Medical student feedback: a mechanism to improve a multi-instructor clinical lecture series?
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Curriculum↗
Biomedical subjects
B Chen
Publications and source records attributed to B Chen.
[Expression of the neural cell adhesion molecule in human astrocytomas].
OBJECTIVE: To investigate the expression of the neural cell adhesion molecule (NCAM) in human astrocytomas, and evaluate the relationship between NCAM and proliferating cell nuclear antigen (PCNA). METHODS: Forty-eight astrocytomas were studied by SP method with monoclonal antibody against NCAM and PCNA proteins. RESULTS: All normal brain tissues expressed NCAM; NCAM expression was positive in Grade I-II glioma [95% (19/20)], Grade III glioma [38.9% (7/18)], Grade IV glioma [20% (2/10)] respectively. An inverse correlation was observed between the degree of NCAM expression and that of PCNA (r = -0.657, P < 0.05). CONCLUSION: NCAM is a down-regulated factor in the development of the malignancy of astrocytomas; and it is suggested that the reduced NCAM expression might be involved in the development of biological malignancy.
Astrocytoma↗
[Analysis of cDNA and protein structure of tree shrew cholesterol ester transfer protein].
OBJECTIVE: To obtain the nucleotide sequence and deduced amino acid sequence of cholesteryl ester transfer protein (CETP) cDNA of tree shrew, mammalian insusceptible to atherosclerosis. METHODS: The first strand of cDNA of tree shrew was obtained from its liver. The sequence of tree shrew CETP cDNA was obtained by using techniques of switching mechanism at 5' end of RNA transcript (SMART) and rapid amplification of cDNA end (RACE), The CETP amino acid sequence was deduced from this cDNA and its primary and secondary structures were predicted by using DNAMAN, a software of molecular biology. Results The tree shrew CETP cDNA sequence covers 1636 bp, including a 178 bp fragment at the 3' of untranslated region and a 1458 bp fragment in the coding region, coding the complete sequence of mature tree shrew CETP except the initiator methionine. There are 477 amino acids in its mature protein, one amino acid more than that in human beings, with an extra Gly318. The homology of tree shrew CETP and human CETP and rabbit CETP is 88% and 82% respectively judged by comparing the amino acid sequence of tree shrew CETP and those of human beings and rabbit. The regions concerning the CETP function of binding and transferring neutral lipids in tree shrew CETP amino acid sequence are highly conservative. However, there is a deletion of N-linked glycosylation site at Asn342 in tree shrew protein that may increase the ability of removing peripheral cholesterol and cholesteryl ester. CONCLUSION: The glycosylation in tree shrew CETP may be one of the mechanisms of insusceptibility to atherosis of tree shrew.
Amino Acid Sequence↗
Evaluation of cytokine toxicity induced by vaccinia virus-mediated IL-2 and IL-12 antitumour immunotherapy.
Single intratumoural treatment of nude mice with a vaccinia virus (VV)-expressing interleukin-1 (IL-2) or IL-12 induced significant tumour growth inhibition associated with clear signs of toxicity. At a low virus dose, only some treated animals showed signs of toxicity. We characterized and compared the activity of NK and B cells and major pro-inflammatory factors (IFN-gamma, TNF-alpha) in treated animals with and without toxicity. One week after treatment animals exhibiting signs of cytokine-related toxicity showed dramatic increases in several measured parameters. High leukocyte and lymphocyte counts in blood and marked increases in NK and CD25(+)cells in both blood and spleen were associated with IL-2-induced toxicity, while IL-12-induced toxicity was related to a great elevation of CD25(+)cells in blood and CD71(+)cells in the spleen. In contrast, immune activation in animals free of toxicity was observed on day 2 after the treatment, which drastically declined by day 7. Thus, immune responses induced by IL-2 and IL-12 therapy appear to play important roles in both tumour inhibition and the accompanying toxicity. Short-term effects induced by IL-2 and IL-12 could be critical for antitumour therapy that prolongs survival and protects from adverse side effects.
Animals↗
The stoichiometry of trimeric SIV glycoprotein interaction with CD4 differs from that of anti-envelope antibody Fab fragments.
Human and simian immunodeficiency viruses infect host lymphoid cells by binding CD4 molecules via their gp160 envelope glycoproteins. Biochemical studies on recombinant SIVmac32H (pJ5) envelope ectodomain gp140 precursor protein show that the envelope is a trimer. Using size exclusion chromatography, quantitative amino acid analysis, analytical ultracentrifugation, and CD4-based competition assay, we demonstrate that the stoichiometry of CD4 receptor-oligomeric envelope interaction is 1:1. By contrast, Fab fragments of both neutralizing and non-neutralizing monoclonal antibodies bind at a 3:1 ratio. Thus, despite displaying equivalent CD4 binding sites on each of the three gp140 protomers within an uncleaved trimer, only one site binds the soluble 4-domain human CD4 extracellular segment. The anti-cooperativity and the faster k(off) of gp140 trimer:CD4 versus gp120 monomer:CD4 interaction suggest that CD4-induced conformational change is impeded in the intact envelope. The implications of these findings for immunity against human immunodeficiency virus and simian immunodeficiency virus are discussed.
Amino Acids↗
Assembly of metal-organic frameworks from large organic and inorganic secondary building units: new examples and simplifying principles for complex structures.
The secondary building unit (SBU) has been identified as a useful tool in the analysis of complex metal-organic frameworks (MOFs). We illustrate its applicability to rationalizing MOF crystal structures by analysis of nine new MOFs which have been characterized by single-crystal X-ray diffraction. Tetrahedral SBUs in Zn(ADC)(2).(HTEA)(2) (MOF-31), Cd(ATC).[Cd(H(2)O)(6)](H2O)(5) (MOF-32), and Zn(2)(ATB)(H2O).(H2O)(3)(DMF)(3) (MOF-33) are linked into diamond networks, while those of Ni(2)(ATC)(H(2)O)(4).(H2O)(4) (MOF-34) have the structure of the Al network in SrAl(2). Frameworks constructed from less symmetric tetrahedral SBUs have the Ga network of CaGa(2)O(4) as illustrated by Zn(2)(ATC).(C(2)H(5)OH)(2)(H2O)(2) (MOF-35) structure. Squares and tetrahedral SBUs in Zn(2)(MTB)(H2O)(2).(DMF)(6)(H2O)(5) (MOF-36) are linked into the PtS network, which is the simplest structure type known for the assembly of these shapes. The octahedral SBUs found in Zn(2)(NDC)(3).[(HTEA)(DEF)(ClBz)](2) (MOF-37) form the most common structure for linking octahedral shapes, namely, the boron network in CaB(6). New structure types for linking triangular and trigonal prismatic SBUs are found in Zn(3)O(BTC)(2).(HTEA)(2) (MOF-38) and Zn(3)O(HBTB)(2)(H2O).(DMF)(0.5)(H2O)(3) (MOF-39). The synthesis, crystal structure, and structure analysis using the SBU approach are presented for each MOF.
Journal Article↗
A convenient chiron for substituted cyclohexanones.
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Cyclohexanones↗
Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication.
BACKGROUND: The cAMP signaling pathway, and its downstream neurotrophic factor BDNF, are major targets of antidepressant medications. Abnormalities in this pathway have previously been reported in postmortem brain of subjects with mood disorders. This study was designed to test whether the diagnosis of a mood disorder, or treatment with an antidepressant or mood stabilizer was associated with changes in hippocampal BDNF in postmortem brain. METHODS: Frozen postmortem anterior hippocampus sections were obtained from the Stanley Foundation Neuropathology Consortium. Tissue from subjects with major depression, bipolar disorder, schizophrenia and nonpsychiatric control subjects were stained for BDNF using immunohistochemistry. RESULTS: Increased BDNF expression was found in dentate gyrus, hilus and supragranular regions in subjects treated with antidepressant medications at the time of death, compared with antidepressant-untreated subjects. Furthermore, there was a trend toward increased BDNF expression in hilar and supragranular regions in depressed subjects treated with antidepressants, compared with the subjects not on these medications at the time of death. CONCLUSIONS: These findings are consistent with recent studies measuring CREB levels in this same subject sample, and support current animal and cellular models of antidepressant function.
Adult↗
Dopamine D5 receptor gene polymorphism and the risk of levodopa-induced motor fluctuations in patients with Parkinson's disease.
Motor fluctuations are the most common complication of levodopa therapy for Parkinson's disease (PD). Genetic factors could play a role in determining the occurrence of motor fluctuations. To investigate whether dopamine receptor D5 (DRD5) T978C polymorphism is associated with the risk of developing motor fluctuations in PD, we studied this polymorphism in a case-control study of 120 subjects with sporadic PD and 110 control subjects. We found that the overall allelic and genotypic frequencies did not differ significantly between patients with PD and control subjects (all P>0.7), and between motor fluctuators (n=50) and non-motor fluctuators (n=50) (all P>0.8). It suggests that DRD5 T978C polymorphism is not associated with the susceptibility to PD, nor with the risk of developing motor fluctuations in PD. Therefore, other polymorphisms that alter the expression of the dopamine receptors should be further studied.
Adult↗
Direction selectivity of excitatory and inhibitory neurons in ferret visual cortex.
Direction selectivity is a characteristic feature of neurons in the visual cortex of higher mammals. Excitatory and inhibitory cortical neurons receive different patterns of synaptic connections resulting in different receptive field properties. We have analyzed the direction tuning of excitatory and inhibitory neurons of ferret visual cortex using single unit recordings. Direction tuning was constant among neurons in a vertical column. The majority (> 80%) of excitatory (regular spiking) neurons were direction tuned or direction biased. Fast spiking (inhibitory) neurons were orientation, but only weakly or not direction tuned. This indicates that excitatory and inhibitory neurons have different functions in visual processing and their different integration in thalamocortical and intracortical circuits results in a diversification of receptive field properties.
Action Potentials↗
Efficacy of antitumoral photodynamic therapy with hypericin: relationship between biodistribution and photodynamic effects in the RIF-1 mouse tumor model.
We investigated the hypericin-mediated PDT effects on the tumor and normal skin and in correlation with its biodistribution. These studies were carried out on C3H mice bearing RIF-1 tumors. The hypericin distribution and PDT effects were recorded at different intervals (0.5-24 hr) after intravenous injection of a 5-mg/kg dose of hypericin. After administration, rapid biphasic exponential decay was observed in the plasma drug concentration. It was found that hypericin was preferentially bound to the plasma lipoproteins. The tumor drug levels increased rapidly over the first few hours and reached a maximum around 6 hr after injection. In contrast, PDT efficacy was maximal when irradiation was performed at 0.5 hr after hypericin administration, which led to 100% cure. The PDT efficacy decreased rapidly as the administration-irradiation interval was prolonged. No tumor cure was obtained at the 6-hr interval, even though it was at this time that the tumor drug level peaked. Fluorescence microscopic studies showed that hypericin was mainly confined within the tumor vasculature at 0.5 hr after injection, whereupon it rapidly diffused to the surrounding tumor tissue. At 6 hr, a strong hypericin fluorescence was observed in the tumor tissue with only faint fluorescence within the vasculature, whereas at 24 hr the fluorescence in the tumor also decreased and became more diffused, and no fluorescence could be seen in the tumor vasculature. Like the tumor response, skin reactions were also found to be much more dramatic at short administration-irradiation intervals. Hypericin distribution and PDT response studies revealed a close correlation between the plasma drug level and the PDT effects, which suggests that vascular damage is the primary effect of hypericin-mediated PDT in this tumor model.
Animals↗
Abnormalities in the cAMP signaling pathway in post-mortem brain tissue from the Stanley Neuropathology Consortium.
There is an established relationship between the monoaminergic neurotransmitter system and mood disorders. In an attempt to define further the pathophysiology of mood disorders, research is focussing on intracellular second messenger systems, including cyclic adenosine 3',5'-monophosphate (cAMP) and the polyphosphoinositol generated second messengers. The availability of tissue from the Stanley Foundation Neuropathology Consortium has offered us the opportunity to make a number of observations with respect to these second messenger systems in tissue from patients with major depressive disorder and bipolar affective disorder. There is evidence that antidepressants stimulate components of the cAMP pathway in patients with depression while mood stabilizers blunt the same pathway in patients with bipolar disorder. Furthermore, downstream targets of this pathway appear to be altered in patients with mood disorders. The relations between changes in second messenger systems, gene transcription, and clinical effects of current therapeutic regimens has implications for development of novel treatments of mood disorders.
Adenylyl Cyclases↗
[Growth inhibition of epidermal growth factor-stimulated human glioblastoma cells by nicardipine in vito].
OBJECTIVE: To study the growth effects of epidermal Growth Factor (EGF) and the calcium channel antagonist nicardipine (NC) on U251 MG, a human malignant glioma cell lime, which has high-affinity EGF receptors. METHODS: The growth effects of EGF and NC on U251 MG cultured in serum-free and serum-containing (10% fetal bovine serum, FBS) media respectively were observed by MTT colorimeritric analysis. RESULTS: (1) EGF significantly enhanced the growth of U251 MG in a dose-dependent manner in serum-free conditions. The near-maximal effect was obtained at 10 mg.ml-1. The addition of serum obscured this effect. (2) NC decreased U251 MG cells proliferation, especially in serum-containing media, and completely blocked the growth-stimulated effect of EGF. The combinated effects of EGF (10 ng.ml-1) and NC equaled those of NC alone. CONCLUSIONS: When serum is absent U251 MG cells showed a pronounced mitogenic response to EGF in a dosedependent manner, which approximated that achieved with 10% FBS. NC suppressed the growth of U251 MG cells and completely blocked the growth-stimulated effects of EGF, it can be used as an adjuvent therapy for human malignant gliomas.
Antineoplastic Agents↗
Association study of dopamine D2, D3 receptor gene polymorphisms with motor fluctuations in PD.
The authors investigated the association between dopamine receptor D2, D3 gene polymorphisms, and the risk of developing motor fluctuations in PD. DRD3 BalI and MspI polymorphisms were not associated with risk of developing motor fluctuations. However, the genotypic distribution of DRD2 TaqIA polymorphism was significantly different in motor fluctuators and nonmotor fluctuators. These findings suggest that DRD2 TaqIA polymorphism may be associated with an increased risk for developing motor fluctuations in PD.
Adult↗
Differential gene expression in fully-grown oocytes between gynogenetic and gonochoristic crucian carps.
Silver crucian carp (Carassius auratus gibelio) is a unique triploid bisexual species that can reproduce by gynogenesis. As all other gynogenetic animals, it keeps its chromosome integrity by inhibiting the first meiosis division (no extrusion of the first pole body). To understand the molecular events governing this reproduction mode, suppression subtractive hybridization was used to identify the genes differentially expressed in fully-grown oocytes of the gynogenetic and gonochoristic crucian carp (gyno-carp and gono-carp). From two specific subtractive cDNA libraries, the clones screened out by dot blots and virtual Northern blots were chosen to clone full-length cDNA by RACE. Four differentially expressed genes were obtained. Two are novel genes and are expressed specifically in the oocytes. The gyno-carp stores much more mRNA of cyclin A2, a new member of the fish A-type cyclin gene, in its fully-grown oocyte than in the gono-carp. The last gene is histone H2A. The histone H2As of these two closely related crucian carps are quite different in the C-terminus. Preliminary characterization of the four genes has been analyzed by nucleotide and deduced amino acid sequence and Northern analysis.
Amino Acid Sequence↗
A rhodium carbene cyclization-cycloaddition cascade strategy toward the pseudolaric acids.
A rhodium carbene intramolecular cyclization-cycloaddition cascade was employed as the key reaction in the synthesis of the nucleus of the cytotoxic diterpenoids pseudolaric acids A and B.
Antineoplastic Agents, Phytogenic↗
Synthesis of (-)-delobanone.
On irradiation in the presence of Fe(CO)(5) under a CO atmosphere, the alkenyl cyclopropane 2 underwent smooth ring expansion to give the sesquiterpene (-)-delobabone 3. The alkenyl cyclopropane 2 was prepared from the enantiomerically enriched epoxide 1.
Epoxy Compounds↗
Design, synthesis, and proposed active site binding analysis of monocyclic 2-azetidinone inhibitors of prostate specific antigen.
A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC(50) = 8.98 +/- 0.90 microM) which was used as a lead compound in this study. A single low energy conformation structure II (Figure 2) was adopted as most likely to represent binding after minimization and dynamics calculations. Systematic analysis of the binding importance of all three side chains appended to the 2-azetidinone was conducted by the synthesis of several analogues. A proposed salt bridge to Lys-145 with 4 (IC(50) = 5.84 +/- 0.92 microM) gave improved inhibition, but generally the binding of the N-1 side chain in a specific secondary aromatic binding site did not tolerate much structural alteration. A hydrophobic interaction of the C-4 side chain afforded inhibitor 6 (IC(50) = 1.43 +/- 0.19 microM), and polar functionality could also be added in a proposed interaction with Gln-166 in 5 (IC(50) = 1.34 +/- 0.05 microM). Reversal of the C-4 ester connectivity furnished inhibitors 7 (IC(50) = 1.59 +/- 0.15 microM), 11 (IC(50) = 3.08 +/- 0.41 microM), and 13 (IC(50) = 2.19 +/- 0.36 microM) which were perceived to bind to PSA by a rotation of 180 degrees relative to the C-4 ester of normal connectivity. Incorporation of hydroxyl functionality into the C-3 side chain provided 16 (IC(50) = 348 +/- 50 nM) with the greatest increase in PSA inhibition by a single modification. Multiple copy simultaneous search (MCSS) analysis of the PSA active site further supported our model and suggested that 18 would bind strongly. Asymmetric synthesis yielded 18 (IC(50) = 226 +/- 10 nM) as the most potent inhibitor of PSA reported to date. It is concluded that our design approach has been successful in developing PSA inhibitors and could also be applied to the inhibition of other enzymes, especially in the absence of crystallographic information.
Azetidines↗