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Biomedical subjects

I Abe

Publications and source records attributed to I Abe.

At least 37 records · Page 2Linked to original sources

Cardiovascular and sympathetic responses to dental surgery with local anesthesia.

We investigated changes in blood pressure and blood variables, including plasma catecholamines, serum glucose and insulin concentrations, during dental surgery. The study included 11 normotensive patients (age, 22.5+/-0.7 years) who underwent tooth extraction at Kyushu Dental College Hospital. Three to 7 days prior to dental surgery, blood pressure, pulse rate, and heart rate variability were measured every 30 min over 24 h. The low frequency (LF: 0.05 to 0.15 Hz) and high frequency (HF: 0.15 to 0.40 Hz) powers were calculated, and the ratio of LF to HF (LF/HF) and HF were used as indexes of sympathetic and parasympathetic activities, respectively. Lidocaine, 2% with epinephrine (1:80,000), was used as the local anesthetic for all patients. Systolic blood pressures significantly increased during dental surgery (+10.8+/-3.5 mmHg); however, this increase failed to correlate not only with baseline systolic blood pressure but with 24-h averaged blood pressures, LF/HF or HF. On the other hand, plasma epinephrine and norepinephrine concentrations increased during dental surgery, and peak values of these variables were obtained after local anesthesia and during tooth extraction, respectively. Serum glucose level increased after local anesthesia (control vs. local anesthesia: 5.16+/-0.11 vs. 5.62+/-0.10 mmol/l; p<0.01); however, plasma insulin concentrations did not change significantly. These results suggest that 1) ambulatory measurements of blood pressure and heart rate variability over 24 h cannot predict the responses of blood pressure during dental surgery, and that 2) administration of local anesthetic and tooth extraction activate sympathoadrenal outflow, resulting in an increase in serum glucose level in normotensive subjects.

Adult↗

Transcranial doppler sonography and ambulatory blood pressure monitoring in patients with hypertension.

To appraise the value of transcranial Doppler sonography (TCD) for assessment of hypertensive cerebrovascular damage, the relationship between ambulatory blood pressure (BP) and indices of cerebral circulation determined by TCD was investigated. Subjects were 55 inpatients with or without hypertension, including 13 patients with histories of cerebrovascular attacks. Mean flow velocity (MFV) in the middle cerebral artery was measured by TCD, then the cerebrovascular resistance index (CVRI; mean BP/MFV) and the Fourier PI1 (pulsatility index of the first Fourier harmonic of the flow-velocity waveform) were determined as indices of cerebrovascular resistance. CO2 reactivity of MFV was estimated as an index of cerebrovascular flow reserve. CVRI positively correlated with both daytime and nighttime BP as well as with age (p<0.01). Fourier PI1 positively correlated with nighttime BP and age (p<0.01). CO2 reactivity did not correlate with any of the ambulatory BP parameters, but negatively correlated with age (p<0.01). LV mass index significantly correlated with ambulatory BP parameters, CVRI, and Fourier PI1 but did not correlate with CO2 reactivity. Multiple regression analyses showed that nighttime systolic BP was a significant correlate for CVRI and Fourier PI1, but not for CO2 reactivity, and that history of cerebrovascular attack was significant for CVRI and CO2 reactivity. We conclude that cerebrovascular resistance determined by TCD accords with the results of ambulatory BP and LVMI, and thus could be successfully used to detect the early stage of hypertensive cerebrovascular change. Cerebrovascular flow reserve would be relatively preserved in hypertensive patients without cerebrovascular diseases.

Adult↗

Trends in the pathophysiological characteristics of malignant hypertension.

The aim of the present study is to investigate the pathophysiological characteristics of a number of recent cases of malignant hypertension (MHT) and to compare them to the characteristics of earlier cases. Patients with MHT (age 25-76, mean 44+/-2 years) who were admitted to our hospital from 1984-1999 were retrospectively studied. All of the patients had either grade III or IV retinopathy and diastolic blood pressure levels higher than 120 mmHg. The observations in this study were compared to previously reported findings regarding 59 MHT patients who were admitted from 1971-1983. Of the 37 recent MHT patients, 20 had essential hypertension (EHT) as the underlying disease, 13 had chronic glomerulonephritis (CGN), and the remaining 4 presented with other diseases including pyelonephritis and renovascular hypertension. A positive family history of hypertension was more prevalent in the EHT patients than in other patients, and persistent proteinuria, microhematuria, and anemia were more prevalent in the CGN patients. These characteristics were similar between the recent and previous cases. Within 4 weeks after admission, hemodialysis was initiated in 3 of the 13 patients (23%) with CGN and 2 of the 20 (10%) patients with EHT. The prevalence of renal death at 1 year after admission was 30%, which was lower than the prevalence in the previous cases (42%). Grade IV retinopathy was seen in 45% of the patients admitted from 1984-1999, significantly less than in the patients admitted from 1971-1983 (66%, p<0.05). In addition, left ventricular hypertrophy was less frequently observed on electrocardiogram in the recent cases (67%) than in the previous cases (88%, p<0.05). Our results suggest that the recent cases of MHT demonstrate less severe organ damage.

Adult↗

Altered diurnal variation of blood pressure in elderly subjects with decreased activity of daily living and impaired cognitive function.

Activity of daily living (ADL) and cognitive are indices of physical and psychological activity in elderly subjects. The present study was performed to clarify the relationship among ADL, cognitive function, and ambulatory blood pressure (ABP) in the elderly. Study subjects were 77 females and 22 males (aged 60 to 101 years) with various levels of ADL and cognition, who were in nursing homes or geriatric hospitals. ABP was recorded every 30 min for 24 h by a noninvasive device. Mini-mental state examination (MMSE) and Barthel index measurement were used to evaluate cognitive function and ADL, respectively. Both the MMSE and Barthel index values showed a significant positive correlation with daytime ABP but not with nighttime ABP. The dip in nighttime BP correlated negatively with age, and positively with MMSE and Barthel index. In the multiple regression analysis, age and Barthel index values remained significant determinants of the dip in nighttime BP. Presence of stroke and MMSE became significant when the Barthel index values were removed from the analyses. When subjects were classified by tertiles of MMSE or Barthel index, subjects in the lowest MMSE group and those in the lowest Barthel index group had both lower daytime ABP and smaller nighttime BP dip than those of the other groups. A low BP level during the daytime was associated with altered diurnal variation of BP in elderly subjects with greater age, impaired cognitive function, and/or decreased ADL. ADL had a greater influence on diurnal BP variation than did cognitive function.

Activities of Daily Living↗

Enzymatic formation of unnatural aromatic polyketides by chalcone synthase.

Substrate specificity of recombinant chalcone synthase (CHS) from Scutellaria baicalensis (Labiatae) was investigated using chemically synthesized aromatic and aliphatic CoA esters. It was demonstrated for the first time that CHS converted benzoyl-CoA to phlorobenzophenone (2,4,6-trihydroxybenzophenone) along with pyrone by-products. On the other hand, phenylacetyl-CoA was enzymatically converted to an unnatural aromatic polyketide, phlorobenzylketone (2, 4,6-trihydroxyphenylbenzylketone), whose structure was finally confirmed by chemical synthesis. Furthermore, in agreement with earlier reports, S. baicalensis CHS also accepted aliphatic CoA esters, isovaleryl-CoA and isobutyryl-CoA, to produce phloroacylphenones. In contrast, hexanoyl-CoA only afforded pyrone derivatives without formation of a new aromatic ring. It was noteworthy that both aromatic and aliphatic CoA esters were accepted in the active site of the enzyme as a starter substrate for the complex condensation reaction. The low substrate specificity of CHS thus provided further insight into the structure and function of the enzyme.

Acyltransferases↗

Inhibition of vertebrate squalene epoxidase by isoprenyl gallates and phenylalkyl gallates.

Galloy esters with 'substrate-like' isoprenoid or phenylalkyl side chains were newly synthesized and tested for the enzyme inhibition activities toward recombinant rat squalene epoxidase. Isoprenyl gallates (4-6) showed good inhibition (IC50 = 1.5 5.1 microM), as potent as previously reported substrate analogues, while phenylalkyl gallates (7-10) were moderate inhibitors of the enzyme (IC50 = 12-61 microM).

Animals↗

Antioxidative galloyl esters as enzyme inhibitors of p-hydroxybenzoate hydroxylase.

Gallic acid and its esters were evaluated as enzyme inhibitors of recombinant p-hydroxybenzoate hydroxylase (PHBH), a NADPH-dependent flavin monooxygenase from Pseudomonas aeruginosa. n-Dodecyl gallate (DG) (IC(50)=16 microM) and (-)-epigallocatechin-3-O-gallate (EGCG) (IC(50)=16 microM), a major component of green tea polyphenols, showed the most potent inhibition, while product-like gallic acid did not inhibit the enzyme significantly (IC(50)>250 microM). Inhibition kinetics revealed that both DG and EGCG inhibited PHBH in a non-competitive manner (K(I)=18.1 and 14.0 microM, respectively). The enzyme inhibition was caused by specific binding of the antioxidative gallate to the enzyme, and by scavenging reactive oxygen species required for the monooxygenase reaction. Molecular modeling predicted that EGCG binds to the enzyme in the proximity of the FAD binding site via formation of three hydrogen bonds.

4-Hydroxybenzoate-3-Monooxygenase↗

Characteristics of Cyclodextrin Adsorption onto Activated Carbons.

Whereas the amount of cyclodextrin (CD) adsorbed onto the large-pore activated carbon A (AC-A) increased with the number of glucose units, the amount adsorbed onto the small-pore activated carbon B (AC-B) showed the opposite tendency. This behavior can be accounted for in terms of a molecular exclusion. It is known that a good linear relationship is obtained between the Freundlich constants log K and 1/N for hydrophobic adsorption. The adsorption of CDs onto AC-A obeyed this relation, but, because of the molecular exclusion, the plots of AC-B deviated greatly. The adsorption of CDs onto AC-A was not explainable in terms of solubility. This could be because, in the case of a solid compound, adsorbability depends on the chemical potential of the molecule in aqueous solution whereas solubility depends also on the heat of fusion of the solid. In order to estimate the relative chemical potential of CDs in water, a method based on the numbers of carbon atoms and oxygen atoms in the molecule was devised which allowed a more accurate estimation of CD adsorbability than did solubility. The mean pore diameter of AC-A increased after CD adsorption, while that of AC-B showed little change. Copyright 2000 Academic Press.

Journal Article↗

Molecular anatomy of the peroxin Pex12p: ring finger domain is essential for Pex12p function and interacts with the peroxisome-targeting signal type 1-receptor Pex5p and a ring peroxin, Pex10p.

The three peroxin genes, PEX12, PEX2, and PEX10, encode peroxisomal integral membrane proteins with RING finger at the C-terminal part and are responsible for human peroxisome biogenesis disorders. Mutation analysis in PEX12 of Chinese hamster ovary cell mutants revealed a homozygous nonsense mutation at residue Trp263Ter in ZP104 cells and a pair of heterozygous nonsense mutations, Trp170Ter and Trp114Ter, in ZP109. This result and domain mapping of Pex12p showed that RING finger is essential for peroxisome-restoring activity of Pex12p but not necessary for targeting to peroxisomes. The N-terminal region of Pex12p, including amino acid residues at positions 17-76, was required for localization to peroxisomes, while the sequence 17-76 was not sufficient for peroxisomal targeting. Peroxins interacting with RING finger of Pex2p, Pex10p, and Pex12p were investigated by yeast two-hybrid as well as in vitro binding assays. The RING finger of Pex12p bound to Pex10p and the PTS1-receptor Pex5p. Pex10p also interacted with Pex2p and Pex5p in vitro. Moreover, Pex12p was co-immunoprecipitated with Pex10p from CHO-K1 cells, where Pex5p was not associated with the Pex12p-Pex10p complex. This observation suggested that Pex5p does not bind to, or only transiently interacts with, Pex10p and Pex12p when Pex10p and Pex12p are in the oligomeric complex in peroxisome membranes. Hence, the RING finger peroxins are most likely to be involved in Pex5p-mediated matrix protein import into peroxisomes.

Amino Acid Sequence↗

Metabotropic glutamate receptor subtypes involved in cardiovascular regulation in the rostral ventrolateral medulla of rats.

We have previously reported that metabotropic glutamate receptors (mGluR) participate in cardiovascular regulation in the rostral ventrolateral medulla (RVLM) of rats. In the present study, we have tried to elucidate which subtype of mGluR contributes to cardiovascular responses elicited by L-glutamate in the RVLM. Adult male Wistar rats (348 +/- 11 g, n = 21) were anesthetized and artificially ventilated. Microinjections of agonists and antagonists for each mGluR subtype were done into unilateral RVLM. Each of group I, II and III mGluR agonist (1 nmol/50 nl) produced significant increases in arterial pressure (18 +/- 2, 9 +/- 2 and 34 +/- 3 mmHg, respectively) and heart rate (18 +/- 4, 13 +/- 3 and 33 +/- 12 bpm, respectively). Microinjections of group I, II and III mGluR antagonists failed to inhibit the cardiovascular responses induced by subsequently injected agonists. However, group I antagonist [(RS)-1-aminoindan-1,5-dicarboxylic acid] elicited transient increases in arterial pressure and heart rate, followed by decreases in both variables (-19 +/- 4 mmHg and -22 +/- 4 bpm). These results suggest that all of three subtypes of mGluR participate in cardiovascular responses induced by L-glutamate, and group I mGluR may play an important role in the maintenance of arterial pressure.

Animals↗

Potent and selective inhibition of squalene epoxidase by synthetic galloyl esters.

n-Alkyl esters (ethyl, octyl, dodecyl, and cetyl) of gallic acid were evaluated as enzyme inhibitors of recombinant rat squalene epoxidase (SE), a rate-limiting enzyme of cholesterol biogenesis. Dodecyl (6) (IC(50) = 0.061 microM) showed the most potent inhibition, which was far more potent than those of previously reported naturally occurring gallocatechins. Octyl gallate (5) (IC(50) = 0.83 microM) and cetyl gallate (7) (IC(50) = 0.59 microM) also showed good inhibition, while gallic acid (IC(50) = 73 microM) itself was not so active. In addition, chemically synthesized galloyl ester of cholesterol (9) (IC(50) = 3.9 microM), farnesol derivative (10) (IC(50) = 0.57 microM), and dodecyl galloyl amide (8) (IC(50) = 3.0 microM) were also potent inhibitors of SE. Inhibition kinetics revealed that dodecyl gallate inhibited SE in competitive (K(I) = 0.033 microM) and no-time-dependent manner. The potent inhibition of the flavin monooxygenase would be caused by specific binding to the enzyme, and by scavenging reactive oxygen species required for the epoxidation reaction.

Animals↗

Green tea polyphenols: novel and potent inhibitors of squalene epoxidase.

The green tea gallocatechins, (-)-epigallocatechin-3-O-gallate (EGCG) (IC(50) = 0.69 microM), (-)-gallocatechin-3-O-gallate (GCG) (IC(50) = 0.67 microM), (-)-epicatechin-3-O-gallate (ECG) (IC(50) = 1.3 microM), and theasinensin A (IC(50) = 0.13 microM), were found to be potent and selective inhibitors of rat squalene epoxidase (SE), a rate-limiting enzyme of cholesterol biogenesis. On the other hand, flavan-3-ols without galloyl group at C-3 did not show significant enzyme inhibition. It was demonstrated for the first time that the cholesterol lowering effect of green tea may be attributed to their potent SE inhibition activities. Inhibition kinetics revealed that EGCG inhibited SE in noncompetitive (K(I) = 0.74 microM), and non-time-dependent manner. The potent enzyme inhibition would be caused by specific binding to the enzyme, and by scavenging reactive oxygen species required for the monooxygenase reaction.

Animals↗

Enantiomer separation of pharmaceuticals by capillary gas chromatography with novel chiral stationary phases.

New chiral stationary phases of polydimethylsiloxane anchored with (S)-(-)-t-leucine derivatives were provided for use in enantiomer separation of pharmaceuticals by capillary gas chromatography. Fifteen pharmaceuticals were separated into their enantiomeric pairs by converting them into pentafluoropropionyl and heptafluorobutyryl derivatives. The separation factor and resolution obtained from the new phases were superior to those from the conventional Chirasil-Val capillary column.

Chromatography, Gas↗

Sustained hemostatic abnormality in patients with steroid-induced osteonecrosis in the early period after high-dose corticosteroid therapy.

To determine whether the development of steroid-induced osteonecrosis in collagen disease patients was related to hemostatic abnormality after corticosteroid administration, we examined levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha2-plasmin inhibitor complex (PIC) in 32 patients who were treated with high-dose corticosteroid. All were prospectively followed for osteonecrosis, with serial magnetic resonance imaging (MRI), for at least 12 months from the beginning of corticosteroid therapy. MRI was performed on bilateral hips and knees. Of the 32 patients, 17 (53.1%) had osteonecrosis in the hip or knee. Osteonecrosis was detected on MRI at an average 3.1 months after the start of high-dose corticosteroid therapy. PIC levels were significantly higher in the group of 17 patients with osteonecrosis (ON group) than in the group of 15 patients without osteonecrosis (non-ON group) (P < 0.0001). The difference in PIC levels was most prominent 20 days after the start of the high-dose corticosteroid therapy. Moreover, the number of osteonecrotic joints was significantly correlated with PIC levels (P < 0.0001). The sustained hemostatic abnormality after corticosteroid therapy in the ON group suggests that microvascular coagulation participates in the development of osteonecrosis.

Adolescent↗

Effects of adrenomedullin and PAMP on membrane potential and neurotransmission.

The effects of adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) on membrane potential and sympathetic neurotransmission were studied in rat mesenteric arteries by using microelectrodes. AM (10(-7) M) but not PAMP (10(-6) M) produced membrane hyperpolarization, which was abolished by high K solution or by glibenclamide, an ATP-sensitive K(+) (KATP) channel blocker. Neither AM nor PAMP affected excitatory junction potentials, a measure of sympathetic, purinergic neurotransmission. These findings suggest that AM hyperpolarizes the membrane via activation of KATP channels, which may contribute to the vasodilatory action of AM, whereas the mechanisms of the vasodepressor action of PAMP remain unclear.

Adrenomedullin↗

Galloyl esters from rhubarb are potent inhibitors of squalene epoxidase, a key enzyme in cholesterol biosynthesis.

Galloyl glucoses and galloyl proanthocyanidins obtained from rhubarb (Rhei Rhizoma, Rheum palmatum L., Polygonaceae); e.g. 1,2,6-tri-O-galloyl-beta-D-glucose (IC50 = 0.63 microM), 1,6-di-O-galloyl-2-O-cinnamoyl-beta-D-glucose (IC50 = 0.58 microM), procyanidin B-2 3,3'-di-O-gallate (IC50 = 0.54 microM), and procyanidin B-5 3,3'-di-O-gallate (IC50 = 0.55 microM), were found to be potent inhibitors of rat squalene epoxidase (SE). The inhibition at submicromolar level was far more potent than that of chemically synthesized substrate analogs. It was demonstrated for the first time that the cholesterol-lowering effect of rhubarb may be attributed to the potent inhibition activities of SE, a rate-limiting enzyme of cholesterol biogenesis.

Animals↗

Acetabular labrum: abnormal findings at MR imaging in asymptomatic hips.

PURPOSE: To determine the prevalence of abnormalities of the acetabular labrum in asymptomatic hips by means of magnetic resonance (MR) imaging and to correlate such abnormalities with age and the portion of the labrum. MATERIALS AND METHODS: MR imaging was performed in 71 asymptomatic hips that were radially sectioned perpendicular to the acetabular labrum at 30 degrees intervals. RESULTS: The shape of the labrum was triangular in 80% (304 of 382) of the labral segments, round in 13% (49 of 382), irregular in 7% (27 of 382), and not identified in 1% (two of 382). A homogeneous low signal intensity was observed in 56% (212 of 382). The frequencies of labral irregularity or its absence and of high signal intensity increased both with subject age and with a more anterior anatomic labral location. CONCLUSION: In asymptomatic hips, abnormal findings regarding the shape and signal intensity of the acetabular labrum can be detected by means of MR imaging. The fact that the findings vary according to age and labral portion should be considered in interpreting MR images in patients suspected of having a labral lesion.

Acetabulum↗

Central effects of leptin on cardiovascular and neurohormonal responses in conscious rabbits.

We determined the cardiovascular and neurohormonal responses to intracerebroventricular injection of leptin in conscious rabbits. Intracerebroventricular injection of leptin elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity while producing no consistent, significant increases in heart rate. Peak values of mean arterial pressure and renal sympathetic nerve activity induced by intracerebroventricular injection of 50 microgram of leptin (+17.3 +/- 1.2 mmHg and +47.9 +/- 12.0%) were obtained at 10 and 20 min after injection, respectively. Plasma catecholamine concentrations significantly increased at 60 min after intracerebroventricular injection of leptin (control vs. 60 min; epinephrine: 33 +/- 12 vs. 97 +/- 27 pg/ml, P < 0.05; norepinephrine: 298 +/- 39 vs. 503 +/- 86 pg/ml, P < 0.05). Intracerebroventricular injection of leptin also caused significant increases in plasma vasopressin and glucose levels. However, pretreatment with intravenous injection of pentolinium (5 mg/kg), a ganglion blocking agent, abolished these cardiovascular and neurohormonal responses. On the other hand, intravenous injection of the same dose of leptin (50 microgram) as used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. These results suggest that intracerebroventricular leptin acts in the central nervous system and activates sympathoadrenal outflow, resulting in increases in arterial pressure and plasma glucose levels in conscious rabbits.

Animals↗