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Biomedical subjects

Hiroyuki Sakai

Publications and source records attributed to Hiroyuki Sakai.

10 recordsLinked to original sources
PubMed2006

Customizable neuroinformatics database system: XooNIps and its application to the pupil platform.

The developing field of neuroinformatics includes technologies for the collection and sharing of neuro-related digital resources. These resources will be of increasing value for understanding the brain. Developing a database system to integrate these disparate resources is necessary to make full use of these resources. This study proposes a base database system termed XooNIps that utilizes the content management system called XOOPS. XooNIps is designed for developing databases in different research fields through customization of the option menu. In a XooNIps-based database, digital resources are stored according to their respective categories, e.g., research articles, experimental data, mathematical models, stimulations, each associated with their related metadata. Several types of user authorization are supported for secure operations. In addition to the directory and keyword searches within a certain database, XooNIps searches simultaneously across other XooNIps-based databases on the Internet. Reviewing systems for user registration and for data submission are incorporated to impose quality control. Furthermore, XOOPS modules containing news, forums schedules, blogs and other information can be combined to enhance XooNIps functionality. These features provide better scalability, extensibility, and customizability to the general neuroinformatics community. The application of this system to data, models, and other information related to human pupils is described here.

Computational Biology↗
PubMed2006

Requirement of E7 oncoprotein for viability of HeLa cells.

Most human papillomavirus (HPV)-positive cervical cancers contain integrated copies of the viral genome in their chromosomes and express the viral oncoproteins E6 and E7. A virus-encoded transcription factor, E2, is known to repress E6/E7 expression in HPV-positive cancer cells, leading to growth inhibition, which indicates that E6/E7 is required for the survival of the cells. We found that the E2-mediated growth inhibition of HeLa cells, an HPV18-positive cancer cell line, was coupled with a reduction in telomerase activity, an effect which was rescued by the complementation of E7 expression, but not E6 expression, indicating that the cell viability and the telomerase activity in HeLa cells are maintained by an E7-associated function. Analysis of E7 mutants suggested that the binding to the pRB family of pocket proteins was involved in the ability of E7 to rescue the growth potential and telomerase activity inhibited by E2 expression. We also showed that the telomerase activity upregulated by E7 expression was determined by the hTERT promoter activity, and that c-Myc upregulation caused by pRB inactivation could account for the promoter activity. The activation of p53 and consequent accumulation of p21Cip1, which were triggered by the downregulation of E6, appeared not to be essential for the E2-mediated growth arrest.

Cell Cycle Proteins↗
PubMed2005

Long-range cooperative binding of kinesin to a microtubule in the presence of ATP.

Interaction of kinesin-coated latex beads with a single microtubule (MT) was directly observed by fluorescence microscopy. In the presence of ATP, binding of a kinesin bead to the MT facilitated the subsequent binding of other kinesin beads to an adjacent region on the MT that extended for micrometers in length. This cooperative binding was not observed in the presence of ADP or 5'-adenylylimidodiphosphate (AMP-PNP), where binding along the MT was random. Cooperative binding also was induced by an engineered, heterodimeric kinesin, WT/E236A, that could hydrolyze ATP, yet remained fixed on the MT in the presence of ATP. Relative to the stationary WT/E236A kinesin on a MT, wild-type kinesin bound preferentially in close proximity, but was biased to the plus-end direction. These results suggest that kinesin binding and ATP hydrolysis may cause a long-range state transition in the MT, increasing its affinity for kinesin toward its plus end. Thus, our study highlights the active involvement of MTs in kinesin motility.

Adenosine Triphosphate↗
PubMed2003

Downregulation of CD4 is required for maintenance of viral infectivity of HIV-1.

Downregulation of virus receptors on the cell surface is considered to be important in preventing superinfection. HIV-1 encodes multiple gene products, Env, Vpu, and Nef, involved in downregulation of CD4, a major HIV-1 receptor. We found that simultaneous mutations in both vpu and nef severely impaired virus replication. We examined the involvement of CD4 downregulation mediated by Vpu and Nef in the modification of virus infectivity. The mutation in vpu increased CD4 incorporation into virions without affecting the Env content in it, inhibiting the attachment step of virions to the CD4-positive cell surface. Although a single mutation in nef suppresses virus infectivity via a CD4-independent mechanism, it could augment CD4 incorporation in virions in combination with a vpu mutation. These results indicated that CD4 downregulation was necessary for maintenance of Env function in the virion.

CD4 Antigens↗
PubMed2002

Modulation of the cell division cycle by human papillomavirus type 18 E4.

The life cycle of human papillomaviruses (HPVs) is tightly coupled to the differentiation program of their host epithelial cells. HPV E4 gene expression is first observed in the parabasal layers of squamous epithelia, suggesting that the E4 gene product contributes to the mechanism of differentiation-dependent virus replication, although its biological function remains unclear. We analyzed the effect of HPV type 18 E4 on cell proliferation and found that E4 expression induced cell cycle arrest at the G(2)/M boundary. The functional region of E4 necessary for the growth arrest activity was located in the central portion of the molecule, and this activity was independent of the E4-mediated collapse of cytokeratin intermediate filament structures.

Animals↗
PubMed2002

Eccrine squamous syringometaplasia and syringomatous hyperplasia in association with linear scleroderma.

It is now well recognized that syringomatous hyperplasia with squamous syringometaplasia is a type of pseudoepitheliomatous hyperplasia responding to a variety of stimuli. We report a case of linear scleroderma with this process. Histopathology of the lesion showed numerous solid and cystic epithelial structures with squamous metaplasia within typical sclerodermatous skin lesions. Although the pathogenesis of the process remains unclear, dermal-derived growth factors in scleroderma and/or the mechanical effect of sclerosis could stimulate the proliferative response of eccrine epithelium. To the best of our knowledge, the association of syringomatous hyperplasia with eccrine squamous syringometaplasia and linear scleroderma has not been described previously.

Child↗
PubMed2002

[The function of accessory genes of HIV-1].

Human immunodeficiency virus type 1 (HIV-1) has 4 auxiliary genes, vpr, vpu, nef, and vif, which are dispensable for viral replication in vitro. However, many studies with animal model revealed that these genes play important roles on the viral replication and the development of AIDS in vivo through many complicated mechanisms. Although several key factors involved in the function have been identified, further studies are required for the complete understandings of the action mechanisms. The elucidation of the function of the auxiliary genes on molecular bases leads to the discovery of new therapeutic strategies against HIV and the understanding of basic cellular mechanisms. In this review, we summarize new observations mainly about the interactions between auxiliary genes and host cell functions.

Acquired Immunodeficiency Syndrome↗
PubMed2002

[Two cases of minocycline-induced vasculitis].

We report two cases of drug-induced vasculitis subsequent to long-term minocycline therapy. Case 1; A 27-year-old woman, who was receiving minocycline hydrochloride for eosinophilic pustular folliculitis of 68-months'duration, showed polyarthralgia, intermittent low-grade fever, and light red reticulated erythemas with subcutaneous nodules on her extremities. Case 2; A 31-year-old man developed reddish-brown, reticulated erythemas with induration on bilateral lower legs after 24-months' duration of minocycline hydrochloride treatment for hidradenitis suppurativa. In both cases, skin biopsies demonstrated vasculitis affecting a small-sized artery at the border of the dermis and subcutis. Serum antineutrophil cytoplasmic antibodies (ANCA) showed borderline elevation. In both cases cessation of minocycline administration resulted in rapid improvement of cutaneous lesions and constitutional symptoms. Recently, attention has been focused on drug-induced ANCA-positive vasculitis. Accumulation of previous case reports of minocycline-induced vasculitis with cutaneous lesions disclosed that the duration of the treatment before clinical symptoms averaged 35 months. Patients may present with livedoid skin lesions accompanied by fever, polyarthritis, autoimmune hepatitis and drug-induced lupus. Early recognition of ANCA-positive vasculitis is essential during long-term minocycline treatment, because cessation of the drug can result in complete resolution.

Adult↗