac)/human immunodeficiency virus type 1(HIV-1) chimeric viruses (SHIVs), designated NM-3 and NM-3n, with env derived from HIV-1 and defective vpr (plus defective nef for NM-3), were inoculated into seven macaques. These macaques were transiently or persistently infected and most of them produced long-lasting neutralizing antibodies and Env-specific killer T cells to HIV-1 with no AIDS-like symptoms. When they were challenged with another SHIV with intact vpr and nef (designated NM-3rN), all were protected as judged by virus recovery, DNA detection by PCR and antibody responses. Anti-HIV-1 Env-specific killer T cells were considered to have played a major role in this protection, but a non-specific defence mechanism as well as specific immunity also appeared to be involved. Thus, these two non-pathogenic SHIVs induced long-lasting protective immunities in macaques, suggesting the possibility of gene-defective SHIVs as attenuated live vaccines for human use.

AIDS Vaccines↗

PubMed1997

Potential efficacy of low metal diets and dental metal elimination in the management of atopic dermatitis: an open clinical study.

We performed an open clinical study on the effects of low metal diets and/or dental metal elimination on 27 patients with moderate to severe atopic dermatitis (AD), who showed positive patch tests for metal allergens and/or clinical exacerbation by oral provocation tests with metal salts. All the patients were recommended to ingest low metal diets for 3 months and/or undergo dental metal elimination. Marked or moderate improvement was noted in 18 patients (67%); 7 patients (26%) showed marked improvement and 11 patients (41%), moderate improvement. Nine patients (33%) showed minimal improvement or no change. In the patients who showed marked or moderate improvement, we observed statistically significant decreases (p < 0.05) in both peripheral blood eosinophil counts and serum LDH levels after 3 months of treatment. The present study suggests that restriction of ingested metal allergens to which patients have positive patch tests and/or oral challenge tests may be useful in the management of some patients with AD who have metal sensitivity.

Administration, Oral↗

PubMed1997

Recent experience of integrated myocardial management: the newest strategy for myocardial protection.

From April 1994 until June 1996, we exclusively utilized the integrated myocardial management (IMM) proposed by Buckberg et al. at UCLA. Two hundred sixty-two consecutive patients undergoing open heart surgery at our hospital were divided into 2 groups, the non-IMM (n = 49, from July 1993 until March 1994) and the IMM (n = 213, from April 1994 until June 1996) groups. Although many older and more severely ill patients were treated with IMM, acceptable clinical outcomes with comparable safety and efficiency were obtained. Shorter durations of total cardiopulmonary bypass (CPB) and aortic cross-clamping (AXC) were needed in the IMM group despite there being many more procedures undertaken during a single cross-clamp period.

Adult↗

PubMed1997

Susceptibility of nude mice carrying the Fv-4 gene to Friend murine leukemia virus infection.

Fv-4 is a mouse gene that dominantly confers resistance to infection with Friend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473-478, 1975). Despite complete resistance to ecotropic MuLV infection in mice carrying the Fv-4 gene, it is known that cells carrying the resistance gene in tissue culture do not always show resistance as extensive as that in vivo (H. Yoshikura and T. Odaka, JNCI 61:461-463, 1978). To investigate the immunological effect on resistance in vivo, we introduced the Fv-4 gene into BALB/c nude mice (Fv-4-/- nude[nu/nu]) by mating them with Fv-4 congenic BALB/c mice (Fv-4r/r nude+/+) and examined the susceptibility of the F2 progeny to F-MuLV. All BALB/c nude mice without the Fv-4 gene (Fv-4-/- nude[nu/nu]) were permissive to F-MuLV and developed erythroleukemia within 2 weeks after virus inoculation. The BALB/c nude mice with the Fv-4 gene (Fv-4r/r nude[nu/nu]) did not develop leukemia, and no or little virus was detected in the spleen 7 weeks after virus inoculation. The resistance to F-MuLV was dominant in (Fv-4 congenic BALB/c x BALB/c nude) F1 mice with the Fv-4r/- nude(nu/+) genotype as strictly as in (Fv-4 congenic BALB/c x BALB/c) F1 mice with the Fv-4r/- nude+/+ genotype. However, almost all BALB/c nude mice with the Fv-4r/- nude(nu/nu) genotype developed the disease within 7 weeks, and the virus was detected in all of their spleens even in the mice without leukemia. These results show that the resistance caused by the Fv-4 gene is recessive in nude mice and dominant in BALB/c mice. Some immunological effects, perhaps cell-mediated immunity, may play important roles in the resistance to F-MuLV infection in vivo in addition to the dosage effect of the Fv-4 product.

Animals↗

PubMed1997

Epitope mapping of murine monoclonal antibodies against human immunodeficiency virus type 1 Nef.

It has shown that the human immunodeficiency virus type 1 (HIV-1) Nef protein has the high antigenicity in HIV-1 seropostive individuals. We newly obtained seven monoclonal antibodies (mAbs). To identify the antigenic determinants of HIV-1 Nef protein against murine, epitope mapping of the mAbs was performed by enzyme-linked immunosorbent assay (ELISA) by using several recombinant truncated Nef fusion proteins, that were expressed in Esherichia coli, and synthetic peptides. The results showed that mAbs A6, A7, F2, F3, F4, F8 and E5 recognized epitopes on Nef protein located at amino acid residues 18-26, 28-45, 115-137, 128-137, 115-126, 128-137, and 170-181, respectively.

Animals↗