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Biomedical subjects

K Chen

Publications and source records attributed to K Chen.

At least 379 records · Page 21Linked to original sources
PubMed1995

An amino-terminal domain of Mxi1 mediates anti-Myc oncogenic activity and interacts with a homolog of the yeast transcriptional repressor SIN3.

Documented interactions among members of the Myc superfamily support a yin-yang model for the regulation of Myc-responsive genes in which transactivation-competent Myc-Max heterodimers are opposed by repressive Mxi1-Max or Mad-Max complexes. Analysis of mouse mxi1 has led to the identification of two mxi1 transcript forms possessing open reading frames that differ in their capacity to encode a short amino-terminal alpha-helical domain. The presence of this segment dramatically augments the suppressive potential of Mxi1 and allows for association with a mammalian protein that is structurally homologous to the yeast transcriptional repressor SIN3. These findings provide a mechanistic basis for the antagonistic actions of Mxi1 on Myc activity that appears to be mediated in part through the recruitment of a putative transcriptional repressor.

Amino Acid Sequence↗
PubMed1995

Changes in markers of disease progression in HIV-1 seroconverters: a comparison between cohorts of injecting drug users and homosexual men.

Comparisons of human immunodeficiency virus (HIV) disease progression between risk groups are difficult primarily because of the long incubation period of acquired immune deficiency syndrome (AIDS) and unknown times of infection. This is believed to be the first study that directly compared changes in T-lymphocyte subsets following HIV-1 seroconversion between cohorts of predominantly black injecting drug users and predominantly white homosexual men. Longitudinal trends of CD4 and CD8 percentages of total lymphocytes during 4 years were modeled as piecewise linear functions with a two-parameter correlation structure to accommodate within-person repeated observations. Prior to seroconversion the 151 injecting drug users started with similar CD4% and CD8% levels compared with the 99 homosexual men. Following seroconversion, larger changes were observed overall in the homosexual men compared with the injecting drug users for both markers (p < or = 0.001). The major discrepancies, however, were limited to the first 2 years. Subsequently, the CD4% levels of the two cohorts converged and then declined at similar rates. These comparative analyses of HIV seroconverters in homosexual men and injecting drug users suggest that risk group has only a minor effect on the initial course of HIV infection.

Adult↗
PubMed1995

Checkpoints in the cell cycle from a modeler's perspective.

The cell division cycle is a complex process by which cells grow and divide into two viable daughter cells. So that mistakes are not made in this crucial replication process, cells stop at one or more "checkpoints" in the cycle to query their internal state and external conditions, before proceeding to the next stage of the cycle. In this paper we study some simple mathematical models of cell cycle arrest in G1 ("Start") and G2. Our models help to relate the molecular mechanisms of these checkpoints with physiological properties of the cell cycle.

Animals↗
PubMed1995

Immunohistochemical studies of sensory neurons in rat olfactory epithelium.

The olfactory sensory neurons undergo continuous turnover under normal physiological conditions. Injured olfactory sensory neurons are also replaceable. In this study, we investigated cellular differentiation and growth of sensory neurons in the rat's olfactory epithelium after nerve transection by using immunohistochemical staining with polyclonal or monoclonal anti-olfactory marker protein (OMP), anti-c-jun protein and anti-p53 protein antibodies. OMP is found exclusively in olfactory sensory neurons, while c-jun functions as a transcription factor. p53 protein functions as a negative regulator of cellular proliferation related to the apoptotic pathway induced by DNA damage. The olfactory epithelium sections incubated with anti-OMP antibody showed staining of mature neurons and axons in the epithelium. Nerve transection resulted in a significant reduction in neurons labelled with OMP. On the 9th day after operation, our study indicated some recovery with an increasing number of neurons expressing OMP. In control animals without nerve lesions, c-jun protein immunoreactive neurons were present in the olfactory epithelium adjacent to the basal region. Following days 1 and 3 after nerve transection, no expression of c-jun protein was seen in neurons of the epithelium. On day 9 after transection, neurons in some basal areas indicated expression of c-jun protein. The immunolocalization demonstrated that p53 protein was present in some neurons located on the upper part of the olfactory epithelium. In contrast, an abundance of neurons expressing p53 protein was evident in the olfactory epithelium 1 and 3 days after nerve transection, indicating more cell deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Muscarinic receptor subtypes in rat dorsal cochlear nucleus.

We previously reported that responses of spontaneously active rat dorsal cochlear nucleus (DCN) neurons to cholinergic agonists are mediated predominantly by muscarinic receptors. We have now tested the effects of 7 antagonists with differing affinities for the muscarinic receptor subtypes M1-M4 on the responses to constant, submaximal doses of carbachol in rat brainstem slices. Each slice was exposed to one or more concentrations of one antagonist applied during extracellular recording of a DCN neuron. The concentrations yielding 50% reduction of test responses (IC50) of regular and bursting neurons were estimated for each antagonist. Correlation coefficients were calculated between log(IC50) values and log(Ki) values of the drugs for the receptor subtypes. Correlation coefficients for both regular and bursting neurons were not significant (P > 0.05) for M1 and M3, but were significant (P < 0.02) for M4. Bursting but not regular neurons also showed a significant correlation for M2 (P < 0.05). Our results suggest that (1) M4 contributes to the cholinergic responses in DCN and M2 may also contribute to the responses of bursting neurons, but the contribution of other subtypes cannot be completely excluded; (2) muscarinic subtypes in DCN probably differ from those reported for cochlea and some brain regions.

Animals↗
PubMed1995

Anti-AIDS agents--XIX. Neotripterifordin, a novel anti-HIV principle from Tripterygium wilfordii: isolation and structural elucidation.

A new kaurane type diterpene lactone, neotripterifordin (1), has been isolated from the roots of Tripterygium wilfordii. The structure of 1 was elucidated by spectroscopic methods, which included the concerted application of a number of 2-D NMR techniques including 1H-1H COSY, phase-sensitive NOESY, HETCOR, and long-range HETCOR. Compound 1 showed potent anti-HIV replication activity in H9 lymphocyte cells with an EC50 of 25 nM and TI of 125.

Animals↗
PubMed1995

Antitumor agents, 154. Cytotoxic and antimitotic flavonols from Polanisia dodecandra.

Three flavonols, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone [1], 5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone [2], and quercetin 3-O-beta-D-glucopyranosyl-7-O-alpha-L-rhamnopyranoside [3], were isolated from Polanisia dodecandra. Compound 1 showed remarkable cytotoxicity in vitro against panels of central nervous system cancer (SF-268, SF-539, SNB-75, U-251), non-small cell lung cancer (HOP-62, NCI-H266, NCI-H460, NCI-H522), small cell lung cancer (DMS-114), ovarian cancer (OVCAR-3, SK-OV-3), colon cancer (HCT-116), renal cancer (UO-31), a melanoma cell line (SK-MEL-5), and two leukemia cell lines (HL-60 [TB], SR), with GI50 values in the low micromolar to nanomolar concentration range. This substance also inhibited rubulin polymerization (IC50 = 0.83 +/- 0.2 microM) and the binding of radiolabeled colchicine to tubulin with 59% inhibition when present in equimolar concentrations with colchicine. Compound 2 also showed cytotoxicity against medulloblastoma (TE-671) tumor cells with an ED50 value of 0.98 microgram/ml. Compound 1 appears to be the first example of a flavonol to exhibit potent inhibition of tubulin polymerization and, therefore, warrants further investigation as an antimitotic agent.

Antineoplastic Agents↗
PubMed1995

The isolation and structural elucidation of three new neolignans, piperulins [corrected] A, B, and C, as platelet activating factor receptor antagonists from Piper puberulum.

Three new neolignans, piperulins [corrected] A [1], B [2], and C [3], were isolated from Piper puberulum. Their structures and relative stereochemistries were determined from spectral data and the X-ray crystallographic analysis of 1. Compounds 1 and 3 inhibit specific platelet activating factor receptor binding with IC50 values of 7.3 and 5.7 microM, respectively.

Animals↗
PubMed1995

Regulated secretion of prolactin by the mouse insulinoma cell line beta TC-3.

Our aim is to use cultured cells capable of regulated protein secretion for the production of recombinant proteins that require particular types of post-translational modifications. Here we have generated a stable transfected beta TC-3 cell line, beta TC-IPR9, that secretes high levels of recombinant prolactin. Transfected cells synthesize both the 27 kDa glycosylated and a 23 kDa nonglycosylated prolactin; the 23 kDa nonglycosylated species was secreted preferentially when cells were placed in secretion medium containing isobutylmethylxanthine (IBMX) and high concentrations of glucose, K+, and Ca2+. When the cells were cultured in medium containing low concentrations of glucose, K+, and Ca2+, most of the prolactin and insulin were not secreted; much of the prolactin was proteolytically converted to a 16 kDa form. Within the first 30 minutes after transferring the cells to medium containing secretagogues there was a 20-fold increase in the rate of secretion of prolactin; all of the 16 kDa species was secreted. The recombinant cells could be cycled several times between medium in which prolactin was biosynthesized and medium in which it was secreted. Preferential secretion of proteolytically processed prolactin in a medium without contaminating proteins offers an example of the advantage of this technology for production of other recombinant proteins.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Mechanical response to functional and therapeutic loading of a retromolar endosseous implant used for orthodontic anchorage to mesially translate mandibular molars.

Three finite element models were created to investigate the potential of rigid osseous fixation (osseointegration) for orthodontic anchorage: a mandible without an implant; a mandible with an implant; and a mandible and implant with a superimposed orthodontic load. Force was applied to different locations and the stresses were computed. The mechanical stress distributions adjacent to the implant were not affected by different biting forces, hence only one case needed to be analyzed. The stresses adjacent to the bone-implant interface changed drastically due to implantation, with major changes occurring on the buccal and mesiobuccal sides. A strong, concordant gradient for intraosseous stress and bone remodeling rate was observed that reflects a mismatch in the moduli of elasticity between the implant and the supporting bone. These results suggest important clinical implications. Osseointegration of symmetrically threaded titanium implants appears to be maintained by a sustained elevation of the mechanical stresses that continuously stimulate the bone remodeling activity within 1 mm of the implant surface. It is unlikely that a rigidly fixed (osseointegrated) implant will lose integration due to an orthodontic load superimposed on normal function.

Alveolar Process↗
PubMed1995

Characterization of protein disulphide isomerase released from activated platelets.

Protein disulphide isomerase (PDI) activity is released by activated platelets. In this study, PDI was purified from platelets and found to have an apparent mass, pI and N-terminal sequence similar to those for other human PDIs. Rabbit antibodies were generated and used to establish that, on activation, platelets release a protein immunologically identical to PDI in platelets. Approximately 10% of total platelet PDI was released by thrombin and 20% by calcium ionophore. The antibody was used to demonstrate PDI on the external surface of platelets by electron microscopy. Flow cytometry was used to demonstrate that upon activation of platelets with ionophore PDI was released by vesiculation. Since platelets are present and become activated at sites of vascular injury, platelet PDI may play a role in the various haemostatic and tissue remodelling processes in which platelets are involved.

Blood Platelets↗
PubMed1995

The natural history of drug use from adolescence to the mid-thirties in a general population sample.

OBJECTIVES: This study sought to describe patterns of initiation, persistence, and cessation in drug use in individuals from their late 20s to their mid-30s, within a broad perspective that spans 19 years from adolescence to adulthood. METHODS: A fourth wave of personal interviews was conducted at ages 34-35 with a cohort of men and women (n = 1160) representative of adolescents formerly enrolled in New York State public secondary high schools. A school survey was administered at ages 15-16, and personal interviews with participants and school absentees were conducted at ages 24-25 and 28-29. Retrospective continuous histories of 12 drug classes were obtained at each follow-up. RESULTS: There was no initiation into alcohol and cigarettes and hardly any initiation into illicit drugs after age 29, the age at which most use ceased. The largest proportion of new users was observed for prescribed psychoactives. Periods of highest use since adolescence based on relative and absolute criteria were delineated. Among daily users, the proportions of heavy users declined for alcohol and marijuana but not for cigarettes. CONCLUSIONS: Cigarettes are the most persistent of any drug used. Drug-focused interventions must target adolescents and young adults.

Adolescent↗
PubMed1995

Acute myeloid leukemia and myelodysplasia following intensive chemotherapy for breast cancer.

Two major classes of therapy-related acute myeloid leukemias (t-AML) and myelodysplastic syndromes (t-MDS) have been described following the use of conventional doses of alkylating agents and epipodophyllotoxins. They are characterized by distinct clinical presentations and chromosomal abnormalities. We report 2 cases of t-AML and 1 case of t-MDS in 3 out of 36 women who underwent high-dose chemotherapy and attempted ABMT for breast cancer. Two patients developed t-AML 4 and 8 months following the initiation of high-dose chemotherapy with or without ABMT. The third patient developed t-MDS 23 months following dose-intensive chemotherapy and ABMT. Cytogenetic studies of the marrow metaphase chromosomes from the two patients who developed t-AML, including FISH analysis in 1 patient, showed a t(9;11)(p22ng,q23) abnormal chromosome 6 (ring chromosome). Neither patient had a preleukemic phase. Cytogenetic studies from the third patient who developed t-MDS showed abnormalities of chromosome 5 (-5) and a derivative of chromosome 17. The use of multiple chemotherapeutic agents in all 3 patients makes it difficult to attribute the development of these cases of t-MDS/t-AML to a single chemotherapeutic agent. The possible role of dose-intensive chemotherapy in the development of these secondary malignancies is discussed.

Acute Disease↗
PubMed1995

Characterization of the human 5-HT2A receptor gene promoter.

The regulation of 5-HT2A receptor (5-HT2AR) expression has been implicated in a variety of pathological processes and has been shown to be extremely complicated and controversial. In order to understand the mechanisms of regulation of this receptor, it is important to characterize its promoter. In this report, the 5' end of the human 5-HT2AR gene was cloned and characterized. Anchored PCR mapped multiple transcription initiation sites at nucleotides -1157, -1137, -1127, and -496. Transfection of chimeric growth hormone plasmids containing various DNA fragments into 5-HT2AR-positive human cell lines (SHSY-5Y, neuroblastoma; HeLa, cervix carcinoma) showed that the 0.74 kb HaeIII/PvuII fragment, which encompasses the initiation sites between -1157 and -1127 and 5' of the downstream initiation site (at -496), exhibited significant promoter activity. This promoter activity was not affected by the sequence upstream of the 0.74 kb fragment. The sequence downstream (the 0.45 kb PvuII/SmaI fragment) strongly repressed this promoter activity, suggesting the presence of a silencer. Sequence analysis combined with gel retardation and Dnase 1 footprinting assay identified multiple cis and trans elements for this fragment, including Sp1, PEA3, cyclic AMP response element (CRE)-like sequence, and E-boxes. Two novel transcription factors have been detected by gel retardation and DNase 1 footprinting assay; one of them may be specific for human. The transcription factors and promoter activities were low in the negative cell line NCI-H460 (human lung large cell carcinoma). Interestingly, the 0.39 kb fragment, isolated from the 3' end of the 0.74 kb fragment, exhibited the highest promoter activity. The possibility that this 0.39 kb fragment may be an alternative promoter is discussed. These new data are essential for further study of the regulation of 5-HT2AR gene expression.

Base Sequence↗
PubMed1995

[Studies on diagnostic bacteriophage of Vibrio fluvialis].

Species of Vibrio fluvialis are identified by their biochemical characteristics so far, with a lot of items to be determined, overelaborate procedure and expensiveness. Inaccordance with the fact that bacteriophage is a specific parasite inhabited in bacteria and has been used in identifying other bacteria with high specificity, some of Vibrio fluvialis bacteriophage isolated from natural environment were selected to make diagnostic preparation for Vibrio fluvialis identification. Diagnostic positivity of Vibrio fluvialis averaged 84.27%, and 87.84% for those of human source. Cross-lysis rates both for the same Vibrio genus and that of different families in the same genus were less then 3%, and no cross-lysis was found for the other enteric bacteria in different genera. There was no significant difference between diagnostic bacteriophage and biochemical tests for Vibrio of unknown species. This method was highly specific, sensitive, rapid, simple and inexpensive, and could be used in diagnosis of Vibrio fluvialis.

Bacteriophages↗