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Biomedical subjects

M Jung

Publications and source records attributed to M Jung.

At least 127 records · Page 7Linked to original sources
PubMed1998

Neuronal basic helix-loop-helix proteins (NEX, neuroD, NDRF): spatiotemporal expression and targeted disruption of the NEX gene in transgenic mice.

Basic helix-loop-helix (bHLH) genes have emerged as important regulators of neuronal determination and differentiation in vertebrates. Three putative neuronal differentiation factors [NEX for neuronal helix-loop-helix protein-1 (mammalian atonal homolog-2), neuroD (beta-2), and NDRF for neuroD-related factor (neuroD2)] are highly homologous to each other in the bHLH region and comprise a new bHLH subfamily. To study the role of NEX, the first bHLH protein identified in this group, we have disrupted the NEX gene by homologous recombination. NEX-deficient mice have no obvious developmental defect, and CNS neurons appear fully differentiated. To investigate further whether the absence of NEX is compensated for by neuroD and NDRF, we compared the spatiotemporal expression of all three genes. We demonstrate, by in situ hybridization, that the transcription patterns of NEX, neuroD, and NDRF genes are highly overlapping in the developing CNS of normal rats between embryonic day 12 and adult stages but are not strictly identical. The most prominent transcription of each gene marks the dorsal neuroepithelium of the telencephalon in early development and is sustained in the adult neocortex, hippocampus, and cerebellum. In general, neuroD provides the earliest marker of neuronal differentiation in any given region compared with NDRF or NEX. Whereas a few CNS regions are specific for neuroD, no region was detected in which solely NEX or NDRF is expressed. This suggests that the function of the mutant NEX gene in neuronal differentiation is compensated for by neuroD and NDRF and that, in analogy with myogenic bHLH proteins, neuronal differentiation factors are at least in part equivalent in function.

Aging↗
PubMed1998

Identification of reggie-1 and reggie-2 as plasmamembrane-associated proteins which cocluster with activated GPI-anchored cell adhesion molecules in non-caveolar micropatches in neurons.

Neurons are believed to possess plasmalemmal microdomains and proteins analogous to the caveolae and caveolin of nonneuronal cells. Caveolae are plasmalemmal invaginations where activated glycosyl-phosphatidylinositol (GPI)-anchored proteins preferentially assemble and where transmembrane signaling may occur. Molecular cloning of rat reggie-1 and -2 (80% identical to goldfish reggie proteins) shows that reggie-2 is practically identical to mouse flotillin-1. Flotillin-1 and epidermal surface antigen (ESA) (flotillin-2) are suggested to represent possible membrane proteins in caveolae. Rat reggie-1 is 99% homologous to ESA in overlapping sequences but has a 49-amino-acid N-terminus not present in ESA. Antibodies (ABs) which recognize reggie-1 or -2 reveal that both proteins cluster at the plasmamembrane and occur in micropatches in neurons [dorsal root ganglia (DRGs), retinal ganglion, and PC-12 cells] and in nonneuronal cells. In neurons, reggie micropatches occur along the axon and in lamellipodia and filopodia of growth cones, but they do not occur in caveolae. By quantitative electronmicroscopic analysis we demonstrate the absence of caveolae in (anti-caveolin negative) neurons and show anti-reggie-1 immunogold-labeled clusters at the plasmamembrane of DRGs. When ABs against the GPI-anchored cell adhesion molecules (CAMs) F3 and Thy-1 are applied to live DRGs, the GPI-linked CAMs sequester into micropatches. Double immunofluorescence shows a colocalization of the CAMs with micropatches of anti-reggie antibodies. Thus, reggie-1 and reggie-2 identify sites where activated GPI-linked CAMs preferentially accumulate and which may represent noncaveolar micropatches (domains).

Amino Acid Sequence↗
PubMed1998

Overexpression of Rb and E2F-1 in ataxia-telangiectasia lymphocytes.

AT cells exhibit defective cell cycle regulation following DNA damage. Previous studies have shown that induction of p53 and p21 proteins are delayed in response to ionizing radiation, resulting in the failure of G1/S checkpoint in AT cells. In this study, further investigation of the molecular mechanisms underlying G1/S phase progression in AT cells was conducted. Exponentially growing normal and AT cells were exposed to 2 Gy of ionizing radiation and the expression levels and functional activities of Rb and E2F-1 proteins were determined. We observed overexpression of hyperphosphorylated Rb and E2F-1 proteins in AT cells, which was unaffected post-irradiation. Furthermore, gel shift assays showed that E2F-1-DNA binding was constitutive in AT cells, whereas it was inhibited in control cells following exposure to ionizing radiation. The data suggests that abnormalities in the function of Rb and E2F-1 proteins may also be responsible for the failure of AT cells to arrest in the G1/S checkpoint in response to DNA damage.

Adenovirus E2 Proteins↗
PubMed1998

Psychophysical methods and passenger preferences of interior designs.

A psychophysical experiment was conducted to evaluate the interior design alternatives of a high-speed train. Preference of each design alternative was quantitatively measured by using the magnitude estimation technique. Subsequent analyses showed that (1) passenger seats should be able to be arranged in the moving direction of a train, (2) a variety of interior convenience facilities, especially, an audio facility, should be provided to enhance passenger comfort and (3) the design requirements suggested by young passengers could improve the overall preference level. In addition, guidelines for collecting, standardizing, and analyzing the data are suggested when the magnitude estimation technique is used. The use of psychophysical data is expected to be very useful when it is necessary to make engineering decisions based on quantitative preference data.

Adult↗
PubMed1998

Coach design for the Korean high-speed train: a systematic approach to passenger seat design and layout.

Proper ergonomic design of a passenger seat and coach layout for a high-speed train is an essential component that is directly related to passenger comfort. In this research, a systematic approach to the design of passenger seats was described and the coach layout which reflected the tradeoff between transportation capacity and passenger comfort was investigated for the Korean high-speed train. As a result, design recommendations and specifications of the passenger seat and its layout were suggested. The whole design process is composed of four stages. A survey and analysis of design requirement was first conducted, which formed the base for designing the first and second class passenger seats. Prototypes were made and evaluated iteratively, and seat arrangement and coach layout were finally obtained. The systematic approach and recommendations suggested in this study are expected to be applicable to the seat design for public transportations and to help modify and redesign existing vehicular seats.

Adult↗
PubMed1998

Novel pluripotential neural progenitor lines exhibiting rapid controlled differentiation to neurotransmitter receptor-expressing neurons and glia.

The immortalization of progenitor cells from embryonic murine hippocampus using oncogene-carrying retroviral vectors is described. Use of a vector encoding the oncogene v-myc results in lines of nestin-positive progenitor cells. Limited differentiation ensues if the cells are cultured in the presence of dibutyryl cyclic adenosine monophosphate. In contrast, use of a vector in which the extracellular portion of the epidermal growth factor (EGF) receptor is fused to the neu tyrosine kinase generates lines of pluripotential nestin-positive progenitor cells, which differentiate upon withdrawal of EGF into neurons and glia. Differentiated neurons expressing action potentials and neurotransmitter receptors make up a high proportion of the cells. These cell lines are useful tools to investigate the characteristics of differentiating neurons and glia, as well as to screen neuroactive drugs. This work has been reported in preliminary form as an abstract (1996 Society for Neuroscience Abstract, #606.20, p. 1537).

Action Potentials↗
PubMed1998

Is pancreatoscopy of any benefit in clarifying the diagnosis of pancreatic duct lesions?

BACKGROUND AND STUDY AIMS: Modern fine-caliber endoscopes enable clinicians to directly visualize the pancreatic duct. They allow intraductal manipulation under optical control. We tried to evaluate the additional diagnostic potential of pancreatoscopy in assessing inconclusive intraductal pancreatic changes. PATIENTS AND METHODS: We prospectively performed 20 pancreatoscopies in 18 patients with inconclusive ductal abnormalities that had been previously investigated by computed tomography (CT) scan, abdominal ultrasound and endoscopic retrograde cholangiopancreatography (ERCP). The CHF-BP 30 (Olympus Optical Co., Japan) endoscope with an outer diameter of 3.1 mm and an instrumentation channel of 1.2 mm was used. Biopsies, cytological brushing and fluid collection were carried out, and the site of ductal abnormality was visualized. Endoscopic sphincterotomy (EST) was carried out in every patient prior to insertion of the pancreatoscope. RESULTS: Seven intraductal tumors were histologically confirmed, i.e. five intraductal papillary mucinous tumors and two adenocarcinomas. Benign appearance of the intraductal lesion plus negative histopathological examinations were confirmed by a follow-up of two years in eight patients. Five had chronic pancreatitis, and a further three had pancreatitis with strictures, blood clot obstruction, and idiopathic benign stricture, respectively. There were no complications with the exception of one bleeding episode after EST; no pancreatitis occurred. CONCLUSIONS: Pancreatoscopy is of diagnostic value in addition to CT, transabdominal ultrasound and ERCP in the differential diagnosis of poorly defined pancreatic lesions, particularly when assessing alterations of the ductal caliber without parenchymatous lesions.

Adenoma↗
PubMed1998

The gene for human fibronectin glomerulopathy maps to 1q32, in the region of the regulation of complement activation gene cluster.

Fibronectin glomerulopathy (GFND) is a newly recognized autosomal dominant disease of the kidney that results in albuminuria, microscopic hematuria, hypertension, renal tubular acidosis type IV, and end-stage renal disease in the 2d to 6th decade of life. The disease is characterized histologically by massive deposits of fibronectin (Fn) present in the subendothelial spaces of renal glomerular capillaries. The cause of human GFND is unknown. In order to localize a candidate gene for GFND, we performed linkage analysis of a large, 193-member pedigree containing 13 affected individuals. Since we had previously excluded the genes for Fn and uteroglobin as candidate genes for GFND, a total-genome search for linkage was performed. Examination of 306 microsatellite markers resulted in a maximum two-point LOD score of 4.17 at a recombination fraction of. 00 for marker D1S249, and a maximum multipoint LOD score of 4.41 for neighboring marker D1S2782. By detection of recombination events, a critical genetic interval of 4.1 cM was identified, which was flanked by markers D1S2872 and D1S2891. These findings confirm that GFND is a distinct disease entity among the fibrillary glomerulopathies. Gene identification will provide insights into the molecular interactions of Fn in GFND, as well as in genetically unaltered conditions.

Adult↗
PubMed1998

Mouse models of myelin diseases.

Dys- and demyelination are the common endpoints of several inherited diseases of glial cells, which elaborate myelin and which maintain the myelin sheath very much like an "external" cellular organelle. Whereas some of the genes that are affected by mutations appear to be glial-specific, other genes are expressed in many cell types but their defect is restricted to oligodendrocytes or Schwann cells. Many of the disease genes and their encoded proteins have been studied with the help of mouse models, and a number of different molecular pathomechanisms have emerged which have been summarized in Figure 8. Some of the new concepts in the field, which have been addressed in this review, have only emerged because similar pathomechanisms were discovered for different myelin proteins. Mouse models have clearly helped to address both, the molecular pathology of myelin diseases and the normal function of myelin genes, but as discussed in this review, these questions turned out to be very different. Despite the progress in understanding the role of the abundant myelin proteins, there also remain a number of open questions that concern, among other things, the initial axon-glia recognition, the assembly process of the myelin sheath, and the long-term interaction of axons with their myelinating glia. Finally, animal models of human neurological diseases should not be restricted to the study of pathology, but they should also contribute to the development of experimental treatments. It is encouraging that a few attempts have been made.

Animals↗
PubMed1998

A simple, inexpensive apparatus for performance of preparative scale solution phase multiple parallel synthesis of drug analogs. I. Preparation of a retrospective library of quinolone antiinfective agents.

A simple inexpensive apparatus is described consisting of conveniently commercially available components which is suitable for the solution phase multiple parallel synthesis of 24-72 analogs of drug-like molecules. The use of the apparatus is illustrated by preparation of a retrospective library of over 100 analogs of antimicrobial fluoroquinolones prepared in 0% to quantitative yields. Each analog was prepared in up to 150 mg quantity and each was analyzed by NMR and mass spectrometric techniques to verify its purity and identity.

Anti-Infective Agents↗
PubMed1998

[Effect of cellular growth factors on hepatocytes in experimental infection--regulation of NF-kappa B and glutathione homeostasis].

Infections, sepsis and trauma lead to cellular damage of different degrees. The formation of nitrogen and reactive oxygen intermediates (NOI and ROI) play a central role in cellular damage. In addition, it is well established that the intracellular GSH content can control both radical species whereas GSH levels are controlled by the presence of cellular growth factors. The aim of the following study was to investigate the ROI and nitric oxide formation depending on the GSH levels and the presence or absence of hepatocellular growth factors. In addition, we investigated their effects on hepatocellular injury and the status of activation of the nuclear transcriptional factor NF-kappa B which is influenced by various radical forms and the cellular GSH contents. Our data clearly demonstrate that hepatocellular growth factors such as EGF and TGF alpha can increase the GSH contents and the NOx production. In addition, we found a reduction of cellular injury and NF-kappa B expression when hepatocytes were preincubated with growth factors. Taken together, we conclude that growth factors are able to protect against hepatocellular injury in experimental sepsis by increasing the cellular GSH contents either to reduce superoxide anion formation or to induce increased NO synthesis activity with subsequent increased NO production.

Cells, Cultured↗
PubMed1998

[Tumor regression in long-term follow-up by administration of liposome encapsulated 5-FU. An animal experiment in WAF rats with CC-531 liver tumor].

Locoregional chemotherapy for inoperable colorectal liver metastases is not yet standard therapy. Only two studies thus far have reported prolonged survival. Better tolerance and an increased response rate speak in favor of regional chemotherapy. Liposome-encapsulated 5-FU is a new approach in regional chemotherapy. In this study i.v. and i.a. application of 5-FU-PEG liposomes were compared to a monosubstance with respect to tumor growth. Starch microspheres were added for flow decrease to examine the synergistic effect. The experiments were done in CC-531 liver tumor-bearing WAG rats. The results show a clear tumor reduction after 3 weeks of i.a. administration of 5-FU-PEG liposomes combined with a flow decrease by starch microspheres. There was a significant tumor reduction compared to all other i.a. groups. Strong tumor growth was observed in groups receiving i.v. application of 5-FU with liposomes or as a monosubstance. The results demonstrate tumor reduction after 3 weeks with locoregional chemotherapy by 5-FU-PEG liposomes combined with starch microspheres.

Animals↗
PubMed1998

[Liposome encapsulation of cystostatic drugs and starch microspheres improve tumor targeting in locoregional therapy. An animal experiment study of CC 531 liver tumor].

Systemic adjuvant chemotherapy achieves unsatisfactory results for inoperable liver tumors and metastases. Various clinical studies have shown that locoregional chemotherapy increased the survival rate by a few months. The aim of this study was to investigate tumor targeting of the most frequently used cytostatic 5-fluouracil by modifying systemic and locoregional therapy by liposome encapsulation. The tumor concentration of 5-FU encapsulated in SUV-PEG liposomes increases by a factor of 27 in systemic therapy and a factor of 90 in locoregional therapy. The tumor concentration of 5-FU increases by a factor of 8000, if the blood flow is additionally slowed by starch microspheres (Spherex) during locoregional therapy with liposome-encapsulated 5-FU.

Adenocarcinoma↗
PubMed1998

Impaired regulation of nuclear factor-kappaB results in apoptosis induced by gamma radiation.

Recent studies have shown that activation of nuclear factor-kappaB (NF-kappaB) is critical for cell survival. Cells from patients with ataxia telangiectasia (AT) have an impaired NF-kappaB response to ionizing radiation. AT cells also exhibit inappropriate regulation of apoptosis. We report here that expression of a dominant negative form of IkappaB-alpha, an inhibitor of NF-kappaB, protects AT fibroblasts from apoptosis induced by gamma radiation, but it enhances apoptosis in normal fibroblasts. Furthermore, the process leading to apoptosis may involve caspase 3-mediated cleavage of IkappaB-alpha. These data suggest that regulation of NF-kappaB may play an important role in programmed cell death induced by DNA damage in AT cells.

Apoptosis↗
PubMed1997

Simultaneous determination of 5-fluorouracil and its active metabolites in serum and tissue by high-performance liquid chromatography.

In order to observe the biodistribution of 5-fluorouracil (5-FU) and its main metabolites in different kinds of tissue (tumor, liver, kidney, spleen, mucosa, lungs, heart, peritoneum, pancreas) and serum according to various novel application forms, a simple and rapid method for the simultaneous determination of 5-FU and its active metabolites 5-fluorouridine (5-FUrd) and 5-fluoro-2'-deoxyuridine (5-FdUrd) has been established. Proteins in serum and tissue samples were precipitated by perchloric acid after addition of the internal standard 5-bromouracil. The compounds were separated using an ODS Hypersil (5 microm) column and detected by UV absorbance (254 nm). Specificity, linearity, reproducibility, intermediate precision and accuracy of the method were established. The lower limit of quantitation (LOQ) for the compounds in serum and various tissue samples was determined. Data on the recovery of the compounds and the internal standard are provided.

Animals↗
PubMed1997

[Risk factors in endoscopic manometry for suspected dysfunction of Oddi's sphincter].

OBJECTIVE: An increased incidence of pancreatitis having been reported after endoscopic manometry (EM) of the sphincter of Oddi, its incidence and severity as well as potential risk factors were investigated prospectively. PATIENTS AND METHODS: Between June 1988 and June 1996, standardised manometry was performed in 207 patients with suspected biliary and 23 with suspected pancreatic sphincter of Oddi dysfunction (SOD). All patients had been observed in hospital for at least 24 hours before the test. The diagnostic criteria of post-manometric pancreatitis (PMP) were epigastric pain and a rise in the concentration of serum amylase to at least three times normal. Potential risk factors for PMP were elucidated by uni- and multivariate analysis. RESULTS: Pancreatitis occurred in 19 patients (9%) with suspected biliary and in 6 (26%) with suspected pancreatic SOD (P < 0.01), 17 of mild and 8 of moderate degree. There were no deaths and no lasting sequelae. Previous pancreatitis after endoscopic retrograde cholangiopancreatography and the presence of SOD were identified as patient-associated risk factors (P < 0.01 for each). Method-associated risk factors were duration of manometry of more than 5 min (P < 0.05) and manometry in the pancreatic duct system (P < 0.05). The risk of pancreatitis was reduced by simultaneous endoscopic sphincterotomy for SOD (P < 0.01). CONCLUSION: Specific and often avoidable risk factors for postmanometric pancreatitis were identified: technical procedure, pancreatitis, SOD. With short duration of manometry, avoiding of manometry in the pancreatic duct system and with patient's informed consent for simultaneous endoscopic sphincterotomy risk of pancreatitis may be lowered.

Adult↗