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Biomedical subjects

Akira Yamazaki

Publications and source records attributed to Akira Yamazaki.

12 recordsLinked to original sources

A versatile method of identifying specific binding proteins on affinity resins.

The isolation of both specific and nonspecific binding proteins on affinity matrices bearing bioactive compounds hinders the identification of drug cellular targets. Although solid-phase elution and competition methods conventionally are used to distinguish between specific and nonspecific receptor-ligand interactions, these approaches often are severely restricted by low ligand solubility and/or slow kinetic dissociation. This article describes an alternative and versatile method, termed serial affinity chromatography, to identify ligand receptors using affinity resins.

Affinity Labels↗

[A case of gastric cancer with DIC caused by multiple bone metastases treated with TS-1].

A 71-year-old woman was admitted for anorexia. Endoscopic findings revealed type 3 gastric cancer. Histological examination of the endoscopic biopsy revealed poorly-differentiated adenocarcinoma. We performed total gastrectomy. However, 18 days after surgery, DIC due to multiple bone metastases occurred. The patient was treated with TS-1 chemotherapy in addition to anti-DIC therapy. TS-1(100 mg/day) was administered on days 1 to 5, 8 to 12, and 15 to 19 . The DIC was resolved. She was discharged after 2 courses of this regimen. This chemotherapy can be applied for the management of DIC caused by multiple bone metastases.

Adenocarcinoma↗

Cobalt-filled apoferritin for suspended single-walled carbon nanotube growth with narrow diameter distribution.

Cobalt-filled apoferritin (Co-ferritin) was, for the first time, used as a wet catalyst for the synthesis of single-walled carbon nanotubes (SWNTs) with narrow diameter distribution. Co-ferritins were spin-coated and converted to cobalt nanoparticles by calcination. Using chemical vapor deposition, suspended networks of SWNTs were formed on pillar-structured substrates. The suspended SWNTs show narrow tube diameter distribution with a relatively good graphite structure. By virtue of the low diffusion coefficient of cobalt, Co-ferritin might be more useful for narrow diameter SWNTs growth than ferritins, which encase iron particles.

Animals↗

Factors affecting short-term mortality in very low birth weight infants in Japan.

No epidemiological surveys have examined risk factors related to the death of very low birth weight infants (VLBWIs) in Japan. The objectives of this study were to examine the death rate and fatalities related to complications among VLBWIs, and to analyze factors possibly determining the death of VLBWIs. The subjects of this study were 811 VLBWIs admitted to the Neonatal Care Center of Niigata City General Hospital between April 1987 and March 2003. We obtained information on gender, birth weight, gestational age, Apgar scores, single/multiple pregnancy, postnatal transfer, mode of delivery, complications and outcome (alive or deceased) at the time of discharge from medical records. Of the 811 infants, 98 died prior to discharge (12.1%). Logistic regression analysis showed that independent risk factors for death of VLBWIs were male gender (relative risk [RR]: 2.0), low birth weight (RR: 0.56), necrotizing enterocolitis (RR: 58.0), pulmonary hypoplasia (RR: 37.8), chromosomal abnormalities (RR: 36.3), congenital heart diseases (RR: 9.8), persistent fetal circulation (RR: 9.6), neonatal asphyxia (RR: 6.3) and sepsis (RR: 4.4). The risk for death rises 1.8-fold if birth weight decreases by 100 g. A very high risk of perinatal death is associated with necrotizing enterocolitis, pulmonary hypoplasia or chromosomal abnormalities. The risk of death due to congenital heart diseases or neonatal asphyxia is relatively lower, but the incidences of these two disorders are high (8% and 6%, respectively). From the viewpoint of prophylactic treatment aimed at reducing the death rate of VLBWIs, measures to increase birth weight are of primary importance. Furthermore, early treatment and improved perinatal management of congenital heart diseases and neonatal asphyxia are anticipated to reduce the overall death rate of VLBWIs.

Apgar Score↗

Host stromal bradykinin B2 receptor signaling facilitates tumor-associated angiogenesis and tumor growth.

We evaluated the significance of the host kallikrein-kinin system in tumor angiogenesis and tumor growth using two rodent models genetically deficient in a kallikrein-kinin system. Inoculation of Walker 256 carcinoma cells into the s.c. tissues of the back of normal Brown Norway Kitasato rats (BN-Ki rats) resulted in the rapid development of solid tumors with marked angiogenesis. By contrast, in kininogen-deficient Brown Norway Katholiek rats (BN-Ka rats), which cannot generate intrinsic bradykinin (BK), the weights of the tumors and the extent of angiogenesis were significantly less than those in BN-Ki rats. Daily administration of B(2) receptor antagonists significantly reduced angiogenesis and tumor weights in BN-Ki rats to levels similar to those in BN-Ka rats but did not do so in BN-Ka rats. Angiogenesis and tumor growth were significantly suppressed in B(2) receptor knockout mice bearing sarcoma 180 compared with their wild-type counterparts. Immunoreactive vascular endothelial growth factor (VEGF) was localized in Walker tumor stroma more extensively in BN-Ki rats than in BN-Ka rats, although immunoreactive B(2) receptor also was detected in the stroma to the same extent in both types of rats. Cultured stromal fibroblasts isolated from BN-Ki rats and BN-Ka rats produced VEGF in response to BK (10(-8)-10(-6) m), and this stimulatory effect of BK was abolished with a B(2) receptor antagonist, Hoe140 (10(-5) m). These results suggest that BK generated from kininogens supplied from the host may facilitate tumor-associated angiogenesis and tumor growth by stimulating stromal B(2) signaling to up-regulate VEGF production mainly in fibroblasts.

Animals↗

Design and synthesis of novel hydrophilic spacers for the reduction of nonspecific binding proteins on affinity resins.

Tubulin and actin often bind nonspecifically to affinity chromatography resins, complicating research toward identifying the cellular targets. Reduction of nonspecific binding proteins is important for success in finding such targets. We herein disclose the design, synthesis, and effectiveness in reduction of nonspecific binding proteins, of novel hydrophilic spacers (2-5), which were introduced between matrices and a ligand. Among them, tartaric acid derivative (5) exhibited the most effective reduction of nonspecific binding proteins, whilst maintaining binding of the target protein. Introduction of 5 on TOYOPEARL reduced tubulin and actin by almost 65% and 90% compared to that without the hydrophilic spacer, respectively, with effective binding to the target protein, FKBP12.

Actins↗

Preparation of enantiopure norbornane ligands bearing both (2S,3S)-bis(phosphinomethyl) and 7-syn-oxygen functional groups and an application to rhodium-catalyzed asymmetric hydrogenation.

Enantiopure bicyclo[2.2.1]heptane derivatives having both (2S,3S)-bis[(diphenylphosphino)methyl] and 7-syn-oxygen functional groups were synthesized by using diastereoselective Diels-Alder reaction of di-(1R)-menthyl fumarate and 5-trimethylsilylcyclopentadiene followed by silver-promoted stereospecific frame rearrangement of a bromolactone intermediate. Rhodium-catalyzed asymmetric hydrogenations were carried out using the diphosphines as a chiral ligand.

Catalysis↗

Amlodipine improves vascular function in patients with moderate to severe hypertension.

The long-term effects of amlodipine, a calcium channel blocker, were examined in patients with moderate to severe hypertension. Eighteen never-treated patients with moderate to severe essential hypertension (49 +/- 8 years) were studied. In all patients, forearm blood flow (FBF) was measured by plethysmography before and 6 months after amlodipine treatment. Endothelium-nondependent and endothelium-dependent vasodilations were assessed by intrabrachial infusion of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively. FBF modification by vitamin C, an oxygen radical scavenger, was also assessed under ACh infusion. The results were compared with those of 13 normal subjects. Blood pressure was significantly lowered (from 176 +/- 17/97 +/- 13 to 144 +/- 12/82 +/- 10 mm Hg) after treatment (P < 0.01). Forearm vascular resistance was increased in the hypertensive patients before treatment; however, it was normalized after treatment during SNP infusion and was improved during ACh infusion. Since vitamin C improved FBF under ACh infusion both before and after the amlodipine treatment, it is suggested that the production of free radicals was not canceled by amlodipine. The analysis of heart rate variability showed that amlodipine does not activate sympathetic nerve function. Therefore, amlodipine is effective in lowering blood pressure associated with the improvement of vascular function, and is suggested to be an effective antihypertensive agent for patients with moderate to severe hypertension.

Acetylcholine↗

Pneumothorax and transient pseudohypoaldosteronism in an infant with hydronephrosis.

Pneumothorax and transient pseudohypoaldosteronism have been noted as complications of obstructive uropathy in infancy. However, they are rare complications, and there have been no reports of a patient with both pneumothorax and pseudohypoaldosteronism in obstructive uropathy. Here we describe a case of pneumothorax and transient pseudohypoaldosteronism in an infant with bilateral hydronephrosis due to ureteropelvic junction obstruction. Nephrostomy improved the patient's condition and laboratory findings rapidly. While the exact pathogenic mechanism of pneumothorax in patients with obstructive uropathy is unclear, some biochemical defects due to obstructive uropathy might impair fetal lung maturation, which results in pneumothorax.

Female↗

Image fusion between 18FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas.

PURPOSE: Accurate diagnosis of tumor extent is important in three-dimensional conformal radiotherapy. This study reports the use of image fusion between (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) and magnetic resonance imaging/computed tomography (MRI/CT) for better targets delineation in radiotherapy planning of head-and-neck cancers. METHODS AND MATERIALS: The subjects consisted of 12 patients with oropharyngeal carcinoma and 9 patients with nasopharyngeal carcinoma (NPC) who were treated with radical radiotherapy between July 1999 and February 2001. Image fusion between 18FDG-PET and MRI/CT was performed using an automatic multimodality image registration algorithm, which used the brain as an internal reference for registration. Gross tumor volume (GTV) was determined based on clinical examination and 18FDG uptake on the fusion images. Clinical target volume (CTV) was determined following the usual pattern of lymph node spread for each disease entity along with the clinical presentation of each patient. RESULTS: Except for 3 cases with superficial tumors, all the other primary tumors were detected by 18FDG-PET. The GTV volumes for primary tumors were not changed by image fusion in 19 cases (89%), increased by 49% in one NPC, and decreased by 45% in another NPC. Normal tissue sparing was more easily performed based on clearer GTV and CTV determination on the fusion images. In particular, parotid sparing became possible in 15 patients (71%) whose upper neck areas near the parotid glands were tumor-free by 18FDG-PET. Within a mean follow-up period of 18 months, no recurrence occurred in the areas defined as CTV, which was treated prophylactically, except for 1 patient who experienced nodal recurrence in the CTV and simultaneous primary site recurrence. CONCLUSION: This preliminary study showed that image fusion between 18FDG-PET and MRI/CT was useful in GTV and CTV determination in conformal RT, thus sparing normal tissues.

Adult↗

Continuous intravenous administration of a low dose of epoprostenol greatly decreased serum concentrations of endothelin-1 in primary pulmonary hypertension--a case report.

Endothelin-1 (ET-1) is known to be a principal factor in the pathogenesis of primary pulmonary hypertension (PPH). Recently intravenous administration of epoprosterol improved the survival rate in PPH. However, the effect of epoprosterol on ET-1 remains to be investigated. Therefore, we studied a patient with PPH who was treated with a low dose of epoprosterol and examined the serum concentration of ET-1 during the treatment. Epoprosterol greatly decreased the serum concentration of ET-1 in parallel with improvement of the clinical course, suggesting that ET-1 level may be a marker for treatment of PPH.

Adult↗