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Biomedical subjects

Masao Doi

Publications and source records attributed to Masao Doi.

At least 19 recordsLinked to original sources
PubMed2006

Simple model of skin formation caused by solvent evaporation in polymer solutions.

A simple model is proposed for the skin formation in the evaporation process of a polymer solution at a free surface. In this model the skin is regarded as a gel phase formed near the free surface, and the dynamics is described by a diffusion equation for the polymer concentration with moving boundaries. The equation is solved both analytically and numerically. It is shown that the skin phase appears when the evaporation rate is high or when the initial polymer concentration is high. An analytical expression is given for the criterion for the skin phase to be formed.

Journal Article↗
PubMed2006

Impaired light masking in dopamine D2 receptor-null mice.

Disruption of overt circadian rhythms can occur without influencing the endogenous pacemaker, the so-called 'masking' effect classically elicited by light. As the physiological pathways involved in light masking remain elusive, we analyzed mice lacking the dopamine D2 receptor. Although circadian rhythmicity was normal, D2R-null mice showed a markedly deficient light masking response, indicating that D2R-mediated signaling is an essential component of the neuronal pathways leading to light masking of circadian rhythms.

Animals↗
PubMed2006

Circadian regulator CLOCK is a histone acetyltransferase.

The molecular machinery that governs circadian rhythmicity comprises proteins whose interplay generates time-specific transcription of clock genes. The role of chromatin remodeling in a physiological setting such as the circadian clock is yet unclear. We show that the protein CLOCK, a central component of the circadian pacemaker, has histone acetyltransferase (HAT) activity. CLOCK shares homology with acetyl-coenzyme A binding motifs within the MYST family of HATs. CLOCK displays high sequence similarity to ACTR, a member of SRC family of HATs, with which it shares also enzymatic specificity for histones H3 and H4. BMAL1, the heterodimerization partner of CLOCK, enhances HAT function. The HAT activity of CLOCK is essential to rescue circadian rhythmicity and activation of clock genes in Clock mutant cells. Identification of CLOCK as a novel type of DNA binding HAT reveals that chromatin remodeling is crucial for the core clock mechanism and identifies unforeseen links between histone acetylation and cellular physiology.

ARNTL Transcription Factors↗
PubMed2006

Signaling mediated by the dopamine D2 receptor potentiates circadian regulation by CLOCK:BMAL1.

Environmental cues modulate a variety of intracellular pathways whose signaling is integrated by the molecular mechanism that constitutes the circadian clock. Although the essential gears of the circadian machinery have been elucidated, very little is known about the signaling systems regulating it. Here, we report that signaling mediated by the dopamine D2 receptor (D2R) enhances the transcriptional capacity of the CLOCK:BMAL1 complex. This effect involves the mitogen-activated protein kinase transduction cascade and is associated with a D2R-induced increase in the recruiting and phosphorylation of the transcriptional coactivator cAMP-responsive element-binding protein (CREB) binding protein. Importantly, CLOCK:BMAL1-dependent activation and light-inducibility of mPer1 gene transcription is drastically dampened in retinas of D2R-null mice. Because dopamine is the major catecholamine in the retina, central for the neural adaptation to light, our findings establish a physiological link among photic input, dopamine signaling, and the molecular clock machinery.

ARNTL Transcription Factors↗
PubMed2006

Computational flow dynamics in abdominal aortic aneurysm using multislice computed tomography.

Following the introduction of a new multislice computed tomography (MSCT) scanner, it has become possible to produce high-speed CT angiography (CTA), the preferred method for imaging in emergent abdominal vascular conditions. Unlike catheter angiography, multislice CTA not only depicts the vessels but also allows perfusion in adjacent organs to be assessed. To make the most effective diagnostic use of multi-detector row CTA and three-dimensional image post-processing, radiologists must be familiar with the optimal CTA protocols and the typical CT findings in various emergent vascular conditions using computational flow dynamics (CFD). This article describes a technical approach to estimating the blood flow state of human abdominal aortic aneurysms (AAA) in more detail by constructing realistic three-dimensional (3D) vessel models using CFD methods, focusing on pre- and postoperative cases.

Aged↗
PubMed2006

Piling-to-buckling transition in the drying process of polymer solution drop on substrate having a large contact angle.

We studied the drying process of polymer solution drops placed on a substrate having a large contact angle with the drop. The drying process takes place in three stages. First, the droplet evaporates keeping the contact line fixed. Second, the droplet shrinks uniformly with receding contact line. Finally the contact line is pinned again, and the droplet starts to be deformed. The shape of the final polymer deposit changes from concave dot, to flat dot, and then to concave dot again with the increase of the initial polymer concentration. This shape change is caused by the gradual transition from the solute piling mechanism proposed by Deegan to the crust buckling mechanism proposed by de Gennes and Pauchard.

Journal Article↗
PubMed2006

Intrapleural cisplatin and OK432 therapy for malignant pleural effusion caused by non-small cell lung cancer.

OBJECTIVE: To evaluate the efficacy of combined intrapleural therapy with cisplatin, an antineoplastic agent, and OK432, a sclerosing agent, in controlling malignant pleural effusions, when compared with monotherapy with either agent. METHODS: A total of 49 non-small cell lung cancer patients with malignant pleural effusion were randomly assigned to one of three groups: intrapleural cisplatin therapy (n = 17), intrapleural OK432 therapy (n = 17), or both (n = 15). They were compared in terms of success rate, duration of indwelling chest tube and adverse reactions. RESULTS: Rates of pleural effusion recurrence within 180 days following cisplatin, OK432, or combination therapy were 64.7%, 52.9% and 13.3%, respectively, being significantly lower in the combination therapy group (P = 0.01). The mean duration of chest tube drainage was 8.4 days, 5.5 days and 12.9 days, respectively, being significantly longer in the combination therapy group (P < 0.001). All procedures were well tolerated. CONCLUSIONS: Although chest tube drainage took longer because of the time required for multiple administration of the agents, intrapleural combination therapy with cisplatin and OK432 was more effective in controlling malignant pleural effusions due to non-small cell lung cancer than monotherapy with either agent.

Aged↗
PubMed2006

Lcg is a light-inducible and clock-controlled gene expressed in the chicken pineal gland.

The circadian clock is an autonomous biological clock that is entrainable to environmental 24-h cycles by receiving time cues such as light. Generally, light given at early and late subjective night, respectively, delays and advances the phase of the circadian oscillator. We previously searched for the chicken pineal genes that are induced by light in a phase-dependent manner. The present study undertook cDNA cloning and characterization of a gene whose expression was remarkably up-regulated by light at late subjective night. The mRNA level of this gene exhibited robust diurnal change in the pineal gland, with a peak in the early (subjective) day under light-dark cycles and constant dark condition, and hence it was designated Lcg (Light-inducible and Clock-controlled Gene). Chicken Lcg encodes a coiled-coil protein composed of 560 amino acid residues. Among chicken tissues, the pineal gland and the retina exhibited relatively high expression levels of LCG. LCG was colocalized with gamma-tubulin, a centrosomal protein, when expressed in COS7 cells, and LCG is the first example of a clock-related molecule being accumulated at the centrosome. Coimmunoprecipitation of LCG with gamma-tubulin in the chicken pineal lysate suggests a link between the circadian oscillator and the centrosomal function.

Amino Acid Sequence↗
PubMed2006

[Carboplatin plus gemcitabine therapy versus carboplatin plus weekly paclitaxel therapy for advanced non-small cell lung cancer].

We compared two chemotherapy regimens for advanced non small-cell lung cancer. The CG regimen consisted of carboplatin (AUC 4 to 5) on day 1 plus gemcitabine (1,000 mg/m(2)) on day 1 and 8, every three weeks, while the CP regimen was carboplatin (AUC 6) on day 1 plus paclitaxel (70 mg/m(2)) on day 1, 8 and 15, every four weeks. There was a total of 62 patients, 23 on the CG regimen and 39 on the CP regimen. In initial treatment, the response rate, time to progression and median survival time in the CG regimen and CP regimens were 40% vs 22%, 124 days vs 67 days, and 422 days vs 328 days, respectively. There was no statistical difference in the outcome. However, the toxicity profile was different in the two regimens. Grade 3/4 neutropenia and thrombocytopenia were frequent in the CG regimen (61% vs 31%, p=0.02, 44% vs 3%, p=0.0002, respectively). Non hematological toxicity including grade 2 alopecia was less in the CG regimen (4% vs 36%, p=0.012). In choosing the chemotherapeutic regimen for non small cell cancer, it is important to consider the toxicity.

Adult↗
PubMed2006

[Antimicrobial susceptibility of Pseudomonas aeruginosa isolated from urine at one hospital to mainly carbapenem and fluoroquinolone drugs].

We tested the drug susceptibility to 8 anti-pseudomonal agents of 97 strains of Pseudomonas aeruginosa isolated from urine between January 1998 and May 2004. The results were as follows. 1. Antimicrobial activity was, in order of superiority to biapenem (BIPM), meropenem (MEPM), ciprofloxacin (CPFX), imipenem (IPM), pazufloxacin (PZFX), amikacin (AMK), ceftazidime (CAZ), piperacillin (PIPC). 2. The resistance rate (intermediate+resistance) to carbapenem drugs was 10.3% for BIPM and MEPM, and 13.4% for IPM. Many of the IPM-resistant strains showed crossover resistance with BIPM and MEPM. 3. The resistance rate (intermediate+resistance) to fluoroquinolone drugs was 23.7% for CPFX and 20.6% for PZFX. 4. One strain showed simultaneous resistance to IPM = 16 microg/mL, CPFX = 4 microg/mL, and AMK = 32 microg/mL, and produced IMP-1 metallo-beta-lactamase. Susceptibility of P. aeruginosa isolated from urine developed resistance to fluoroquinolone drugs. It is important to promote appropriate use of antimicrobial agents and continue to survey emerging resistance in the clinical isolates.

Amikacin↗
PubMed2005

Common pathways in circadian and cell cycle clocks: light-dependent activation of Fos/AP-1 in zebrafish controls CRY-1a and WEE-1.

The cell cycle and the circadian clock are endogenous pacemakers, which coexist in most eukaryotic cells and share a number of conceptual features. In the zebrafish, light directly regulates the timing of both clocks, although the signaling and transcriptional pathways that convey photic information to essential nuclear regulators have yet to be deciphered. We have previously established the Z3 cell line, which recapitulates the features of zebrafish circadian clock and represents an ideal system to study light-dependent signaling and gene regulation. We conducted a search for light-responsive transcription factors and found that AP-1 DNA binding is highly induced. Light induces the expression of zWee1, a cell cycle gene essential for G2/M transition, and zCry1a, a clock gene of the feedback regulatory loop. We have found consensus AP-1 sites in the regulatory regions of both zWee1 and zCry1a genes, and we show that light inducibility of both genes is abrogated by inhibition of AP-1 function. Light also elicits chromatin remodeling by stimulating hyperacetylation at Lys-14 of histone H3 at both zWee1 and zCry1a promoters, as assessed by chromatin immunoprecipitation assays by using anti-Fos antibody. These findings provide strong evidence that circadian and cell cycle clocks share unique light-responsive pathways in zebrafish.

Animals↗
PubMed2005

Variational bounds for the relaxation times of swelling gels.

Variational bounds are found for the relaxation times of a gel of general shape swelling in a solvent based on the stress-diffusion coupling model. It is shown that in the case of free swelling, the longest relaxation time is inversely proportional to the osmotic modulus K in the limit of K-->0 and K-->infinity . This indicates that the relaxation time diverges at the point of K=0 . The divergence, however, disappears if a part of the gel is mechanically constrained.

Journal Article↗
PubMed2005

The stress diffusion coupling in the swelling dynamics of cylindrical gels.

The swelling dynamics of long cylindrical gel is analyzed by the stress diffusion coupling model [T. Yamaue and M. Doi, Phys. Rev. E 69, 41402 (2004)]. Two situations are analyzed: (i) stress induced swelling, where the swelling is caused by an elongational force applied on the gel, and (ii) free swelling, where the swelling is caused by thermodynamic force. The relaxation times characterizing these processes are calculated. It is shown that earlier calculations for the relaxation time, which are based on some physical or mathematical approximations, give results surprisingly close to the rigorous calculation, but the difference can be still seen experimentally.

Journal Article↗
PubMed2005

Crystal structure and interactions of the PAS repeat region of the Drosophila clock protein PERIOD.

PERIOD proteins are central components of the Drosophila and mammalian circadian clock. Their function is controlled by daily changes in synthesis, cellular localization, phosphorylation, degradation, as well as specific interactions with other clock components. Here we present the crystal structure of a Drosophila PERIOD (dPER) fragment comprising two tandemly organized PAS (PER-ARNT-SIM) domains (PAS-A and PAS-B) and two additional C-terminal alpha helices (alphaE and alphaF). Our analysis reveals a noncrystallographic dPER dimer mediated by intermolecular interactions of PAS-A with PAS-B and helix alphaF. We show that alphaF is essential for dPER homodimerization and that the PAS-A-alphaF interaction plays a crucial role in dPER clock function, as it is affected by the 29 hr long-period perL mutation.

Amino Acid Sequence↗
PubMed2005

Transplantation of mouse embryo fibroblasts: an approach to study the physiological pathways linking the suprachiasmatic nucleus and peripheral clocks.

One of the unresolved issues in the field of circadian biology is dissection of the communication pathways between central and peripheral oscillators. We have developed an experimental procedure in which an implant of mouse embryo fibroblasts of a specific genotype can be successfully grafted into a host animal of a different genotype. This methodology provides an excellent tool to study how peripheral clocks are entrained under various physiological settings and the contribution of individual signaling effectors in this process.

Animals↗
PubMed2004

Swelling dynamics of constrained thin-plate gels under an external force.

We analyze the swelling kinetics of constrained thin-plate gels using the linearized stress-diffusion coupling model proposed in the previous paper [Phys. Rev. E 69, 041402 (2004)]]. The gel is chemically clamped on the disk-like glass plates at the top and the bottom surfaces and can swell and shrink only along the thickness direction. We analyze how the top plate moves when a force is applied at a certain point on the top plate while the bottom plate is fixed. We predict that (i) the translation and the rotation of the top plate are described by a single exponential relaxation process, that (ii) the rotational relaxation process is three times faster than the translational one, and that (iii) when the force is applied to the edge, the displacement by the rotation is four times larger than that by the translation at the edge point where the force is applied. We also analyze how the gel deforms when it is clamped on the flexible film on which external load is applied.

Journal Article↗
PubMed2004

Negative control of circadian clock regulator E4BP4 by casein kinase Iepsilon-mediated phosphorylation.

Light-dependent transcriptional regulation of clock genes is a crucial step in the entrainment of the circadian clock. E4bp4 is a light-inducible gene in the chick pineal gland, and it encodes a bZIP protein that represses transcription of cPer2, a chick pineal clock gene. Here, we demonstrate that prolonged light period-dependent accumulation of E4BP4 protein is temporally coordinated with a delay of the rising phase of cPer2 in the morning. E4BP4 was phosphorylated progressively and then disappeared in parallel with induced cPer2 expression. Characterization of E4BP4 revealed Ser182, a phosphoacceptor site located at the amino-terminal border of the Ser/Thr cluster, which forms the phosphorylation motifs for casein kinase 1epsilon (CK1epsilon). CK1epsilon physically associated with E4BP4 and phosphorylated it. CK1epsilon-catalyzed phosphorylation of E4BP4 resulted in proteasomal proteolysis-dependent decrease of E4BP4 levels, while E4BP4 nuclear accumulation was attenuated by CK1epsilon in a kinase activity-independent manner. CK1epsilon-mediated posttranslational regulation was accompanied by reduction of the transcriptional repression executed by E4BP4. These results not only demonstrate a phosphorylation-dependent regulatory mechanism for E4BP4 function but also highlight the role of CK1epsilon as a negative regulator for E4BP4-mediated repression of cPer2.

Amino Acid Sequence↗