Biomedical subjects

Haruhiko Sato

Publications and source records attributed to Haruhiko Sato.

13 recordsLinked to original sources

PubMed2006

Discovery of 7alpha-substituted dihydrotestosterones as androgen receptor pure antagonists and their structure-activity relationships.

A series of 7alpha-substituted dihydrotestosterone derivatives were synthesized and evaluated for androgen receptor (AR) pure antagonistic activity. From reporter gene assay (RGA), the compound with a side chain containing N-n-butyl-N-methyl amide (19a) showed pure antagonistic activity (IC(50)=340nM, FI(5)>10,000nM), whereas known AR antagonists showed partial agonistic activities. The optimization of 19a led to compound 23 (CH4892280), which showed more potent pure antagonistic activity (IC(50)=190nM, FI(5)>10,000nM). The SARs of tested compounds suggested that the length of the side chain and the substituents on the amide nitrogen are important for pure antagonistic activities.

Androgen Receptor Antagonists↗

PubMed2005

Structure-based design of P3 moieties in the peptide mimetic factor VIIa inhibitor.

Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. Structure-based designs of the P3 moiety in the peptide mimetic factor VIIa inhibitor successfully lead to novel inhibitors with selectivity for FVIIa/TF and extrinsic coagulation the same as or even higher than those of previously reported peptide mimetic factor VIIa inhibitors. X-ray crystal structure analysis reveals that one of the novel inhibitors shows improved selectivity by forming interactions between the inhibitor and FVIIa as expected. Another of the novel inhibitors achieves improved selectivity through an unexpected hydrogen bond with Gln217, with a unique bent conformation in FVIIa/TF accompanied by conformational changes of the inhibitor and the protein.

Amino Acid Sequence↗

PubMed2005

Novel interactions of large P3 moiety and small P4 moiety in the binding of the peptide mimetic factor VIIa inhibitor.

Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. A novel peptide mimetic factor VIIa inhibitor, ethylsulfonamide-d-biphenylalanine-Gln-p-aminobenzamidine, shows 100-fold selectivity against thrombin in spite of its large P3 moiety, unlike previously reported FVIIa/TF selective inhibitors. X-ray crystal structure analysis reveals that the large P3 moiety, d-biphenylalanine, and the small P4 moiety, ethylsulfonamide, make novel interactions with the 170-loop and Lys192 of FVIIa/TF, respectively, accompanying ligand-induced conformational changes of the 170-loop, Gln217, and Lys192. Structural comparisons of FVIIa with thrombin and amino acid sequence comparisons among coagulation serine proteases suggest that these interactions play an important role in achieving selective inhibition for FVIIa/TF.

Amino Acid Sequence↗

PubMed2005

Structure of human factor VIIa/tissue factor in complex with a peptide-mimetic inhibitor: high selectivity against thrombin by introducing two charged groups in P2 and P4.

The crystal structure of human factor VIIa/soluble tissue factor (FVIIa/sTF) in complex with a highly selective peptide-mimetic FVIIa inhibitor which shows 1670-fold selectivity against thrombin inhibition has been solved at 2.6 A resolution. The inhibitor is bound to FVIIa/sTF at the S1, S2 and S3 sites and at the additional S1 subsite. Two charged groups, the amidino group in P2 and the carboxylate group in P4, form ionic interactions with Asp60 and Lys192 of FVIIa, respectively. Structural comparisons between factor VIIa and thrombin show that thrombin has oppositely charged residues, Lys60F and Glu192, in the S2 site and the S1 subsites, respectively. These data suggest that the utilization of the differences of charge distribution in the S2 site and the S1 subsites between FVIIa and thrombin is critical for achieving high selectivity against thrombin inhibition. These results will provide valuable information for the structure-based drug design of specific inhibitors for FVIIa/TF.

Anticoagulants↗

PubMed2004

Crystal structure of human factor VIIa/tissue factor in complex with peptide mimetic inhibitor.

The 3D structure of human factor VIIa/soluble tissue factor in complex with a peptide mimetic inhibitor, propylsulfonamide-D-Thr-Met-p-aminobenzamidine, is determined by X-ray crystallography. As compared with the interactions between thrombin and thrombin inhibitors, the interactions at S2 and S3 sites characteristic of factor VIIa and factor VIIa inhibitors are revealed. The S2 site has a small pocket, which is filled by the hydrophobic methionine side chain in P2. The small S3 site fits the small size residue, D-threonine in P3. The structural data and SAR data of the peptide mimetic inhibitor show that these interactions in the S2 and S3 sites play an important role for the improvement of selectivity versus thrombin. The results will provide valuable information for the structure-based drug design of specific inhibitors for FVIIa/TF.

Anticoagulants↗

PubMed2004

Discovery and structure-activity relationship of coumarin derivatives as TNF-alpha inhibitors.

The discovery and structure-activity relationship of a novel series of coumarin-based TNF-alpha inhibitors is described. Starting from the initial lead 1a, various derivatives were prepared surrounding the coumarin core structure to optimize the in vitro inhibitory activity of TNF-alpha production by human peripheral blood mononuclear cells (hPBMC), stimulated by bacterial lipopolysaccharide (LPS). Selected compounds also demonstrated in vivo inhibition of TNF-alpha production in rats.

Cells, Cultured↗

PubMed2004

A Java mobile phone-based "Home Helper" care report creation support system.

In Japan, Home Helpers are employed by hospitals, care companies or the welfare office and are sent to the homes of elderly persons to provide home welfare and care services. They are required to input their reports into the computer at their central office after each care visit. We developed a new Java mobile phone-based Home Helper care report creation support system for reducing the data entry time and the communication costs of their reports. The system consists of a Java mobile phone for each Home Helper and a server computer at their office. The server computer sends a Java care report creation support program to the Java mobile phone. The program runs on the mobile phone and supports the report creation in a short time. Therefore, the developed system enables easy report entry by the Home Helper and saves a significant amount of time and communication costs.

Adult↗

PubMed2004

A welfare facility resident care support system.

We have developed a new care support system to monitor the overall health of welfare facility residents who need constant care. The system is designed with wireless sensors, wireless repeaters and a host computer. The wireless sensor, which consists of a piezoelectric sensor, a 2 axis accelerometer, a microcontroller and a low power 303 MHz ASH transceiver. It records respiration, activity and indicators of posture and behavior for 24 hours. These data are transmitted to the wireless repeater by the transceiver. The wireless repeaters, which are installed throughout the welfare facility, send data, including the repeater's ID, to the host computer. The ID is used to detect the resident's location in the welfare facility. The host computer stores the data, which can be used to analyze the resident's overall health condition. When the resident is in an emergency situation, such as falling or in an inactive state for more that the allotted time, the host computer automatically alerts the situation to the care staff by an alarm sound and also by mobile phone.

Activities of Daily Living↗

PubMed2003

Accelerated aging of senescence accelerated mice R-1 demonstrated by flash visually evoked cortical potentials.

To determine the physiological alterations of visual functions induced by aging, the latency of the N40 peak of the flash visual evoked cortical potentials at several stimulus frequencies were analyzed from senescence accelerated mice (SAM). The senescence prone (P-8) and senescence resistant (R-1) SAM lines were studied. In both the P-8 and ICR (the standard outbred albino laboratory mouse also called CD-1) mice, the peak latency was not significantly different at 6 and 12 months of age. In contrast, there was a prolongation of the peak latency in the R-1 line at 12 months compared to that at 6 months. We conclude that there is an acceleration of the aging process in the R-1 line for visually evoked responses. Thus, the R-1 line might be an independent line suited for the study of aging effects on visual functions.

Aging↗

PubMed2003

A Web-based home welfare and care services support system using a pen type image sensor.

A long-term care insurance law for elderly persons was put in force two years ago in Japan. The Home Helpers, who are employed by hospitals, care companies or the welfare office, provide home welfare and care services for the elderly, such as cooking, bathing, washing, cleaning, shopping, etc. We developed a web-based home welfare and care services support system using wireless Internet mobile phones and Internet client computers, which employs a pen type image sensor. The pen type image sensor is used by the elderly people as the entry device for their care requests. The client computer sends the requests to the server computer in the Home Helper central office, and then the server computer automatically transfers them to the Home Helper's mobile phone. This newly-developed home welfare and care services support system is easily operated by elderly persons and enables Homes Helpers to save a significant amount of time and extra travel.

Aged↗

PubMed2002

Relationship between the curvature constant parameter of the power-duration curve and muscle cross-sectional area of the thigh for cycle ergometry in humans.

For high-intensity cycle ergometer exercise, the relationship between power output ( P) and its tolerable duration ( t) has been well characterized by the hyperbolic relationship: ( P- theta;(F)). t=W', where theta;(F) has been termed the "critical power" or "fatigue threshold". The curvature constant (W') reflects a constant amount of work which can be performed above theta;(F), and it may be regarded as a muscle energy store. The relationship of this energy store to muscle mass is not known. Therefore, the purpose of this study was to determine the relationships among W', accumulated peak oxygen deficit (accumulated peak O(2)-deficit), and muscle cross-sectional area (CSA) of the thigh for high-intensity cycle ergometry in humans. A group of 17 healthy male subjects (aged 21-41 years) participated in this study. The theta;(F) and W' of the P- t hyperbolic relationship and the accumulated peak O(2)-deficit was calculated by standard procedures. The CSA of muscle, fat and bone in the right thigh were measured using ultrasonography. The mean (SD) of theta;(F), W', accumulated peak O(2)-deficit, and muscle CSA of the thigh were 200.0 (17.8) W, 12.60 (2.94) kJ, 2.29 (0.41) l, and 185.3 (22.6) cm(2), respectively. The muscle CSA of the thigh was positively correlated with W' ( r=0.59, P<0.01) and with accumulated peak O(2)-deficit ( r=0.54, P<0.05). The relationship between W' and accumulated peak O(2)-deficit also showed a positive correlation ( r=0.63, P<0.005). Our results indicated that W' derived from the P- t hyperbolic curve as anaerobic working capacity is related to the CSA of muscle.

Adult↗

PubMed2002

Evaluation of the web-based "home helper" support system using wireless Internet mobile phones.

In Japan, Home Helpers provide the home welfare and care services such as cooking, bathing, washing, cleaning, shopping, etc. Last year, we developed the web-based Home Helper support system using wireless Internet mobile phones for improving scheduling and record keeping efficiency and for eliminating unnecessary travel. We have evaluated by questionnaire whether the system can be easily operated. All in all, the system has performed satisfactorily and is in functional use daily.

Adult↗

PubMed2002

Kinetic study of seita-fitting.

We have already presented two studies of the traditional carrier frame, the seita. In our first study, we reported on seita users supporting loads not on the lumbar vertebrae but on the sacrum. In the second study, we showed that carrying a load on the sacrum was efficient in terms of metabolic rate, muscle activity, cadence and subjective responses. The purpose of this study was to verify the effect of carrying a load on the sacrum in terms of gait pattern. We compared the kinetic parameters produced while carrying a load on the sacrum (LOS) with those produced while carrying a load on the lumbar vertebrae (LOLV). Maximum propulsive force and medial impulse were significantly larger in LOS than in LOLV. These results suggested that a normal gait pattern was maintained more in LOS conditions than in LOLV conditions. This indicated that seita-fitting was efficient for carrying and transporting loads.

Adult↗