p38 MAP kinase: molecular target for the inhibition of pro-inflammatory cytokines.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Biomedical subjects
J C Lee
Publications and source records attributed to J C Lee.
Neurophysiologic testing in chronic pelvic pain syndrome: a pilot study.
OBJECTIVES: Studies of male chronic pelvic pain syndrome (CPPS) have generally centered on the pathologic features of the prostate rather than on the neurology of pain. Electrodiagnostic studies examine the integrity of somatosensory nerve pathways consisting of large, group A fibers. Heat sensation and visceral (autonomic) pain is mediated through small, unmyelinated C fibers, which can be tested cutaneously by thermal sensory analysis. We hypothesized that CPPS pain is mediated by these small C fibers. METHODS: All subjects and controls had no history of neurologic disease and had normal neurologic examinations. Phase I: 14 patients with CPPS underwent electrodiagnostic testing using pudendal somatosensory evoked potentials and bulbocavernosus reflex latency measurements. Phase II: 31 patients with CPPS and 14 controls underwent thermal sensory analysis testing on the perineum and anterior thigh using noxious heat stimuli. Subjects used a computer-generated visual analog scale to dynamically report their discomfort. The peak and slope of the computer-generated visual analog scale were analyzed. RESULTS: Phase I: two patients had delayed latency of the somatosensory evoked potentials, but additional evaluation with magnetic resonance imaging revealed no definable lesion. Phase II: with thermal sensory analysis, men with CPPS reported higher intensity pain at lower temperatures (P = 0.03). Men with CPPS also had higher peak computer-generated visual analog scale scores on perineal testing. No difference in thermal testing on the anterior thigh was found between the two groups. CONCLUSIONS: Large, myelinated somatic fibers do not play a significant role in the pathophysiology of CPPS. Patients with CPPS have an altered sensation of perineal pain elicited by heat, which may represent a C-fiber-mediated effect.
Chronic Disease↗
BAPTA/AM, an intracellular calcium chelator, induces delayed necrosis by lipoxygenase-mediated free radicals in mouse cortical cultures.
1. Disruption of calcium homeostasis during neurodegenerative diseases is known to trigger apoptotic or necrotic death in neuronal cells. Recently, the authors reported that intracellular calcium restriction by NMDA receptor antagonists induces apoptosis in cortical cultures. To evaluate whether further restriction of intracellular free calcium can induce apoptosis or necrosis, we examined the neurotoxic characterization of BAPTA/AM, a permeable free calcium chelator, in mouse cortical cultures. 2. Exposure of mixed (glia and neuron) cortical cultures (DIV 13-16) to 3-10 microM BAPTA/AM (non-toxic concentration for glial cells) for 24-48 hr resulted in delayed and necrotic neuronal death. The necrotic findings included swelling and loss of mitochondria and endoplasmic reticulum (ER) with neuronal membrane rupture 24 hr after treatment with BAPTA/AM. Simultaneously, we observed a few TUNEL-positive cells in the neuronal subpopulation of the same cultures. 3. The neurotoxicity evoked by BAPTA/AM (10 microM) was significantly attenuated by the addition of 0.5 microM cycloheximide (a protein synthesis inhibitor), 10 microM actinomycin D (an RNA transcription inhibitor), a high extracellular potassium concentration (total 15 mM KCl), 100 microM t-ACPD (a metabotrophic agonist), 100 microM alpha-tocopherol (a free radical scavenger), 100 microM deferoxamine (a ferric ion chelator), 100 microM L-NAME (a nitric oxide synthase (NOS) inhibitor), 50 microM DNQX (a non-NMDA receptor blocker), and 3-30 microM esculetin (a lipoxygenase inhibitor). However, 0.3-3 mM ASA (a cyclooxygenase inhibitor), 100 ng/ml nerve growth factor (NGF), 10 microM MK-801 (a NMDA receptor antagonist), 20 microM zVAD-fmk (caspase inhibitor) and 50 U/ml catalase failed to inhibit the injury. 4. However, NGF and catalase blocked the neurotoxicity induced by BAPTA/AM in young neuronal cells (DIV 6). BAPTA/AM (10 microM) did not alter the expression of inducible nitric oxide synthase (iNOS) on glial cells. 5. These results suggest that the feature of neuronal death induced by BAPTA/AM exhibits predominantly delayed necrosis mediated by lipoxygenase-dependent free radicals.
Animals↗
Moving with the sun.
A global 24-hour telemedicine conference entitled, "Moving with the Sun" was successfully completed on June 30 and July 1 1997 between participants from Hong Kong and China, as well as with sixteen major international medical centres around the globe. In addition to celebrating the return of Hong Kong to the People's Republic of China, the conference also signified the establishment of the Chinese University of Hong Kong, and Hong Kong as a bridge between Western countries and the PRC.
Humans↗
Telemedicine in China.
Telemedicine has been shown to have a considerable impact in medical education, conferencing and consultation. As a result, the People's Republic of China has been keen to develop telemedicine. In her attempts to further the development of telemedicine, China has looked to the progress of medical services in Western countries such as Europe and North America. The United States of America, however, has exceeded the rest in exchange of health-care information and telemedicine technologies with China. Although China has been enthusiastic about the exchange, telemedicine in China requires development in the technical infrastructure and professional infrastructure.
China↗
Wiring a medical school and teaching hospital for telemedicine.
The planning and installation of a telemedicine system for communication within a teaching hospital and its academic and hospital units with a capacity for accommodation of up to 400 video-stations is described. The system is intended for improving the communication between patients and health professionals, and between the health professionals themselves. It also provides the basis for improving pre-graduate teaching, especially problem-based learning, and all aspects of postgraduate teaching.
Computers↗
Antimicrobial resistance of Shigella sonnei in Korea during the last two decades.
Eighty-eight strains of Shigella sonnei isolated in Korea during the period 1980 to 1999 were tested for susceptibility to 13 antimicrobial agents. S. sonnei isolates demonstrated high frequencies of resistance to sulfamethoxazole (97.7%), tetracycline (96.6%), and trimethoprim (95.5%). S. sonnei isolates from the 1990s were more resistant to nalidixic acid than isolates from the 1980s (100 vs 7.7%), while isolates from the 1990s were more susceptible to chloramphenicol than isolates from the 1980s (0 vs 100%). Ampicillin-resistant S. sonnei isolates produced the TEM-1 beta-lactamase with a pI of 5.4. The TEM-1 gene was located on conjugally transferable plasmids in the majority of isolates. S. sonnei isolates were all susceptible to cefotaxime, cefoxitin, ceftazidime, ciprofloxacin, and norfloxacin. These results indicate that cephalosporins and quinolones may be alternative antibiotics for the treatment of S. sonnei infections in Korea.
Anti-Bacterial Agents↗
Apoptotic cell death induced by Acinetobacter baumannii in epithelial cells through caspase-3 activation.
Epithelial cell death induced by Acinetobacter baumannii infection was investigated using in vitro assays. Eight hours after live A. baumannii infection, HeLa cells exhibited detachment from the dish, rounding morphologies, high proportions of trypan blue-positive cells and extensive DNA breakdown with faint apoptotic banding, which is indicative of cells undergoing apoptosis. The enzymatic activity of caspase-3 was increased in cells as early as 2 h after infection. In addition, apoptosis of HeLa cells was induced by treatment with bacterial culture filtrates but not with formalin-killed bacteria. These results indicate that A. baumannii infection triggers apoptosis in HeLa cells through caspase-3 activation.
Acinetobacter↗
p21(WAF1) is associated with CDK2 and CDK4 protein during HL-60 cell differentiation by TPA treatment.
TPA-treated HL-60 cells are mainly arrested in G1 by p21(WAF1) accumulation. We investigate the downstream changes following such accumulation. Increased p21(WAF1) is associated with CDK2 and CDK4. pRb is dephosphorylated in the presence of p21-CDK2/4 complexes, and the Rb-E2F1 complex increases after TPA treatment, whereas the Rb-HDAC1 complex decreases slightly. Our results suggest that increased p21(WAF1) is associated with CDK2/4, and that these complexes induce pRb dephosphorylation. In turn, hypophosphorylated pRb are mainly complexed with E2F1, but HDAC1 appears not to be a key component in this process.
CDC2-CDC28 Kinases↗
Rhinosinusitis in transplant patients.
The control of perioperative infection has become more important to increase the success rate of organ transplantation. Thorough examination for occult infection prior to transplantation, careful postoperative monitoring and prompt treatment of infections are required. We reviewed the medical records of 278 patients who received organ transplantation over 4 years and analysed the clinical course of rhinosinusitis during the pre- and post-transplantation period. Thirty-two (11.5%) patients had rhinosinusitis. Nineteen were detected during preoperative examination and 13 were postoperative. Sinus surgery was performed in nine patients before organ transplantation. Ten out of 13 patients who had rhinosinusitis detected after transplantation required sinus surgery and three patients had invasive fungal infections. In the immunocompromised host, the clinical presentation of rhinosinusitis may be subtle, but the subsequent clinical course may be fulminant or even fatal. If the transplant recipient has unexplained fever or any nasal symptom, thorough evaluation with a high index of suspicion and prompt management are required.
Adolescent↗
Identification and initial characterization of 5000 expressed sequenced tags (ESTs) each from adult human normal and osteoarthritic cartilage cDNA libraries.
OBJECTIVE: To prepare, sequence and analyse adult human cartilage cDNA libraries to study the gene expression pattern between normal and osteoarthritic cartilage. METHODS: Poly A(+)RNA from adult human normal and osteoarthritic articular cartilage was isolated and used to prepare cDNA libraries. Approximately 5000 ESTs from each library were sequenced and analysed using bioinformatic tools. The expression of select genes was confirmed by Northern blot and in situ hybridization analysis. RESULTS: Multiple gene families including several classical cartilage matrix protein encoding genes were identified. Approximately 28-40% of the genes sequenced from these libraries were novel, while half of the genes encoded known proteins and 4-6% of the genes encoded novel homologs of known proteins. Several known genes, whose expression has not been reported previously in cartilage, were also identified. We have confirmed the cartilage expression of three known (CTGF, CTGF-L and clusterin) and two novel homologs of known genes (PCPE-2 and Gal-Nac transferase) by Northern blot and in situ hybridization analysis. CONCLUSION: This is the first report of the preparation and sequencing of cDNA libraries from adult human normal and osteoarthritic articular cartilage. Further analysis of genes identified from these libraries may provide molecular targets for diagnosis and/or treatment of osteoarthritis (OA).
Adult↗
The prevalence of trimethoprim-resistance-conferring dihydrofolate reductase genes in urinary isolates of Escherichia coli in Korea.
One-hundred and twenty-two urinary isolates of Escherichia coli were studied for trimethoprim resistance. Seventy-seven (63.1%) of the 122 isolates were found to be resistant to trimethoprim. Of the 77 trimethoprim-resistant isolates, 75 dfr genes were detected in 72 isolates as follows: the dfrA17 gene was the most prevalent, being found in 27 isolates, followed by dfrA12 in 26, dfrA1 in 15, dfrA5 in four and dfrA7 in three. Southern blot and PCR mapping analysis revealed that all of the dfrA17, dfrA12, dfrA5 and dfrA7 genes were located on class 1 integrons. The dfrA1 gene inserted as a gene cassette in class 1 integrons was found in 10 of 15 isolates, and the intI2 gene of Tn7 was detected in two out of five isolates. In conjugation experiments, the dfr genes inserted in class 1 integrons were transferred to a recipient E. coli in 32 (42.7%) of the 75 dfr genes. In conclusion, the dfrA17 and dfrA12 genes were the most prevalent genes responsible for trimethoprim resistance in urinary tract isolates of E. coli from Korea and the dfr genes inserted in integrons are more widespread than those that are not related to gene cassettes.
Anti-Bacterial Agents↗
The long-term use of azathioprine in patients with psoriatic arthritis.
Despite the widespread use of methotrexate in the treatment of psoriatic arthritis (PsA), there are patients who are either refractory, develop toxicity to, or refuse to take methotrexate. In search of an alternative, we studied long-term tolerability of and clinical response to azathioprine (AZA) in PsA patients in comparison with matched controls and followed them in a longitudinal clinic. Twenty-eight of 485 patients followed prospectively between 1978 and 1998 took AZA during their clinic follow-ups. Eighteen of the 28 took AZA for 12 months and were included in the study. AZA was well tolerated by most patients, even in the long-term. Although there was no statistically significant difference in the reduction in number of actively inflamed joints between AZA-treated patients and controls, and AZA was no better in preventing progression of damage, AZA was still as good as the other medications. Consequently, AZA was often given to individuals who had not responded to other medications in the past. We provide illustrative case reports in which AZA also controlled psoriasis, and we conclude that, whereas AZA is not superior to other medications in the treatment of PsA, it may be safely used and it provides an alternative therapy for patients with PsA.
Journal Article↗
The essential and ancillary role of glutathione in Saccharomyces cerevisiae analysed using a grande gsh1 disruptant strain.
A grande gsh1 disruptant mutant of Saccharomyces cerevisiae was generated by crossing a petite disruptant to a wild-type grande strain. This strain was relatively stable, but generated petites at an elevated frequency, illustrating the ancillary role of glutathione (GSH) in the maintenance of the genetic integrity of the mitochondrial genome. The availability of the grande gsh1 deletant enabled an evaluation of the role of GSH in the cellular response to hydrogen peroxide independent of the effects of a petite mutation. The mutant strain was more sensitive to hydrogen peroxide than the wild-type strain but was still capable of producing an adaptive stress response to this compound. GSH was found to be essential for growth and sporulation of the yeast, but the intracellular level needed to support growth was at least two orders of magnitude less than that normally present in wild-type cells. This surprising result indicates that there is an essential role for GSH but only very low amounts are needed for growth. This result was also found in anaerobic conditions, thus this essential function does not involve protection from oxidative stress. Suppressors of the gsh1 deletion mutation were isolated by ethylmethanesulfonate mutagenesis. These were the result of a single recessive mutation (sgr1, suppressor for glutathione requirement) that relieved the requirement for GSH for growth on minimal medium but did not affect the sensitivity to H(2)O(2) stress. Interestingly, the gsh1 sgr1 mutant generated petites at a lower rate than the gsh1 mutant. Thus, it is suggested that the essential role of GSH is involved in the maintenance of the mitochondrial genome.
Anaerobiosis↗
Capsule production and growth phase influence binding of complement to Staphylococcus aureus.
Complement-mediated opsonization of bacteria by C3 binding is an important component of the host innate immune system. Little information is available concerning the interaction between complement proteins and capsule type 5 and 8 Staphylococcus aureus strains, even though these isolates are responsible for approximately 70% of human staphylococcal infections. To investigate the importance of an intact complement pathway in an experimental staphylococcal infection, control and C3-depleted mice were challenged intravenously with 10(7) CFU of a serotype 5 S. aureus isolate. Whereas only 8% of the control mice succumbed to the infection, 64% of the complemented-depleted animals died. In vitro parameters of C3 binding to two heavily encapsulated (CP++) strains, three encapsulated (CP+) strains, and an isogenic capsule-negative (CP-) mutant were examined. The alternative pathway contributed 90% of C3 binding in 20% serum at 30 min, whereas it accounted for only 13% of C3 binding in 2% serum. Stationary-phase organisms bound only 10% as much C3 as mid-log-phase organisms; this was only in part due to capsule. When the S. aureus strains were cultivated on solid medium, the CP++ isolates bound 50% less C3 than CP+ strains; a CP+ strain bound 42% less C3 than the CP- mutant. Both C3b and iC3b fragments of C3 bound to S. aureus cells, and about one-third of the bound C3 was shed from the staphylococcal surface as iC3b, regardless of the CP phenotype of the strain. Thus, the phase of growth and presence of capsule are critical to opsonization.
Agammaglobulinemia↗
Staphylococcus aureus Cap5O has UDP-ManNAc dehydrogenase activity and is essential for capsule expression.
The Staphylococcus aureus serotype 5 capsular polysaccharide (CP5) has a repeating unit composed of (-->4)-3-O-acetyl-beta-D-ManNAcA-(1-->4)-alpha-L-FucNAc (1-->3)-beta-D-FucNAc-(1-->)(n). Sixteen chromosomal genes (cap5A through cap5P) are involved in the synthesis of CP5. We recently demonstrated that Cap5P, a 2-epimerase, catalyzes the conversion of UDP-N-acetyl glucosamine (UDP-GlcNAc) to UDP-N-acetylmannosamine (UDP-ManNAc). In this study, we show that UDP-ManNAc is oxidized to UDP-N-acetylmannosaminuronic acid (UDP-ManNAcA) by a UDP-ManNAc dehydrogenase encoded by S. aureus cap5O. We expressed Cap5O in Escherichia coli and purified the recombinant protein. The UDP-ManNAc dehydrogenase activity of purified Cap5O was assessed by incubating Cap5P and UDP-GlcNAc (to produce UDP-ManNAc), together with Cap5O, NAD(+), and a reducing agent. Enzymatic activity was quantitated indirectly by measuring the increase in absorbance at 340 nm resulting from NADH formation. The product of the reaction was confirmed as UDP-ManNAcA by gas chromatography-mass spectroscopy. A cap5O mutation, created by deletion of 727 bp in the 5' end of the gene, was introduced by allelic replacement into S. aureus Reynolds, rendering it CP5 negative. Mice inoculated intravenously or subcutaneously with the wild-type strain Reynolds had greater numbers of S. aureus recovered from their kidneys (P = 0.019) or their subcutaneous abscesses (P = 0.0018), respectively, than did animals inoculated with the cap5O mutant. The results of this study indicate that S. aureus cap5O is essential for capsule production and that capsule promotes staphylococcal virulence in mouse models of abscess formation.
Animals↗
Incidence of concussion in high school football players of Ohio and Pennsylvania.
Football injuries account for more concussions than any other sport in North America. A 1977 survey of high school football players in Minnesota found that 19% of players reported at least one concussion (characterized by loss of awareness) during a season. These results have not been confirmed in subsequent studies. This study sought to estimate the incidence of concussion among high school football players in our region, establish the frequency of the most common symptoms, and determine the duration of subsequent restriction from participation in the sport. The athletic boards of area high schools distributed a three-page survey to 450 high school football players. Of the 450 surveys distributed, 234 (52%) were returned, only 1 of which was excluded because of contradictory information. The incidence of concussion in football players was 47.2% (110/233, P < .001 versus a previously determined rate of 19%). Eighty-one of 233 players (34.9%) had multiple concussions. A total of 376 concussions were reported. The distribution of severity of the 376 reported concussive events was grade I, 87.8%; grade II, 9.9%; and grade III, 2.4%. Only 12 athletes were required to stop play for one or more games. The incidence of high school football players sustaining a concussion is much higher than previously established. The majority of these are mild (grade I) concussions. Further research is needed since multiple low-grade concussions may incur cumulative neuropsychologic impairments.
Adolescent↗
Regulation of the pancreatic pro-endocrine gene neurogenin3.
Neurogenin3 (ngn3), a basic helix-loop-helix (bHLH) transcription factor, functions as a pro-endocrine factor in the developing pancreas: by itself, it is sufficient to force undifferentiated pancreatic epithelial cells to become islet cells. Because ngn3 expression determines which precursor cells will differentiate into islet cells, the signals that regulate ngn3 expression control islet cell formation. To investigate the factors that control ngn3 gene expression, we mapped the human and mouse ngn3 promoters and delineated transcriptionally active sequences within the human promoter. Surprisingly, the human ngn3 promoter drives transcription in all cell lines tested, including fibroblast cell lines. In contrast, in transgenic animals the promoter drives expression specifically in regions of ngn3 expression in the developing pancreas and gut; and the addition of distal sequences greatly enhances transgene expression. Within the distal enhancer, binding sites for several pancreatic transcription factors, including hepatocyte nuclear factor (HNF)-1 and HNF-3, form a tight cluster. HES1, an inhibitory bHLH factor activated by Notch signaling, binds to the proximal promoter and specifically blocks promoter activity. Together with previous genetic data, these results suggest a model in which the ngn3 gene is activated by the coordinated activities of several pancreatic transcription factors and inhibited by Notch signaling through HES1.
Animals↗