Biomedical subjects

J Han

Publications and source records attributed to J Han.

At least 217 records · Page 12Linked to original sources

PubMed1999

[Inhibitory Effects of Etoposide Combined with 8-methoxypsoral en on Highly Metastatic Human Mucoepidermoid Carcinoma Cells].

OBJECTIVE: To study the inhibitory effects of Etoposide (VP16) combined with 8-methoxypsoralen (8-MOP) on human highly metastatic mucoepidermoid carcinoma cells (Mc3). METHODS: Mc3 cells were exposed to the drugs and their combinations at various concentrations. The inhibitory effects were tested with microculture tetrazolium colorimetric assay (MTT assay) and cologenic assay. RESULTS: The IC50 values of VP16 and 8-MOP were 1625. 25 ng/ml and 750000 ng/ml respectively, the CI50 of the combination at 100320 and 1000 ng/ml of VP16 with 8-MOP were 0.350, 0.599 and 0.880 respectively. CONCLUSION: The data indicate that combination of VP16 and 8-MOP is synergic in the inhibition of Mc3 cell growth.

Carcinoma, Mucoepidermoid↗

PubMed1999

[Preliminary study of a new concept for left ventricular assistance dynamic aortic valve].

Dynamic aortic valve, a novel design for left ventricular assistance is proposed. An impeller similar to the airscrew is placed in the position of aortic valve. The impeller is held by a pair of bearings in the center of a cylindrical supporting cage which is located in the lumen of the aorta ascendens. The supporting cage is attached to the valve annulus by a sewing ring of textile cuff around the outside of the cage. A rotor is fitted into the cage and connected to the impeller with a common shaft. The cage supports the aortic wall, thus prevents the rotor from founching the wall and allows the rotor to rotate freely. A stator, functioning as that of the electric motor, is located outside the aortic wall. When actuated, the magnetic field generated by the stator would drive the rotor to turning, and the axial flow of blood from ventricular to the aorta would be produced, resulting in the reduction of the ventricular load. We studied this concept in a simulating model. The result suggests that this design be reasonable. Further exploration of this concept is justified.

Heart Valve Prosthesis↗

PubMed1999

[Solid-state fermentation with Penicillium sp. PT95 for carotenoid production].

A preliminary study on solid-state fermentation (SSF) with Penicillium sp PT95 for carotenoid production was performed. The results showed that the production of carotenoid in sclerotia of PT95 was more efficient in corn meal medium than in either wheat bran medium or cottonseed hull medium. Addition of nitrogen and carbon sources as well as vegetable oil to media was required for increasing the dry weight of sclerotia and carotenoid yield. Among several tested compounds for nitrogen and carbon sources, sodium nitrate and maltose were the best. Through orthogonal experiments, the optimum culture medium was obtained by supplement of NaNO3 3g, maltose 10 g, soybean oil 2.5 g to per liter of salt solution. Under the optimum culture conditions, the sclerotia dry weight increased from 5.36 g to 9.70 g per 100 g dry substrate, the carotenoid yield from 2149 micrograms to 5260 micrograms per 100 g dry substrate, the proportion of beta-carotene in carotenoids from 61.4% to 71.3%.

Carotenoids↗

PubMed1999

[A preliminary study of two Chinese herbs protective tablets on some Chinese traditional medicines].

The protective action of 2 tablets of Chinese herb to 5 Chinese traditional medicines against harm of insects and mildews was tested. It was found that 2 tablets have a obvious effects of insect-repellency and mouthproof in the test with Homalomena occulta and Prunus armeniaca, the bore in the medicinal materials was decreased 94.95% and 95.55% respectively than that of check. The tablets have some effects of mildewproof in the test with Tussilago farfara.

Alisma↗

PubMed1998

Interaction of E1B 19K with Bax is required to block Bax-induced loss of mitochondrial membrane potential and apoptosis.

The Bcl-2 homologous region 3 (BH3) is sufficient for interaction of pro-apoptotic with anti-apoptotic Bcl-2 family members, and functional antagonism may determine whether cell survival or death is the outcome of this protein-protein interaction. To address the biological role of BH3, two Bax-Bcl2 chimeras were generated in which 13 amino acids encompassing BH3 was swapped between anti-apoptotic Bcl-2 and pro-apoptotic Bax, thereby generating Bax with BH3 of Bcl-2 (Bax-BH3Bcl2), and Bcl-2 with BH3 of Bax (Bcl2-BH3Bax). Function and binding of the chimeras was then assessed utilizing the adenoviral Bcl-2 homologue, E1B 19K, which blocks apoptosis, and interacts with Bax, but not with Bcl-2. E1B 19K did not interact with Bax-BH3Bcl2 but did interact with Bcl2-BH3Bax. Bax-BH3Bcl2 retained pro-apoptotic function, while Bcl2-BH3Bax did not exhibit either pro- or anti-apoptotic activity. Thus, BH3 of Bcl-2 encodes binding specificity but not the apoptotic propensity. E1B 19K could not block Bax-BH3Bcl2-induced apoptosis, suggesting that E1B 19K may act to antagonize pro-apoptotic proteins rather than as an effector of survival. Furthermore, Bax expression disrupted the mitochondrial membrane potential, which could be rescued by E1B 19K expression. Thus, BH3 controls the binding specificity among Bcl-2 family members, and direct interaction between pro-apoptotic and anti-apoptotic proteins is a mechanism to regulate mitochondrial membrane potential and apoptosis.

Adenovirus E1B Proteins↗

PubMed1998

p38 Kinase is a negative regulator of angiotensin II signal transduction in vascular smooth muscle cells: effects on Na+/H+ exchange and ERK1/2.

Activation of the Na+/H+ exchanger isoform-1 (NHE-1) by angiotensin II is an early signal transduction event that may regulate vascular smooth muscle cell (VSMC) growth and migration. Many signal transduction events stimulated by angiotensin II are mediated by the mitogen-activated protein (MAP) kinases. To define their roles in angiotensin II-mediated NHE-1 activity, VSMCs were treated with angiotensin II and the activities of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured. Angiotensin II rapidly (peak, 5 minutes) activated p38 and ERK1/2, whereas JNK was activated more slowly (peak, 30 minutes). Because angiotensin II stimulated Na+/H+ exchange within 5 minutes, the effects of p38 and ERK1/2 antagonists on Na+/H+ exchange were studied. The MEK-1 inhibitor PD98059 decreased ERK1/2 activity and Na+/H+ exchange stimulated by angiotensin II. In contrast, the specific p38 antagonist SKF-86002 increased Na+/H+ exchange. Two mechanisms were identified that may mediate the effects of p38 and SKF-86002 on angiotensin II-stimulated Na+/H+ exchange. First, angiotensin II activation of ERK1/2 was increased 1. 5- to 2.5-fold (depending on assay technique) in the presence of SKF-86002, demonstrating that p38 negatively regulates ERK1/2. Second, the ability of angiotensin II-stimulated MAP kinases to phosphorylate a glutathione S-transferase fusion protein containing amino acids 625 to 747 of NHE-1 in vitro was analyzed. The relative activities of endogenous immunoprecipitated p38, ERK1/2, and JNK were 1.0, 2.0, and 0.05 versus control, respectively suggesting that p38 and ERK1/2, but not JNK, may phosphorylate NHE-1 in VSMC. These data indicate important roles for p38 and ERK1/2 in angiotensin II-mediated regulation of the Na+/H+ exchanger in VSMC.

Angiotensin II↗

PubMed1998

PRAK, a novel protein kinase regulated by the p38 MAP kinase.

We have identified and cloned a novel serine/ threonine kinase, p38-regulated/activated protein kinase (PRAK). PRAK is a 471 amino acid protein with 20-30% sequence identity to the known MAP kinase-regulated protein kinases RSK1/2/3, MNK1/2 and MAPKAP-K2/3. PRAK was found to be expressed in all human tissues and cell lines examined. In HeLa cells, PRAK was activated in response to cellular stress and proinflammatory cytokines. PRAK activity was regulated by p38alpha and p38beta both in vitro and in vivo and Thr182 was shown to be the regulatory phosphorylation site. Activated PRAK in turn phosphorylated small heat shock protein 27 (HSP27) at the physiologically relevant sites. An in-gel kinase assay demonstrated that PRAK is a major stress-activated kinase that can phosphorylate small heat shock protein, suggesting a potential role for PRAK in mediating stress-induced HSP27 phosphorylation in vivo.

Amino Acid Sequence↗

PubMed1998

Molecular cloning and characterization of a human protein kinase that specifically activates c-Jun N-terminal kinase.

The c-Jun N-terminal kinases (JNKs), also called stress-activated protein kinases (SAPKs), belong to the mitogen-activated protein kinase (MAPK) gene super-family. Like all the MAPKs, JNKs are activated through dual phosphorylation of a theronine residue and a tyrosine residue by a dual specificity kinase such as JNKK1/MKK4/SEK1. Here, we report the molecular cloning and characterization of hJNKK2 alpha, a human homolog of the recently reported murine MKK7 alpha. hJNKK2 alpha belongs to the MAPK kinase gene family and is expressed in many adult tissues. It is nearly identical to a recently reported human JNKK2 at the kinase domain but with major differences in both amino- and carboxyl-terminal sequences, suggesting that hJNKK2 alpha may be an alternative spliced form of this kinase. Expression of hJNKK2 alpha, but not its related kinases JNKK1/MKK4/SEK1, MEK1, MKK3, or MKK6, leads to strong activation of JNK in several cell lines. No activation of ERK or p38 kinases was observed with this kinase. An in-vitro kinase assay demonstrated that JNK1 activation by hJNKK2 alpha requires phosphorylation of the theronine and tyrosine residues at positions 183 and 185 in JNK1. Furthermore, hJNKK2 alpha activated the JNK-dependent signal transduction pathway in vivo by induction of c-Jun- and ATF2-mediated gene transcription. In conclusion, we have cloned the human homolog of murine MKK7 alpha, which may be an alternative spliced form of human JNKK2 involved in transducing specific upstream signals to regulate JNK activity in vivo.

Adult↗

PubMed1998

Cellular activation mechanisms in septic shock.

Septic shock is an increasingly important clinical condition, characterized by systemic hypotension, ischemia, and ultimately organ failure. In Gram negative infection, the bacterial cell wall component, lipopolysaccharide (endotoxin, LPS), has been strongly linked to the pathophysiological responses that result in septic shock. LPS is bound in plasma to a protein called LPS-binding protein (LBP), which facilitates the binding of LPS to a cell surface receptor, CD14. Binding to CD14 stimulates cell signaling mechanisms that result in the production of inflammatory cytokines. However, the events which follow LPS binding to CD14 and which lead to the production of cytokines remain unclear. It has recently become evident that a number of phosphorylation cascades including MAP kinase pathways and NF-kappaB activation pathway are initiated by exposure of cells to LPS. These cascades act at both the transcriptional and translational levels to regulate cytokine production. This review will focus on the signaling pathways that are initiated by LPS and the cellular effects of the signaling pathways.

Gram-Negative Bacterial Infections↗

PubMed1998

Cardiac hypertrophy induced by mitogen-activated protein kinase kinase 7, a specific activator for c-Jun NH2-terminal kinase in ventricular muscle cells.

Activation of stress-activated protein kinases, including the p38 and the c-Jun NH2-terminal kinases (JNK), have been associated with the onset of cardiac hypertrophy and cell death in response to hemodynamic overload and ischemia/reperfusion injury. Upon infection of cultured neonatal rat cardiac myocytes with recombinant adenoviral vectors expressing a wild type and a constitutively active mutant of MKK7 (or JNKK2), JNK was specifically activated without affecting other mitogen-activated protein kinases, including extracellular signal-regulated protein kinases and p38. Specific activation of the JNK pathway in cardiac myocytes induced characteristic features of hypertrophy, including an increase in cell size, elevated expression of atrial natriuretic factor, and induction of sarcomere organization. In contrast, co-activation of both JNK (by MKK7) and p38 (by MKK3 or MKK6) in cardiomyocytes led to an induction of cytopathic responses and suppression of hypertrophic responses. These data provide the first direct evidence that activation of JNK alone is sufficient to induce characteristic features of cardiac hypertrophy, thereby supporting an active role for the JNK pathway in the development of cardiac hypertrophy. The cytopathic response, as a result of co-activation of both JNK and p38, may contribute to the loss of contractile function and viability of cardiomyocytes following hemodynamic overload and cardiac ischemia/reperfusion injury.

Adenoviridae↗

PubMed1998

The stress inducer arsenite activates mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 via a MAPK kinase 6/p38-dependent pathway.

Cell response to a wide variety of extracellular signals is mediated by either mitogenic activation of the Raf/MEK/ERK kinase cascade or stress-induced activation of the mitogen-activated protein kinase (MAPK) family members c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) or p38. We have examined communications between these stress- and mitogen-induced signaling pathways. We show here that the stress cascade activator arsenite activates extracellular signal-regulated kinase (ERK) in addition to p38 albeit with different kinetics. Whereas p38 is an early response kinase, ERK activation occurs with delayed time kinetics at 2-4 h. We observed activation of ERK upon arsenite treatment in many different cell lines. ERK activation is strongly enhanced by overexpression of p38 and mitogen-activated protein kinase kinase 6 (MKK6) but is blocked by dominant negative kinase versions of p38 and MKK6 or the specific p38 inhibitor SB203580. Arsenite-induced ERK activation is mediated by Ras, Raf, and MEK but appears to be independent of de novo protein synthesis. These data provide the first evidence for a p38 dependent activation of the mitogenic kinase cascade in stress-stimulated cells.

Arsenites↗

PubMed1998

Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family.

p38 mitogen-activated protein (MAP) kinase activities were significantly increased in mouse hearts after chronic transverse aortic constriction, coincident with the onset of ventricular hypertrophy. Infection of cardiomyocytes with adenoviral vectors expressing upstream activators for the p38 kinases, activated mutants of MAP kinase kinase 3b(E) (MKK3bE) and MAP kinase kinase 6b(E) (MKK6bE), elicited characteristic hypertrophic responses, including an increase in cell size, enhanced sarcomeric organization, and elevated atrial natriuretic factor expression. Overexpression of the activated MKK3bE in cardiomyocytes also led to an increase in apoptosis. The hypertrophic response was enhanced by co-infection of an adenoviral vector expressing wild type p38 beta, and was suppressed by the p38 beta dominant negative mutant. In contrast, the MKK3bE-induced cell death was increased by co-infection of an adenovirus expressing wild type p38 alpha, and was suppressed by the dominant negative p38 alpha mutant. This provides the first evidence in any cell system for divergent physiological functions for different members of the p38 MAP kinase family. The direct involvement of p38 pathways in cardiac hypertrophy and apoptosis suggests a significant role for p38 signaling in the pathophysiology of heart failure.

Adenoviridae↗

PubMed1998

Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav.

Mitogen stimulation of cytoskeletal changes and c-jun amino-terminal kinases is mediated by Rac small guanine nucleotide-binding proteins. Vav, a guanosine diphosphate (GDP)-guanosine triphosphate (GTP) exchange factor for Rac that stimulates the exchange of bound GDP for GTP, bound to and was directly controlled by substrates and products of phosphoinositide (PI) 3-kinase. The PI 3-kinase substrate phosphatidylinositol-4,5-bisphosphate inhibited activation of Vav by the tyrosine kinase Lck, whereas the product phosphatidylinositol-3,4,5-trisphosphate enhanced phosphorylation and activation of Vav by Lck. Control of Vav in response to mitogens by the products of PI 3-kinase suggests a mechanism for Ras-dependent activation of Rac.

Amino Acid Sequence↗

PubMed1998

Interpretation of the osmotic behavior of sickle cell hemoglobin solutions: different interactions among monomers and polymers.

It has long been known that a simple hard particle model quantitatively explains the osmotic properties of monomeric hemoglobin near its isoelectric point. However, we find that a hard particle model is not consistent with the osmotic properties of polymerized hemoglobin and that substantial soft repulsions are indicated. With allowance for different interactions among monomers and among polymers, a self-consistent quantitative fit to the experimental data is obtained. The results suggest that the decreasing "solubility" of deoxy sickle cell hemoglobin with increasing temperature from 20 to 37 degrees C is due to weaker repulsions between polymers at higher temperatures rather than stronger polymerization. The temperature dependence of these variables indicates that the aggregation of monomers is enthalpically and entropically driven (the latter effect being stronger), while the approach of polymers toward each other is enthalpically disfavored and entropically favored (with the former dominating). In both cases, the entropic contribution suggests that water is released.

Biopolymers↗

PubMed1998

cGMP facilitates calcium current via cGMP-dependent protein kinase in isolated rabbit ventricular myocytes.

The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on L-type Ca current (ICa) was investigated in a study of rabbit ventricular myocytes using the whole-cell patch-clamp technique. Intracellular application of cGMP (100 MUm) increased ICa in the absence of isoprenaline or forskolin. 8-Bromo-cGMP (100 muM) and 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP, 400 muM), relatively specific stimulators of cGMP-dependent protein kinase (cGMP-PK), also increased ICa. The stimulatory effect of 8-pCPT-cGMP was suppressed by Rp-8-chlorophenylthio-cGMP (400 muM), a phosphodiesterase-resistant cGMP-PK inhibitor. When ICa was increased by bath application of the non-specific phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX, 100 muM), 8-pCPT-cGMP (400 muM) resulted in additional stimulation of ICa. In the presence of 8-pCPT-cGMP, additional applications of isoprenaline (1 muM) or forskolin (1 muM) induced a further increase in ICa. From these results, it could be concluded that the activation of cGMP-dependent protein kinase is involved in the facilitation of ICa by cGMP in rabbit ventricular myocytes.

1-Methyl-3-isobutylxanthine↗

PubMed1998

Surgical resection of mucoepidermoid carcinoma at the carina in a 9-year-old boy.

Mucoepidermoid carcinoma of trachea and bronchi is a rare tumor, especially in children. The authors report a case of 9-year-old boy with mucoepidermoid carcinoma at the carina. His presenting symptoms were hemoptysis of recent onset and intermittent cough of 2 years' duration. Preoperative assessment of the tumor was an intraluminal polypoid mass arising from the carina extending into the trachea and right main stem bronchus. A complete resection with reconstruction of carina was successful. The tumor was 12 mm in size, polypoid with a broad base. It had characteristic features of a low-grade mucoepidermoid tumor, namely, admixture of islands of intermediate cells and glandular components with invasion of submucosa. The patient is now 15 months postsurgery free of disease.

Bronchial Neoplasms↗

PubMed1998

The p38 MAP kinase pathway and its biological function.

p38 is a mitogen-activated protein (MAP) kinase with structural and functional characteristics that distinguish it from JNK and ERK MAP kinases. p38 activity is upregulated when cells are exposed to a variety of stimuli including bacterial pathogens, proinflammatory cytokines, certain growth factors, and other forms of environmental stress. By regulating downstream substrates that include protein kinases and transcription factors, p38 participates in transmission, amplification, and diversification of the extracellular signal, initiating several different cellular responses. Studies have revealed that activation of p38 pathway is related to many pathological changes that occur in the course of inflammatory/immunologic and cardiovascular diseases.

Journal Article↗

PubMed1998

Traditional and evidence-based acupuncture: history, mechanisms, and present status.

BACKGROUND: In 1983, the Southern Medical Journal advised its readers that a scientific basis might underlie the popular practice of ancient Chinese acupuncture. Recent studies have proven this to be correct, and a 1997 National Institutes of Health consensus panel recommended acupuncture as a useful clinical procedure. METHODS: Pertinent articles in the literature were reviewed, including our own research. Significantly, we had access to recent important studies from China. RESULTS AND CONCLUSIONS: Most of the 10,000 acupuncturists in the country today practice metaphysically explained "meridian theory" acupuncture using needles to supposedly remove blockages of a hypothesized substance "Qi." Scientific research has shown that healing is not by manipulating Qi but rather by neuroelectric stimulation for the gene expression of neuropeptides. Needles are not necessary. Evidence-based neuroelectric acupuncture requires no metaphysical rituals. It is a simple, useful clinical tool for pain modulation and other conditions and can be easily taught to physicians.

Acupuncture Therapy↗