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Biomedical subjects

M Suh

Publications and source records attributed to M Suh.

At least 19 recordsLinked to original sources
PubMed2004

Caregiver's burden, depression and support as predictors of post-stroke depression: a cross-sectional survey.

To examine the effects of caregiver's burden, depression, and support on post-stroke depression (PSD), cross-sectional data were obtained from an epidemiologic survey of 225 stroke survivors and their caregivers living in Seoul, Korea. Multivariate analyses showed that, taking the clinical status of patients into account, caregiver's burden, depression and support were related to higher PSD. Perceived burden exerts adverse effects on PSD through its influence on the depression in caregivers. Hence, the care of stroke survivors that incorporates the care of caregivers is likely to reduce the risk of post-stroke depression in patients.

Activities of Daily Living↗
PubMed2004

Dietary lipids containing gangliosides reduce Giardia muris infection in vivo and survival of Giardia lamblia trophozoites in vitro.

We examined whether a ganglioside supplemented diet affected the course of Giardia muris infection in mice and survival of Giardia lamblia trophozoites in vitro. Female CD-1 mice were fed 1 of 5 experimental diets: standard lab chow as a control diet; semi-synthetic diets containing 20% (w/w) triglyceride based on the fat composition of a conventional infant formula; triglyceride diet; triglyceride diet containing a low level of ganglioside (0.1% w/w); and triglyceride diet containing a high level of ganglioside (1.0% w/w of diet). After 2 weeks of feeding, mice were inoculated with G. muris by gastric intubation and fed the experimental diets during the course of the infection. Cysts released in the faeces and trophozoites present in the small intestine were enumerated at various times post-infection. The average cyst output and the number of trophozoites during the course of the infection in mice fed ganglioside-containing diet were found to be significantly lower (3-log10 reduction) compared to animals fed control diets. The results of in vitro growth studies indicated that gangliosides may be directly toxic to the parasites. Thus, gangliosides have a protective effect against G. muris infection in vivo and affect the survival of G. lamblia trophozoites in vitro.

Animals↗
PubMed2002

Complex spike activity in the flocculus signals more than the eye can see.

Modulation of the complex spike activity of Purkinje cells in the cerebellar flocculus can convey not only visual signals but also nonvisual signals. The nonvisual complex spike modulation, which is readily observed with vestibular stimulation of the awake rabbit in darkness, is approximately in-phase with the concomitant simple spike modulation. This nonreciprocal relationship contrasts to the reciprocal relationship found when the rabbit is afforded vision.

Action Potentials↗
PubMed2002

Complex predictive eye pursuit in monkey: a model system for cerebellar studies of skilled movement.

Smooth pursuit eye movements provide a good model system for cerebellar studies of complex motor control in monkeys. First, the pursuit system exhibits predictive control along complex trajectories and this control improves with training. Second, the flocculus/paraflocculus region of the cerebellum appears to generate this control. Lesions impair pursuit and neural activity patterns are closely related to eye motion during complex pursuit. Importantly, neural responses lead eye motion during predictive pursuit and lag eye motion during non-predictable target motions that require visual control. The idea that flocculus/paraflocculus predictive control is non-visual is also supported by a lack of correlation between neural activity and retinal image motion during pursuit. Third, biologically accurate neural network models of the flocculus/paraflocculus allow the exploration and testing of pursuit mechanisms. Our current model can generate predictive control without visual input in a manner that is compatible with the extensive experimental data available for this cerebellar system. Similar types of non-visual cerebellar control are likely to facilitate the wide range of other skilled movements that are observed.

Action Potentials↗
PubMed2001

HCV core protein modulates Rb pathway through pRb down-regulation and E2F-1 up-regulation.

It has been recognized that the HCV (hepatitis C virus) core protein plays an important role in hepatocarcinogenesis. The functional inactivation of the Rb pathway appears to be a major event for multi-step cancer carcinogenesis. To elucidate the role of the HCV core protein in hepatocarcinogenesis, we investigated the effect of the HCV core protein on the Rb pathway in both Rat-1 cell lines, stably expressing the HCV core protein and the doxycycline-regulated cell lines. The HCV core stable transfectants showed a dramatic decrease in the pRb levels and E2F-1 up-regulation. In the doxycycline-regulated cell lines, the pRb levels were significantly decreased which are followed by E2F-1 up-regulation. HCV core stable transfectants showed higher cell growth rates and were sensitize to apoptosis. Thus, our results first indicate that the HCV core protein decreases the expression of pRb, thereby allowing E2F-1 to be constitutively active, which is thought to result in rapid cell proliferation or sensitizing to apoptosis.

Animals↗
PubMed2000

Failure to induce inhibition of cyclin A and up-regulation of p21 expression in phorbol ester-resistant U937 cells by phorbol ester.

Differentiation resistant U937 cells were derived from parental U937 cells by selecting for continuously growing U937 cells in cell cultures continuously exposed to phorbol 12 myristate 13-acetate (PMA). Unlike in other known PMA resistant U937, the basal expression of protein kinase C (PKC) isozymes in these PMA resistant cells (R-U937) was significantly decreased. Subsequent analyses revealed differences between the wild type U937 and the R-U937 cells with respect to G1 phase arrest, which seemed to occur in U937 because of low levels of cdk2 kinase activity. This abolished cdk2 kinase activity is mainly due to inhibition of cdk2 phosphorylation, cyclin A down-regulation and cyclin dependent kinase inhibitor p21 up-regulation. Our data suggest that events down-stream of PKC activation may mediate cell cycle control. Thus, the R-U937 cells could be useful for further PKC mediated cell cycle control studies.

Blotting, Western↗
PubMed2000

Identification of a second site compensatory mutation in the Fe-protein that allows diazotrophic growth of Azotobacter vinelandii UW97.

Azotobacter vinelandii UW97 is defective in nitrogen fixation due to a replacement of serine at position 44 by phenylalanine in the Fe-protein [Pulakat, L., Hausman, B.S., Lei, S. and Gavini, N. (1996) J. Biol. Chem. 271, 1884-1889]. Serine residue 44 is located in a conserved domain that links the nucleotide binding site and the MoFe-protein docking surface of the Fe-protein. Therefore, it is possible that the loss of function by A. vinelandii UW97-Fe-protein may be caused by global conformational disruption or disruption of the conformational change upon MgATP binding. To determine whether it is possible to generate a functional nitrogenase complex via a compensating second site mutation(s) in the Fe-protein, we have attempted to isolate genetic revertants of A. vinelandii UW97 that can grow on nitrogen-free medium. One such revertant, designated A vinelandii BG9, encoded a Fe-protein that retained the Ser44Phe mutation and also had a second mutation that caused the replacement of a lysine at position 170 by glutamic acid. Lysine 170 is highly conserved and is located in a conserved region of the Fe-protein. This region is implicated in stabilizing the MgATP-induced conformation of the Fe-protein and in docking to the MoFe-protein. Further complementation analysis showed that the Fe-protein mutant that retained serine 44 but contained the substitution of lysine at position 170 by glutamic acid was also non-functional. Thus, neither Ser44Phe nor Lys170Glu mutants of Fe-protein were functional; however, the Fe-protein in A. vinelandii BG9 that contained both substitutions could support diazotrophic growth on the strain.

Adenosine Triphosphate↗
PubMed2000

Human ERK1 induces filamentous growth and cell wall remodeling pathways in Saccharomyces cerevisiae.

Expression of an activated extracellular signal-regulated kinase 1 (ERK1) construct in yeast cells was used to examine the conservation of function among mitogen-activated protein (MAP) kinases. Sequence alignment of the human MAP kinase ERK1 with all Saccharomyces cerevisiae kinases reveals a particularly strong kinship with Kss1p (invasive growth promoting MAP kinase), Fus3p (pheromone response MAP/ERK kinase), and Mpk1p (cell wall remodeling MAP kinase). A fusion protein of constitutively active human MAP/ERK kinase 1 (MEK) and human ERK1 was introduced under regulated expression into yeast cells. The fusion protein (MEK/ERK) induced a filamentation response element promoter and led to a growth retardation effect concomitant with a morphological change resulting in elongated cells, bipolar budding, and multicell chains. Induction of filamentous growth was also observed for diploid cells following MEK/ERK expression in liquid culture. Neither haploids nor diploids, however, showed marked penetration of agar medium. These effects could be triggered by either moderate MEK/ERK expression at 37 degrees C or by high level MEK/ERK expression at 30 degrees C. The combination of high level MEK/ERK expression and 37 degrees C resulted in cell death. The deleterious effects of MEK/ERK expression and high temperature were significantly mitigated by 1 m sorbitol, which also enhanced the filamentous phenotype. MEK/ERK was able to constitutively activate a cell wall maintenance reporter gene, suggesting misregulation of this pathway. In contrast, MEK/ERK effectively blocked expression from a pheromone-responsive element promoter and inhibited mating. These results are consistent with MEK/ERK promoting filamentous growth and altering the cell wall through its ability to partially mimic Kss1p and stimulate a pathway normally controlled by Mpk1p, while appearing to inhibit the normal functioning of the structurally related yeast MAP kinase Fus3p.

Cell Division↗
PubMed2000

The deltaF508 mutation in the cystic fibrosis transmembrane conductance regulator alters control of essential fatty acid utilization in epithelial cells.

Essential fatty acid (EFA) incorporation into phospholipid is influenced by chloride channels, suggesting that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) may regulate aspects of EFA metabolism. The objective of this study was to determine whether the DeltaF508 mutation in the CFTR lowers 18:2(n-6) levels in phospholipid. Control cells, CF cells and CF cells transfected with the "normal" CFTR gene or the DeltaF508 CFTR gene were cultured for 3-5 d and used to determine [1-(14)C]18:2(n-6) incorporation into cell lipids. CF cells exhibited low 18:2(n-6) levels in phospholipid, reduced [1-(14)C]18:2(n-6) incorporation into phospholipid (50% of control) and greater [1-(14)C]18:2(n-6) incorporation into the triacylglycerol fraction (400% of control; P: < 0.05). Kinetic modeling of time course data for [1-(14)C]18:2(n-6) incorporation revealed a loss of metabolic control over the intracellular partitioning of 18:2(n-6) between phospholipid and triacylglycerol pools in CF cells. Expression of the normal CFTR gene in transfected CF cells increased chloride efflux and the incorporation of [1-(14)C]18:2(n-6) into phospholipid and triacylglycerol fractions. The increased incorporation of [1-(14)C]18:2(n-6) into phospholipid was attributed to significantly increased incorporation of [1-(14)C]18:2(n-6) into phosphatidylcholine and phosphatidylinositol. In CF cells expressing the defective DeltaF508 CFTR gene, conversion of [1-(14)C]18:2(n-6) to 20:4(n-6) by desaturation-chain elongation was 1.8-fold greater (P: < 0.05) than observed for CF cells transfected with the normal gene. The observations suggest that CF results in a defect in the utilization of 18:2(n-6), which is attributed in part to the defective CFTR.

Cells, Cultured↗
PubMed2000

Cerebellar flocculus and paraflocculus Purkinje cell activity during circular pursuit in monkey.

Responses from 69 Purkinje cells in the flocculus and paraflocculus of two rhesus monkeys were studied during smooth pursuit of targets moving along circular trajectories and compared with responses during sinusoidal pursuit and fixation. A variety of interesting responses was observed during circular pursuit. Although some neurons fired most strongly in a single preferred direction during clockwise (CW) and counterclockwise (CCW) pursuit, others had directional preferences that changed with rotation direction. Some of these neurons showed similar modulation amplitudes during CW and CCW pursuit, whereas other neurons showed a preference for a particular rotation direction. Response specificity also was observed during sinusoidal pursuit. Some neurons showed responses that were much stronger during centrifugal pursuit, others showed a preference for centripetal pursuit, and still others showed responses during both centripetal and centrifugal motion. Differences in preferred response direction were sometimes observed for centripetal versus centrifugal pursuit. CW/CCW and centrifugal/centripetal preferences were not explained by a breakdown in component additivity. That is, modulations in firing rate during pursuit along a circular trajectory equaled the sum of modulations during horizontal and vertical sinusoidal components as well as for diagonal components. Instead all responses were well fit by a model that expressed the instantaneous firing rate of each neuron as a multilinear function of the two-dimensional position and velocity of the eye. This model generalized well to performance at different sinusoidal frequencies. It did somewhat less well for responses during fixation, suggesting some separation in the neural mechanisms of dynamic and static positioning. The model indicates that position sensitivity accounted for approximately 36% of the modulation during circular pursuit, and velocity sensitivity accounted for approximately 64%. When position and velocity sensitivity vectors were aligned, responses were simpler and modulations were similar during CW versus CCW pursuit. In contrast, when these vectors pointed in different directions, response complexity increased. Nonaligned position and velocity influences tended to reinforce during circular pursuit in one direction and to cancel each other during pursuit in the opposite direction. They also tended to produce response differences during centripetal versus centrifugal sinusoidal pursuit. The distinct roles played by position and velocity in shaping Purkinje cell responses are compatible with the control signals required to generate smooth pursuit along circular and other two-dimensional trajectories.

Animals↗
PubMed2000

Cerebellar flocculus and ventral paraflocculus Purkinje cell activity during predictive and visually driven pursuit in monkey.

Purkinje cells in the flocculus and ventral paraflocculus were studied in tasks designed to distinguish predictive versus visually guided mechanisms of smooth pursuit. A sum-of-sines task allowed studies of complex predictive pursuit. A perturbation task examined visually driven pursuit during unpredictable right-angle changes in target direction. A gap task examined pursuit that was maintained when the target was turned off. Neural activity patterns were quantified using multi-linear models with sensitivities to the position, velocity, and acceleration of both motor output (eye motion) and visual input (retinal slip). During the sum-of-sines task, neural responses led eye motion by an average of 12 ms, a value larger than the 9-ms transmission delay between flocculus stimulation and eye motion. This suggests that flocculus/paraflocculus neurons drove pursuit along predictable sum-of-sines trajectories. In contrast, neural responses led eye motion by an average of only 2 ms during the perturbation task and by 6 ms during the gap task. These values suggest a follow-up role during tasks more heavily dependent on visual processing. Activity in all three tasks was explained primarily by sensitivities to eye position and velocity. Eye acceleration played a minor role during ongoing pursuit, although its influence on firing rate increased during the high accelerations following unexpected changes in target motion. Retinal slip had a relatively small influence on responses during pursuit. This was particularly true for the sum-of-sines and gap tasks where predictive control eliminated any consistent retinal-slip signals that might have been used to drive the eye. Surprisingly, the influence of retinal slip did not increase appreciably during unpredictable perturbations in target direction that generated large amounts of retinal slip. Thus although visual control signals are needed in varying amounts during the three pursuit tasks, they have been converted to motor control signals by the time they leave the flocculus/paraflocculus system. Individual neurons showed a remarkable constancy in eye-sensitivity direction across tasks that indicated direct links to oculomotor neurons. However, some neurons showed changes in sensitivity magnitude that suggested changes in control strategy for different tasks. Magnitude differences were largest for the perturbation task. We conclude that the flocculus/paraflocculus system plays a major role in driving predictive pursuit. It also processes visually driven control signals that originate in other brain regions after a slight delay.

Animals↗
PubMed2000

Dietary 20:4n-6 and 22:6n-3 modulates the profile of long- and very-long-chain fatty acids, rhodopsin content, and kinetics in developing photoreceptor cells.

The objective of this study was to determine whether addition of dietary 20:4n-6 and 22:6n-3 to a conventional infant formula fat blend influences membrane long-chain and very-long-chain fatty acid composition, rhodopsin content, and rhodopsin kinetics in developing rat photoreceptor cells. The dietary fats were formulated based on the fat composition of a conventional infant formula providing an 18:2n-6/18:3n-3 ratio of 7:1 (SMA, Wyeth Nutritionals), which served as the control fat blend. This dietary fat blend was modified to contain 20:4n-6 [arachidonic acid (AA)], 22:6n-3 [docosahexaenoic acid (DHA)], AA + DHA, or an 18:2n-6/18:3n-3 ratio of 4:1 (alpha-linolenic acid). Dams were fed diets from birth, and rat pups were fed the same diet after weaning. Retinas and rod outer segments were prepared in the dark from pups at 2, 3, and 6 wk of age for fatty acid analysis of individual phospholipids, rhodopsin content, and rhodopsin disappearance kinetics after light exposure. Feeding AA + DHA in the diet increased 22:6n-3 levels in phosphatidylcholine and phosphatidylethanolamine. In phosphatidylcholine, total n-6 tetraenoic very-long-chain fatty acids and total n-3 pentaenoic and n-3 hexaenoic very-long-chain fatty acids increased after feeding AA and DHA, respectively. Developmental changes were characterized by a decrease in 20:4n-6 in the major phospholipids, whereas 22:6n-3 increased with age in rod outer segments. The highest rhodopsin content occurred in the retina of rats fed diets containing AA and/or DHA. The kinetics of rhodopsin disappearance after light exposure was highest in rats fed DHA at 6 wk of age. This study demonstrates that small manipulations of the dietary level of 20:4n-6 and 22:6n-3 are important determinants of fatty acid composition of membrane lipid and visual pigment content and kinetics in the developing photoreceptor cell.

Animals↗
PubMed1996

Relationship between dietary supply of long-chain fatty acids and membrane composition of long- and very long chain essential fatty acids in developing rat photoreceptors.

The present study was designed to determine if dietary supply of long-chain fatty acid (LCFA, C20:4n-6, and/or C22:6n-3), reflecting levels that might be incorporated into infant formulas, influences the fatty acid composition of the visual cell membrane. The rod outer segment (ROS) of the retina was analyzed from rats fed diets varying in the ratio of 18:2n-6 to 18:3n-3 with or without 20:4n-6 [arachidonic acid (AA)] and 22:6n-3 (docosahexaenoic acid) from birth to six weeks of age. The level of very long chain fatty acids (VLCFA, C24-C36) was identified using gas chromatography and gas chromatography-mass spectrometry. In the ROS, the highest relative percent of AA was attained in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of animals fed 1% AA diet, whereas feeding 0.7% docosahexaenoic acid (DHA) diet significantly increased the DHA level in PC, phosphatidylserine, and phosphatidylinositol compared to feeding diets containing AA. VLCFA of n-6 and n-3 up to C36 were found in PC, with the most abundant fatty acids being C32 and C34. In PC, phosphatidylserine and PE, the n-6 tetraenoic VLCFA level was highly increased in animals fed 1% AA compared to other dietary groups. This study suggests that dietary fat containing small amounts of AA or DHA is an important factor influencing membrane fatty acid composition of the visual cell during development.

Animals↗
PubMed1996

Streptozotocin-induced diabetes in rats is associated with impaired metabolic availability of vitamin A (retinol).

Using streptozotocin-induced diabetic Wistar rats, studies were carried out to examine the metabolic availability of vitamin A in the plasma, liver and the retina of the eye. Control and diabetic rats were fed ad lib. on a semi-purified diet either with or without (basal) vitamin A supplementation, or pair-fed on the basal diet for 4 weeks. Despite the fact that diabetic rats consumed 48% more feed, they had lower plasma concentrations of retinol (P < 0.003). The decrease in plasma retinol concentration was a response to diabetes (or diabetes-induced trauma), since neither pair-feeding (P < 0.01) nor vitamin A supplementation altered this effect (P < 0.05). Furthermore, the hepatic concentrations of the vitamin in these animals remained elevated and this increase was greater in the supplemented diabetic group (P < 0.001). Decreases in 11-cis retinal (a component of rhodopsin) concentrations in the retina were also observed in diabetic animals. The increased hepatic and the decreased plasma and retina vitamin A levels suggest a defect in the transport of the vitamin from the liver.

Animals↗
PubMed1995

Identification and quantitation of dibenzo[a,l]pyrene--DNA adducts formed by rat liver microsomes in vitro: preponderance of depurinating adducts.

Dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogen known among aromatic hydrocarbons. DB[a,l]P-11,12-dihydrodiol, precursor to the bay-region diol epoxide, is slightly less carcinogenic than the parent compound. DB[a,l]P and its 11,12-dihydrodiol were covalently bound to DNA by cytochrome P-450 in 3-methylcholanthrene-induced rat liver microsomes, and DB[a,l]P was also bound to DNA by horseradish peroxidase. The "stable" (remaining intact in DNA under normal conditions of purification) and "depurinating" (released from DNA by cleavage of the glycosidic link between the purine base and deoxyribose) adducts were identified and quantified. Stable adducts were analyzed by the 32P-postlabeling technique. Depurinating adducts were identified by comparison of their retention times with those of standard adducts on HPLC in two solvent systems. Confirmation of their identity was obtained by means of fluorescence line-narrowing spectroscopy. When DB[a,l]P was activated by horseradish peroxidase, the depurinating adducts 3-(DB[a,l]P-10-yl)adenine (DB[a,l]P-10-N3Ade, 33%), 7-(DB[a,l]P-10-yl)adenine (DB[a,l]P-10-N7Ade, 27%), and 7-DB[a,l]P-10-yl)guanine (DB[a,l]P-10-N7Gua, 5%) were formed. Unidentified stable adducts comprised the remaining 35% of the detected adducts. When DB[a,l]P was activated by microsomes, the one-electron oxidation depurinating adducts DB[a,l]P-10-N3Ade (28%), DB[a,l]P-10-N7Ade (14%), DB[a,l]P-10-N7Gua (2%), and DB[a,l]P-10-C8Gua (6%), as well as the diol epoxide depurinating adducts (+/-)-syn-DB[a,l]P-diol epoxide (DE)-14-N7Ade (31%) and (+/-)-anti-DB[a,l]PDE-14-N7Gua (3%), were formed. Stable adducts predominantly formed via the DB[a,l]PDE pathway represented 16% of the adducts detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Conformational studies of the (+)-trans, (-)-trans, (+)-cis, and (-)-cis adducts of anti-benzo[a]pyrene diolepoxide to N2-dG in duplex oligonucleotides using polyacrylamide gel electrophoresis and low-temperature fluorescence spectroscopy.

Using polyacrylamide gel electrophoresis (PAGE) and low-temperature, laser-induced fluorescence line narrowing (FLN) and non-line narrowing (NLN) spectroscopic methods, the conformational characteristics of stereochemically defined and site-specific adducts derived from the binding of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (anti-BPDE, a metabolite of the environmental carcinogen benzo[a]pyrene), to DNA were studied. The focus of these studies was on the four stereochemically distinct anti-BPDE modified duplexes 5'-d(CCATCGCTACC).(GGTAGCGATGG), where G denotes the lesion site derived from trans or cis addition of the exocyclic amino group of guanine to the C10 position of either (+) or (-)-anti-BPDE. PAGE experiments under non-denaturing conditions showed that the (+)-trans adduct causes a significantly greater retardation in the electrophoretic mobility than the other three adducts, probably the result of important adduct-induced distortions of the duplex structure. Low-temperature fluorescence studies in frozen aqueous buffer matrices showed that the (+)-trans adduct adopts primarily an external conformation with only minor interactions with the helix, but a smaller fraction (approximately 25%) appears to exists in a partially base-stacked conformation. The (-)-trans adduct exists almost exclusively (approximately 97%) in an external conformation. Both cis adducts were found to be intercalated; strong electron-phonon coupling observed in their FLN spectra provided additional evidence for significant pi-pi stacking interactions between the pyrenyl residues and the bases. FLN spectroscopy is shown to be suitable for distinguishing between trans and cis adducts, but lesions with either (+)- or (-)-trans, or (+)- or (-)-cis stereochemical characteristics showed very similar vibrational patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗