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Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 253 records · Page 14Linked to original sources

Effects of fluid resuscitation with recombinant human serum albumin solution on maintaining hepatic energy metabolism in hemorrhagic shock rabbits.

The objective of this study was to examine the effects of volume replacement with recombinant human serum albumin (rHSA), which was developed to reduce the consumption of human blood derivatives, on maintaining hepatic energy metabolism. Hemorrhagic shock with a mean blood pressure of 50 mmHg was induced within 20 min and maintained for 60 min by Wiggars' method in rabbits. Fluid resuscitation replacing two thirds of the blood withdrawn with plasma-derived 5% human serum albumin (pHSA; n = 7) or rHSA (n = 10), or replacing double the volume of blood withdrawn with lactated Ringer's solution (n = 7) was completed within 20 min, and observed for 120 min. No significant differences were observed in the blood pressures, blood gas analyses, blood counts, biochemical parameters (e.g., alanine aminotransferase, lactate dehydrogenase, creatine kinase, blood urea nitrogen, creatinine) or blood glucose levels among the three groups. There were also no significant differences in the parameters of hepatic energy metabolism such as blood pyruvate and lactate levels and their ratios, ketone body concentrations and their ratios, and hepatic tissue energy charge levels among the experimental groups. It is suggested that volume replacement with rHSA, like pHSA, is able to maintain hemodynamics and organ function in hemorrhagic shock, particularly hepatic energy metabolism.

Animals↗

Effects of platelet-activating factor antagonist E5880 on intrahepatic and systemic metabolic responses to transient hepatic inflow occlusion and reperfusion in the rabbit.

We investigated the effects of pretreatment with a potent platelet-activating factor (PAF) receptor antagonist (E5880) on the changes in hepatic and systemic metabolism induced by transient hepatic ischemia and reperfusion. Sixty-five rabbits were assigned to four groups that either did or did not undergo a period of hepatic ischemia and reperfusion with or without pretreatment. E5880 was administered intraportally 1 minute prior to inflow occlusion. Twenty minutes of warm ischemia was followed by 30 minutes of reperfusion. Blood gas analyses and measurements of levels of arterial pyruvate, lactate, and ketone bodies, arterial and portal ammonia and endotoxin, and intrahepatic adenine nucleotide, pyruvate, and lactate were performed. Results were analyzed by either ANOVA or chi-square analysis. Hepatic tissue ATP and energy charge levels were significantly increased and the AMP level was significantly decreased after 30 minutes of reperfusion in the pretreatment group compared to those without pretreatment. At the same time, parameters reflecting hepatic mitochondrial function, such as the arterial ketone body ratio and arterial ammonia level, improved, although they were not statistically significant. No difference was observed for parameters reflecting systemic changes, such as arterial blood gas values and pyruvate and lactate levels. PAF is thought to mediate metabolic changes after hepatic ischemia and reperfusion. PAF released in the liver may exert local effects, which appear to be attenuated by pretreatment with E5880. Systemic metabolic changes seen after hepatic ischemia and reperfusion may be mediated by factors other than PAF.

6-Ketoprostaglandin F1 alpha↗

The heparin-bound fraction of human lipoprotein-deficient serum inhibits endocytic uptake of oxidized low density lipoprotein by macrophages.

We recently demonstrated that bovine lactoferrin, a cationic whey protein from bovine milk, interacts with the negative charges of modified low density lipoproteins (modified LDL) such as acetylated LDL (acLDL) and oxidized LDL (oxLDL), which markedly interferes with their endocytic uptake by rat peritoneal macrophages (Kajikawa M, Ohta T, Takase M, Kawase K, Shimamura S, Matsuda I. Biochim Biophys Acta 1994;1213:82-90). In the present study, we examined whether human lipoprotein-deficient serum (LPDS) might contain protein(s) that could inhibit the endocytic uptake of oxLDL by mouse macrophages. We fractionated LPDS by heparin affinity chromatography and found that the cellular binding of oxLDL to mouse macrophages and subsequent endocytic uptake were inhibited by 50%-60% with the heparin-bound fraction, whereas the heparin-unbound fraction had no effect. Similar results were obtained in the experiments with acetylated LDL. Sephacryl S-300 gel-filtration chromatography of a mixture of oxLDL and the heparin-bound fraction revealed that a 150-kDa protein was associated with oxLDL. These results indicate that the electrostatic interaction of oxLDL with some component(s) of the heparin-bound fraction might interfere with the endocytic uptake of oxLDL by the macrophage scavenger receptor.

Animals↗

Monoclonal antibodies specific to the integral membrane protein P0 of bovine peripheral nerve myelin.

Two monoclonal antibodies (mAbs), 58A and 46E, were generated against the major protein P0 of bovine peripheral nervous system myelin (PNSM). The reactivities of the mAbs were assessed by enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemistry. Both mAbs, 58A and 46E, reacted to PNSM of bovine, human, rat and rabbit, but not to chicken PNSM or the brains of rat and rabbit. In the Western blot, these mAbs showed specific binding to bovine P0 as well as deglycosylated P0, but not to myelin-associated glycoprotein (MAG) of bovine spinal cord. The analyses of the lysylendopeptidase-digested peptides of bovine P0 revealed that the epitopes for the mAbs 58A and 46E were located on the amino acid residues 68-79 and 210-216, respectively. Since the mAbs 58A and 46E recognize the extracellular domain and the cytoplasmic domain of P0, respectively, they could be useful for studies on P0's role in myelin formation, its adhesive properties, and functions of the N-terminal extracellular and C-terminal cytoplasmic domains of the protein.

Amino Acid Sequence↗

A stress-sensitive chemokinergic neuronal pathway in the hypothalamo-pituitary system.

Recently we found that cytokine-induced neutrophil chemoattractant influenced anterior pituitary hormone release in vitro. These observations prompted us to investigate the possibility of the existence of cytokine-induced neutrophil chemoattractant in the hypothalamus. Immunohistochemistry showed that cytokine-induced neutrophil chemoattractant-like immunoreactivity existed in the paraventricular hypothalamic nucleus, the supraoptic nucleus, both the internal and the external layers of the median eminence and the posterior pituitary. Since the paraventricular hypothalamic nucleus plays a pivotal role in response to stressful stimuli, we examined the effect of a single episode of immobilization stress on cytokine-induced neutrophil chemoattractant messenger RNA expression in the paraventricular hypothalamic nucleus. Immobilization stress induced strong hybridization signals of cytokine-induced neutrophil chemoattractant messenger RNA in the parvocellular and magnocellular subdivision of the paraventricular hypothalamic nucleus within 15 min, and cytokine-induced neutrophil chemoattractant-like immunostaining intensity in the posterior pituitary started to increase around the periphery of the posterior lobe at 30 min after stress and extended to the whole lobe at 1 h after stress. The increase in the serum cytokine-induced neutrophil chemoattractant in response to stress showed a kinetically biphasic pattern. A first phase occurred within 15 min which may be due to an immediate release of stored cytokine-induced neutrophil chemoattractant in the neurohypophysis, since hypophysectomy completely blocked this phase. A second phase may reflect the release of newly synthesized cytokine-induced neutrophil chemoattractant in the paraventricular hypothalamic nucleus and/or peripheral cytokine-induced neutrophil chemoattractant, since hypophysectomy could not reduce this phase. These data suggest that cytokine-induced neutrophil chemoattractant in the paraventricular hypothalamic nucleus was immediately synthesized in response to stress, and then released into the peripheral blood via the hypothalamo-neurohypophysial system, revealing the presence of a stress-sensitive chemokinergic neuronal pathway in the hypothalamo-pituitary system.

Animals↗

Enhanced ketogenesis in the kidney during hepatic inflow occlusion with the administration of Ringer's acetate solution.

BACKGROUND: The blood levels of ketone bodies, which are synthesized principally in the liver, were maintained even during hepatic inflow occlusion if Ringer's acetate solution (AR) was administered, resulting in an improvement of hepatic energy level in the reperfusion phase, as reported in our previous experimental study. The current study was designed to prove that the kidneys are the organs that contribute to synthesize ketone bodies during hepatic inflow occlusion if AR is administered. METHODS: The arterial, central venous, renal venous, and renal tissue ketone body concentrations were determined in rabbits administered AR or Ringer's lactate solution (LR) at 20 minutes of hepatic ischemia and at 30 minutes of reperfusion. The concentrations were also compared in rabbits under AR infusion with or without hepatic ischemia for 20 minutes. Statistical analyses were performed by means of ANOVA: RESULTS: With AR the renal venous ketone body concentration not only was higher than that with LR (p < 0.001) but also was higher than the arterial concentration (p = 0.05). The renal tissue ketone body concentration was higher than in those with LR (p < 0.001) and also than in those without occlusion (p < 0.001). CONCLUSIONS: Ketogenesis is enhanced in the kidney and may compensate for hepatic loss of ketogenic function during hepatic inflow occlusion under AR administration.

Animals↗

Effect of various glucagon/insulin molar ratios on blood ketone body levels in rats by use of osmotic minipumps.

The bihormonal control by insulin and glucagon of blood ketone body level was studied. Mixed solutions with various molar ratios of glucagon and insulin (G/I) were subcutaneously infused continuously for five days by use of the osmotic minipump in the normal rats. The concentrations of insulin and glucagon solution were set at the high G/I molar ratio, the moderate G/I molar ratio and the low G/I molar ratio. In addition, the moderate G/I molar ratio group was divided into three sub-groups: low glucagon and low insulin, moderate glucagon and moderate insulin, and high glucagon and high insulin. After five days, the rats were decapitated to measure plasma ketone body, free fatty acid (FFA), glucose, insulin and glucagon. The FFA level was not significantly different among three groups. The glucose level was not different between the high and moderate G/I molar ratio groups, and decreased in the low G/I molar ratio group. 3-beta-hydroxybutyrate (3-OHBA) and acetoacetate (AcAc) levels in the high G/I molar ratio group were elevated, and 3-OHBA level in the low G/I molar ratio group was lowered compared to those in the moderate G/I molar ratio group. Among three moderate G/I molar ratio sub-groups, there was no difference in 3-OHBA and AcAc levels. These results demonstrate that plasma ketone body levels are controlled by the plasma G/I molar ratio.

3-Hydroxybutyric Acid↗

Mn(2+)-induced transient contraction of the longitudinal muscle of guinea-pig stomach through prostaglandin synthesis.

1. A low concentration of Mn2+ (less than 0.3 mM) transiently enhanced a contractile force (Mn(2+)-induced TC) of the longitudinal muscles of the guinea-pig stomach. 2. The Mn(2+)-induced transient contraction (TC) was not blocked by TTX (10(-7) M) or atropine (10(-6) M), nor by nifedipine (10(-6) M) or D-600 (10(-6) M), but was blocked by Ca2+ removal from the Krebs solution. 3. A preapplication of indomethacin (10(-7) M) completely inhibited an induction of the Mn(2+)-induced TC, but exogenous PGE2 (10(-7) M) was able to induce Mn(2+)-induced TC even with the presence of indomethacin (10(-7) M) and Mn2+ (0.1 mM) in the Krebs solution. 4. Quinacrine (10(-5) M), a phospholipase A2 inhibitor, partially inhibited the Mn(2+)-induced TC. 5. These results suggest that Mn(2+)-induced TC is probably mediated through cyclooxygenase and the subsequent generation of prostaglandin leading to the contraction.

Animals↗

Captopril increases renin release stimulated by furosemide and hypotension in isolated perfused guinea pig kidneys.

To clearly understand the feedback mechanism of renin secretion by intrarenal angiotensin II synthesis, we studied the stimulatory effect of captopril, an angiotensin converting enzyme inhibitor, on renin release from the isolated perfused guinea pig kidneys. Captopril did not affect the basal renin secretion. Captopril increased on a dose dependent basis renin release induced by 0.1 mg/ml furosemide; 5.8 +/- 1.3 ng/ml/hr at 0 mg/ml of captopril vs. 8.8 +/- 1.6 ng/ml/hr at 0.01 mg/ml (p < 0.05) and 11.8 +/- 2.4 ng/ml/hr at 0.1 mg/ml (p < 0.01), 15-20 min after furosemide infusion. After lowering the flow rates from 10 to 5 ml/min, renin secretion was not altered during the first 12 minutes. However, after adding 0.1 mg/ml captopril, renin secretion was enhanced within the following 8 minutes (8.3 +/- 1.5 vs. 3.7 +/- 0.5 ng/ml/hr at the end of low flow rate period, p < 0.01). Lowering the perfusion flow of the guinea pig kidneys decreases the NaCl flux at the macula densa and also seems to have a similar effect to furosemide. Therefore, these effects of captopril suggest that intrarenal angiotensin II production has an important role in the regulation of renin secretion, probably via effects on the macula densa function.

Angiotensin-Converting Enzyme Inhibitors↗

T2 shortening in the motor cortex: effect of aging and cerebrovascular diseases.

PURPOSE: To evaluate the effect of aging and cerebrovascular diseases on T2 shortening in the motor cortex at magnetic resonance (MR) imaging. MATERIALS AND METHODS: High-field-strength (1.5-T) MR images of 298 neurologically normal patients (157 male patients, 141 female patients; age range, 2-86 years) and 107 patients with cerebrovascular diseases (66 men, 41 women; age range, 41-86 years) were evaluated retrospectively. On T2-weighted spin-echo images, the signal intensities of the motor, sensory, parietal, temporal, and prefrontal cortices were divided into three grades compared with the signal intensity of the frontal subcortical white matter. RESULTS: Decreased signal intensity (grade III) was not seen in any region in the neurologically normal patients younger than 60 years. After the age of 60 years, however, the signal intensity of the motor cortex decreased, and 43 (66%) of 65 neurologically normal patients reached grade III by age 80 years. In patients with cerebrovascular disease, grade III was seen in 12 (34%) of the 35 patients younger than 60 years (5th and 6th decades). CONCLUSION: T2 shortening of the motor cortex was seen frequently in the older neurologically normal individuals and in patients with cerebrovascular diseases. These findings are compatible with those of a previously reported histochemical study of normal iron deposition in the motor cortex.

Adolescent↗

Evaluation of transparency and barrier function of the cornea by Scheimpflug images.

Two new methods of corneal analysis with Scheimpflug images will be introduced in this paper. The first study was to document the light scattering of the cornea itself using a newly modified Scheimpflug camera with higher magnification. Details of the slit images of the cornea could be evaluated more precisely than those of images taken with an existing camera. The second study was to evaluate the corneal epithelial barrier function by measuring the intensity of the light scattering originating from instilled fluorescein excited through filters. Fluorescein accumulation in the damaged epithelium and diffusion with time into the stromal tissue could be observed in two-dimensional images and the changes could also be documented by measuring the intensity and extent of light scattering. These newly developed methods will be useful for studies of the cornea.

Adolescent↗

Three-dimensional volume visualization of the in vivo human ocular lens showing localization of the cataract.

An in vivo human lens containing a cataract has been visualized by volume rendering a transformed series of 60 rotated Scheimpflug digital images. The data set was obtained by rotating the Scheimpflug camera about the optic axis of the lens in 3-degree increments. The set of 60 Scheimpflug digital images were mathematically transformed into a new data set in which the images are oriented perpendicular to the optic axis of the eye. The transformed set of optical sections were first aligned to correct for eye movements during the data collection process, then rendered into a three-dimensional volume reconstruction with volume-rendering computer graphics techniques. The viewpoint and the transparency of the volume rendered in vivo human lens were varied in order to observe volume opacities in various regions of the lens. To help visualize lens opacities, the intensity of light scattering was pseudocolor-coded as an integral part of the three-dimensional volume rendering. Three-dimensional, pseudocolored volume rendering of the in vivo human ocular lens represents a new technique to visualize in vivo human cataracts.

Aged↗

Carotid-cavernous sinus fistula and aneurysmal rupture associated with fibromuscular dysplasia. A case report.

A patient with carotid-cavernous sinus fistula associated with fibromuscular dysplasia, who died from rupture of an associated splenic aneurysm despite successful treatment of the CCF, is reported. When multivessel involvement with aneurysmal dilatation is observed in patients with fibromuscular dysplasia, the possibility of aneurysm ruptures in any of the arteries should be considered.

Adult↗

Lingual carcinoma. Correlation of MR imaging with histopathological findings.

PURPOSE: To determine the utility of MR imaging in the evaluation of lingual carcinomas. MATERIAL AND METHODS: Eleven patients with lingual carcinoma were evaluated with MR imaging including dynamic study within one week before surgery. Nine patients underwent preoperative chemotherapy or irradiation, and 2 patients had no preoperative treatment. Delineation of the tumor, the contrast between tumor and surrounding tissue, and extent of the tumor were evaluated in a blinded manner. After glossectomy, MR images were correlated with pathological findings. Statistical analysis was performed on the visual assessment ratings. RESULTS: Blinded evaluation suggested that dynamic and T2-weighted images (T2WI) were significantly superior to postcontrast T1WI in demonstrating the lesion. There were no significant differences between dynamic MR images and T2WIs. However, histopathological correlation showed that in patients with preoperative treatment, dynamic MR imaging demonstrated more accurately the size and extent of the residual tumor than did T2WI and postcontrast T1WI, which tended to demonstrate an area of signal abnormality that was more extensive than the true size of the residual lesion. In patients without preoperative treatment, dynamic MR imaging, T2WI, and postcontrast T1WI gave an equivalent depiction of the extent of the carcinoma. CONCLUSION: In patients with no preoperative treatment, dynamic MR imaging does not appear to offer any advantage over T2WI. However, in patients with preoperative treatment, dynamic MR imaging provides a more accurate assessment of the residual tumor than do T2WI and postcontrast T1WI.

Aged↗

Endotoxin activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system.

Cytokines play a critical role in the cascade of events that cause septic shok. One regulatory system suggested to be important in controlling inflammatory response is the neuroendocrine axis. One of the chemokines is cytokine induced neutrophil chemoattractant (CINC), which was first described as an immuno-modulator of peripheral tissue in inflammatory responses. To assess further the contribution of the chemokine to the central nervous system, we performed immunohistochemistry on rat brains and found strong CINC-like immunoreactivity in the posterior pituitary gland. Treatment with bacterial endotoxin (lipopolysaccharide; LPS) markedly enhanced CINC-like immunoreactivity in the posterior pituitary. Before the LPS challenge, signal for CINC mRNA was undetectable in the paraventricular hypothalamic nucleus (PVN). The LPS challenge induced strong hybridization signals of CINC mRNA in the parvocellular and magnocellular subdivision of the PVN within 15 minutes (min) and peaked at 30 min. The LPS challenge provoked no observable change in the supraoptic nucleus. These studies demonstrate the presence of an endotoxin-sensitive chemokinergic neuronal pathway in the hypothalamo-neurohypophysial system and this newly-described pathway will provide a novel information to understand another possible neuralimmune mechanism.

Animals↗

Serum immunoreactive activin A levels in normal subjects and patients with various diseases.

We developed and validated a RIA for measuring serum activin A. The least detectable value of this assay was 0.1 micrograms/L, and the antibody used cross-reacted slightly with bovine inhibin (3.2%) and porcine activin AB (10.0%) but not with porcine activin B (< 0.5%). Serum activin A was extracted with acetonitrile and trifluoroacetic acid to get rid of the interaction with possible binding proteins in serum. As a result of this extraction procedure, the dose-response curve of serum extract was parallel to the standard curve and a single immunoreactive (ir-) peak was demonstrated on gel chromatographic analysis with constant recovery rates over 80%. Serum ir-activin A level in healthy adults was 1.27 +/- 0.03 micrograms/L (mean +/- SEM, n = 180); being 1.38 +/- 0.05 micrograms/L (n = 90) in male, and 1.16 +/- 0.05 micrograms/L (n = 90) in female subjects, with a tendency to increase with age. Serum ir-activin A level during pregnancy showed a marked increase with the advance of gestation; 1.65 +/- 0.41 micrograms/L (n = 7) in the early, 4.50 +/- 1.13 micrograms/L (n = 21) in the middle, and 16.32 +/- 2.25 micrograms/L (n = 26) in the late trimester, with a rapid decline after delivery. On the other hand, serum ir-activin A level was elevated in patients with hyperthyroidism (1.91 +/- 0.37 micrograms/L, n = 31), liver cirrhosis (2.03 +/- 0.71 micrograms/L, n = 10), chronic renal failure (3.41 +/- 0.34 micrograms/L, n = 41), and advanced solid cancer (2.24 +/- 0.52 micrograms/L, n = 67). These findings indicate that serum ir-activin A level varies with physiological conditions such as aging and pregnancy, and that it may reflect the altered production and metabolism of activin A in certain diseased conditions.

Activins↗

Relationship between the 13C-NMR chemical shift and the carcinogenic activity of benz[a]anthracenes.

A thorough NMR spectroscopic investigation was made on 7,12-dimethylbenz[a]anthracene (1) and the 1H- and 13C-NMR spectra were completely assigned. We compared the 13C-NMR chemical shifts (delta) of three benz[a]anthracenes, including compound 1, whose carcinogenicities vary largely, and investigated the relationship of the delta and carcinogenicity. It was found that the delta values at the C1, C2, and C6 positions differed significantly between the carcinogenic and noncarcinogenic compounds.

Benz(a)Anthracenes↗

Meisenheimer rearrangement of azetopyridoindoles. VIII. Synthesis and antiviral activities of 12-carbaeudistomin analogs.

Eudistomins, isolated from the colonial tunicate Eudistoma olivaceum, have been a synthetic target due to their strong antiviral activity against Herpes simplex virus (HSV-1) and activities against certain types of tumors in vivo. In order to examine the structure-activity relationship of eudistomins, 12-carbaeudistomin analogs were synthesized and their activities against influenza A and B virus, HSV-1, HSV-2 and human cytomegalovirus were investigated. Among them, racemic 6-methoxy-12-carbaeudistomin showed similar activity to (-)-debromoeudistomin K, synthesized as a control compound.

Animals↗