Biomedical subjects

D C Lu

Publications and source records attributed to D C Lu.

11 recordsLinked to original sources

PubMed2006

Abeta induces cell death by direct interaction with its cognate extracellular domain on APP (APP 597-624).

Amyloid beta-peptide (Abeta) is postulated to play a central role in the pathogenesis of Alzheimer's disease. We recently proposed a pathway of Abeta-induced toxicity that is APP dependent and involves the facilitation of APP complex formation by Abeta. The APP-dependent component requires cleavage of APP at position 664 in the cytoplasmic domain, presumably by caspases or caspase-like proteases, with release of a potentially cytotoxic C31 peptide. In this study we show that Abeta interacted directly and specifically with membrane-bound APP to facilitate APP homo-oligomerization. Using chimeric APP molecules, this interaction was shown to take place between Abeta and its homologous sequence on APP. Consistent with this finding, we demonstrated that Abeta also facilitated the oligomerization of beta-secretase cleaved APP C-terminal fragment (C99). We found that the YENPTY domain in the APP cytoplasmic tail and contained within C31 is critical for this cell death pathway. Deletion or alanine- scanning mutagenesis through this domain significantly attenuated cell death apparently without affecting either APP dimerization or cleavage at position 664. This indicated that sequences within C31 are required after its release from APP. As the YENPTY domain has been shown to interact with a number of cytosolic adaptor molecules, it is possible that the interaction of APP, especially dimeric forms of APP, with these molecules contribute to cell death.

Amino Acid Motifs↗

PubMed2001

The amyloidogenic pathway of amyloid precursor protein (APP) is independent of its cleavage by caspases.

Amyloid beta-protein (A beta) is the main constituent of senile plaques in Alzheimer's disease and is derived by proteolysis from the amyloid precursor protein (APP). Generation and secretion of both A beta 40 and A beta 42 isoforms depend largely on internalization of APP and occurs mainly in the endocytic pathway. Evidence has also been presented (Gervais, F. G., Xu, D., Robertson, G. S., Vaillancourt, J. P., Zhu, Y., Huang, J., LeBlanc, A., Smith, D., Rigby, M., Shearman, M. S., Clarke, E. E., Zheng, H., Van der Ploeg, L. H. T., Ruffolo, S. C., Thornberry, N. A., Xanthoudakis, S., Zamboni, R. J., Roy, S., and Nicholson, D. W. (1999) Cell, 97, 395--406) that caspase cleavage of APP at its cytosolic tail affects its processing such that it is redirected to a more amyloidogenic pathway, resulting in enhanced A beta generation. However, caspase cleavage of APP also results in loss of its endocytosis signal (YENP), an event that would predict a decline in internalization and a concomitant decrease, not an increase, in A beta generation. In the present work, we examined whether caspase cleavage of APP is relevant to amyloidogenesis. We found that 1) caspase cleavage of APP results in reduced internalization and, accordingly, a decline in A beta secretion; 2) masking of the caspase site in APP did not affect A beta levels and, 3) caspase activation in cells by serum withdrawal did not increase A beta secretion. Thus, caspase cleavage of APP is unlikely to play a direct role in amyloidogenesis.

Alzheimer Disease↗

PubMed2000

A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor.

The amyloid beta-protein precursor gives rise to the amyloid beta-protein, the principal constituent of senile plaques and a cytotoxic fragment involved in the pathogenesis of Alzheimer disease. Here we show that amyloid beta-protein precursor was proteolytically cleaved by caspases in the C terminus to generate a second unrelated peptide, called C31. The resultant C31 peptide was a potent inducer of apoptosis. Both caspase-cleaved amyloid beta-protein precursor and activated caspase-9 were present in brains of Alzheimer disease patients but not in control brains. These findings indicate the possibility that caspase cleavage of amyloid beta-protein precursor with the generation of C31 may be involved in the neuronal death associated with Alzheimer disease.

Alzheimer Disease↗

PubMed1999

[Vancomycin-resistant enterococci in north-eastern Taiwan].

Vancomycin-resistant enterococci (VRE) is a world-wide emerging pathogen. The first confirmed VRE isolate in Taiwan was detected in 1995. After that, more and more isolates of VRE were found in western part of Taiwan. However, before this report, there was no any isolate of VRE found in eastern part of Taiwan. In December 1997 and January 1998, two cases of VRE urinary tract infection were found in two regional hospitals in north-eastern Taiwan. They had received prolonged treatment with multiple antibiotics for other infections before they got VRE infection. The isolates showed susceptibility to other antimicrobial agents by routine disk diffusion susceptibility test and these two patients were successfully treated. The VRE did not spread in those two hospitals. After further study, the 3 isolates from these two patients all had minimum inhibitory concentration of vancomycin >256 microg/mL. They all carried van A gene and the pulsed-field gel electrophoresis demonstrated they belonged to different DNA types. It was concluded that VRE appeared in north-eastern Taiwan but the strains were not from a common source.

Aged↗

PubMed1998

Diethyl pyrocarbonate (DEPC) inhibits CO2 chemosensitivity in Helix aspersa.

Central CO2 chemoreceptors in poikilothermic vertebrates may not regulate ventilation at a particular pH setpoint; central chemoreceptor responses may more accurately reflect the relative charge state (alpha) of the imidazole of histidine. We have tested the alphastat hypothesis in the terrestrial, air breathing, pulmonate snail, Helix aspersa, by chemically modifying histidine residues in the central CO2 chemoreceptor area of this animal using diethyl pyrocarbonate (DEPC). After focal application of 20 mM DEPC to the central CO2 chemoreceptor region, the pneumostome, a respiratory, CO2 responsive organ in the snail, no longer responded to hypercapnic, acidotic stimulation of the central chemoreceptor area. However, pneumostomal responses to hypoxic stimulation of the pneumostome and to focal stimulation of the central chemoreceptor area with sodium nitroprusside, a respiratory stimulant in H. aspersa, remained intact after DEPC treatment. Furthermore, DEPC treatment of the central chemoreceptor area blocked pneumostomal responses to ammonia pre-pulse treatment, which changes intracellular pH, while extracellular pH is held constant. These results resemble mammalian responses to DEPC treatment and indicate that central chemoreceptor responses in H. aspersa may originate from changes in the alpha of intracellular histidine residues.

Ammonium Chloride↗

PubMed1998

Emphysematous prostatic abscess due to Klebsiella pneumoniae.

Prostatic abscess is an unusual occurrence in the era of modern antibiotics. We report a rare case of emphysematous prostatic abscess owing to Klebsiella pneumoniae in a 45-year-old man with a 10-year history of alcoholism and a 6-year history of diabetes mellitus. Prostatic abscess is a difficult clinical diagnosis without specific symptoms and signs. Computerized tomography can assist in making the diagnosis of emphysematous prostatic abscess. Definitive treatment is complete surgical drainage and the use of effective antibiotics.

Abscess↗

PubMed1997

In vitro activities of antimicrobial agents, alone and in combinations, against Burkholderia cepacia isolated from blood.

Burkholderia cepacia is a widespread, environmental gram-negative bacillus that is associated with nosocomial infections. This bacterium is considered to be an important pathogen in immunocompromised patients and is inherently resistant to multiple antimicrobial agents. To compare the activity of different antimicrobial agents and the potential of combinations against invasive strains of B. cepacia, we collected 36 isolates of B. cepacia from blood cultures and checked their susceptibilities to 13 antimicrobials by broth microdilution method. Most strains tested were susceptible to minocycline (94.4%), ceftazidime (86.1%), ciprofloxacin (83.3%), and trimethoprim-sulfamethoxazole (83.3%). All strains were resistant to aminoglycosides, and only some strains were susceptible to imipenem (16.7%), aztreonam (19.4%), moxalactam (25.0%), piperacillin (25.0%), and carbenicillin (47.2%). The effects of combinations of ceftazidime with amikacin, ceftazidime with ciprofloxacin, and ciprofloxacin with amikacin were assayed by checkerboard titration method. Synergistic effect was found in 28 out of 36 tested strains (77.8%), when ceftazidime was combined with amikacin, in 25 out of 36 strains (69.4%) when ceftazidime was combined with ciprofloxacin, and in only 8 out of 36 strains (22.2%) when ciprofloxacin was combined with amikacin.

Anti-Bacterial Agents↗

PubMed1997

Burkholderia cepacia bacteremia: a retrospective analysis of 70 episodes.

Burkholderia cepacia, a widespread gram-negative environmental bacillus associated with nosocomial infections, is considered to be of relatively low virulence and rarely to cause invasive disease. We retrospectively analyzed the risk factors, clinical manifestations, antimicrobial susceptibilities, and prognostic factors of B. cepacia bacteremia cases. From 1982 through 1995, 70 episodes of bacteremia due to B. cepacia occurred in 52 patients at the National Taiwan University Hospital. The overall case fatality rate was 11%. Sixty-four episodes were nosocomial infections. The common predisposing conditions were stay in an intensive care unit (61%) and invasive procedures, including urinary catheter (54%), intravenous catheter (70%), and intubation (57%). Three episodes involved polymicrobial bacteremia. In 41 episodes in which the infectious focus was identified, the respiratory tract was the most common portal of entry (17/41) followed by intravascular catheters (11/41). Most strains tested were susceptible to ceftazidime (95%), piperacillin (93%), minocycline (85%), and cefotaxime (82%); but most were resistant to aminoglycosides, tetracycline, carbenicillin, and ticarcillin. For empirical therapy of B. cepacia bacteremia, ceftazidime or piperacillin should be the drug of choice.

Adolescent↗

PubMed1995

Polymicrobial bacterial pericarditis with mediastinitis after endotracheal intubation.

Polymicrobial bacterial pericarditis with mediastinitis after traumatic endotracheal intubation is an unusual condition. We report a 54-year-old man, a victim of nasopharyngeal carcinoma, who developed pericardial effusion with tamponade after traumatic endotracheal intubation. The diagnosis of polymicrobial bacterial pericarditis was made when pericardiocentesis revealed purulent fluid that grew a mixed culture of anaerobic and aerobic bacteria, reflecting the normal upper airway flora. By bronchoscopic study, a laceration over the lower trachea was detected. The patient received prolonged aggressive antibiotic therapy and pericardial drainage. The infection improved, but the patient later died from another episode of nosocomial infection.

Anti-Bacterial Agents↗

PubMed1995

Outcome analysis of preoperative embolization with N-butyl cyanoacrylate in cerebral arteriovenous malformations.

PURPOSE: To determine the influence of preoperative N-butyl cyanoacrylate embolization on outcome in the treatment of cerebral arteriovenous malformations. METHODS: Two groups were compared: 30 patients who underwent surgery and embolization versus 41 patients who underwent surgery only. Both groups were categorized by Spetzler-Martin grade and evaluated with the Glasgow Outcome Scale at various intervals. The long-term follow-up in months was, for surgery only, mean of 35 and range of 4 to 59, and for surgery and embolization, mean of 10 and range of 1 to 19). RESULTS: The arteriovenous malformations in the surgery and embolization group had a larger average greatest diameter (4.2 +/- 1.5 cm versus 3.4 +/- 1.8 cm) and were of higher Spetzler-Martin grade (89% versus 68% grade III-V). No significant difference in the preoperative or immediate postoperative (less than 24 hours) Glasgow Outcome Scale was identified between the two groups. At I week after surgery, the surgery and embolization group displayed a significantly better outcome evaluation (70% versus 41% with Glasgow Outcome Scale score of 5). The long-term evaluation continued to favor the surgery and embolization patients (86% versus 66% with Glasgow Outcome Scale score of 5). CONCLUSION: Preoperative N-butyl cyanoacrylate embolization improves postsurgical outcome.

Adult↗

PubMed1994

[Effect of jian yan ling on serum lipids, apoprotein and lipoprotein-a].

Effect of Jian Yan Ling (JYL, mainly consisted of Succinum, Pteria margaritifers and Astragalus membranaceus etc.) on serum lipids was studied by double-blind method in 128 hyperlipemia patients. Patients were divided randomly into two groups, the test groups (64 cases) treated with JYL, while the other 64 cases treated with placebo as control for 3 months. Serum total cholesterol (TC), triglyceride (TG), TC-high density lipolipid-cholesterol (TC-HDL-C), apoproteins were observed before and after treatment. Results showed that the TC, TG, apoproteins and lipoprotein-a of test group were all dropped significantly after JYL treatment (P < 0.01). The results suggested that JYL could regulate the blood lipids and could also exert an effect of antiatherosclerosis through reducing blood lipoprotein-a level. It is worth while to use JYL as an antihyperlipemic agent clinically.

Apolipoproteins A↗