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Biomedical subjects

T Yuasa

Publications and source records attributed to T Yuasa.

At least 19 recordsLinked to original sources

A third-generation bisphosphonate, minodronic acid (YM529), successfully prevented the growth of bladder cancer in vitro and in vivo.

Minodronic acid (YM529) is a third-generation bisphosphonate (BP) that has been shown to directly and indirectly prevent proliferation, induce apoptosis, and inhibit metastasis of various types of cancer cells. In this study, we have investigated the therapeutic efficacy of YM529 against bladder cancer, both in vitro and in vivo. YM529 inhibited geranylgeranylation as well as farnesylation and reduced the growth of all seven bladder cancer cell lines in a dose- and time-dependent manner in vitro. YM529 demonstrated a good synergistic or additive antiproliferative effect when administered in combination with cisplatin or paclitaxel. Immunohistochemical study revealed YM529 inhibited the prenylation of Rap1A in vivo. YM529 administered systemically did not markedly inhibit the growth of visceral metastases but it showed a significant anticancer effect on bone metastases monitored by an in vivo imaging system. Moreover, intravesical YM529 demonstrated significant growth inhibition in a bladder cancer orthotopic model. No adverse effects were associated with the systemic as well as the intravesical treatment regimens. In conclusion, our study suggests that YM529 may be a potent anticancer agent for bladder cancer. The efficacy and safety of this BP as an agent for combination chemotherapies against bladder cancer should be verified by early-phase clinical trials.

Animals↗

Osteopetrosis complicated by osteomyelitis of the mandible: a case report including characterization of the osteopetrotic bone.

A case of a 53-year-old Japanese man with osteopetrosis complicated by osteomyelitis of the mandible is presented. The patient experienced frequent exacerbations and remissions of osteomyelitis of the mandible, despite undergoing several surgical debridements and sequesterectomies with appropriate antimicrobial therapy, for 3 years. Finally, the patient underwent mandibular segmental resection followed by reconstruction with a titanium reconstruction plate. Fifty-one months after surgery there is no evidence of recurrent osteomyelitis of the mandible, suggesting that a more radical surgical approach is preferable for patients with severe complications resulting from osteopetrosis. Also presented here are the histopathological and biochemical features of the osteopetrotic bone. The osteopetrotic cortical bone was morbidly sclerotic with compact and irregular laminations. Degradation of osteocytes in the osteopetrotic bone was due to hypoxia and lack of nutrition resulting from osteosclerosis. There were no significant differences between osteopetrotic and normal bone according to X-ray diffraction, Fourier transform infrared spectroscopy, collagen content or mineral content. Micro-Vickers hardness measurements showed that osteopetrotic bone was significantly harder than normal bone, and the standard deviation of hardness was greater in osteopetrotic bone. Such a loss of integrity in osteopetrotic bone is considered to be a primary reason for the greater risk of a variety of complications such as pathological fracture and refractory osteomyelitis.

Bone Plates↗

Diagnosis of bone metastasis in men with prostate cancer by measurement of serum ICTP in combination with alkali phosphatase and prostate-specific antigen.

AIMS: Carboxy-terminal telopeptide of type I collagen (ICTP) is a parameter of bone absorption, and has recently been introduced to monitor bone metastases. The aim of this retrospective study was to investigate the potential of ICTP as a candidate serum marker of bone metastasis in prostate cancer. MATERIALS AND METHODS: Serum markers in 155 men pathologically diagnosed with prostate cancer were measured. The serum levels of ICTP, prostate-specific antigen (PSA), and alkali phosphatase (ALP) were compared to assess the extent of disease (EOD) scores from bone scans and then analysed statistically. RESULTS: The serum ICTP levels were not well correlated with the EOD scores in the total group of men, men newly diagnosed with prostate cancer, or men previously diagnosed with prostate cancer who were followed up. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ICTP (cut-off value, 5.0 ng/ ml) of the men newly diagnosed with prostate cancer were 78.6%, 88.0%, 78.6%, and 88.0%, respectively. In these men, the specificity and PPV of ALP (cut-off value, 335 IU/l) were 100%, whereas the sensitivity and NPV of PSA (cut-off value, 40 ng/ml) were 100% in this study. The serum levels of ICTP in the men with low ALP (< 335 IU/l) and high PSA (> or = 40 ng/ ml) clearly separated the men with or without bone metastasis, as judged by bone scans. CONCLUSION: We found that the ICTP is not a superior serum marker for bone metastases compared with ALP or PSA. Our study suggests, however, that the ICTP measurement is useful in a certain subset of men with the combination of PSA and ALP in distinguishing men with bone metastasis from those without.

Aged↗

Four-digit allele genotyping of the HLA-A and HLA-B genes in Japanese patients with Behcet's disease by a PCR-SSOP-Luminex method.

The present study represents the first four-digit allele genotyping of HLA-A and -B in Japanese Behcet's disease (BD) patients and controls using a new genotyping method (named the PCR-SSOP-Luminex method) to determine the association of certain HLA-A or -B alleles with BD. Peripheral blood lymphocytes were collected from 180 Japanese BD patients and 170 healthy controls. The genotype frequency of HLA-B*5101 was significantly increased in the patients (61.7%) as compared with the controls (15.9%) (Pc = 1 x 10(-16), OR = 8.5). When we recalculated the phenotype frequencies after excluding the HLA-B*51-positive patients and controls to account for the effects of the linkage disequilibrium and the abundance of the HLA-B*51 allele, the frequencies of HLA-A*2602 and HLA-B*3901 had a weak association in the patient group without HLA-B*51 as compared with the control group without HLA-B*51 (A*2602; Pc = 0.130, OR = 4.3, B*3901; Pc = 0.099, OR = 3.5). This study confirmed on the basis of using a new and more accurate genotyping method that Japanese BD patients have a strong primary association with HLA-B*5101. The significant increase of HLA-A*2602 and B*3901 in the patient group without HLA-B*51 suggests that these two alleles might also have some secondary influence on the onset of BD.

Alleles↗

Chronic inflammatory demyelinating polyneuropathy in a patient with hyperIgEaemia.

We herein report the case of a 46 year old man with chronic inflammatory demyelinating polyneuropathy (CIDP) with hyperIgEaemia. The patient presented with bilateral weakness, generalized hyporeflexia, and mild paresthesia of the fingers of both hands. Nerve conduction studies revealed multiple sites of motor conduction block in the absence of sensory abnormalities. Muscle strength increased, as did compound muscle action potential (CMAP) amplitude immediately after the intravenous infusion of immunoglobulin (IVIg). Serum IgE levels also fluctuated in parallel with his relapsing-remitting clinical course. We propose that pure motor CIDP may be immune mediated and suggest that IgE-mediated allergy may be one potential cause of this condition.

Action Potentials↗

Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker of Hashimoto's encephalopathy.

We investigated autoantibodies and their epitope(s) in Hashimoto's encephalopathy associated with Hashimoto's thyroiditis. In a proteomic analysis, they proved to recognize alpha-enolase. We further searched the epitope region in alpha-enolase using different regions of recombinant proteins expressed in cultured human cells. The amino terminal region was recognized by autobodies from a much higher proportion of patients with Hashimoto's encephalopathy (83.3%; 5/6) than from patients with Hashimoto's thyroiditis (11.8%; 2/17), and not at all by sera from controls (25 healthy individuals and 25 controls with other neurological disorders) (0%; 0/50). Neither the carboxyl terminal nor the mid-region of alpha-enolase showed specificity for Hashimoto's encephalopathy. Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker for Hashimoto's encephalopathy.

Adult↗

[Traumatic aortic regurgitation complicating chronic bronchitis; report of a case].

A 61-year-old man with diabetes mellitus and chronic bronchitis was brought to the hospital after falling from a roof accidentally. He received blunt trauma to the left chest wall including left rib fractures, pneumothorax, hemothorax and a fracture of left scapula. After endotracheal intubation and chest drainage, he was transferred to the intensive care unit. Sixteen days later, congestive heart failure appeared. Echocardiography showed a severe aortic valve regurgitation with a prolapse of non-coronary cusp. Eight months after the injury, his heart failure deteriorated. He underwent aortic valve replacement with a mechanical prosthesis. Upon examining the aortic valve, we noted 2 perforations in the non-coronary cusp of the aortic valve. Postoperative course was uneventful.

Accidents, Home↗

[Sequential bypass grafting with arterial grafts can be functioned? Assessment of evaluation for function of sequential bypass grafting from theoretical model].

As total arterial revascularization in coronary artery bypass grafting (CABG) has been recommended, a sequential bypass technique using arterial grafts has been induced. We evaluate whether a sequential bypass graft can be functioned or not by using a simple simulation model for coronary circulation analogous to the electrical circuit based on Ohm law. The ratio of flow between graft and native coronary artery was determined by the severity of stenosis in the bypassed vessels and the graft diameter. In selection for sequential bypass technique, these factors should be taken into consideration.

Arteries↗

Percutaneous transluminal mitral valvuloplasty improves cardiopulmonary baroreflex sensitivity in patients with mitral stenosis.

Patients with heart failure frequently have increased sympathetic tone, which could result in part from impairment of the inhibitory influence of cardiopulmonary baroreflexes. Percutaneous transluminal mitral valvuloplasty (PTMV) provides a unique model for evaluating functional changes in cardiopulmonary baroreflexes without open-heart surgical manipulation. We examined the effects of PTMV on cardiopulmonary baroreflexes and sympathetic nerve activity in 10 patients with mitral stenosis. We measured muscle sympathetic nerve activity using microneurography. Cardiopulmonary baroreflex provocation was performed by applying a lower body negative pressure of -10 mm Hg, and its sensitivity was determined by dividing the percent change in muscle sympathetic nerve activity by the change in central venous pressure. Response to isometric exercise was assessed by handgrip at 30% of maximal voluntary contraction for 3 min. PTMV significantly increased mitral valve area and cardiac index and decreased mean left atrial pressure. PTMV significantly decreased burst rate from 25.1+/-2.5 to 15.6+/-2.6 bursts/min (p < 0.01) and burst incidence from 37.1+/-3.7 to 23.6+/-3.3 bursts/100 heart beats (p < 0.01). After PTMV, cardiopulmonary baroreflex sensitivities measured using burst rate and burst incidence were -39.9+/-4.9%/mm Hg and -38.7+/-6.2%/mm Hg, respectively, which were significantly steeper than those before PTMV (-9.2+/-1.1%/mm Hg and -8.4+/-1.1%/mm Hg; p < 0.01). There were significant correlations between muscle sympathetic nerve activity at rest and cardiopulmonary baroreflex sensitivity. PTMV did not affect muscle sympathetic responses to handgrip exercise. These results suggest that patients with mitral stenosis have baseline sympathetic nerve activation, which could result in part from impaired cardiopulmonary baroreflexes.

Adult↗

Preliminary experiment of fluorescent X-ray computed tomography to detect dual agents for biological study.

The simultaneous observation of various information, such as blood flow, tissue metabolism and distribution of receptors, is quite important in order to understand the functional state of biomedical objects. The simultaneous detectability of contrast agents by fluorescent X-ray computed tomography (FXCT) with synchrotron radiation is examined in this study. The system consisted of a silicon (111) double-crystal monochromator, an X-ray slit system, a scanning table, a PIN diode, a highly purified germanium detector and an X-ray charge-coupled device (CCD) camera. The monochromatic X-ray beam energy was adjusted to 37.0 keV and collimated into a pencil beam of 1 x 1 mm. The fluorescent spectra of the K alpha lines for iodine and xenon were detected simultaneously. FXCT could image the distribution of both iodine and xenon agents in a phantom clearly and the contrast ratio was significantly better than that of transmission X-ray computed tomography images.

Fluorescence↗

Effect of added NaHCO3 on the basic properties of apatite cement.

Alternation of a composition of set apatite cement (AC) from carbonate-free apatite (CO3-free AP) to carbonate apatite (CO3-AP) may accelerate replacement of the set AC with bone because CO3-AP can be dissolved much faster than CO3-free AP in the weak acidic solution produced by osteoclasts. In this investigation, NaHCO3 was added to the AC component and the effects of added NaHCO3 on cement-setting behavior and on set mass were studied as an initial step for the fabrication of AC, which can be replaced with bone faster than current AC. When NaHCO3 was added to AC, the resultant set mass contained CO3. Although not all CO3 was incorporated in the set AC, the amount of CO3 incorporated into the set AC increased with the amount of added NaHCO3. Powder X-ray diffraction analysis and Fourier transform infrared spectrometer measurements revealed the formation of B-type CO3-AP. The setting time measured in an incubator at 37 degrees C and 100% relative humidity slowed from 30 to 45 min, indicating that NaHCO3 has an inhibitory effect on AP formation. The diametral tensile strength of the set AC decreased significantly with the addition of NaHCO3. Scanning electron microscopic observation revealed that fine crystals were formed in the set AC when NaHCO3 was added to AC. As a result, the crystallinity indices of the set AC measured using X-ray diffraction and Fourier transform infrared spectroscopy decreased with an increase in the amount of added NaHCO3. The dissolution rate of set AC in weak acid, pH 5.5, increased with the amount of added NaHCO3. We concluded that the formation of B-type CO3-AP and the resulting faster dissolution of set AC in weak acidic solution is preferable for the faster replacement of set AC with bone even though the decreased diametral tensile strength value is a shortcoming.

Apatites↗

In vitro resorption of three apatite cements with osteoclasts.

To evaluate the replacement of apatite cement (AC) with bone, osteoclasts were incubated for 48 h on the surface of three AC types: conventional AC (c-AC), fast-setting AC (fs-AC), and anti-washout AC (aw-AC), using sintered apatite (AP) and cortical bone as control materials. We found osteoclasts attached to the surface of AC and osteoclastic resorption pits after 48 h of incubation for all experimental AC types. In contrast, no resorption pit was observed on the surface of sintered AP although osteoclasts were attached to the surface of sintered AP. There was no significant difference among the types of AC with respect to the resorption area, but the resorption areas were only approximately 1% of that on the surface of cortical bone. We concluded, therefore, that ACs could be replaced with bone regardless of the type but that it takes extensive time for the ACs to be completely replaced with bone.

Animals↗

Lyn is essential for fcgamma receptor III-mediated systemic anaphylaxis but not for the Arthus reaction.

The Src family kinase Lyn initiates intracellular signal transduction by associating with a variety of immune receptors such as antigen receptor on B cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (FcepsilonRI) on mast cells. Involvement of Lyn in the IgE-mediated immediate-type hypersensitivity is well documented, but the physiological significance of Lyn in IgG-dependent, type III low-affinity FcR for IgG (FcgammaRIII)-mediated responses is largely unknown. In this study, we generated a double-mutant mouse strain deficient in both type II FcR for IgG (FcgammaRIIB) and Lyn to exclude any involvement of inhibitory signaling by FcgammaRIIB, which otherwise downregulates FcgammaRIII-mediated cellular responses. FcgammaRIIB-deficient but Lyn-sufficient mice served as controls. The Lyn deficiency attenuated IgG-mediated systemic anaphylaxis in vivo, and significantly reduced calcium mobilization and degranulation responses of bone marrow-derived mast cells (BMMCs) in vitro. However, we found that either interleukin 4 or tumor necrosis factor alpha release by BMMCs was comparable to that from Lyn-deficient and control mice, and the reverse-passive Arthus reaction was equally induced in both mutant mice, indicating that Lyn is not involved in the onset of the IgG-mediated, FcgammaRIII-dependent late phase responses of mast cells. These findings provide us with insight into distinct signaling mechanisms in mast cells underlying the development of diverse pathologies as well as a therapeutic potential for selective treatment of allergic disorders.

Anaphylaxis↗

Diurnal variations in alpha power density and subjective sleepiness while performing repeated vigilance tasks.

OBJECTIVE: Diurnal variations in EEG activity and subjectively rated sleepiness while performing repeated vigilance tasks were examined. METHODS: Nine diurnally active healthy males underwent repeated vigilance tasks at 08:00, 11:00, 14:00, 17:00 and 20:00 h. An electroencephalogram (EEG) was taken while the subjects performed the tasks with their eyes open. The alpha power spectra (8.6-13.3 Hz) of EEG was integrated. Subjectively rated sleepiness, reaction time and oral temperature were also measured. RESULTS: Significant diurnal variations were found for alpha power, subjectively rated sleepiness and oral temperature. The alpha power was significantly smaller at 08:00 than at 11:00, 14:00, 17:00 and 20:00 h. The subjectively rated sleepiness was significantly larger at 08:00 than at 11:00, 17:00 and 20:00 h. The diurnal variation in alpha power did not correspond to that in subjectively rated sleepiness. On the other hand, repeated vigilance tasks increased the alpha power, subjectively rated sleepiness and reaction time at each time of day. The increase in alpha power was significantly greater at 14:00 than at 08:00 and 20:00 h. CONCLUSIONS: The diurnal variation was found in alpha power while performing vigilance tasks. Furthermore, the increase in alpha power with repetition of the task depended on the time of day.

Adult↗

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.

Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.

Amino Acid Sequence↗

Diagnosis of Toxoplasma meningoencephalitis in a non-AIDS patient using PCR.

We report herein a rare case of Toxoplasma gondii meningoencephalitis in a non-AIDS patient. Although T. gondii itself was not detected in nucleated cells in peripheral blood and cerebrospinal fluid under the microscope, the polymerase chain reaction method effectively detected the B1 gene of T. gondii in the cells. A serological examination showed increased levels of the IgG but not the IgM antibody to T. gondii, suggesting reactivation of the infection in the brain.

Animals↗

Oxidative stress activates ATMPK6, an Arabidopsis homologue of MAP kinase.

Mitogen-activated protein kinase (MAPK) cascades function in biotic and abiotic stress responses in plants. We analysed effect of oxidative stress on the activation of ATMPK6, an Arabidopsis thaliana MAPK, in Arabidopsis T87 cultured cells and rosette leaves using anti-ATMPK6 specific antibody. ATMPK6 in T87 cells was strongly activated by reactive oxygen species (ROS) such as H(2)O(2) and KO(2). In leaves, ATMPK6 was activated by paraquat and 3-amino-1,2,4-triazole (a catalase inhibitor). These results indicate that ATMPK6 is one of the candidates for signal mediators in response to abiotic or biotic sources for ROS in Arabidopsis.

Adaptation, Physiological↗