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Biomedical subjects

A Hirabayashi

Publications and source records attributed to A Hirabayashi.

At least 19 recordsLinked to original sources
PubMed2001

Discovery of novel N-phenylglycine derivatives as potent and selective beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence.

With a novel assay using isolated ferret detrusor to estimate beta(3)-adrenoceptor agonistic activity, we found that a series of glycine derivatives of ritodrine, a beta(2)-adrenoceptor agonist, are potent beta(3)-adrenoceptor agonists, with excellent selectivity versus beta(1) and beta(2) subtypes. Substitution of halogens in the phenyl ring increased potency and selectivity for the beta(3)-adrenoceptor, and this was dependent upon the position of the halogens. The chlorine-substituted derivatives 3f-i exhibited potent beta(3)-adrenoceptor-mediated relaxation of ferret detrusor (EC(50) = 0.93, 11, 14, and 160 nM) and higher potency at beta(3)-adrenoceptors than at beta(1) or beta(2). The intravenous administration of 3h significantly reduced the urinary bladder pressure in anesthetized male rats (ED(50) = 48 microg/kg) without cardiovascular side effects. This article is the first report of structure-activity relationships (SAR) concerning beta(3)-adrenoceptor agonists as agents for the treatment of urinary frequency and incontinence.

Adrenergic beta-Agonists↗
PubMed2001

Error correcting memorization learning for noisy training examples.

In order to avoid overfitting, we propose error correcting memorization learning. This method is derived from minimization of error between outputs of a trained neural network and correct values for noisy training examples, although the correct values are unknown. We show that noise is adequately suppressed by error correcting memorization learning. The noise suppression mechanism is theoretically clarified. It is found that redundancy plays an essential role for noise suppression and depends on a set of training inputs. We give the condition for the training inputs to provide the redundancy. Moreover, by clarifying the relationships between the proposed method and the weighted least squares estimation with the Mahalanobis norm, we reveal effectiveness of the weighted least squares estimation on noise suppression.

Models, Theoretical↗
PubMed2001

Beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence: 2-[4-(2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl)phenoxy]-2-methylpropionic acid.

In a search for novel analogues of beta(3)-adrenoceptor (AR) agonists relaxing the bladder for treatment of urinary dysfunction, 2-[4-(2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl)phenoxy]-2-methylpropionic acids (1a-e), into which a fibrate-like structure had been incorporated, were synthesised. Compound 1a was found to be a selective beta(3)-AR agonist in functional assays using the ferret detrusor (beta(3)-AR), rat uterus (beta(2)-AR), and rat atrium (beta(1)-AR); beta(3): EC(50)=7.8 nM, beta(2): IC(50)=7,300 nM, beta(1): EC(20)=23,000 nM. The introduction of a chlorine atom or methyl substituent at the ortho-position on the phenyl ring of 1a further improved beta(3)-AR selectivity. In an in vivo study, 1a lowered intrabladder pressure (ED(50)=31 microg/kg) in rats, without increasing heart rate, in keeping with the in vitro results. Consequently, it is proposed that 1a and its analogues (1b-e), possess beta(3)-AR agonistic activity in the absence of undesirable beta(1)- or beta(2)-AR mediated actions, and may be useful for clinical treatment and pharmacological studies.

Adrenergic beta-3 Receptor Agonists↗
PubMed2000

A multimicrospray nebulizer for microwave-induced plasma mass spectrometry

We have developed a nebulizer, called a multimicrospray nebulizer (MMSN), that efficiently introduces analytes for plasma mass spectrometry and plasma emission spectrometry. In this nebulizer, both the sample solution and the nebulizer gas are divided into several streams to produce a multispray. That is, the MMSN is a nebulizer that contains several micronebulization units, each unit including an orifice for passing the nebulizer gas and a capillary for introducing a sample solution. The microspray from each micronebulization unit can be operated at a microliter per minute sample uptake rate to achieve high nebulization efficiency. The multimicrospray nebulizer is capable of introducing more analyte to the plasma compared with a single-orifice micronebulizer, which has a very low sample uptake rate. In this work, an MMSN with three orifices was found to be suitable for microwave-induced plasma mass spectrometry (MIP-MS). The sample uptake rate can be varied within a range of 5-250 microL/min. Therefore, the nebulizer is unique in its ability to deal with various sample volumes and provide high nebulization efficiency. The sensitivity for all elements obtained with the MMSN was higher than that obtained with a conventional concentric nebulizer (CCN), which is difficult to achieve with other types of microintroduction nebulizers. For most elements, the MIP-MS sensitivity was improved about 2-fold at a sample uptake rate of 150 microL/min, a much lower rate than that for the CCN (usually 0.5-1.5 mL/min). The sensitivity for arsenic was improved by a factor of 5. The relative standard deviation was found to be less than 2.0%.

Journal Article↗
PubMed1999

Tc-99m DTPA used as reference imaging to evaluate the distribution of other tumor-seeking tracers in tumors associated with neurofibromatosis.

Two patients with multiple benign and malignant tumors associated with neurofibromatosis underwent radionuclide imaging with Tc-99m DTPA, Tl-201, and Ga-67. In these patients, Tc-99m DTPA accumulated intensively in both the benign and malignant tumors and localized and defined the extent of every tumor. In contrast, Ga-67 and Tl-201 uptake was seen only in focal areas of tumor where there was malignant transformation or at sites that showed progressive tumor growth. Tc-99m DTPA imaging accurately demonstrated areas of neoplastic involvement and identified the areas that would be seen with the other two tracers in individual tumors. Tc-99m DTPA may not always be used for the differential diagnosis of malignant and benign tumors of neurofibromatosis, but it can provide a reference pattern for imaging to evaluate accurately the distribution of Tl-201 and Ga-67 by mapping out the anatomic extent of these tumors.

Adolescent↗
PubMed1999

Repeated 131I treatment of a residual ovarian teratoma containing malignant thyroid tissue.

A 49-year-old woman with ovarian teratoma received 131I treatment three times for an unresectable mass containing malignant thyroid tissue after surgery. Repeated 131I treatment effectively reduced serum thyroglobulin (Tg) level and tumour uptake of 131I, despite absence of any change in size of the treated tumour. Treatment did not inhibit the increase of serum CA-125 and tumour 201Tl uptake, associated with progression of a radioresistant intratumoral hyper-perfused tissue component, detected by colour Doppler ultrasound. Serum CA-125 level and tumour 201Tl uptake were not significantly changed despite temporary increases in serum Tg level after each 131I treatment. These observations indicate the importance of diagnostic measures using combined functional imaging and tumour markers in managing this rare tumour.

Biomarkers, Tumor↗
PubMed1998

Abnormal brain perfusion demonstrated by Tc-99m MAA total-body scan in two children with complex congenital heart disease.

This paper describes abnormal brain perfusion unexpectedly demonstrated by Tc-99m MAA total-body imaging in two children with intracardiac right-to-left shunt (RLS) associated with complex congenital heart disease. One child was a 12-year-old girl with asplenia cardiac syndrome and multiple cerebral infarctions caused by thromboembolism in the internal carotid artery, and the other child was a 6-month-old boy who developed focal cerebral infarction following shunt operation. In both children, the total-body imaging depicted the brain due to RLS, where radioactivity decreased unilaterally in the cerebral hemisphere. In the first patient, radioactivity also decreased in the contralateral cerebellum, suggesting the crossed cerebellar diaschisis phenomenon. These abnormalities in brain perfusion were confirmed by Tc-99m HMPAO brain SPECT. Careful review of the distribution of the radiotracer in the depicted brain on Tc-99m MAA total-body imaging may provide important information regarding brain perfusion in some patients with a high risk of stroke complication associated with RLS.

Brain↗
PubMed1996

Role of neuropeptide Y and its receptor subtypes in neurogenic pulmonary edema.

The effect of neuropeptide Y on the number of perivascular carbon deposits, assessed as a measure of lung vascular permeability, was examined in isolated perfused lung preparations of rats. The number of carbon particle deposits after bronchial application of neuropeptide Y was increased in a dose-dependent manner. In the presence of a beta-adrenoceptor antagonist, norepinephrine augmented the effects of neuropeptide Y. Peptide YY, an analog of neuropeptide Y, demonstrated a much lower potency for increasing the number of carbon deposits, and neuropeptide Y-(18-36), which elicits a weak antagonist action on the neuropeptide Y Y3 receptor, significantly decreased the neuropeptide Y-induced increase. Furthermore, examination of the influence of neuropeptide Y-(18-36) pretreatment on fibrin-induced neurogenic pulmonary edema, in rats, revealed a reduction of the protein concentration ratio of tracheal fluid to serum. Therefore, we conclude that neuropeptide Y may elevate vascular permeability in the pulmonary circulation, conceivably through the neuropeptide Y Y3 receptor, and that neuropeptide Y may in fact play a physiological role even in the in-situ pulmonary circulation.

Animals↗
PubMed1996

Involvement of bacterial antigens in immunoglobulin A nephropathy.

To investigate the involvement of bacterial antigens in Immunoglobulin A (IgA) nephropathy, we measured IgA, IgG and IgM antibodies to gram-negative Escherichia coli (E.coli) and Haemophilus influenzae (H.influenzae) by ELISA in 24 patients (11 males and 13 females) with IgA nephropathy and 22 normal controls (11 males and 11 females). The titers of IgA and IgM antibodies for E.coli and H.influenzae were significantly higher in the IgA nephropathy group than in the controls. In addition, IgA and IgM antibody titers for E.coli and H.influenzae showed a significant positive correlation with serum IgA and IgM levels. These findings suggest that subclinical infection by these bacteria stimulates IgA production and that this may be a factor in the development and progression of IgA nephropathy.

Adolescent↗
PubMed1995

Sonic spray mass spectrometry.

We have developed a sonic spray ionization method, in which a methanol and water solution is sprayed from a fused-silica capillary with gas flow coaxial to the capillary. Ions as well as charged droplets are produced under atmospheric pressure, and their intensities depend on the gas flow rate (gas velocity). Positive ions produced from dilute solutions of molecules regarded as neurotransmitters, such as catecholamine, by this ionization method have been analyzed with a quadrupole mass spectrometer. The protonated dopamine molecule is detected in the spray of the 10 nM solution, and the mass spectrum is compared with that obtained by the ion spray ionization method. A comparison between the mass-analyzed ion intensity and the ion current, which represents the sum of ions and charged droplets, shows that most ions are produced from the charged droplets after spraying. Furthermore, we found that the charged droplet formation cannot be ascribed to the traditional models of friction electrification, electrical double layer, or statistical charging. An explanation is proposed based on the ion concentration distribution in a small droplet.

Catecholamines↗
PubMed1994

Effects of neuropeptide Y on lung vascular permeability in the pulmonary circulation of rats.

The effects of neuropeptides on the capillary filtration coefficient in the vessels of the pulmonary circulation were examined, using isolated lung perfusion preparations from rats. Neuropeptide Y and neurokinin A elevated the filtration coefficient, and calcitonin gene related peptide diminished it. Neurotensin and substance P did not affect the value at concentrations less than 10(-7) M. The number of extravasated carbon particle deposits subsequent to tracheal application of neuropeptide Y during spontaneous respiration increased in a dose-dependent manner. From these results, we conclude that neuropeptide Y may increase vascular permeability in the pulmonary circulation.

Animals↗
PubMed1994

An immunohistochemical study of extracellular matrix components and integrins in human glomerular diseases.

The localization of extracellular matrix components and their cell surface receptors (integrins) was studied in 130 subjects in order to clarify their participation in the progression and aggravation of various types of nephritis. Included in the study were 2 normal subjects, 14 patients with minimal change disease, 2 patients with minimal change nephrotic syndrome, 65 patients with IgA nephropathy, 18 patients with mesangial proliferative glomerulonephritis, 15 patients with membranous glomerulonephritis, 5 patients with membranoproliferative glomerulonephritis and 9 patients with systemic lupus erythematosus (SLE). The distribution of fibronectin (FN), vitronectin (VN), laminin (LN), heparan sulfate proteoglycan (HSPG), type III, IV, V, VI collagen, fibronectin receptor (FNR) and vitronectin receptor (VNR) in the glomerulus was studied employing the indirect immunoperoxidase method. FN, LN, type IV, V and VI collagen, FNR and VNR were found to be distributed in the expanded mesangial region in IgA nephropathy, mesangial proliferative glomerulonephritis and membranoproliferative glomerulonephritis. Deposition of VN was observed in some of the patients. In membranous glomerulonephritis and membranoproliferative glomerulonephritis, the distribution of FN, LN, type IV collagen, FNR and VNR was increased in the thickened loop wall and VN deposition was also observed. Quantitative and functional changes in the extracellular matrix and integrins, therefore, appear to participate in the progression and aggravation of glomerulonephritis.

Adolescent↗
PubMed1990

Serum soluble interleukin-2 receptor in patients with glomerulonephritis.

Serum soluble interleukin-2 receptor (IL-2R) concentrations were determined using the ELISA method in 55 cases of glomerulonephritis. These patients can be classified as 29 cases of IgA nephropathy, 10 cases of membranous glomerulonephritis and 16 cases of mesangial proliferative glomerulonephritis. Our results showed that serum soluble IL-2R concentrations in glomerulonephritis cases were significantly higher than those in healthy controls. Among the different types of glomerulonephritis cases, however, no significant differences in serum soluble IL-2R were observed. While we found a significant positive correlation of serum soluble IL-2R to BUN and creatinine, we also found a significant negative correlation between serum soluble IL-2R and creatinine clearance. These findings suggest that serum soluble IL-2R can serve as an indicator of exacerbation of glomerulonephritis.

Adult↗