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Biomedical subjects

H P Lu

Publications and source records attributed to H P Lu.

11 recordsLinked to original sources

Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner.

We have identified a novel glutamate receptor subunit on the human and mouse genome. Cloning of the mouse cDNA revealed a protein consisting of 1003 amino acids encoded by at least nine exons. This protein showed the highest similarity (51%) to the NR3A subunit of the NMDA receptor and therefore was termed NR3B. NR3B has a structure typical of glutamate receptor family members with a signal peptide and four membrane-associated regions. Amino acids forming a ligand-binding pocket are conserved. When coexpressed with NR1 and NR2A in heterologous cells, NR3B suppressed glutamate-induced current similarly to NR3A. Thus members of the NR3 class of NMDA receptors act as dominant-negative subunits in the NMDA receptor complex. NR3B shows very restricted expression in somatic motoneurons of the brainstem and spinal cord. Its expression in other types of motoneurons, including autonomic motoneurons in Onuf's nucleus and oculomotor neurons, is significantly weaker. Our results indicate that NR3B is important as a regulatory subunit that controls NMDA receptor transmission in motoneurons. It may be involved in the pathogenesis of neurodegenerative diseases involving motoneurons as well.

Animals↗

Cloning and characterization of LUN, a novel ring finger protein that is highly expressed in lung and specifically binds to a palindromic sequence.

We isolated cDNAs encoding a novel RING finger protein (LUN), the mRNAs of which were expressed at high levels in the lung. In situ hybridization revealed that LUN mRNAs were expressed in the alveolar epithelium of the lung. The LUN gene locus was assigned to chromosome 9p21, which contains candidate tumor suppressor genes associated with loss of heterozygosity in more than 86% of small cell lung cancers. We clarified that LUN is localized to the nucleus and reveals Zn(2+)-dependent DNA binding activity. The region from amino acids 51 to 374 of LUN is responsible for DNA binding. Furthermore, we identified a novel palindromic binding consensus (5'-TCCCAGCACTTTGGGA-3') for the LUN binding. Interestingly, this LUN binding palindromic sequence is found in the upstream transcriptional regulatory region of the E-cadherin gene and two intervening regions of the talin gene. Our results suggested that LUN might be an important trans-acting transcriptional regulator for lung cancer-associated genes including E-cadherin and talin genes.

Amino Acid Sequence↗

[Mechanism of sini decoction in regulating beta-adrenergic receptor signal transduction in rats with myocardial ischemia].

OBJECTIVE: To investigate the effect of Sini Decoction (SND) on beta-adrenergic receptor (beta-AR) signal transduction in rats with myocardial ischemia. METHODS: After beta-AR had been blocked by propranolol, the myocardial ischemia rats were established by pituitrin injection. The density of beta-AR in myocardial cell membrane was determined by radioligand binding assay, cAMP level in plasma and myocardial tissue was detected by radioimmunoassay (RIA), and the mRNA expression of beta 1-AR and beta 1-AR kinase (beta ARK-1) was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) amplifying assay. RESULTS: In myocardial ischemia group, the density of beta 1-AR was up-regulated and the mRNA expression of beta ARK-1 increased (P < 0.01), but the cAMP level in plasma and myocardium was lower than that in the normal group (P < 0.01 and P < 0.05). SND could promote beta 1-AR mRNA expression and inhibit beta ARK-1 mRNA expression so as to increase the density of beta-AR and cause significant raising of cAMP level in plasma and myocardium. CONCLUSION: SND could reduce the desensitization of beta 1-AR during myocardial ischemia and improve signal transduction of beta-AR.

Animals↗

Single-molecule enzymatic dynamics.

Enzymatic turnovers of single cholesterol oxidase molecules were observed in real time by monitoring the emission from the enzyme's fluorescent active site, flavin adenine dinucleotide (FAD). Statistical analyses of single-molecule trajectories revealed a significant and slow fluctuation in the rate of cholesterol oxidation by FAD. The static disorder and dynamic disorder of reaction rates, which are essentially indistinguishable in ensemble-averaged experiments, were determined separately by the real-time single-molecule approach. A molecular memory phenomenon, in which an enzymatic turnover was not independent of its previous turnovers because of a slow fluctuation of protein conformation, was evidenced by spontaneous spectral fluctuation of FAD.

Binding Sites↗

[Three dimensional finite element analysis of stress induced by orthodontic forces in the periodontal tissue].

The purpose of this study was to investigate the stress induced in the periodontal tissue of the upper central incisor by application of orthodontic forces. A three dimensional finite element model consist of tooth, periodontal ligament (PDL), cancellous and compact bone was established and the following results were obtained: (1) The highest stresses were observed on the root surface, the intermediate on the alveolar bone and the lowest in the PDL. (2) Stress condition on the surface of root and alveolar bone is very complex. The maximum, intermediate and minimum principle stresses on the same area are quite different, but the three principal stresses in the PDL are similar. (3) Regarding to tipping and torque movement, the stress value varied largely from the cervix to the apex, and there is stress concentration at the cervix and the apex. For bodily movement when M/F is -10.30, the stress induced is homogeneous and the difference of the stress values from the cervix to the apex is little, which seems to be more physiological.

Alveolar Process↗

Skeletal muscle ventricles: update after 18 months in circulation.

Skeletal muscle ventricles (SMVs) have been constructed from canine latissimus dorsi muscle and connected to the aorta as aortic diastolic counterpulsators. Presently one dog remains alive and well with an SMV that has been functioning continuously in circulation for 18 months, without evidence of thromboembolic complications. SMVs are able to perform cardiac-type work with an output equal to that of the left ventricle at physiologic preloads, when tested with a mock circulation device in our laboratory. SMVs have been used for right-sided cardiac assist. In acute experiments these ventricles have functioned effectively, bypassing the right side of the heart for up to 8 h. Most recently we have tested SMVs using them chronically to pump blood in the right-sided circulation, and at the time of writing they have been shown to function effectively in this configuration for up to 18 days. SMVs may be used in the future as a method of treating patients with left- or right-sided heart failure.

Animals↗

Autologous skeletal muscle, an alternative for cardiac assistance.

Original attempts to use skeletal muscle for cardiac assistance were soon abandoned when the problem of muscle fatigue could not be solved. In the last 2 decades, better understanding of muscle physiology and the development of successful protocols of electrical muscle conditioning have given new impetus to researchers around the world to proceed in the effort to identify useful applications of skeletal muscle to support the heart. More than 100 patients around the world have undergone cardiomyoplasty, mostly for cardiac failure. While subjective improvement in symptoms was noticed in the majority of the patients, only recently favorable hemodynamic changes have been documented. The other alternative that has been pursued in the laboratory is the construction of skeletal muscle ventricles that, after conditioning and vascular delay, have been shown to provide significant cardiac support when used for diastolic counterpulsation or for right heart bypass in animal models.

Cardiac Surgical Procedures↗

Experience with human immunodeficiency virus infection in patients with hepatitis B virus and hepatitis delta virus infections in Los Angeles, 1977-1985.

Stored serum specimens from 723 patients with acute hepatitis B and 228 patients with chronic hepatitis B seen between 1977 and 1985 in the Hepatitis Clinic of the Los Angeles County-University of Southern California Medical Center, Los Angeles, CA, were tested for antibody to human immunodeficiency virus (anti-HIV). Risk factors were ordered hierarchically; cases with multiple risk factors were tabulated only in the risk group listed first on the clinic records. Anti-HIV was first detected in 1979, and by 1983 was found in about half of all homosexual men with chronic hepatitis B. The prevalence was significantly lower in patients with acute hepatitis B than in patients with chronic hepatitis B, and in nonhomosexual subjects compared with homosexual subjects. By 1985, 30 per cent of intravenous drug users with chronic hepatitis B were anti-HIV-positive. The highest annual seroconversion rate for anti-HIV, 21 per cent, was found in homosexual men in 1983. A significant association existed between anti-HIV positivity and hepatitis delta virus infection in homosexual men but not in drug abusers. This study provides data on the natural history of the human immunodeficiency virus epidemic in Los Angeles. Further study on the interaction of these different viruses is warranted.

Acute Disease↗