Biomedical subjects

S Jinno

Publications and source records attributed to S Jinno.

At least 19 recordsLinked to original sources

PubMed2002

Presynaptic inhibition of GABAergic miniature currents by metabotropic glutamate receptor in the rat CNS.

The modulation of spontaneous miniature GABAergic inhibitory postsynaptic currents (mIPSC) by the metabotropic glutamate receptors was investigated in the mechanically dissociated rat nucleus basalis of Meynert neurons using the conventional whole-cell patch recording configuration. An application of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (tACPD) reversibly reduced the frequency of mIPSC without affecting the current amplitude distribution. The application of K+ channel blockers such as 4-aminopyridine, Cs+, Ba2+ or tetraethylammonium increased the mIPSC frequency, but failed to inhibit the tACPD action on mIPSC. Although the removal of Ca2+ from the extracellular solution reduced the mIPSC frequency, the inhibitory effect of tACPD on mIPSC was unaltered. These results suggested that neither voltage-dependent K+ or Ca2+ channels are involved in the inhibitory effect of tACPD on mIPSC frequency. Forskolin, an activator of adenylate cyclase, facilitated the mIPSC frequency in a concentration-dependent manner and inhibited the tACPD-induced suppression of mIPSC frequency. 8-Br-cAMP, a membrane permeable analog of cAMP, also prevented the inhibitory action of tACPD. However, Sp-cAMP, an activator of protein kinase A, could not prevent the inhibitory action of tACPD. L-CCG-I and (2R,4R)-APDC, group II mGluR agonists, mimicked the tACPD action on mIPSC frequency, but L-AP4, a group III mGluR agonist, had no such effect. MCCG, a group II mGluR antagonist, fully blocked the tACPD action. It was concluded that the activation of group II mGluR on the GABAergic presynaptic nerve terminals projecting to the rat nucleus basalis of Meynert neurons therefore inhibits the GABA release by reducing the activity of the cAMP-dependent pathway.

Adenylyl Cyclases↗

PubMed2002

Immunocytochemical localization of neuronal calcium sensor-1 in the hippocampus and cerebellum of the mouse, with special reference to presynaptic terminals.

Neuronal calcium sensor-1 (NCS-1) is a member of the EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. In this work, we first examined the distribution patterns of NCS-1 in the hippocampus and cerebellum. The intense NCS-1-immunoreactive (IR) elements in the hippocampus were restricted to dendritic layers, while those in the cerebellum occurred in both dendritic and cellular layers. Then, we examined the exact localization of NCS-1 using immunofluorescent double labeling for NCS-1 and synaptophysin, a marker of presynaptic terminals. In the hippocampus, the mossy fiber systems (terminals and bundles) exhibited intense NCS-1 immunoreactivity. On the other hand, the presumed principal cell dendrites were also NCS-1-IR in the stratum lacunosum-moleculare of Ammon's horn and molecular layer of the dentate gyrus, where NCS-1-IR elements and synaptophysin-IR presynaptic terminals showed characteristic complementary distribution patterns. In the cerebellum, some of the basket cell axon terminals surrounding the somata of Purkinje cells exhibited NCS-1 immunoreactivity, while the pinceau showed consistent labeling for NCS-1. Higher magnification observations revealed that the NCS-1-IR presumed granule cell dendrites and synaptophysin-IR mossy fiber terminals in the glomeruli of the cerebellum showed characteristic complementary distribution patterns. Furthermore, we estimated quantitatively the relative amount of NCS-1 in the presynaptic terminals in individual layers, and confirmed that the mossy fiber terminals in the hippocampus contained comparatively high amounts of NCS-1. These results showed the diverse localization of NCS-1 in pre- and/or postsynaptic elements of the hippocampus and cerebellum, and suggest potential roles in specific synaptic transmission.

Animals↗

PubMed2001

Oncogenic cell cycle start control.

The ability to proliferate in the absence of anchorage is a fundamental attribute of cancer cells, yet how it is acquired is one central problem in cancer biology. By utilizing growth factor-transformable NRK cells and its insensitive mutants, we recently found that oncogenic stimulation invokes Cdk6 to participate in a critical step of the cell cycle start, but not via the regulation of its catalytic activity and that Cdk6 participation closely correlates with the anchorage-independent growth ability. Since many hematopoietic cells employ predominantly Cdk6 for the cell cycle start and perform anchorage-independent growth by nature, this finding raises the possibility that the mechanism by which oncogenic stimulation invokes anchorage-independent growth of NRK cells is similar to the one used for hematopoietic cell proliferation. We discuss this novel mechanism and its implication.

Animals↗

PubMed2001

Morphometric multivariate analysis of GABAergic neurons containing calretinin and neuronal nitric oxide synthase in the mouse hippocampus.

Several studies reported the morphology of calretinin-positive (CR+) neurons and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) labeled or neuronal nitric oxide synthase-positive (nNOS+) neurons in the rodent hippocampus, where these neurons showed similar morphological features. In addition, a previous study reported the frequent colocalization of CR and NADPH-d in the rat hippocampus. In this study, we aimed to examine whether CR+ neurons and nNOS+ neurons belong to a same morphological subpopulation of GABAergic neurons in the mouse hippocampus. Neurons were immunocytochemically classified into three groups, i.e., CR+/nNOS-, CR-/nNOS+ and CR+/nNOS+ groups. The present morphometric analysis was performed in the mouse Ammon's horn, because CR+/nNOS+ neurons were rarely found in the mouse dentate gyrus. We selected three morphometric parameters, i.e., soma area, soma form factor (FF) and number of primary dendrites. Dunnett's post-hoc analysis revealed that soma area, soma FF and number of primary dendrites were significantly larger in CR-/nNOS+ group than in CR+/nNOS- and CR+/nNOS+ groups. The morphometric data of CR+/nNOS+ group were quite similar to those of CR+/nNOS- group. The morphometric multivariate logistic regression analysis revealed that these three morphometric parameters were independent significant variables to discriminate between CR+/nNOS- and CR-/nNOS+ groups, and the majority of CR+/nNOS- and CR-/nNOS+ groups were correctly classified from the morphometric features. The present results clearly indicate that CR+/nNOS- neurons and CR-/nNOS+ neurons belong to different morphological subpopulations, and lead us to speculate that they might play different functional roles in the hippocampal circuit. The further application of morphometric multivariate analysis would be valuable to understand the functional roles of chemically defined neurons in the various brain regions.

Animals↗

PubMed2001

Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence.

Mammalian cells require a cyclin D-dependent kinase for the cell cycle start, yet many mesenchymal cells express three seemingly redundant D cyclins and similarly, seemingly redundant Cdk4 and Cdk6 as their kinase partners. We have found that the Cdk6-cyclin D3 complex is unique among the D cyclin and kinase combinations in the ability to promote the cell cycle start. In an anchorage-minus G(1)-arrested rat fibroblast, only Cdk6-D3 retains kinase activity due mainly to its ability to evade inhibition by p27(KIP1) and p21(CIP1) with a resemblance to viral cyclin-bound Cdk6. Rodent fibroblasts engineered to overexpress both Cdk6 and cyclin D3 highly resist serum starvation- or cell-cell contact-imposed G(1)-arrest. In BALB/c 3T3 cells, D3 is constitutively expressed, but Cdk6 is markedly induced with concomitant activation upon stimulation with a growth-promoting factor. These results suggest a role for the Cdk6-D3 complex in regulating cell's proliferation ability in response to external stimuli.

3T3 Cells↗

PubMed2000

Colocalization of parvalbumin and somatostatin-like immunoreactivity in the mouse hippocampus: quantitative analysis with optical dissector.

The colocalization of parvalbumin (PV) and somatostatin (SS)-like immunoreactivity was studied quantitatively in the mouse hippocampus, with particular reference to their areal and dorsoventral differences. The optical disector method was applied by using a confocal laser scanning microscope with immunofluorescent double-labeling. In the present study, we found a particular subpopulation of hippocampal nonprincipal neurons that contained both PV and SS-like immunoreactivity, i.e., PV-immunoreactive (IR)/SS-like immunoreactive (LIR) neurons. In the CA1 region, PV-IR/SS-LIR neurons were restricted to the stratum oriens (SO). In the CA3 region, they were scattered in the SO, stratum pyramidale (SP), and stratum radiatum (SR). However, they were rarely seen in the dentate gyrus (DG). The proportion of PV-IR/SS-LIR neurons in the PV-IR neurons or SS-LIR neurons was about 10% in the CA1 region, 15-30% in the CA3 region, 0-5% in the DG, and 10-20% in total. Laminar analysis revealed that the proportions of PV-IR/SS-LIR neurons in the PV-IR neurons were high in the SO (about 25%) of the CA1 region, and in the SO (about 50%) and SR (30-45%) of the CA3 region. The proportion of PV-IR/SS-LIR neurons in the SS-LIR neurons was low in the SO of the CA1 region (about 10%), but high in the SO (35-65%) and SR (35-45%) of the CA3 region. Morphologically, medium-sized horizontal fusiform and multipolar PV-IR/SS-LIR neurons were frequently observed, and they showed weak immunoreactivity for PV. Large-sized vertical bitufted and triangular PV-IR neurons lacked SS-like immunoreactivity, and most of them showed moderate to intense immunoreactivity for PV. In addition, we provide direct evidence that some PV-IR/SS-LIR neurons projected to the medial septum by using retrograde labeling with Fluoro-Gold injection. These observations indicate that PV-IR/SS-LIR neurons constitute a particular subpopulation of hippocampal nonprincipal neurons.

Animals↗

PubMed1999

Oncogenic stimulation recruits cyclin-dependent kinase in the cell cycle start in rat fibroblast.

The rat fibroblast NRK cells are transformed reversibly by a combination of growth factors. When stimulated with serum, NRK cells rely on cyclin-dependent kinase 4 (Cdk4) for their S phase entry. However, when stimulated with serum containing oncogenic growth factors, they come to rely on either Cdk4 or Cdk6, and their S phase entry cannot be blocked unless both Cdk4 and Cdk6 are immunodepleted. Such change of dependence does not occur in the NRK cell mutants defective in an oncogenic signal pathway and, therefore, deficient in anchorage-independent cell cycle start ability, correlating Cdk6 dependence with this remarkable, cancer-associated phenotype. However, both Cdk4 and Cdk6 are activated upon serum stimulation, and neither the amounts of Cdk6, Cdk4, cyclin D1, and cyclin-dependent kinase inhibitors nor the activities or subcellular localization of Cdk6 and Cdk4 are significantly influenced by oncogenic stimulation. Thus, oncogenic stimulation invokes Cdk6 to participate in a critical step of the cell cycle start in a rat fibroblast, but by a mechanism seemingly unrelated to the regulation of the kinase. Given that many hematopoietic cells employ predominantly Cdk6 for the cell cycle start and perform anchorage-independent growth by nature, our results raise the possibility that the oncogenic stimulation-induced anchorage-independent cell cycle start of NRK is elicited by a mechanism similar to the one used for hematopoietic cell proliferation.

Animals↗

PubMed1999

Quantitative analysis of neuronal nitric oxide synthase-immunoreactive neurons in the mouse hippocampus with optical disector.

A detailed quantitative analysis of immunocytochemically identified nonprincipal neurons containing neuronal nitric oxide synthase (nNOS) was performed on the mouse hippocampus, with particular reference to the dorsoventral gradient. The present study applied two variations of a stereologic technique, the optical disector--one that used confocal laser-scanning microscope optical sections to examine colocalization of nNOS and glutamic acid decarboxylase 67 (GAD67), and the other that used conventional thick sections to examine numerical densities (NDs) and cell sizes of nNOS-immunoreactive (IR) neurons. Colocalization analysis indicated that practically all nNOS-IR neurons (97.6%) were GAD67-IR, whereas a part of the GAD67-IR neurons (about 30%) were nNOS-IR in the whole hippocampus at both dorsal and ventral levels. The percentages of GAD67-IR neurons containing nNOS were higher in the dentate gyrus (DG, about 50%), and lower in the Ammon's horn (about 20%). Laminar analysis revealed that the majority of GAD67-IR neurons contained nNOS in the stratum lacunosum-moleculare of the CA3 region (about 60%) and in the molecular layer of the DG (about 80%). The NDs of nNOS-IR neurons in the whole hippocampus showed a dorsoventral gradient, which increased from dorsal (1.6 x 10(3)/mm3) to ventral (2.2 x 10(3)/mm3) levels. The NDs were relatively higher in the principal cell layers, where about 40% of nNOS-IR neurons were situated both in the Ammon's horn and DG. The mean cell sizes of nNOS-IR neurons showed no remarkable laminar differences or dorsoventral gradient in the Ammon's horn, but they were extensively larger in the hilus of the DG than in other layers. These results indicate that nNOS-IR neurons in the mouse hippocampus represent a subpopulation of gamma-aminobutyric acid (GABA)ergic neurons and suggest that the laminar distributions of nNOS-IR neurons related to possible functional heterogeneity of GABAergic neurons in each hippocampal layer.

Animals↗

PubMed1999

Total synthesis of an antioxidant isolated from yeast via palladium-catalyzed coupling and its application for related compounds.

A total synthesis of an antioxidant (1) having a benzofuran skeleton was achieved in four steps via the palladium(0)-catalyzed cross-coupling reaction. We also prepared several related compounds bearing a variety of aromatic or heterocyclic rings. Some of these compounds demonstrate more potent than 1 for antioxidative activity using guinea pig liver microsomes.

Animals↗

PubMed1999

Cell cycle start from quiescence controlled by tyrosine phosphorylation of Cdk4.

In mammals Cdk4 (or Cdk6 in some cell types) is required for starting the cell cycle. Recently we showed that Cdk4 is regulated by tyrosine phosphorylation and dephosphorylation, and that this regulation is required for a DNA damage-induced G1 arrest. We report here that a generic anti-phosphotyrosine antibody can detect tyrosine-phosphorylated Cdk4 and that as revealed by immunoblot detection and kinase assay, this regulation is employed for DNA damage-responsive checkpoint control during cell cycle start from quiescence. In rat fibroblasts traversing G1 or arrested in G1 by deprivation of anchorage, Cdk4 does not undergo tyrosine phosphorylation. Tyrosine phosphorylation occurs only during cell's arrest in quiescence and dephosphorylation during their cell cycle start. Ultraviolet irradiation blocks dephosphorylation and concomitant activation of Cdk4, thereby preventing the start of cell cycling. Thus, unlike tyrosine phosphorylation of Cdc2, which controls phase transition in the regular cell cycle, tyrosine phosphorylation of Cdk4 is employed for controlling cell cycle start from quiescence in a rat fibroblast.

3T3 Cells↗

PubMed1999

Isolation of a mammalian homologue of a fission yeast differentiation regulator.

In the fission yeast Schizosaccharomyces pombe the nrd1(+) gene encoding an RNA binding protein negatively regulates the onset of differentiation. Its biological role is to block differentiation by repressing a subset of the Ste11-regulated genes essential for conjugation and meiosis until the cells reach a critical level of nutrient starvation. By using the phenotypic suppression of the S. pombe temperature-sensitive pat1 mutant that commits lethal haploid meiosis at the restrictive temperature, we have cloned ROD1, a functional homologue of nrd1(+), from rat and human cDNA libraries. Like nrd1(+), ROD1 encodes a protein with four repeats of typical RNA binding domains, though its amino acid homology to Nrd1 is limited. When expressed in the fission yeast, ROD1 behaves in a way that is functionally similar to nrd1(+), being able to repress Ste11-regulated genes and to inhibit conjugation upon overexpression. ROD1 is predominantly expressed in hematopoietic cells or organs of adult and embryonic rat. Like nrd1(+) for fission yeast differentiation, overexpressed ROD1 effectively blocks both 12-O-tetradecanoyl phorbol-13-acetate-induced megakaryocytic and sodium butyrate-induced erythroid differentiation of the K562 human leukemia cells without affecting their proliferative ability. These results suggest a role for ROD1 in differentiation control in mammalian cells. We discuss the possibility that a differentiation control system found in the fission yeast might well be conserved in more complex organisms, including mammals.

Amino Acid Sequence↗

PubMed1999

Total synthesis of a natural antioxidant and structure-activity relationships of related compounds.

A total synthesis of benzodioxole derivative 1 was achieved via a palladium(0)-catalyzed cross-coupling reaction in a 68% overall yield (4 steps). A novel series of benzodioxoles bearing a variety of aromatic and heterocyclic rings was also prepared and the antioxidative activity evaluated using in vitro model systems. Structure-activity studies revealed that i) intramolecular hydrogen-bonding in the phenol moiety reduced activity, ii) introduction of disubstituents at the ortho location relative to the phenol increased activity, and iii) the methylenedioxy function contributed to stabilization of the phenoxy radical. Among of these compounds, 5,7-di-(4-methoxyphenyl)-4-methoxy-6-hydroxy-1,3-benzodioxole (7p) was the most favorable agent and more potent than n-propyl gallate.

Animals↗

PubMed1999

[Large cell carcinoma of the lung with metastasis of the gastric submucosa].

A 66-year-old man was admitted with dyspnea on exertion and an abnormal shadow on chest roentgenogram. Transbronchial biopsy yielded a diagnosis of large cell carcinoma of the lung. His dyspnea improved following irradiation and corticosteroid treatment and one month later, he was admitted again for chemotherapy. Because occult blood in stool was detected, upper gastrointestinal endoscopy was performed. Gastric submucosal large cell carcinoma was diagnosed, and this was considered to be metastatic from the lung. Such cases diagnosed prior to death are rare.

Aged↗

PubMed1999

[Interstitial pneumonitis associated with Sweet's syndrome in the elderly].

Sweet's syndrome occurring during the course of interstitial pneumonitis in a 70-year-old woman was encountered. She was admitted because of dyspnea on exercise, dry cough and interstitial shadow on chest x-ray. Lung biopsy, together with other findings confirmed interstitial pneumonitis. Five days after admission, genital ulcer and aphtha on the oral mucosa were detected and exudative erythema appeared on her right shoulder, chest and back. Histological examination of the skin lesions demonstrated numerous nutrophilic infiltration in the upper dermis, indicating Sweet's syndrome. The skin eruption rapidly disappeared on treatment with colchicine. Although six months after admission interstitial pneumonitis caused respiratory failure, treatment with prednisolone and cyclophosphamide was effective. Serological and immunological tests demonstrated hyper-gammaglobulinemia and positive reaction for anti SS-A antibody. Pathological examination of the lip revealed numerous lymphocyte infiltrates around the duct of the minor salivary gland, suggesting Sjögren's syndrome as the background disease of Sweet's syndrome and interstitial pneumonitis. This evidence indicating that even in elderly patients, skin lesions of Sweet's syndrome may reveal the background disease.

Aged↗

PubMed1998

Quantitative analysis of GABAergic neurons in the mouse hippocampus, with optical disector using confocal laser scanning microscope.

The numerical densities (NDs) of glutamic acid decarboxylase (GAD) 67 immunoreactive (IR) neurons in the mouse hippocampus were estimated according to the optical disector method using a confocal laser scanning microscope (CLSM), and the cell sizes of disector-counted neurons were measured. Particularly, we focused on the dorsoventral differences of the NDs and cell sizes in individual subdivisions and layers. The NDs of GAD67-IR neurons were larger at the ventral level than at the dorsal level in most subdivisions and layers, except in the stratum pyramidale (SP) of the CA1 region and stratum radiatum (SR) of the CA3 region. In the whole hippocampus, the ND of GAD67-IR neurons was 5.7+/-0.2x103/mm3 at the dorsal level, and 7.3+/-0.3x103/mm3 at the ventral level. The laminar differences showed that the NDs of GAD67-IR neurons in the principal cell layers were generally larger than those in the dendritic layers in each subdivision. The ND of GAD67-IR neurons was largest in the SP of the CA1 region at the dorsal level (13.5+/-0.9x103/mm3), and smallest in the molecular layer (ML) of the dentate gyrus (DG) at the dorsal level (1.7+/-0.2x103/mm3). The mean cell sizes of GAD67-IR neurons also showed prominent dorsoventral and laminar differences. In the CA3 region, the mean cell size of GAD67-IR neurons was smaller at the dorsal level than at the ventral level, while in the DG, it was larger at the dorsal level than at the ventral level. On the other hand, the mean cell size of GAD67-IR neurons in the CA1 region showed no significant dorsoventral difference. In the whole hippocampus, the mean cell size of GAD67-IR neurons was slightly smaller at the dorsal level (somatic profile area 149.2+/-2.5 microm2) than at the ventral level (154.2+/-2.9 microm2). The laminar differences showed that the mean cell sizes of GAD67-IR neurons in the principal cell layers were generally larger than those in the dendritic layers in each subdivision. The mean cell size of GAD67-IR neurons was largest in the SP of the CA3 region at the ventral level (180.7+/-8.7 microm2), and smallest in the stratum lacunosum-moleculare (SLM) of the CA3 region at the dorsal level (115.9+/-7.9 microm2). The cell size distributions in individual layers revealed that GAD67-IR neurons were roughly classified into two subgroups. The composition of these subgroups suggested the heterogeneity of GAD67-IR neurons in the mouse hippocampus in view of cell size

Animals↗

PubMed1998

Development of novel chitosan derivatives as micellar carriers of taxol.

PURPOSE: To develop an intravenous injectable carrier composed of chitosan derivatives for taxol. METHODS: A chitosan with lauryl groups attached to amino groups to provide the hydrophobic moieties and, carboxymethyl groups attached to hydroxy groups to provide the hydrophilic moieties (N-lauryl-carboxymethyl-chitosan = LCC), was newly synthesized. The solubility of taxol in LCC micelles in aqueous solution was examined. The hemolysis test of LCC and the growth inhibition experiment of taxol-loading micelle using KB cells were also performed as in vitro assay. RESULTS: It was found that LCC solubilized taxol by forming micelles with particle sizes less than 100nm. This particle size was considered effective for passive targeting for tumors. The concentration of taxol in the micellar solution was very high, with a maximum of 2.37mg/mL. This maximum was 1000 times above that in a saturated solution of taxol at pH 7.4. Hemolysis testing as an in vitro assay indicated that LCC was safer than Polysorbate 80 (TO-10M) as intravenous surfactant in terms of induction of membrane damage. As judged by cytostatic activity against KB cells, taxol retained activity even when included in LCC micelles. LCC-entrapped taxol was more effective in cytostatic activity than free taxol in low concentrations. CONCLUSIONS: The results of solubilization capacity examination, hemolysis testing, and cytostatic activity suggest that LCC may be useful as a carrier of taxol.

Animals↗

PubMed1998

The analysis of mRNA expression of cytokines from skin lesions in Churg-Strauss syndrome.

We report our recent clinical experience with a patient suffering from Churg-Strauss syndrome and the results of our investigation into the mRNA expression of cytokines in the patient's lesions as well as in the frozen sections from a previous patient. In both cases, blood IgG was at a high level. Cytokine mRNA expression differed according to the degree of cellular infiltration. In the presence of marked infiltration, counteracting Th1 and Th2 cytokines were simultaneously detected; the former included IL-12 and IFN-gamma, and the latter, IL-6 and IL-10. The concurrence of both types of cytokine could be attributed to several factors. For example, IL-6 is involved through some mechanism in the formation of immune complexes by IgG, and IL-12 and IFN-gamma appeared to participate in the development of granuloma. These suppositions support the suggested immunological etiology of the disease. It is also inferred that the dominance of one of the two types of cytokines depends on the clinical phase of the disease.

Biomarkers↗

PubMed1998

3-(5-Dimethylamino-1-naphthalenesulphonyl)-2-(3-pyridyl)thiazolidine (YHI-1) selectively inhibits human immunodeficiency virus type 1.

3-(5-Dimethylamino-1-naphthalenesulphonyl)-2-(3-pyridyl)thiazolidi ne (YHI-1), a synthetic analogue of D-cysteinolic acid isolated from sardines (Sardinops melanostictus), was found to be a specific inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in various cell cultures. YHI-1 inhibited HIV-1IIIB replication with a 50% effective concentration (EC50) of 3.35, 10.23 and 4.61 microM in MT-4 cells, peripheral blood mononuclear cells and MAGI-CCR5 cells, respectively. However, no antiviral activity was observed with non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 strains, such as nevirapine-resistant HIV-1HE/NEV and MKC-442-resistant HIV-1IIIB-R, or with HIV-2ROD or SIVMAC. YHI-1 failed to inhibit reverse transcriptase (RT) activity in vitro with different template-primer systems. Time-of-addition experiments, the failure to inhibit NNRTI-resistant strains and the failure to show in vitro activity against RT suggest that a metabolite of YHI-1 inside the cell acts like an NNRTI. Thus, YHI-1 seems to belong to a new class of HIV-1 inhibitor and is a good candidate for further development.

Animals↗