Biomedical subjects
Publications and source records attributed to S Han.
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PURPOSE: The gastrointestinal permeability of a number of retinoic acids was determined in order to evaluate whether the gastrointestinal membrane was able to distinguish between retinoids in which the polyene chain was present in several different isomeric forms. In addition, the structure of the six-membered ring was varied in order to determine which portion of the molecule was most important for its recognition by the membrane. The role of bile salt micelle composition in the intestinal absorption of retinoids was also evaluated. METHODS: In situ perfused rat intestinal segment preparations (= 78) were used, and the retinoids were each perfused at a concentration of approximately 1 microg/ml in either simple micelles of sodium taurocholate (10 mM) or mixed micelles of sodium taurocholate/egg phosphatidylcholine (10 mM/10 mM). The flow rate of the perfusate was either 0.1 or 0.35 ml/min. RESULTS: For each retinoid, the mixed micelles were associated with a higher degree of retinoid uptake into the jejunal cells than were the simple micelles. In addition, the permeability was higher when the perfusate flow was greater, indicating that the aqueous boundary layer of the intestine contributes to the resistance to the disappearance of the retinoid from the intestinal lumen. Retinoid structure was also found to have a significant effect on the permeability in the mixed micelle systems at both low and high flow rates, but not with simple micelles. The structure of the six-membered ring was not a major determinant of the permeability. However, the permeability of the retinoids with the polyene chain in the 13-cis position was significantly greater than when the chain was all-trans or in the 9-cis position. CONCLUSIONS: The isomeric position of the polyene chain and the presence of phospholipid in the micellar vehicle have a significant influence on the membrane transport of the retinoic acids.
brlA is a primary regulator of asexual development in Aspergillus nidulans. Activation of brlA is necessary and sufficient for conidiophore development. It is known that brlA produces two overlapping transcripts, designated brlAalpha and brlAbeta. We found that expression of brlA is subject to complex regulation, in that activation of the two brlA transcripts is regulated at different levels. While brlAalpha is regulated at the transcriptional level, brlAbeta is regulated at both the transcriptional and translational levels. brlAalpha expression requires both abaA and brlA, but overexpression of brlAbeta can induce brlAalpha in an abaA mutant. brlAbetamuORF, a short ORF located upstream of the brlA initiator codon, regulates expression of brlA by damping translation of the brlAbeta ORF, and translational repression of brlA expression prevents premature development in A. nidulans. Transcriptional control of brlAbeta is apparently independent of BrlA. In order to understand better the transcriptional control of brlAalpha and brlAbeta, we have made 5' deletions in the essential approximately 2-kb upstream control sequences that regulate brlAbeta transcription and fused them to the E. coli lacZ reporter gene. Various deletions in this region resulted in only minor changes in the regulation of beta-galactosidase expression. The results of the deletion experiments indicate that there are probably several cis-acting control sequences involved in the regulation of brlAbeta. As a complementary approach, we fused various fragments of the 2034-bp brlAbeta and 754-bp brlAalpha control sequences to an otherwise inactive amdS::lacZ fusion, in order to search for regions that are sufficient to place the reporter under developmental control. We identified two approximately 600-bp brlAbeta fragments extending from -2901 to -2293 and -967 to -414, respectively, and a approximately 150-bp brlAalpha segment from -271 to -127, that confer activity on the inactive amdS promoter. brlA is overexpressed in an abaA null mutant and one site for abaA-dependent repression is apparently located in the -742 to -414 brlAbeta fragment. This indicates that abaA-mediated repression of brlA expression occurs through control of brlAbeta, but apparently involves a mechanism that does not require AbaA binding to brlA(p) sequences, because there are no AbaA binding sites in this region.
Pericardial cysts are uncommon benign abnormalities and are most often found in either cardiophrenic angle. We present the cases of 3 patients with a cyst in the mediastinum and review the literature. Pathological examination confirmed the diagnosis of pericardial cyst. Clinicians should include pericardial cyst in the differential diagnosis of mediastinal masses.
Acute 12 h and 24 h lethal toxicity (12 h-LC50 and 24 h-LC50) of 31 substituted phenols to Rana japonica tadpoles was determined. Results indicate that toxicity of phenols to tadpoles varied only slightly with length of exposure and the 12-h test could serve as surrogate of the 24-h test. A mechanism-based quantitative structure-activity relationship (QSAR) method was employed and 1-octanol/water partition coefficient (log K(ow))-dependent models were developed to study different modes of toxic action. Most phenols elicited their response via a polar narcotic mechanism and an excellent logK(ow)-dependent model was obtained. Soft electrophilicity and pro-electrophilicity were observed for some phenols and a good log K(ow)-dependent model was also achieved. Additionally, the significant dissociation of carboxyl on benzoic acid derivatives sharply reduced their toxicity. A statistically robust QSAR model was developed for all studied compounds with the combined application of log K(ow), energy of lowest unoccupied orbital (E(lumo)), heat of formation (HOF) and the first-order path molecular connectivity dices (1chi(p)).
Systematic analyses on the effects of chemical structures of 31 polychlorinated organic compounds (PCOCs) on their bioconcentration behavior in rainbow trout (Oncorhynchus mykiss) were conducted using quantitative structure-activity relationship (QSAR) techniques. The cluster analyses of individual variables as well as the quality control chart of QSAR model implies the existence of outliers, while the simulation model excluding such samples showed an extreme robustness even if it was tested with different methods. Furthermore, the quantum chemical parameters entering into QSAR model were used to describe the bioconcentration pathways, and the results indicated that bioconcentration behaviors of selected compounds were complicated processes involving permeation stages as well as bio-chemical reaction stages.
The current study aimed to investigate the effect of attentional selection of distinctive local elements on the processing of hierarchically organized patterns. Event-related brain potentials (ERPs) were recorded from subjects during identifications of global or local shapes of hierarchical patterns where either all local elements were identical (homogeneous stimulus) or a local element closest to fixation was distinguished by color from others (pop-out stimulus). One group of subjects was presented with the homogeneous stimuli and required to identify global or local shapes in separate blocks of trials. The other group was presented with the pop-out stimuli and asked to attend to the unique local item in the local task. A global precedence effect was observed in behavioral data. ERPs showed enlarged posterior P1 and N2 amplitudes in the local relative to global conditions. Top-down attention to the pop-out item resulted in increased frontal/central N2 amplitudes in the local condition but eliminated the temporal/occipital N2 enhancement in the local relative to global conditions. Top-down attention to the pop-out item also increased local-to-global interference in reaction times and frontal N2 latencies. The results suggest that a frontal mechanism is involved in directing top-down attention to a specific local item whereas a temporal/occipital mechanism is engaged in an attentional filtering process in the identification of local shapes in hierarchical analysis.
We investigated the efficacy of a 4-wk supplementation of conjugated linoleic acid (CLA) as free fatty acid (FFA) or triacylglycerol (TG) on serum leptin concentration, body-fat accumulation, and mitochondrial beta-oxidation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. A significant reduction of serum leptin concentration (42%) and a decrease in the wet weights of perirenal, epididymal, and omental/visceral-adipose tissue in TG-CLA and FFA-CLA groups were found in comparison with the OLETF control group. Both forms of CLA supplementation produced a 5.2% decrease in body weight compared with the control even though food intake was similar in the OLETF groups. Moreover, both forms of CLA enhanced carnitine-palmitoyltransferase activity in brown adipose tissue, perirenal adipose tissue, red gastrocnemius muscle, and liver in comparison with the OLETF control group. Serum concentrations of non-esterified fatty acid and TG also were reduced in rats fed diets supplemented with TG-CLA and FFA-CLA.
A methylene blue-mediated enzyme biosensor has been developed for the detection of inhibitors including mercury(II), mercury(I), methylmercury, and mercury-glutathione complex. The inhibition to horseradish peroxidase was apparently reversible and noncompetitive in the presence of HgCl2 in less than 8 s and irreversibly inactivated when incubated with different concentrations of HgCl2 for 1-8 min. The binding site of horseradish peroxidase with HgCl2 probably was a cysteine residue SH. Mercury compounds can be assayed amperometrically with the detection limits 0.1 ng ml(-1) Hg for HgCl2 and methylmercury, 0.2 ng ml(-1) Hg for Hg2(NO3)2 and 1.7 ng ml(-1) Hg for mercury glutathione complex. Inactivation of the immobilized horseradish peroxidase was displayed in the AFM images of the enzyme membranes.
A series of novel (4-piperidin-1-yl)-phenyl sulfonamides was prepared and evaluated for their biological activity on the human beta(3)-adrenergic receptor (AR). Replacement of the 3,4-dihydroxyl group of the catechol moiety with 4-hydroxyl-3-methyl sulfonamide on the left-hand side of the compounds resulted in a number of potent full agonists at the beta(3) receptor. Modification of the right-hand side of the compounds by incorporation of a free carboxylic acid resulted in a few potent human beta(3) agonists with low affinities for beta(1)- and beta(2)-ARs. N-Alkyl substitution on the 4-piperidin-1-yl-phenylamine further increased the beta(3) potency while maintaining the selectivity. For example, sulfonamide 48 is a potent full beta(3) agonist (EC(50)=0.004 microM, IA=1.0) with > 500-fold selectivity over beta(1)- and beta(2)-ARs.
Immunohistochemical assay for p16 protein expession was performed in 192 breast carcinoma patients treated with adjuvant chemotherapy. p16 expression was observed in 78 cases (40.6%). The frequency of p16 expression significantly decreased in moderately differentiated (histologic grade II) cancers, 20 (19.6%) of 102. In poorly differentiated cancers (histologic grade III), p16 expression was not observed in all 16 cases. p16 expression was significantly associated with histologic grade of the breast carcinomas (p < 0.001). The proliferative index (PI: S + G2/M) of individual tumors was measured by DNA flow cytometry. In 114 tumors with PI less than 20%, p16 expression was observed in 59 tumors (49.1%). In the tumors with PI equal or more than 20%, p16 expression was observed in 22 (28.2%) of 78 cases. p16 expression was significantly decreased in the tumor with higher PI (p =0.003). For the other clinicopathologic variables, no significant association was found with p16 expression status. Immunohistochemical assay for p53 protein expression was performed on the same breast carcinomas. There was no significant association between p16 and p53 expression in breast carcinomas. During median follow-up period of 52 months (range: 40-72 months), 46 patients (25.8%) had recurrent disease and 32 patients (18.91%) died of recurrent disease. p16 expression was observed in 20 (43.5%) of 46 patients with recurrent disease, while its expression was observed in 58 patients (39.7%) of 146 patients who were free of recurrence during the study period. p16 expression had no significant impact on predicting recurrence of breast carcinoma. Fourteen patients (12.2%) of 114 patients whose tumors did not show p16 expression died of recurrent breast carcinoma, whereas 18 patients (23.1%) of 78 patients with p16 expressing tumor died during the follow-up period. There was a significant difference of patient survival according to p16 expression status (p = 0.039). These results indicate that p16 expression is useful in predicting response to chemotherapy in breast cancer patients. p16 protein seems to have a role in tumor growth and differentiation of the breast carcinoma.
Rhythmic noradrenergic signaling from the hypothalamic clock in the suprachiasmatic nucleus to the pineal gland causes an increase in intracellular cAMP which regulates the circadian fluctuation of melatonin synthesis. The activation of phospholipase C (PLC)-coupled P2Y(2) receptors upon treatment with ATP and UTP exclusively inhibited the isoproterenol-stimulated cAMP production in mouse pineal gland tumor cells. However, the activation of other PLC-coupled receptors including P2Y(1) and bombesin receptors had little or no effect on the isoproterenol-stimulated cAMP production. Also, ATP did not inhibit cAMP production caused by forskolin, prostaglandin E(2), or the adenosine analog NECA. These results suggest a selective coupling between signalings of P2Y(2) and beta(2)-adrenergic receptors. The binding of [(3)H]CGP12177 to beta(2)-adrenergic receptors was not effected by the presence of ATP or UTP. Ionomycin decreased the isoproterenol-stimulated cAMP production, whereas phorbol 12-myristate 13-acetate slightly potentiated the isoproterenol response. Chelation of intracellular Ca(2+), however, had little effect on the ATP-induced inhibition of cAMP production, while it completely reversed the ionomycin-induced inhibition. Treatment of cells with pertussis toxin almost completely blocked the inhibitory effect of nucleotides. Pertussis toxin also inhibited the nucleotide-induced increase in intracellular Ca(2+) and inositol 1,4,5-trisphosphate production by 30-40%, suggesting that the ATP-mediated inhibition of the cAMP generation and the partial activation of PLC are mediated by pertussis toxin-sensitive G(i)-protein. We conclude that one of the functions of P2Y(2) receptors on the pineal gland is the selective inhibition of beta-adrenergic receptor-mediated signaling pathways via the inhibitory G-proteins.
There are many methods for the correction of cicatricial lagophthalmos. Skin and soft tissue should be used to reconstruct the defect after release of tension. We used a very small orbicularis oculi muscle pedicled skin flap for the correction of mild to moderate degrees of cicatricial lagophthalmos in six cases. A small skin island flap from near the skin defect, pedicled on the orbicularis oculi muscle, was transposed to fill the defect. The length of the skin flap ranged from 5 mm to 11 mm. With a follow-up period ranging from 6 months to 18 months (mean: 11 months),we obtained satisfactory functional and aesthetic results. The eyelid closure was much improved and the discomfort was relieved. All the flaps survived without any healing problems. This small orbicularis oculi myocutaneous flap is very reliable and has a wide range of motion. This technique can be applied to eyelid-skin defects of various causes.
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The polyketide antibiotic Frenolicin-B (FB) produces anorexia and esophageal epithelial hyperplasia (EH) in rats, findings that are characteristic of zinc deficiency. Because FB also chelates divalent cations in vitro, we conducted studies to determine whether FB modifies blood and organ concentrations of zinc and other essential metals (calcium, copper, iron and magnesium). Groups of male Sprague-Dawley rats ( approximately 250g; n = 20/group) consumed diets with adequate (40 microg/g), deficient (<2 microg/g) or fortified (100 microg/g) zinc concentrations ad libitum for 28 d. Two groups fed either Zn-adequate or Zn-fortified diets also were given 100 mg/(kg. d) of FB in diet, and 2 groups were pair-fed controls. Histopathology or metal analyses were performed on tissues from 10 rats/group. FB caused EH of the nonglandular stomach but not of other tissues. Of the metals evaluated, only copper concentrations were significantly reduced in all tissues examined except kidney. A broad range of kidney copper concentrations was found; these concentrations were associated with plasma copper and proteinaceous deposits within tubules. In rats, FB substantially and selectively depletes Cu in vivo, suggesting that drugs with structures that permit metal chelation should be evaluated for their potential to alter trace metal nutriture.
Two experiments investigated the neural mechanisms of Gestalt grouping by recording high-density event-related brain potentials (ERPs) during discrimination tasks. In Experiment 1, stimulus arrays contained luminance-defined local elements that were either evenly spaced or grouped into columns or rows based on either proximity or similarity of shape. Proximity grouping was indexed by a short-latency positivity (110-120 ms) over the medial occipital cortex and a subsequent right occipitoparietal negativity. Grouping by similarity was reflected only in a long-latency occipitotemporal negativity. In Experiment 2, proximity grouping was examined when local elements were defined by motion cues, and was again associated with a medial occipital positivity. However, the subsequent long-latency negativity was now enhanced over the left posterior areas. The implications of these results to the neural substrates subserving different grouping processes are discussed.
Endothelial nitric oxide contributes to the vascular hyporesponsiveness to norepinephrine (NE) observed in carotid arteries from rats exposed to simulated microgravity. The goal of the present study was to determine whether a cyclooxygenase product of arachidonic acid also influences vascular responsiveness in this setting. Microgravity was simulated in rats by hindlimb unweighting (HU). After 20 days of HU, carotid arteries were isolated from control and HU-treated rats, and vascular rings were mounted in tissue baths for the measurement of isometric contraction. Two cyclooxygenase inhibitors, indomethacin and ibuprofen, and the selective thromboxane A(2) prostanoid-receptor antagonist, SQ-29548, had no effect on the contraction to NE in control vessels but markedly reduced contraction to NE in HU vessels. When the endothelium was removed, indomethacin no longer had any effect on the NE-induced contraction in HU vessels. In endothelium-intact vessels in the presence of indomethacin, the addition of the nitric oxide synthase inhibitor, N(G)-L-nitro-arginine methyl ester, to the medium bathing HU vessels increased the contraction to NE to the level of that of the control vessels. These results indicate that HU treatment induced two endothelial changes in carotid artery that opposed each other. Nitric oxide activity was increased and was responsible for the vascular hyporesponsiveness to NE. The activity of a vasoconstrictor prostaglandin was also increased, and attenuated the vasodilating effect of nitric oxide.
A new reconstruction algorithm for phase-object imaging is proposed that is based on the principle of diffraction tomography and utilizes the Fourier transformation property of a finite-size phase object. From the measured scattered intensity, the imaginary part of the Fourier transform of the object can be extracted, and the three-dimensional structure of the object can be reconstructed. Numerical simulations show that the algorithm also can be used for a weak absorption object if the phase shift is much larger than the absorption.