Antiprogestin-progesterone interactions.
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Animals↗
Biomedical subjects
Y Nishino
Publications and source records attributed to Y Nishino.
Mitogenic effect of HIV-infected human T cell lines on mouse B cells mediated by surface immunoglobulin.
Following HIV-1 infection, a number of disorders are induced in both normal T and B cells by virus products derived from infected CD4+ T cells. In the present study, we found that HIV-infected, but not uninfected, human T cell lines generated vigorous blastogenesis and proliferation of freshly isolated mouse B cells in a short-term culture. Neither human B cells nor rat B cells showed significant responses to the HIV-infected T cell lines in the present condition. The mitogenic effect of HIV-infected human T cell line requires direct cell-cell interaction between mouse B cells and HIV-infected T cell lines. Since either mitomycin c treatment or paraformaldehyde fixation of HIV-infected T cell lines resulted in complete loss of the mitogenic effect, it seems that de novo synthesized viral products are responsible for this effect. Furthermore, anti-mouse immunoglobulin antibody inhibited completely the B cell stimulation by the HIV-infected human T cell lines. Thus, surface immunoglobulin (sIg) on mouse B cells appears to be an essential molecule which transduces activation signals from HIV-infected human T cells into cytoplasm of the B cells.
Animals↗
Long-lasting immune response induced by recombinant bacillus Calmette-Guérin (BCG) secretion system.
The recombinant bacillus Calmette-Guérin (rBCG) secretion system utilizing an extracellular alpha antigen of Mycobacterium kansasii (alpha-K) was characterized biochemically and immunologically. The human immunodeficiency virus type 1 (HIV-1) p17gag B cell epitope fused to alpha-K was secreted in extremely large amounts. At least three mice out of seven inoculated with rBCG generated high titres of antibody to the epitope. The long-lasting antibody production persisted more than 14 months.
Amino Acid Sequence↗
A novel 1 beta-methylcarbapenem antibiotic, S-4661. Synthesis and structure-activity relationships of 2-(5-substituted pyrrolidin-3-ylthio)-1 beta-methylcarbapenems.
The synthesis and biological activity of (1R,5S,6S)-2-[(3S,5S)-5-substituted pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1- methylcarbapen-2-em-3-carboxylic acids are described. These compounds exhibit potent antibacterial activity against a wide range of both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. Of these new carbapenems, (1R,5S,6S)-2-[(3S,5S)-5-sulfamoylaminomethyl pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarb apen- 2-em-3-carboxyli c acid (S-4661) showed the most potent and well balanced activity and was selected as a candidate for further evaluation.
Anti-Bacterial Agents↗
Temporal change in the reproducibility of a self-administered food frequency questionnaire.
The authors studied temporal change in the reproducibility of a self-administered food frequency questionnaire. During 1988-1994, 492 residents of a rural Japanese town completed five questionnaires including 27 food items, with intervals ranging from 2 weeks through 5.5 years. The reproducibility decreased steadily over time for pairs of the questionnaires administered in the same season (median Spearman's r at 2 weeks and 5 years = 0.62 and 0.28, respectively). The reduction was less marked for those surveyed in different seasons (median r at 5 months and 5.5 years = 0.35 and 0.28, respectively). The short-term, different season correlation at 5 months was lower than the short-term, same season correlation at 1 year. For individual food items, a lower initial reproducibility, infrequent consumption, and a larger difference in seasonal intake were associated with a greater reduction in reproducibility over time. The results indicate that reproducibility studies should deliberately choose the intervals and the seasons for surveys.
Epidemiologic Methods↗
Nucleotide sequence and the molecular evolution of a new A2 gene in the DQ subregion of the bovine major histocompatibility complex.
cDNA clones encoding the bovine major histocompatibility complex (MHC) class II DQ alpha chain were isolated. One clone, MQ9, encoded a primary translated product of 255 amino acids, with a signal peptide of 23 amino acids and a mature polypeptide of 232 amino acids. A new A2 gene in the DQ subregion of the bovine genome was identified from a comparison of amino acid sequences encoded by class II A genes among several species and the construction of a phylogenetic tree. It was revealed that MQ9 is most closely related to the ovine DQA2 genes among sequences from various mammalian species. By contrast, the BoLA-DQA genes previously isolated are more closely related to ovine DQA1 than to the BoLA-DQA2 gene, and they represent BoLA-DQA1 genes. Thus, the presence of two BoLA A genes, which may be expressed and functional in the bovine, as well as in sheep was confirmed. A large number of amino acids unique to products of DQA2 genes of bovine and ovine origin were identified when the predicted amino acid sequences for both species were compared, and most of the DQA2-specific residues were located in the alpha 1 domain and were conserved with respect to products of DQA1 genes of ruminants. Thus, several characteristics of the bovine DQA genes were found to differ from those of human and rodent genes, despite similarities in gene structure and in nucleotide sequence.
Amino Acid Sequence↗
Differentiation therapy with progesterone antagonists.
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Animals↗
Cattle cDNA clone encoding a new allele of the MHC class II DQA1 gene.
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Alleles↗
Maintenance of high virus load even after seroconversion in newborn cats acutely infected with feline immunodeficiency virus.
The viral loads in adult and newborn cats have been compared following injection with feline CD4+ FeL-039 line cells acutely infected with feline immunodeficiency virus (FIV). The level of virus genome in peripheral blood mononuclear cells (PBMC) increased progressively despite seroconversion in the newborn cats, whereas the virus genome was apparently cleared after seroconversion in the adult cats. Immunohistochemical staining of thymus of the FIV-infected newborn cats showed clusters of viral antigen-positive cells. These results indicate that FIV infection of the newborn cat results in higher virus loads than infection of the adult cat. We discuss these findings in relation to FIV as a model system for studies of the infection of neonates with an immunosuppressive retrovirus.
Acute Disease↗
Disturbance of follicular development and endocrine reactions induced by the antiovulatory effective progesterone antagonist Onapristone.
The present study was undertaken to investigate whether inhibition of ovulation, which is known to occur after treatment with progesterone antagonists, is due to the effect of high levels of prolactin. Therefore, rats with 4-day cycles were treated with the antiprogestin, Onapristone (ON), once daily starting on the evening of estrus. It was detected that the profile of peripheral prolactin levels during the treatment with ON was not remarkably different from that found in the controls. Furthermore, bromocriptine, a prolactin antagonist, was not able to reverse the antiovulatory potency of ON. It is concluded that the antiovulatory effect of ON might not be related to changes in the level of prolactin. Nevertheless, prolactin levels remained high after the preovulatory surge. Thus, we cannot exclude the possibility that PRL plays a role in the induction of anovulatory cycles observed during long term treatment. In animals treated for the length of one cycle we found that the preovulatory LH surge decreased but it remains questionable whether this contributes to the inhibition of ovulation by ON. Interestingly, basal LH, androgen and estrogen levels were elevated. Accordingly, we favour the idea that LH stimulates the theca interstitial cells to produce excessive amounts of androgens which may be aromatized into estrogens. These high levels of androgens and estrogens may contribute to the antiovulatory mechanism of ON by disturbing physiological follicular development. In fact, a morphometrical analysis revealed an increase in the volume density of late tertiary follicles. The increased progesterone levels may also be related to high basal LH levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Androstenedione↗
The carboxyl-terminal region of HIV-1 Nef protein is a cell surface domain that can interact with CD4+ T cells.
Our previous studies have shown that the HIV-1 Nef Ag is expressed, at least in part, on the surface of infected cells. We demonstrated this by using membrane immunofluorescence and flow cytometry with Nef murine mAbs. To identify the domain of Nef exposed on the cell surface, epitope mapping of these and a new mAb was performed by ELISAs by using several recombinant truncated Nef fusion proteins and synthetic peptides. The results showed that mAbs F1, E7, E9, and 4H4 recognized Nef epitopes located at amino acid residues 148-157, 192-206, 158-206, and 1-33, respectively. The intensity of cell surface Nef staining was stronger with mAbs E7 and E9 than with F1, and there was no staining by 4H4, which indicates that the carboxyl-terminal region of Nef is predominantly exposed on the surface of HIV-1-infected T cell lines and PBMC. This surface Nef domain displayed high affinity for the surface of uninfected CD4+ T cells, because the binding of a soluble form of recombinant Nef protein to the cell surface was specifically blocked by the E7 and E9 mAbs or by synthetic peptides that contained the carboxyl-terminal region of Nef. In addition, syncytium formation between infected and uninfected cells also was specifically reduced by the same mAbs or peptides. Thus, the cell surface domain of Nef seems to play an important role in the interaction between HIV-1-infected and CD4+ uninfected T cells.
Antibodies, Monoclonal↗
Enhancement of the antitumor efficacy of the antiprogestin, onapristone, by combination with the antiestrogen, ICI 164384.
So far, no combination of endocrine treatments has been routinely used in the therapy of breast Cancer. It was, therefore, our interest to determine whether the combination of the antiprogestin, onapristone (ON), and the pure antiestrogen, ICI 164384 (ICI) might provide a more effective therapy than either monotherapy in experimental mammary tumors containing both estrogen and progesterone receptors. In the MXT-mammary tumor of the mouse, ON (5 mg/kg) administered for 3 weeks exerted an ovariectomy-like antitumor effect (56% inhibition), whereas ICI (30 mg/kg) was weakly effective (28% inhibition). The combination of ON and ICI was, however, distinctly more effective than the monotherapies or ovariectomy, causing 78% inhibition. A similar potentiation of antitumor effect by the combination was manifested in the dimethylbenzanthracene-induced mammary tumor of the rat when ON (5 mg/kg) and ICI (30 mg/kg) were administered once daily for 4 weeks (s.c.). The remission rates of tumors found after treatment with ICI, ON, the combination and ovariectomy (complete and partial remission) were 15%, 46%, 71% and 100% respectively. In the animals bearing DMBA-induced tumors, treatment with ON alone significantly increased the serum levels of luteinizing hormone and prolactin, but caused only a slight increase in the peripheral levels of estradiol and progesterone. ON had no appreciable effect on the uterine and ovarian weights. ICI reduced the uterine weight and the serum progesterone level. In the combination with ON, ICI reversed the effect of ON on the progesterone level without influencing the luteinizing hormone and prolactin levels. These findings suggest that the augmentation of antitumor effectiveness by the combination of two antihormones can be ascribed not only to their effects at estrogen- and progesterone-receptor-binding sites, but also to the decrease in the peripheral level of progesterone. Thus, an appropriate combination of antiprogestin and pure antiestrogen may be useful in the management of breast cancer.
9,10-Dimethyl-1,2-benzanthracene↗
Cytotoxic T lymphocyte response in mice induced by a recombinant BCG vaccination which produces an extracellular alpha antigen that fused with the human immunodeficiency virus type 1 envelope immunodominant domain in the V3 loop.
The host immune response of cell-mediated immunity, particularly that of cytotoxic T lymphocytes (CTLs), is a major immune defence mechanism which may provide resistance to a human immunodeficiency virus type 1 (HIV-1) spread leading to acquired immune deficiency syndrome (AIDS). To prevent the accompanying activity of HIV-1 proteins responsible for the loss of helper T-lymphocyte function, it is crucial to develop a live attenuated recombinant vaccine expressing only T- or both T- and B-cell epitopes. Here, we examined the expression of the HIV-1 Env protein V3 region (15 amino acids from Arg315 to Lys329) in Mycobacterium bovis BCG as a fused form with an extracellular alpha antigen of Mycobacterium kansasii. Balb/c mice inoculated with this recombinant BCG (rBCG), rapidly induced V3 peptide-specific CTLs. Target cell lysis was restricted to the murine class I major histocompatibility complex, H-2d. A similar CTL response was also elicited after Balb/c mice were immunized with the same rBCG even when pre-inoculated with non-recombinant BCG. Thus, the rapid induction of HIV-1-specific CTLs indicates that this vaccine may be a therapeutic approach to preventing progression to AIDS.
AIDS Vaccines↗
In vivo induction of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes and delayed-type hypersensitivity by a 23-amino acid peptide from the highly conserved region in major core protein p24.
Cell-mediated immune responses are a major immune defence mechanism against the spread of human immunodeficiency virus type 1 (HIV-1) which may lead to acquired immune deficiency syndrome (AIDS). Therefore, the best candidate for a peptide vaccine preventive from the onset of the disease might be a chain section containing both B- and T-cell epitopes in regions of conserved sequences between the different HIV-1 isolates. We previously identified the highly conserved linear B-cell epitope (23 amino acids in the major core protein p24). Since the epitopes of cytotoxic T lymphocytes (CTLs) can be defined by short synthetic peptides, we examined whether this highly conserved region can elicit viral-specific, cell-mediated immune responses. The results showed specific induction of CD8+ CTLs in mice by immunization with the Gag 13-mer peptide. Lysis of targets is specific since unpulsed cells with the same MHC haplotype or cells with a different MHC haplotype pulsed with the peptide were resistant to lysis. This in vivo response induced by the Gag 23-mer peptide was almost the same as that induced by the 15-amino acid peptide from the HIV-1 Env gp120 which is an immunodominant domain in the V3 loop. Lymphocyte proliferation of T-cell fraction from immune spleen cells was observed after in vitro stimulation with the Gag 23-mer peptide, whereas there was no apparent lymphocyte proliferation with the Env 15-mer peptide. In addition, specific antibodies were raised against Gag p24 in mice immunized with the Gag 23-mer peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Persistent infection of MT-4 cells by human immunodeficiency virus type 1 becomes increasingly likely with in vitro serial passage of wild-type but not nef mutant virus.
Our previous studies have shown that human immunodeficiency virus type 1 (HIV-1), with mutations in accessory genes such as vif, vpr or vpu, can generate persistent infection of MT-4 cells, whereas infection by wild-type or nef mutant HIV-1 causes extensive cell death. The possibility of generating a naturally attenuated form of HIV-1 with reduced cytopathogenicity in MT-4 cells was examined by in vitro serial passage of the wild-type and a nef mutant form of HIV-1, each derived from the infectious molecular clone pNL432. The ability to cause persistent infection was observed after four passages of wild-type HIV-1 with the frequency of persistence becoming progressively higher with serial passage. In contrast, persistent infection was not observed even after 50 passages of the nef mutant virus. Sequence analysis of the accessory gene loci in genomes recovered from the persistent infections caused by passaged virus revealed mutations in vif and vpr, but not in vpu. The processing of the Env precursor to mature forms was not modified in any of the passages of either wild-type or nef mutant HIV-1. However, when compared with acute infections caused by similarly passaged virus of both wild-type and nef mutant HIV-1, persistent infections by passaged wild-type HIV-1 showed a significant decrease in the cell surface expression and function of Env. Cell surface CD4 was only partially down-regulated on cells acutely infected with the passaged viruses, whereas on cells persistently infected with passaged wild-type HIV-1 it was completely down-regulated. These results suggest that, during serial passage of HIV-1, mutations accumulate at least in the accessory genes vif and vpr in parallel with a lesser interaction between cell surface Env and CD4 molecules, and lead to the generation of less cytopathogenic viruses capable of persistent infection. Our results also suggest an important role for the nef gene product in the generation of HIV-1 strains that are less cytopathogenic.
Amino Acid Sequence↗
[Quantitative analysis of dihydroisocoumarin constituents of Hydrangeae Dulcis Folium by means of high performance liquid chromatography. Chemical characterization of the processing, distribution in plant, and seasonal fluctuation].
In order to characterize the chemical change of the constituents during the processing of Hydrangeae Dulcis Folium, quantitative analyses of phyllodulcin, hydrangenol, and their 8-O-glucosides were developed by means of high performance liquid chromatography. As an application of this HPLC method, the distribution of those dihydroisocoumarins in different parts of Hydrangea macrophylla var. thunbergii was investigated. It was found that these dihydroisocoumarins were contained at the highest concentration in the leaves. Furthermore, the seasonal fluctuation of these compounds in the leaves, together with the height of the plant and total dry weight of the leaves, were clarified and so that the suitable period for the harvest of Hydrangea macrophylla var. thunbergii was deduced to be from Oct. to Nov.
Benzopyrans↗
[Crude drugs from aquatic plants. III. Quantitative analysis of triterpene constituents in alismatis rhizoma by means of high performance liquid chromatography on the chemical change of the constituents during alismatis rhizoma processing].
As a series of study on the evaluation of Alismatis Rhizoma and the chemical characterization of the processing, a quantitative method by high performance liquid chromatography (HPLC) for ten triterpene constituents, alisols A, A monoacetate, B, B monoacetate, E 23-acetate, F, and G and 13,17-epoxyalisol A, 11-deoxyalisols B and B 23-acetate, has been developed. By the use of this HPLC method, the contents of these triterpenes in various Alismatis Rhizoma and the fresh rhizoma of Alisma oriental JUZEPC, originated from in China, Taiwan, and Japan were examined. Furthermore, the chemical change of the triterpene constituents during the drying process of the rhizoma of Alisma oriental has been investigated and it was found that the bioactive triterpenes of Alismatis Rhizoma such as alisol A and alisol A monoacetate were artificially formed during the drying process.
Chromatography, High Pressure Liquid↗
A male case of synchronous double cancers of the breast and prostate.
A male case of synchronous double cancers of the breast and prostate is reported. An 84-year-old male was admitted to the hospital complaining of general malaise, anorexia and weight loss. A tumor 3 cm in diameter was noted in his left breast, which was removed by mastectomy, and was diagnosed as papillotubular carcinoma. An induration of his prostate and elevated prostate specific antigen, gamma-seminoprotein and prostatic acid phosphatase levels were also noted. Needle biopsy of his prostate revealed adenocarcinoma. Among the previous 18 reported cases of this combination of cancers, those with no prior estrogen therapy were very rare, the present case being the third ever reported.
Adenocarcinoma↗