Biomedical subjects

S Jung

Publications and source records attributed to S Jung.

At least 19 recordsLinked to original sources

PubMed2006

Enrichment of integral membrane proteins from small amounts of brain tissue.

Subcellular fractionation represents an essential technique for functional proteome analysis. Recently, we provided a subcellular fractionation protocol for minute amounts of tissue that yielded a nuclear fraction, a membrane and organelle fraction, and a cytosolic fraction. In the current study, we attempted to improve the protocol for the isolation of integral membrane proteins, as these are particularly important for brain function. In the membrane and organelle fraction, we increased the yield of membranes and organelles by about 50% by introducing a single re-extraction step. We then tested two protocols towards their capacity to enrich membrane proteins present in the membrane and organelle fraction. One protocol is based on sequential solubilization using subsequent increases of chaotropic conditions such as urea, thereby partitioning hydrophobic proteins from hydrophilic ones. The alternative protocol applies high-salt and high-pH washes to remove non-membrane proteins. The enrichment of membrane proteins by these procedures, as compared to the original membrane and organelle fraction, was evaluated by 16-BAC-SDS-PAGE followed by mass spectrometry of randomly selected spots. In the original membrane and organelle fraction, 7 of 50 (14%) identified proteins represented integral membrane proteins, and 15 (30%) were peripheral membrane proteins. In the urea-soluble fraction, 4 of 33 (12%) identified proteins represented integral membrane proteins, and 10 (30%) were peripheral membrane proteins. In the high-salt/high-pH resistant sediment, 12 of 45 (27%) identified proteins were integral membrane proteins and 13 (29%) represented peripheral membrane proteins. During the analysis, several proteins involved in neuroexocytosis were detected, including syntaxin, NSF, and Rab3-interaction protein 2. Taken together, differential centrifugation in combination with high-salt and high-pH washes resulted in the highest enrichment of integral membrane proteins and, therefore, represents an adequate technique for region-specific profiling of membrane proteins in the brain.

Animals↗

PubMed2006

Spinal metastasis from cranial meningeal hemangiopericytomas.

Spine metastasis from cranial meningeal hemangiopericytomas are extremely rare, with five surgically verified cases. We describe a case of a 55-year-old female diagnosed with metastatic hemangiopericytoma to the cervical spine 78 months after the first operation. Because of the long latency period, aggressive spinal surveillance should be advocated along with repeated bone scintigraphy and MRI.

Cervical Vertebrae↗

PubMed2006

[Are we testing the right people? Results of a patient questionnaire in the STD and HIV counselling office of the local health authority in the city of Cologne].

BACKGROUND: HIV testing and counselling is offered free of charge in most local health offices in Germany. During 2003, a survey was performed among German-speaking clients of the Cologne local health office to look at socio-demographic background, reasons for testing and sexual risk behaviour. METHODS: All German-speaking clients attending the HIV counselling office from March to July 2003 were asked to fill in an anonymous standardised questionnaire. Questions included demographic characteristics, social status, STI history, reasons for HIV testing, sexual orientation and number of sexual partners. Data were compared to the general Cologne population regarding demographic characteristics. Female respondents were compared to heterosexual men and men who have sex with men (MSM); German respondents were compared to migrants using SPSS 14.0. RESULTS: A total of 457 female and 488 male clients participated (response rate 93.9 %). Average age was 28.4 years. Of all participants, 17.7 % were of non-German origin. The respondents had a high school degree in 80.8 % of the cases compared to 33.5 % in the general Köln population (p < 0.001). Among men, 30.2 % were MSM. Having a "new partner" or "unprotected sex with a person with unknown HIV status" were reported by 483 (39.8 %) and 373 (30.8 %) as reasons for testing. 38.7 % of the respondents reported choosing the local health office for HIV testing because it was free of charge and 24.5 % because it was anonymous. Women and heterosexual men had a median of 1, MSM a median of 3 sexual partners within the past 6 months (p < 0.001). Vaccination against hepatitis B was reported by 34.4 % of the clients, the proportion was higher among MSM (46.9 % p < 0.001) and lower among migrants. 112 (11.9 %) persons reported having had a previous STI. CONCLUSIONS: With the exception of MSM, the offer of free and anonymous HIV testing and counselling does not reach persons who carry a higher risk for HIV. As the risk for STI is higher than for HIV in Germany and there is a low public awareness, HIV counselling should be used for comprehensive sexual health counselling and include the offer for STI testing, Further outreaching efforts and other settings are necessary to reach persons with a low education level and highly vulnerable persons.

Adult↗

PubMed2006

Application of neuronavigation system to brain tumor surgery with clinical experience of 420 cases.

A new era of neurosurgery has recently been unveiled with the advent of image-guided surgery. The use of neuronavigation is beginning to have a significant impact on a variety of intracranial procedures. Herein, we report our clinical experience using a neuronavigation system with different surgical applications and techniques for a variety of brain tumors. We used the BrainLab VectorVision neuronavigation system, which is a frameless and image-guided system. We operated on 420 cases having various types of brain tumor with the help of this system. The mean target localizing accuracy and mean volume were 1.15 mm and 30.8 mL (0.2-216.4 mL), respectively. We utilized this system to effectively make bone flaps, to detect critically located, deep-seated, subcortical, skull-base and skull bone tumors, and to operate on intraparenchymal lesions with grossly unclear margins, such as gliomas. We also performed tumor biopsy using the combination of a conventional stereotactic biopsy instrument and an endoscope. The application of the neuronavigation system not only revealed benefits for operative planning, appreciation of anatomy, lesion location and the safety of surgery, but also greatly enhanced surgical confidence.

Adolescent↗

PubMed2006

Posterior circulation ischemic stroke in Korean population.

To understand the characteristics of posterior circulation ischemic stroke (PCS) in the Korean population better, we retrospectively reviewed the data from the Hallym Stroke Registry (HSR). We analyzed the demographic features, risk factors, stroke subtypes, lesion distributions and clinical outcomes of 591 consecutive patients with PCS, enrolled in HSR between January 1996 and July 2002. PCS was 39.8% of all ischemic strokes. Mean age of PCS patients was 63.4 years and 55.7% were men. Hypertension was the most common risk factor (69.9%). However, potential cardioembolic sources were found only in 11.0%. The most frequent stroke subtype was large artery disease (50.0%), followed by small vessel disease (33.8%). Only 5.2% of patients were classified as affected with cardioembolism. The most common location of infarcts was in the middle territory (36.5%), followed by distal (28.1%), proximal (19.0%), and multiple territories (16.4%). The hospital mortality rate (4.1%) and discharge outcome of PCS were comparable with those of the anterior circulation stroke (ACS). In conclusion, the etiology and lesion topography of PCS in the Korean population appeared to be different from those of the Caucasians.

Aged↗

PubMed2006

Diastolic dysfunction in human cardiac allografts is related with reduced SERCA2a gene expression.

Previous studies demonstrated that impaired left ventricular (LV) relaxation in cardiac allografts limits exercise tolerance post-transplant despite preserved systolic ejection fraction (EF). This study tested in human cardiac allografts whether the isovolumic relaxation time (IVRT), which provides the basis for most of diastolic LV filling, relates with gene expression of regulatory proteins of calcium homeostasis or cardiac matrix proteins. Gene expression was studied in 31 heart transplant recipients (25 male, 6 female) 13-83 months post-transplant with LVEF >50%, LV end-diastolic pressure <20 mmHg, normal LV mass index and without allograft rejection or significant cardiac pathology. IVRT related with the other diastolic parameters e-wave velocity (r = -0.46; p = 0.01), e/a-wave ratio (r = -0.5; p < 0.01) but not with heart frequency (r = -0.16; p = 0.4). No relation of IVRT was observed for immunosuppression, mean rejection grade or other medication. IVRT was not related with gene expression of desmin, collagen I, phospholamban, the Na+-Ca2+ exchanger, the ryanodine receptor or interstitial fibrosis but correlated inversely with SERCA2a (r = -0.48; p = 0.02). Prolonged IVRT is associated with decreased SERCA2a expression in cardiac allografts without significant other pathology. Similar observations in non-transplanted patients with diastolic failure suggest that decreased SERCA2a expression is an important common pathomechanism.

Adult↗

PubMed2004

High-oleate peanut mutants result from a MITE insertion into the FAD2 gene.

A high-oleate trait in the cultivated peanut ( Arachis hypogaea L.) was reported to rely on the allelic composition of the two homeologous, microsomal oleoyl-PC desaturase genes ( ahFAD2A or ahFAD2B). The enzyme activity of either ahFAD2A or ahFAD2B is sufficient for a normal oleate phenotype, and a significant reduction in the levels of ahFAD2B and a mutation in ahFAD2A were reported to be responsible for the high-oleate phenotype in one chemically induced mutant (M2-225) and one derived from a naturally occurring (8-2122) mutant. Here, we report an insertion of the same miniature inverted-repeat transposable element (MITE) in the ahFAD2B gene in another chemically induced mutant (Mycogen-Flavo) and the previously characterized M2-225 mutant. In both cases, this MITE insertion in ahFAD2B causes a frameshift, resulting in a putatively truncated protein sequence in both mutants. The insertion of this MITE in ahFAD2B, in addition to the point mutation in ahFAD2A, appears to be the cause of the high-oleate phenotype in Mycogen-Flavo and M2-225 mutants. Utilizing sequences of the MITE, we developed a DNA marker strategy to differentiate the two insertion-containing mutants from the normal oleate peanut variety (AT-108) and the naturally occurring, high-oleate mutant 8-2122. Reverse transcript-PCR/differential digestion results reveal the expression of both ahFAD2A and ahFAD2B genes in Mycogen-Flavo mutant. This result is in contrast to the observation that ahFAD2B transcripts are greatly reduced in the M2-225 mutant having the MITE insertion further 3' in ahFAD2B gene.

Amino Acid Sequence↗

PubMed2004

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗

PubMed2004

Effect of chlorophyll reduction in Arabidopsis thaliana by methyl jasmonate or norflurazon on antioxidant systems.

Methyl jasmonate (MeJA) and norflurazon (NF) treatments resulted in a substantial decrease in photosynthetic activities and chlorophylls (Chls) in Arabidopsis thaliana plants, causing a senescence-like yellowing and a bleaching in MeJA- and NF-treated plants, respectively. Non-radiative energy dissipation through q(N) and non-photochemical quenching increased greatly in NF-treated plants in concomitance with an increase in photoprotectants antheraxanthin and zeaxanthin from interconversion of violaxanthin, although they were not changed in MeJA-treated plants. A significant accumulation of anthocyanin was observed only in MeJA-treated plants, not in NF-treated plants. Total activities of catalase (CAT, EC 1.11.1.6), peroxidase (POD, EC 1.11.1.7), superoxide dismutase (EC 1.15.1.1) and glutathione reductase (EC 1.6.4.2) increased greatly in response to MeJA, particularly a 100-fold increase in POD activity 7 days after MeJA treatment. NF application to plants exhibited less increase in antioxidant enzymes than MeJA-treated plants. NF-treated young leaves had a greater decline in Chls and CAT activity, and less zeaxanthin accumulation compared to NF-treated mature leaves, indicating that NF-treated young leaves are more susceptible to excess light exposure and a possible photooxidative stress. Both MeJA- and NF-treated Arabidopsis plants suffered destruction of Chls, however, they developed differential antioxidant responses during the stress, in large part by an increased anthocyanin level in the epidermis and enzymatic antioxidants in MeJA-treated plants and by accumulation of antheraxanthin and zeaxanthin, and enhanced energy dissipation in NF-treated plants.

Acetates↗

PubMed2004

Neuronavigation-guided endoscopic surgery for pineal tumors with hydrocephalus.

We have applied the neuronavigation system to endoscopic biopsy and third ventriculostomy in the management of patients with a pineal tumor with hydrocephalus. With the guidance of neuronavigation, the two optimal sites of burr hole and trajectories were planned preoperatively, and the advancing endoscopic device was monitored in real time during the procedure. In our five patients, the diameters of the tumors were 2-3 cm, and the mean systemic accuracy of registration with neuronavigation was 1.2 mm. The biopsy and third ventriculostomy were performed successfully via the respective optimal burr hole and the trajectory determined using preoperative neuronavigation. There were no procedure-related complications, and none of the patients needed another procedure for CSF diversion during the follow-up periods. We present our technique which includes the application of the neuronavigation system to the biopsy and third ventriculostomy in pineal tumor with associated hydrocephalus. This technique can be performed using a simple rigid endoscope via the determined optimal entries and trajectories. The optimal preoperative planning and the intraoperative guidance by neuronavigation are thought to be able to give more chances to minimize the brain injury related to movements or deviation of endoscopic device.

Adolescent↗

PubMed2004

Distinct clinical expressions of striatocapsular infarction according to cortical manifestations.

Striatocapsular infarction is known to have various neurologic manifestations including cortical symptoms. However, striatocapsular infarction patients without cortical dysfunctions can be easily found. Therefore, we tried to evaluate the properties and pathogenesis of two distinct expressions of striatocapsular infarction, striatocapsular infarction with and without cortical dysfunctions respectively. Forty-eight patients were divided into two groups according to their initial manifestations. Forty-eight patients with striatocapsular infarction were divided into cortical type of striatocapsular infarction (CSCI) and non-cortical type (NCSCI) according to their initial manifestations. We compared the properties such as stroke risk factors, laboratory data, and clinical features and assessed magnetic resonance imaging (MRI) and MR angiography for possible mechanisms in each type of striatocapsular infarction. Patients with CSCI and those with NCSCI had similar characteristics, laboratory data and morphologic findings in MRI. CSCI patients had more profound initial neurologic manifestations [Both National Institutes of Health Stroke Scale (NIHSS) score and Barthel index]. In MR angiography, patients with CSCI showed more frequent single middle cerebral artery (MCA) stenosis, whereas NCSCI patients had findings that were more heterogeneous. In conclusion, we found that not all the patients with striatocapsular infarction had cortical dysfunctions. It is possible for lesions with similar size and location to have different manifestations (cortical or non-cortical) according to their vascular integrity.

Aged↗

PubMed2003

Independent association of HLA-DR and FCgamma receptor polymorphisms in Korean patients with systemic lupus erythematosus.

OBJECTIVES: To determine the distribution of HLA-DR type and FcgammaRIIa/IIIa polymorphisms, and to analyse the combined effects of these genes for susceptibility in Korean systemic lupus erythematosus (SLE) patients. METHODS: A total of 299 SLE patients meeting 1982 ACR criteria and 144 Korean disease-free controls were enrolled. Genotyping for the FcgammaRIIa 131 R/H and FcgammaRIIIa 176 F/V was performed by polymerase chain reaction (PCR) of genomic DNA using allele-specific primers. HLA-DRB1 typing was performed by the PCR-SSOP method. RESULTS: There was significant skewing in the distribution of the three FcgammaRIIa genotypes between the SLE patients and the controls [P = 0.002 for R/R131 vs R/H131 and H/H131, relative risk (RR) 2.6 (95% CI 1.3-5.2)], but not in FcgammaRIIIa genotypes. HLA-DRB1*15 allele was significantly more prevalent among SLE patients than the control population [P < 0.02, RR = 1.7 (1.1-2.6)]. HLA-DRB1 genotypes or allele frequencies of the SLE patients with nephritis did not differ significantly from those of the SLE patients without nephritis. We analysed the combined effects of the two candidate genes on SLE susceptibility. HLA-DRB1*15 allele was a significant predictor of SLE in individuals who were not homozygous for FcgammaRIIa-R/R131 [RR = 2.1 (1.2-3.7), P < 0.008], and the FcgammaRIIa-R/R131 genotype vice versa [RR = 5.3 (1.9-15.4), P < 0.001]. However, an additive or synergistic effect of both susceptible genes on relative risk for SLE was not evident. CONCLUSIONS: Our results suggest that FcgammaRIIa-R/R131 homozygote and HLA-DRB1*15 allele are independent risk factors in Korean SLE patients without additive or synergistic effects.

Adult↗

PubMed2003

Molsidomine ameliorates experimental allergic encephalomyelitis in Lewis rats.

Experimental allergic encephalomyelitis (EAE) is an autoimmune CD4+ T cell-mediated disease of the central nervous system (CNS). Nitric oxide (NO) plays an important role in preventing the development of EAE. Molsidomine (Mol) is a drug used for the treatment of coronary artery disease. Its therapeutic effects are the consequences of NO formation. In this study, we investigated the effects of Mol on EAE development in myelin basic protein (MBP)-immunized Lewis rats. All rats immunized with MBP developed typical clinical signs of acute EAE. In the EAE rats receiving Mol, the severity of clinical signs and the infiltration of inflammatory cells in CNS were clearly reduced. Furthermore, Mol administration significantly reduced the production of interferon-gamma, a Th1 inflammatory cytokine, but increased the production of interleukin-10, a Th2 anti-inflammatory cytokine. Our findings suggest that the administration of the exogenous NO donor Mol is of considerable benefit in limiting the development of EAE and other Th1 cell-mediated inflammatory diseases.

Animals↗

PubMed2003

Deletion of the alpha1 or beta2 subunit of GABAA receptors reduces actions of alcohol and other drugs.

Enhancement of the activation of GABAA receptors is a common feature of many sedative and hypnotic drugs, and it is probable that the GABAA receptor complex is a molecular target for these drugs in the mammalian central nervous system. We set out to elucidate the role of the two predominant (alpha1 and beta2) subunits of GABAA receptor in sedative drug action by studying mice lacking these two subunits. Both alpha1 (-/-) and beta2 (-/-) null mutant mice showed markedly decreased sleep time induced by nonselective benzodiazepine, flurazepam, and GABAA agonist, 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol. The sleep time induced by the beta-selective drug etomidate was decreased only in beta2 (-/-) knockout mice. In contrast, alpha1 (-/-) mice were more resistant to the alpha1-selective drug zolpidem than beta2 (-/-) or wild-type animals. Knockout mice of both strains were similar to wild-type mice in their responses to pentobarbital. The duration of loss of the righting reflex produced by ethanol was decreased in male mice for both null alleles compared with wild-type mice, but there were no differences in ethanol-induced sleep time in mutant females. Deletion of either the alpha1 or beta2 subunits reduced the muscimol-stimulated 36Cl36 influx in cortical microsacs suggesting that these mutant mice have reduced number of functional brain GABAA receptors. Our results show that removal of either alpha1 or beta2 subunits of GABAA receptors produce strong and selective decreases in hypnotic effects of different drugs. Overall, these data confirm the crucial role of the GABAA receptor in mechanisms mediating sedative/hypnotic effects.

Animals↗

PubMed2002

Geometric fractal growth model for scale-free networks.

We introduce a deterministic model for scale-free networks, whose degree distribution follows a power law with the exponent gamma. At each time step, each vertex generates its offspring, whose number is proportional to the degree of that vertex with proportionality constant m-1 (m>1). We consider the two cases: First, each offspring is connected to its parent vertex only, forming a tree structure. Second, it is connected to both its parent and grandparent vertices, forming a loop structure. We find that both models exhibit power-law behaviors in their degree distributions with the exponent gamma = 1+ln(2m-1)/ln m. Thus, by tuning m, the degree exponent can be adjusted in the range, 2 < gamma < 3. We also solve analytically a mean shortest-path distance d between two vertices for the tree structure, showing the small-world behavior, that is, d approximately ln N/ln K macro, where N is system size, and k macro is the mean degree. Finally, we consider the case that the number of offspring is the same for all vertices, and find that the degree distribution exhibits an exponential-decay behavior.

Journal Article↗

PubMed2002

Functional relevance of activin A in the intestinal epithelium.

BACKGROUND: Activin A modulates inflammation and repair in various tissues. The aim of this study was to characterize the effects of activin A on intestinal epithelial cell function and to evaluate a potential role in intestinal epithelial wound repair and inflammation. METHODS: The expression of activin A and its receptors ActRI and ActRII in intestinal epithelial IEC-6 cells and in tissues from IBD patients and non-inflamed controls was evaluated using RT-PCR and immunohistochemistry. Functional effects of activin A on intestinal epithelial cell migration and proliferation were assessed using an in vitro wounding model and colorimetric MTT assays. RESULTS: Expression of the activin betaA subunit and the activin receptors ActRI and ActRII in IEC-6 cells was demonstrated using RT-PCR. Activin A (50 ng/ml) caused a significant, on average 2.8-fold enhancement of epithelial cell migration and a significant on average 4.1-fold inhibition of IEC-6 cell proliferation. Expression of ActRI and ActRII was observed in all intestinal tissues from patients with IBD and in all controls. In contrast, no expression of the activin betaA-subunit was observed in controls, while betaA expression was found in intestinal tissues from IBD patients. CONCLUSIONS: Activin A may play an important role in the modulation of intestinal epithelial cell function, thus providing a new approach to modulate intestinal wound repair.

Activin Receptors↗

PubMed2001

Regulation of nuclear poly(A) addition controls the expression of immunoglobulin M secretory mRNA.

B-cell differentiation is accompanied by a dramatic increase in cytoplasmic accumulation and stability of the IgM heavy chain (mu) secretory mRNA. Despite considerable effort, the mechanism is unknown. We have identified three short motifs upstream of the secretory poly(A) site, which, when mutated in the mu heavy chain gene, significantly increase the accumulation of the secretory form of poly(A)(+) mRNA relative to the membrane form and regulate the expression of the secretory poly(A) site in a developmental manner. We show that these motifs bind U1A and inhibit polyadenylation in vitro and in vivo. Overexpression of U1A in vivo results in the selective inhibition of the secretory form. Thus, this novel mechanism selectively controls post-cleavage expression of the mu secretory mRNA. We present evidence that this mechanism is used to regulate alternative expression of other genes.

Amino Acid Motifs↗

PubMed2001

Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues.

Interstitial fluid is constantly drained into lymph nodes (LNs) via afferent lymph vessels. This conduit enables monocyte-derived macrophages and dendritic cells to access LNs from peripheral tissues. We show that during inflammation in the skin, a second recruitment pathway is evoked that recruits large numbers of blood-borne monocytes to LNs via high endothelial venules (HEVs). Inhibition of monocyte chemoattractant protein (MCP)-1 blocked this inflammation-induced monocyte homing to LNs. MCP-1 mRNA in inflamed skin was over 100-fold upregulated and paralleled MCP-1 protein levels, whereas in draining LNs MCP-1 mRNA induction was much weaker and occurred only after a pronounced rise in MCP-1 protein. Thus, MCP-1 in draining LNs was primarily derived from inflamed skin. In MCP-1(-/-) mice, intracutaneously injected MCP-1 accumulated rapidly in the draining LNs where it enhanced monocyte recruitment. Intravital microscopy showed that skin-derived MCP-1 was transported via the lymph to the luminal surface of HEVs where it triggered integrin-dependent arrest of rolling monocytes. These findings demonstrate that inflamed peripheral tissues project their local chemokine profile to HEVs in draining LNs and thereby exert "remote control" over the composition of leukocyte populations that home to these organs from the blood.

Adoptive Transfer↗