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Biomedical subjects

T Sakuma

Publications and source records attributed to T Sakuma.

At least 37 records · Page 2Linked to original sources

Quantification of myocardial perfusion and determination of coronary stenosis severity during hyperemia using real-time myocardial contrast echocardiography.

Although regional myocardial perfusion can be currently quantified with myocardial contrast echocardiography (MCE) by using intermittent harmonic imaging (IHI), the method is tedious and time-consuming in the clinical setting. We hypothesized that regional myocardial perfusion can be quantified and the severity of coronary stenosis determined during hyperemia with MCE using real-time imaging (RTI) where microbubbles are not destroyed. Six open-chest dogs were studied during maximal hyperemia induced by adenosine in the absence or presence of coronary stenoses varying from mild to severe. Myocardial blood flow (MBF) was measured at each stage by using radiolabeled microspheres. MCE was performed using both IHI and RTI. Data for the latter were acquired in both end-systole and end-diastole. No differences were found between myocardial flow velocity (MFV) derived from IHI and RTI when end-systolic frames were used for the latter. MFV was consistently higher for RTI (P <.01) when end-diastolic frames were used. A linear relation was noted between MFV and radiolabeled microsphere-derived MBF ratios from the stenosed and the normal beds when end-systolic frames were used for RTI (r = 0.78, P <.001), whereas no relation was found when end-diastolic frames were used (r = 0.08, P =.78). The scatter for assessing MBF (A.beta) was minimal for IHI and RTI (9%-10%) with end-systolic frames, whereas that for RTI with end-diastolic frames was large (30%). Furthermore the correlation with radiolabeled microsphere-derived MBF was significantly (P <.01) weaker with RTI when end-diastolic frames were used (r = 0.53) than when end-systolic frames (r = 0.94) or IHI was used (r = 0.99). Data acquisition for IHI was 10 minutes, whereas it was 8 seconds for RTI. Thus, RTI can be used to quantify regional myocardial perfusion and stenosis severity during MCE. Only end-systolic frames, however, provide accurate data. RTI offers a rapid and easy means of assessing regional myocardial perfusion with MCE.

Animals↗

Different expression of hepatic and renal cytochrome P450s between the streptozotocin-induced diabetic mouse and rat.

1. Since limited information is available about alterations of cytochrome P450 levels in diabetic animals other than rat, expression of P450s in the liver and kidney of the streptozotocin (STZ)-induced diabetic mouse was investigated. 2. The mRNA levels of CYP2B10, 3A11, 4A10 and 4A14 in the liver were increased in the STZ-induced diabetic mouse of both sexes. The CYP2B9 mRNA level was increased in the liver of the male diabetic mouse. These alterations were observed even at 2 weeks after administration. Insulin treatment restored these changes. The findings were consistent with changes reported in rat. 3. The levels of hepatic CYP1A2 and 2E1 and renal 2E1 and 4A did not change in the diabetic mouse at any time-point examined. No changes were seen in CYP2A- or 2C-related proteins in the diabetic mouse. These findings were in contrast to those in rat. 4. The results indicate that mouse P450s respond to insulin-dependent diabetes mellitus differently from those of the rat, and suggest that the expression of P450s in diabetes is not generally the same across animal species.

Animals↗

Structure of [110] tilt grain boundaries in zirconia bicrystals.

Cubic stabilized zirconia bicrystals with [110] symmetric tilt grain boundaries were fabricated by diffusion bonding of two single crystals with the composition of ZrO2-9.6mol%Y2O3. The structures of symmetric tilt small angle grain boundary and two types of symmetric tilt sigma3 grain boundaries with different grain boundary planes were observed by transmission electron microscopy (TEM). High-resolution transmission electron microscopy (HREM) observations clarified that the [110] small angle tilt grain boundary consists of periodic array of b = a/2[110] type edge dislocations. This result is consistent with Frank's dislocation model for small angle grain boundary. HREM observation also revealed that the 70.5 degrees sigma3 grain boundary shows atomically coherent grain boundary structure with the boundary plane of [111], while the 109.5 degrees sigma3 grain boundary accompanies grain boundary facets taking [111]/[115] asymmetric grain boundary plane. Because of the very low surface energy of [111] plane and/or high lattice matching of [111] and [115] type planes, the grain boundary faceting may be preferred in spite of increasing grain boundary area to about 6%. TEM-energy-dispersive X-ray spectroscopy (EDS) analyses were performed on both sigma3 grain boundaries, and the segregation of yttrium ions to the boundaries was detected in both cases. The amount of segregation is about the same in both sigma3 boundaries. It can be concluded that the segregation of yttrium ions to sigma3 grain boundary exists in cubic zirconia.

Journal Article↗

Denopamine, a beta(1)-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs.

The effect of denopamine, a selective beta(1)-adrenergic agonist, on alveolar fluid clearance was determined in both ex vivo rat and guinea pig lungs. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue-labeled albumin over 1 h at 37 degrees C. Denopamine (10(-6) to 10(-3) M) increased alveolar fluid clearance in a dose-dependent manner in ex vivo rat lungs. Denopamine also stimulated alveolar fluid clearance in guinea pig lungs. Atenolol, a selective beta(1)-adrenergic antagonist, and amiloride, a sodium channel inhibitor, inhibited denopamine-stimulated alveolar fluid clearance. The potency of denopamine was similar to that of similar doses of isoproterenol or terbutaline. Short-term hypoxia (100% nitrogen for 1-2 h) did not alter the stimulatory effect of denopamine. Denopamine (10(-4), 10(-3) M) increased intracellular adenosine 3',5'-cyclic monophosphate levels in cultured rat alveolar type II cells. In summary, denopamine, a selective beta(1)-adrenergic agonist, stimulates alveolar fluid clearance in both ex vivo rat and guinea pig lungs.

Acute Disease↗

Effects of hypoxia on alveolar fluid transport capacity in rat lungs.

There is little information regarding the effect of hypoxia on alveolar fluid clearance capacity. We measured alveolar fluid clearance, lung water volume, plasma catecholamine concentrations, and serum osmolality in rats exposed to 10% oxygen for up to 120 h and explored the mechanisms responsible for the increase in alveolar fluid clearance. The principal results were 1) alveolar fluid clearance did not change for 48 h and then increased between 72 and 120 h of exposure to hypoxia; 2) although nutritional impairment during hypoxia decreased basal alveolar fluid clearance, endogenous norepinephrine increased net alveolar fluid clearance; 3) the changes of lung water volume and serum osmolality were not associated with those of alveolar fluid clearance; 4) an administration of beta-adrenergic agonists further increased alveolar fluid clearance; and 5) alveolar fluid clearance returned to normal within 24 h of reoxygenation after hypoxia. In conclusion, alveolar epithelial fluid transport capacity increases in rats exposed to hypoxia. It is likely that a combination of endogenous norepinephrine and nutritional impairment regulates alveolar fluid clearance under hypoxic conditions.

Adrenergic alpha-Antagonists↗

Reduction of acetals with samarium diiodide in acetonitrile in the presence of Lewis acids.

Transformation of acetals into ethers by partial reduction using a samarium diiodide-Lewis acids-acetonitrile system is described. The reaction with aromatic acetals occurred in good yields in the presence of aluminum chloride (2 eq) whereas the corresponding aliphatic, vinylic, and alkynyl derivatives did not afford ethers under the same conditions. Beta-elimination to give an enol ether becomes predominant when aliphatic acetals that possess a hydrogen at the 2-position are treated with iodotrimethylsilane in the presence of SmI2 or SmI3.

Acetals↗

Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in hyperoxic rat lungs.

Because it was still uncertain whether a stimulation of beta1-adrenoceptors accelerated alveolar fluid clearance in hyperoxic lung injury, the effect of denopamine, a selective beta1-adrenergic agonist, on alveolar fluid clearance was determined in rats exposed to 93% oxygen for 48 and 56 h. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue labeled albumin instilled into the alveolar spaces over 1 h at 37 degrees C in isolated rat lungs. The principle results were as follows: 1) Although lung water volume increased in rats exposed to hyperoxia for 48 and 56 h, basal alveolar fluid clearance did not change for up to 56 h; 2) Denopamine increased alveolar fluid clearance in rats exposed to hyperoxia as well as in rats without exposure to hyperoxia; 3) Denopamine primarily increased amiloride-insensitive alveolar fluid clearance in rats exposed to hyperoxia; 4) The potency of denopmaine was similar to that of terbutaline, a selective beta2-adrenergic agonist. In summary, denopamine is a potent stimulator of alveolar fluid clearance in rats exposed to hyperoxia.

Adrenergic beta-1 Receptor Agonists↗

[A case report of granulomatous orchitis--review of 20 cases in Japan].

We report a case of granulomatous orchitis. A 31-year-old male complained of right lumbago and scrotal pain. The ultrasonographic finding was multiple hypo-echoic areas in the right testis as highly suggestive of testicular cancer. The diagnosis was made after orchiectomy. Granuromatous orchitis is a rare disease which true etiology remains obscure. Only 20 cases have been reported in Japan. The clinical, radiological and pathological features of 20 cases are presented and discussed. Patients' age ranged from 29 to 79 years, an average of 55 years. The left testis was involved in 7 patients, the right in 9 and 4 cases were bilateral. Ultrasonographic examination of the affected testis revealed hypoechoic mass, so little value in differentiating granulomatous orchitis from neoplasm. The correct diagnosis of granulomatous orchitis has never been made prior to surgery, because it clinically bears a lot of resemblance to testicular cancer. The diagnosis usually is made on histological examination. Orchiectomy is the main form of treatment to date, because antibiotics have little effect on the course of the disease and at the time of diagnosis, the testis is already destroyed and there is hardly any viable testicular tissue in the removed specimens.

Adult↗

[Amiodarone-induced keratopathy].

BACKGROUND: We studied 17 patients who received oral administration of amiodarone. CASES: The patients were 13 males and 4 females with the mean age of 65.7 years. The periods of follow-up observation ranged from 120 to 1,085 days. Keratopathy was found in 7 cases(41.2%), during the follow-up period. The grade of keratopathy showed no fixed tendency in age, total drug dose, or duration of administration, nor was there any correlation between the grade on the one hand and the period from inception of amiodarone administration to the development of keratopathy and total drug dose on the other. The effects of amiodarone on the cornea, conjunctival epithelium, anterior subcapsular lens, and tear fluid were studied histologically in 2 cases. Effects of amiodarone were found in the cornea and anterior subcapsular lens, but not in the conjunctival epithelium and tear fluid. CONCLUSION: It is possible that keratopathy may be an indicator for long-term administration and for predicting the development of other complications of amiodarone.

Aged↗

Comparison of [(18)F]FDG PET and (201)Tl SPECT in evaluation of pulmonary nodules.

UNLABELLED: Recent reports have indicated the value of [(18)F]FDG PET and (201)Tl SPECT in diagnosing lung cancer. In this study, we compared the diagnostic value of FDG PET and (201)Tl SPECT in the evaluation of pulmonary nodules. METHODS: Sixty-three patients with 66 pulmonary nodules suspected to be lung cancer on the basis of chest CT were examined by FDG PET and (201)Tl SPECT (early and delayed scans) within a week of each study. For semiquantitative analysis, the standardized uptake value (SUV) or the tumor-to-nontumor activity ratio (T/N) (or both) was calculated. All of these lesions were completely removed thoracoscopically or by thoracotomy and were examined histologically. RESULTS: Fifty-four nodules were histologically confirmed to be malignant tumors, and 12 were benign. Both techniques delineated focal lesions with an increase in tracer accumulation in 41 of 54 lung cancers. (201)Tl SPECT on early or delayed scans (or both) identified 4 additional lung cancers that FDG PET images did not reveal: 3 bronchioloalveolar carcinomas and a well-differentiated adenocarcinoma. FDG PET identified 3 additional lung cancers that (201)Tl SPECT images did not reveal; 2 of these lung cancers were <2 cm in diameter. The mean FDG SUV and T/N of bronchioloalveolar carcinomas (2.06 +/- 0.76 and 3.49 +/- 1.03, respectively) were significantly lower than those of poorly differentiated adenocarcinomas (5.55 +/- 2.01 [P = 0.026] and 8.23 +/- 2.16 [P = 0.01], respectively). However, no significant difference was found in (201)Tl T/N on early and delayed scans between bronchioloalveolar carcinomas (1.64 +/- 0.29 and 1.87 +/- 0.42, respectively) and poorly differentiated adenocarcinomas (1.58 +/- 0.32 and 2.76 +/- 1.36, respectively). Of the 12 benign nodules, FDG PET and (201)Tl SPECT showed false-positive results for the same 7 benign nodules (58.3%) (4 granulomas, 1 sarcoidosis, 1 inflammatory pseudotumor, and 1 aspergilloma). Negative FDG PET findings and positive (201)Tl SPECT findings were obtained only for bronchioloalveolar carcinomas or a well-differentiated adenocarcinoma but not for other histologic types of lung cancers or benign pulmonary nodules. CONCLUSION: No significant difference was found between FDG PET and (201)Tl SPECT in specificity for the differentiation of malignant and benign pulmonary nodules. The degree of differentiation of lung adenocarcinoma correlated with FDG uptake but not with (201)Tl uptake. Bronchioloalveolar carcinoma (a well-differentiated, slow-growing tumor) findings typically were positive with (201)Tl but were negative with FDG. The combination of FDG PET and (201)Tl SPECT may provide additional information regarding the tissue characterization of pulmonary nodules.

Adenocarcinoma↗

Discriminating activation of CYP2B9 expression in male C57BL/6 mouse liver by beta-estradiol.

The inducible expression of the cytochrome P450 2B subfamily was investigated in male C57BL/6 (B6) and DBA/2 (D2) mice, as well as their hybrids, B6D2F1, at the mRNA level. The expression of hepatic CYP2B mRNAs in B6 was lightly induced by beta-estradiol (ES), while that by phenobarbital (PB) or 1,1,1-trichloro-2, 2-bis(p-chlorophenyl) ethane (DDT) was prominent. Discriminating analysis showed a novelty that ES markedly induced CYP2B9 mRNA expression, whereas PB and DDT increased CYP2B10 more than CYP2B9 expression: albeit both mRNA species responded to all three inducers. Furthermore, the specific induction by ES of CYP2B9 mRNA in B6 male mice, but not D2 male mice, suggests strain dependency in the regulatory pathway of CYP2B9 expression.

Animals↗

Lung deflation impairs alveolar epithelial fluid transport in ischemic rabbit and rat lungs.

BACKGROUND: Because the fluid transport capacity of the alveolar epithelium after lung ischemia with and without lung deflation has not been well studied, we carried out experimental studies to determine the effect of lung deflation on alveolar fluid clearance. METHODS: After 1 or 2 hr of ischemia, we measured alveolar fluid clearance using 125I-albumin and Evans blue-labeled albumin concentrations in in vivo rabbit lungs in the presence of pulmonary blood flow and in ex vivo rat lungs in the absence of any pulmonary perfusion, respectively. RESULTS: The principal results were: (1) lung deflation decreased alveolar fluid clearance while inflation of the lungs during ischemia preserved alveolar fluid clearance in both in vivo and ex vivo studies; (2) alveolar fluid clearance was normal in the rat lungs inflated with nitrogen (thus, alveolar gas composition did not affect alveolar fluid clearance); (3) amiloride-dependent alveolar fluid clearance was preserved when the lungs were inflated during ischemia; (4) terbutaline-simulated alveolar fluid clearance was preserved in the hypoxic rat lungs inflated with nitrogen; (5) lecithinized superoxide dismutase, a scavenger of superoxide anion, and N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide, preserved normal alveolar fluid clearance in the deflated rat lungs. CONCLUSION: Lung deflation decreases alveolar fluid clearance by superoxide anion- and nitric oxide-dependent mechanisms.

Amiloride↗

A novel female-specific member of the CYP3A gene subfamily in the mouse liver.

Expression of a female-specific CYP3A in the adult mouse liver was observed on immunoblotting analysis. To characterize this cytochrome P450, we determined the primary structure of its cDNA and examined its expression profile. This cytochrome P450 consisted of 504 amino acids and showed 92, 68, 88, and 69% amino acid sequence identity with mouse CYP3A11, 3A13, 3A16, and 3A25, respectively, and was designated as CYP3A41, a new mouse CYP3A gene. In the female liver, levels of CYP3A41 mRNA expression were comparable to those of CYP3A11, the major CYP3A enzyme in the adult mouse liver. Expression of CYP3A41 mRNA was detected immediately after birth in the livers of animals of both sexes, but increased with age in females, whereas it was gradually reduced in males, resulting in predominantly female-specific expression in livers. Lesser amounts of CYP3A41 mRNA were detected in the kidneys of female mice, with traces in the stomach, ovary, and heart of female mice and in the testis of male mice. Gonadectomy and sex hormone treatment indicated that estradiol and testosterone were able to induce and suppress the expression of CYP3A41 mRNA in the liver, respectively. Among the classical CYP3A inducers, dexamethasone, rifampicin, and 3-methylcholanthrene did not affect the level of CYP3A41 mRNA in the liver of either sex. On the other hand, pregnenolone 16alpha-carbonitrile and phenobarbital suppressed CYP3A41 level to half that of untreated female mice. These observations indicated that CYP3A41 is a female-specific CYP3A and one of the major CYP3A forms in the female mouse liver.

Amino Acid Sequence↗

Alveolar epithelial barrier. Role in lung fluid balance in clinical lung injury.

Several studies have established that transport of sodium from the air spaces to the lung interstitium is a primary mechanism driving alveolar fluid clearance, although further work is needed to determine the role of chloride in vectorial fluid transport across the alveolar epithelium. Although there are significant differences among species in the basal rates of sodium and fluid transport, the basic mechanism seems to depend on sodium uptake by channels on the apical membrane of alveolar type II cells, followed by extrusion of sodium on the basolateral surface by Na,K-ATPase. This process can be upregulated by several catecholamine-dependent and independent mechanisms. The identification of water channels expressed in lung, together with the high water permeabilities, suggest a potential role for channel-mediated water movement between the air space and capillary compartments, although definitive evidence will depend on the results of transgenic mouse knock-out studies. The application of this new knowledge regarding salt and water transport in alveolar epithelium in relation to pathologic conditions has been successful in clinically relevant experimental studies, as well as in a few clinical studies. The studies of exogenous and endogenous catecholamine regulation of alveolar fluid clearance are a good example of how new insights into the basic mechanisms of alveolar sodium and fluid transport can be translated to clinically relevant experimental studies. Exogenous catecholamines can increase the rate of alveolar fluid clearance in several species, including the human lung, and it is also apparent that release of endogenous catecholamines can upregulate alveolar fluid clearance in animals with septic or hypovolemic shock. It is possible that therapy with beta-adrenergic agonists might be useful to accelerate the resolution of alveolar edema in some patients. In some patients, the extent of injury to the alveolar epithelial barrier may be too severe for beta-adrenergic agonists to enhance the resolution of alveolar edema, although some experimental studies indicate that alveolar fluid clearance can be augmented in the presence of moderately severe lung injury. A longer-term upregulation of alveolar epithelial fluid transport might be achieved by strategies that accelerate the proliferation of alveolar type II cells repopulating the injured epithelium in clinical lung injury. More clinical research is needed to evaluate the strategies that can upregulate alveolar epithelial fluid transport with both short-term therapy (i.e., beta-agonists) and more sustained, longer-term effects of epithelial mitogens such as keratinocyte growth factor. These approaches may be useful in reducing mortality in the acute respiratory distress syndrome.

Animals↗

Metabolism of 26,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 and 26,27-hexafluoro-1 alpha,23(S)25-trihydroxyvitamin D3 in ROS17/2.8 cells transfected with a plasmid expressing CYP24.

1. To clarify the possibility that the metabolism of 26,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 [F6-1,25(OH)2D3] to 26,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3 [F6-1,23,25(OH)3D3 and that of F6-1,23,25(OH)3D3 to 26,27-hexafluoro-23-oxo-1 alpha,25-dihydroxyvitamin D3 [F6-23-oxo-1,25(OH)2D3] are catalysed by 25-hydroxyvitamin D3 24-hydroxylase (CYP24), ROS17/2.8 cells transfected with a plasmid expressing CYP24 [pSVL-CYP24(+)] and a corresponding blank plasmid [pSLV-CYP24R(-)] were used. 2. Incubation of [1 beta-3H]-F6-1,25(OH)2D3 for 2 and 5 days with ROS17/2.8 cells transfected with pSVL-CYP24(+) generated a metabolite that co-migrated with authentic F6-1,23,25(OH)3D3 in both normal phase and reversed-phase HPLC systems. 3. Incubation of [1 beta-3H]-F6-1,23,25(OH)3D3 for 5 days with pSVL-CYP24(+)- transfected ROS 17/2.8 cells generated a metabolite that co-migrated with authentic F6-23-oxo-1,25(OH)2D3. In contrast, the metabolites F6-1,23,25(OH)3D3 or F6-23-oxo-1,25(OH)2D3 were not generated in the cells transfected with pSVL-CYP24R(-). 4. The results indicate that CYP24 catalyses the conversion of F6-1,25(OH)2D3 to F6-1,23,25(OH)3D3 and that of F6-1,23,25(OH)3D3 to F6-23-oxo-1,25(OH)2D3.

Animals↗

Thyroid hormone regulation of apoptosis induced by retinoic acid in promyeloleukemic HL-60 cells: studies with retinoic acid receptor-specific and retinoid x receptor-specific ligands.

3,5,3'-Triiodo-L-thyronine (T3) potentiates apoptosis during the all-trans-retinoic acid-induced differentiation of promyeloleukemic HL-60 cells. We examined whether the retinoid receptor-specific thyroid hormone action is present during differentiation of HL-60 cells in this study. We used two distinct retinoid receptor agonists. T3 potentiates G1 arrest induced by Am80, a retinoic acid receptor (RAR)-specific agonist, but had no effect on G1 arrest induced by HX600, a retinoid x receptor (RXR)-specific agonist. Am80 alone induces the apoptosis, and T3 enhances it. Although HX600 alone fails to increase the apoptotic fraction, T3 enables the compounds to induce apoptosis. Am80-induced expression of CD11b, a marker for the differentiation, is enhanced by T3. However, T3 or HX600 or both do not affect the expression of CD11b. T3 does not alter the amount of mRNAs of various members of the bcl-2 family. T3, however, enhances the Am80-induced expression of bfl-1 and suppression of bcl-2. In contrast, T3 does not alter either bfl-1 and bcl-2 expression in the presence of HX600. Our observations suggest that cooperative action of T3 with an RXR-specific ligand is different from that with an RAR ligand in cellular apoptotic regulation and that thyroid hormone may be available as a chemotherapeutic agent in acute leukemia.

Apoptosis↗

Connection designs of three different implant systems in the resorbed edentulous maxilla: a case report.

This report presents the mixed use of three different system implants for an implant-supported fixed bridge in a resorbed maxilla. Two of six implants that had been placed were lost. New implants were combined with the remaining implants that had been placed by the previous dentists in 1992 and 1997. The three implant systems consisted of the following: one incorporated an intramobile element into an implant device, and the other two were whole titanium screw-type implants (one with a machined surface and the other with a plasma-sprayed surface). This clinical report describes the connection designs of these different system implants to the fixed bridge and lists the complications that followed.

Bone Resorption↗