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Biomedical subjects

H Lin

Publications and source records attributed to H Lin.

At least 127 records · Page 7Linked to original sources
PubMed2000

Inhibition of testosterone secretion by S-petasin in rat testicular interstitial cells.

S-petasin, a kind of sesquiterpene ester, is the anti-inflammatory ann analgesic component of the butterbur (Petasites hybridus). The clinical benefit of S-petasin is the spasmolytic activity, but its side effects on the reproductive endocrinology are not clear yet. The present study was to explore the effects of S-petasin on the secretion of testosterone in vivo and in vitro. We found that single intravenous injection of S-petasin (1 microg/kg) decreased basal plasma testosterone concentration in adult male rats. The enzymatically dispersed rat testicular interstitial cells were incubated with S-petasin (0-4.3 x 10(-5)M) in the presence or absence of human chorionic gonadotropin (hCG, 0.05 IU/ml), forskolin (adenylyl cyclase activator, 10(-5) M), and androstenedione (testosterone biosynthesis precursor, 10(-9) M) at 34 degrees C for 1 h. The concentrations of testosterone in the incubation medium were measured by radioimmunoassay. S-petasin at 4.3 x 10(-7) M was effective to reduce the basal and hCG-stimulated release of testosterone in rat testicular interstitial cells. The stimulatory effects of testosterone secretion induced by forskolin and androstenedione were significantly reduced by S-petasin at 4.3 x 10(-5) M and 4.3 x 10(-6) M, respectively. These results suggest that S-petasin inhibits the production of testosterone in rat testicular interstitial cells in part through diminishing the activities of adenylyl cyclase and 17-ketosteroid reductase.

17-Hydroxysteroid Dehydrogenases↗
PubMed2000

Signaling via LAT (linker for T-cell activation) and Syk/ZAP70 is required for ERK activation and NFAT transcriptional activation following CD2 stimulation.

Activation of T cells can be initiated through cell surface molecules in addition to the T-cell receptor-CD3 (TCR-CD3) complex. In human T cells, ligation of the CD2 molecule by mitogenic pairs of anti-CD2 monoclonal antibodies activates T cells via biochemical signaling pathways similar but not identical to those elicited on TCR engagement. This study describes a key role for the p36/38 membrane adapter protein linker for T cell activation (LAT) in CD2-mediated T-cell activation. Following ligation of CD2 on the surface of the Jurkat T-cell line and human purified T cells, LAT was tyrosine phosphorylated and shown to associate in vivo with a number of other tyrosine phosphorylated proteins including PLCgamma-1, Grb-2, and SLP-76. Using Jurkat cell lines deficient in ZAP70/Syk (P116) or LAT (ANJ3) expression, CD2-dependent PLCgamma-1 and SLP-76 tyrosine phosphorylation required expression both of ZAP70 or Syk and of LAT. As predicted, the absence of either LAT or ZAP70/Syk kinases correlated with a defect in the induction of nuclear factor of activated T cells (NFAT) transcriptional activity, activation of the interleukin-2 promoter, and ERK phosphorylation following CD2 stimulation. These data suggest that LAT is an adapter protein important for the regulation of CD2-mediated T-cell activation.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Cytoprotection by electromagnetic field-induced hsp70: a model for clinical application.

A unique approach to clinical application of cytoprotection is offered by electromagnetic (EM) field induction of stress proteins. EM fields are noninvasive and easily applied, as compared with the current hyperthermia protocols. Fertilized dipteran eggs and cultured rodent cardiomyocytes (H9c2 cells) were used as models to test EM fields for their ability to induce increased hsp70 levels for effective cytoprotection. Eggs preconditioned with an 8 microT 60Hz EM field for 30 min had 114% increase in hsp70 levels, and an average 82% increase in survival, following a lethal temperature of 36.5 degrees C. Thermal preconditioning at 32 degrees C was not nearly as effective in dipteran eggs, inducing only a 44% increase in survival. Preconditioning of cultured murine cardiomyocytes (H9c2 cells) with an 8 microT 60 Hz field induced a 77% average increase in hsp70 levels.

Animals↗
PubMed2000

Human THP-1 monocytic leukemic cells induced to undergo monocytic differentiation by bryostatin 1 are refractory to proteasome inhibitor-induced apoptosis.

The ubiquitin-proteasome pathway is the principal mechanism for the degradation of short-lived proteins in eukaryotic cells. We demonstrated that treatment of THP-1 human monocytic leukemia cells with Z-LLL-CHO, a reversible proteasome inhibitor, induced cell death through an apoptotic pathway. Apoptosis in THP-1 cells induced by Z-LLL-CHO involved a cytochrome c-dependent pathway, which included the release of mitochondrial cytochrome c, activation of caspase-9 and -3, and cleavage of Bcl-2 into a shortened 22-kDa fragment. Induction of apoptosis by protease inhibitor also was detected in U937 and TF-1 leukemia cell lines and cells obtained from acute myelogenous leukemia patients but not in normal human blood monocytes. Treatment of human blood monocytes with Z-LLL-CHO did not induce apoptosis or Bcl-2 cleavage in these cells that rarely proliferate. Interestingly, when THP-1 cells were induced to undergo monocytic differentiation by bryostatin 1, a naturally occurring protein kinase C activator, they were no longer susceptible to apoptosis induced by Z-LLL-CHO. Bryostatin 1-induced differentiation of THP-1 cells was associated with growth arrest, acquisition of adherent capacity, and expression of membrane markers characteristic of blood monocytes. Likewise, differentiated THP-1 cells were refractory to Z-LLL-CHO-induced cytochrome c release, caspase activation, and Bcl-2 cleavage. Resistance to Z-LLL-CHO-induced apoptosis in differentiated THP-1 cells was not due to cell cycle arrest. These findings show that the action of proteasome inhibitors is mediated primarily through a cytochrome c-dependent pathway and induces apoptosis in leukemic cells that are not differentiated.

Antineoplastic Agents↗
PubMed2000

Local overall volumetric gas-liquid mass transfer coefficients in gas-liquid-solid reversed flow jet loop bioreactor with a non-Newtonian fluid.

The local overall volumetric gas-liquid mass transfer coefficients at the specified point in a gas-liquid-solid three-phase reversed flow jet loop bioreactor (JLB) with a non-Newtonian fluid was experimentally investigated by a transient gassing-in method. The effects of liquid jet flow rate, gas jet flow rate, particle density, particle diameter, solids loading, nozzle diameter and CMC concentration on the local overall volumetric gas-liquid mass transfer coefficient (K(L)a) profiles were discussed. It was observed that local overall K(L)a profiles in the three-phase reversed flow JLB with non-Newtonian fluid increased with the increase of gas jet flow rate, liquid jet flow rate, particle density and particle diameter, but decreased with the increase of the nozzle diameter and CMC concentration. The presence of solids at a low concentration increased the local overall K(L)a profiles, and the optimum of solids loading for a maximum profile of the local overall K(L)a was found to be 0.18x10(-3)m(3) corresponding to a solids volume fraction, varepsilon(S)=2.8%.

Journal Article↗
PubMed2000

Mitochondrial adaptations to obesity-related oxidant stress.

It is not known why viable hepatocytes in fatty livers are vulnerable to necrosis, but associated mitochondrial alterations suggest that reactive oxygen species (ROS) production may be increased. Although the mechanisms for ROS-mediated lethality are not well understood, increased mitochondrial ROS generation often precedes cell death, and hence, might promote hepatocyte necrosis. The aim of this study is to determine if liver mitochondria from obese mice with fatty hepatocytes actually produce increased ROS. Secondary objectives are to identify potential mechanisms for ROS increases and to evaluate whether ROS increase uncoupling protein (UCP)-2, a mitochondrial protein that promotes ATP depletion and necrosis. Compared to mitochondria from normal livers, fatty liver mitochondria have a 50% reduction in cytochrome c content and produce superoxide anion at a greater rate. They also contain 25% more GSH and demonstrate 70% greater manganese superoxide dismutase activity and a 35% reduction in glutathione peroxidase activity. Mitochondrial generation of H(2)O(2) is increased by 200% and the activities of enzymes that detoxify H(2)O(2) in other cellular compartments are abnormal. Cytosolic glutathione peroxidase and catalase activities are 42 and 153% of control values, respectively. These changes in the production and detoxification of mitochondrial ROS are associated with a 300% increase in the mitochondrial content of UCP-2, although the content of beta-1 ATP synthase, a constitutive mitochondrial membrane protein, is unaffected. Supporting the possibility that mitochondrial ROS induce UCP-2 in fatty hepatocytes, a mitochondrial redox cycling agent that increases mitochondrial ROS production upregulates UCP-2 mRNAs in primary cultures of normal rat hepatocytes by 300%. Thus, ROS production is increased in fatty liver mitochondria. This may result from chronic apoptotic stress and provoke adaptations, including increases in UCP-2, that potentiate necrosis.

Animals↗
PubMed2000

A latent class mixed model for analysing biomarker trajectories with irregularly scheduled observations.

This paper considers a latent class model to uncover subpopulation structure for both biomarker trajectories and the probability of disease outcome in highly unbalanced longitudinal data. A specific pattern of trajectories can be viewed as a latent class in a finite mixture where membership in latent classes is modelled with a polychotomous logistic regression. The biomarker trajectories within a latent class are described by a linear mixed model with possibly time-dependent covariates and the probabilities of disease outcome are estimated via a class specific model. Thus the method characterizes biomarker trajectory patterns to unveil the relationship between trajectories and outcomes of disease. The coefficients for the model are estimated via a generalized EM (GEM) algorithm, a natural tool to use when latent classes and random coefficients are present. Standard errors of the coefficients are calculated using a parametric bootstrap. The model fitting procedure is illustrated with data from the Nutritional Prevention of Cancer trials; we use prostate specific antigen (PSA) as the biomarker for prostate cancer and the goal is to examine trajectories of PSA serial readings in individual subjects in connection with incidence of prostate cancer.

Adolescent↗
PubMed2000

Bcl-2 antibodies induce hemoglobin release by red blood cells loaded with in vitro translated Bcl-2 and its cleaved fragment.

Apoptosis induced by proteasome inhibitor in human THP-1 leukemia cells is associated with the cleavage of Bcl-2 into a shortened fragment, Bcl-2/Delta34. Both Bcl-2 and its cleaved fragment were located exclusively on the mitochondria of THP-1 cells. No translocation of Bcl-2 or Bcl-2/Delta34 to the cytosolic fraction was detected during apoptosis. Treatment of isolated mitochondria with recombinant caspase-3 induced the same cleavage of Bcl-2 in vitro and triggered the release of cytochrome c from the mitochondria. The ability of Bcl-2/Delta34 in regulating the opening of membrane "pores" was investigated using a sheep red blood cell (RBC) model with in vitro translated Bcl-2/Delta34 and Bcl-2 proteins. Bcl-2 and Bcl-2/Delta34 generated in vitro were relocated rapidly to sheep RBC but caused no hemoglobin release in either case. Addition of anti-Bcl-2 antibodies directly to the RBC that had been loaded with either Bcl-2 or Bcl-2/Delta34 resulted in a rapid release of hemoglobin from the blood cells. Treatment of the sheep RBC with anti-Bcl-2 or anti-sheep RBC antibodies alone did not trigger hemoglobin release from the RBC. Based on these findings, we proposed that, upon "enforced aggregation," both Bcl-2 and Bcl-2/Delta34 can form "pores" in membranes, which may contribute to the release of cytochrome c in apoptosis.

Animals↗
PubMed2000

[Effects of tea polyphenols on cell kinetics and apoptosis of primary cultured rat skin keratinocytes].

In order to study the effects of tea polyphenols on cell growth and apoptosis of primary cultured rat skin keratinocytes, the safe dosage of tea polyphenols was determined by the release of lactate dehydrogenase(LDH). Cell counting(cytometry) and flow cytometry(FCM) were used to estimate the cell growth and the percentages of cells in different cell cycle phases or apoptosis. The results showed that tea polyphenols stimulated the cell growth from G1/G0 to G2/M phase, enhanced the synthesis of DNA(increase S phase) and increased the proliferative index(PI) from 18.17% to 25.62%. Also, it could block the occurrence of apoptosis. It is concluded that tea polyphenols could stimulate the growth of skin keratinocytes through stimulating the synthesis of cell DNA and inhibiting apoptosis.

Animals↗
PubMed2000

Imaging and mapping heparin-binding sites on single fibronectin molecules with atomic force microscopy.

Fibronectin is composed of multiple homologous repeats and contains many functional domains. Two major heparin-binding domains have previously been identified: the Hep I site near the amino terminus and the Hep II site near the carboxyl terminus. The Hep II site has been considered the high-affinity heparin-binding site based on studies of fibronectin fragments. However, few studies have been carried out on heparin binding by intact fibronectin. We imaged single fibronectin molecules as well as heparin-coated gold particles bound to whole dimeric plasma fibronectin molecules with tapping mode atomic force microscopy. We observed heparin-gold particles preferentially bound at two locations that correspond to the Hep I and Hep II sites. Quantitative analysis of images of individual fibronectin-heparin-gold complexes showed that almost twice as many heparin-gold particles bound to the N-terminal Hep I site compared to the Hep II site. In contrast to previous findings with fibronectin fragments, these results suggest that the Hep I site has a binding affinity higher than or comparable to the Hep II site in the intact fibronectin molecule.

Animals↗
PubMed2000

Caltech Faint Galaxy Redshift Survey. XI. The Merger Rate to Redshift 1 from Kinematic Pairs.

The rate of mass accumulation due to galaxy merging depends on the mass, density, and velocity distribution of galaxies in the near neighborhood of a host galaxy. The fractional luminosity in kinematic pairs combines all of these effects in a single estimator that is relatively insensitive to population evolution. Here we use a k-corrected and evolution-compensated volume-limited sample having an R-band absolute magnitude of Mk,eR</=-19.8+5logh mag drawing about 300 redshifts from the Caltech Faint Galaxy Redshift Survey and 3000 from the Canadian Network for Observational Cosmology field galaxy survey to measure the rate and redshift evolution of merging. The combined sample has an approximately constant comoving number and luminosity density from redshift 0.1 to 1.1 (OmegaM=0.2, OmegaLambda=0.8); hence, any merger evolution will be dominated by correlation and velocity evolution, not density evolution. We identify kinematic pairs with projected separations less than either 50 or 100 h-1 kpc and rest-frame velocity differences of less than 1000 km s-1. The fractional luminosity in pairs is modeled as fL&parl0;Deltav,rp,Mk,er&parr0;&parl0;1+z&parr0;mL, where &sqbl0;fL,mL&sqbr0; are &sqbl0;0.14+/-0.07,0+/-1.4&sqbr0; and &sqbl0;0.37+/-0.7,0.1+/-0.5&sqbr0; for rp</=50 and 100 h-1 kpc, respectively (OmegaM=0.2, OmegaLambda=0.8). The value of mL is about 0.6 larger if Lambda=0. To convert these redshift-space statistics to a merger rate, we use the data to derive a conversion factor to a physical space pair density, a merger probability, and a mean in-spiral time. The resulting mass accretion rate per galaxy (M1,M2>/=0.2M*) is 0.02+/-0.01&parl0;1+z&parr0;0.1+/-0.5M* Gyr-1. Present-day high-luminosity galaxies therefore have accreted approximately 0.15M* of their mass over the approximately 7 Gyr to redshift 1. Since merging is likely only weakly dependent on the host mass, the fractional effect, deltaM&solm0;M approximately 0.15M*&solm0;M, is dramatic for lower mass galaxies but is, on the average, effectively perturbative for galaxies above 1M*.

Journal Article↗
PubMed2000

Biomimetic total syntheses of (-)-TAN1251A, (+)-TAN1251B, (+)-TAN1251C, and (+)-TAN1251D.

[reaction: see text] The muscarinic antagonists (-)-TAN1251A (1), (+)-TAN1251B (2), (+)-TAN1251C (3), and (+)-TAN1251D (4) have been synthesized biomimetically by enamine formation from an amino aldehyde to give TAN1251C ketal 18. Oxidation and reduction lead to TAN1251A (1), which has been hydroxylated to give TAN1251B (2). Stereospecific reduction of TAN1251C ketal 18 leads to TAN1251D (4).

Molecular Mimicry↗
PubMed2000

Physiological role of gap-junctional hemichannels. Extracellular calcium-dependent isosmotic volume regulation.

Hemichannels in the overlapping regions of apposing cells plasma membranes join to form gap junctions and provide an intercellular communication pathway. Hemichannels are also present in the nonjunctional regions of individual cells and their activity is gated by several agents, including calcium. However, their physiological roles are unknown. Using techniques of atomic force microscopy (AFM), fluorescent dye uptake assay, and laser confocal immunofluorescence imaging, we have examined the extracellular calcium-dependent modulation of cell volume. In response to a change in the extracellular physiological calcium concentration (1.8 to </=1.6 mM) in an otherwise isosmotic condition, real-time AFM imaging revealed a significant and reversible increase in the volume of cells expressing gap-junctional proteins (connexins). Volume change did not occur in cells that were not expressing connexins. However, after the transient or stable transfection of connexin43, volume change did occur. The volume increase was accompanied by cytochalasin D-sensitive higher cell stiffness, which helped maintain cell integrity. These cellular physical changes were prevented by gap-junctional blockers, oleamide and beta-glycyrrhetinic acid, or were reversed by returning extracellular calcium to the normal level. We conclude that nongap-junctional hemichannels regulate cell volume in response to the change in extracellular physiological calcium in an otherwise isosmotic situation.

Animals↗
PubMed2000

Translational repression: a duet of Nanos and Pumilio.

Recent studies have shed new light on translational repression by Nanos and Pumilio proteins. The ancestral function of this repression mechanism appears to be in early germline development; later, species-specific applications in embryonic patterning and spermatogenesis-oogenesis switching evolved.

Animals↗
PubMed2000

Interleukin-12 promotes neurite outgrowth in mouse sympathetic superior cervical ganglion neurons.

To determine the role of cytokines in the nervous system, we examined the effect of interleukin-12(IL-12) on the nerve regeneration of mouse superior cervical ganglion cells (SCG). IL-12 enhanced the neurite outgrowth in a concentration-dependent manner. Immunocytochemical studies demonstrated the expression of IL-12 receptors in neuronal bodies and neurites. The mRNA expression of IL-12 receptors in SCG cells was confirmed by reverse transcription-polymerase chain reaction. Our data demonstrated the presence of IL-12 receptors in sympathetic neurons and suggest that IL-12 plays an important role in neuronal regeneration.

Animals↗
PubMed2000

Anterolateral thigh vastus lateralis myocutaneous flap for vulvar reconstruction after radical vulvectomy: a preliminary experience.

BACKGROUND: There are many myocutaneous flap methods which have been reported for the immediate reconstruction of large vulvar defects created by deforming radical cancer surgery in the female perineum except for the anterolateral thigh vastus lateralis myocutaneous flap. The present report describes our preliminary experience with the use of this flap in a patient who underwent radical vulvectomy for locally advanced squamous cell carcinoma of the vulva. CASE: A 75-year-old woman underwent radical vulvectomy with bilateral inguinal lymphadenectomy due to right vulvar squamous cell carcinoma. The large vulvar defect was immediately reconstructed by using anterolateral thigh vastus lateralis myocutaneous flap. The postoperative course was uneventful. In addition to the expected primary healing, the neovulva had a relatively normal appearance with satisfactory sensation and function and the donor defect was found to be minimal both functionally and aesthetically. CONCLUSION: This technique can be used as an alternative method for vulvar reconstruction after radical vulvectomy. Further studies are warranted to prove the efficacy of this myocutaneous flap in reconstructing large vulvar defects.

Aged↗
PubMed2000

High external parametrial dose can increase the probability of radiation proctitis in patients with uterine cervix cancer.

OBJECTIVE: The aim of this study was to evaluate the relationship between external parametrial dose and radiation proctitis after external irradiation and high-dose-rate intracavitary (HDR-IC) brachytherapy among patients with cervical cancer. METHODS: From May 1993 through December 1996, 191 patients with stage IB-IVA cervical cancer were managed by curative-intent radiotherapy. External irradiation to the whole pelvis (44-45 Gy/ 22-25 fractions) was delivered to all patients initially. One hundred twenty-seven patients received additional bilateral parametrial and sidewall boost (5.4-14.4 Gy/ 3-8 fractions) with 4-cm midline shielding. HDR-IC brachytherapy, 19.2-24 Gy/ 5 fractions to Point A, was given after external irradiation. Patients receiving an external dose of 44-45, 50-54, and >54 Gy were categorized as no parametrial boost (NPMB), low parametrial boost (LPMB), and high parametrial boost (HPMB) group, respectively. The actuarial proctitis rate was compared among the three groups. RESULTS: Three-year overall and Grade 2-4 proctitis rates were 30 and 15%, respectively. Overall proctitis rates were 12, 34, and 51% in the NPMB, LPMB, and HPMB groups (P < 0.0001), respectively. Grade 2-4 proctitis rates were 5, 17, and 27% in the NPMB, LPMB, and HPMB groups (P = 0.0022), respectively. In multivariate analysis of overall and Grade 2-4 radiation proctitis, external parametrial dose was the only independent prognostic factor (P = 0.0002 and 0.0030, respectively). CONCLUSION: Regardless of central shielding after 44-45 Gy whole pelvis irradiation, more patients with high external parametrial dose developed radiation proctitis. Incomplete midline shielding of the upper rectum may be the cause. Diminishing the external beam doses further may decrease rectal complications.

Adult↗