Biomedical subjects

R Schilling

Publications and source records attributed to R Schilling.

At least 19 recordsLinked to original sources

PubMed2005

A multivalent HIV-vaccine: development of a plasmid DNA for the expression of HIV envelope glycoproteins with hypervariable V3-loop domains.

The third hypervariable (V3) loop of the HIV-1 envelope glycoprotein gp120 plays an essential role in the process of viral entry. It contributes to the tropism, coreceptor usage and immune-escape of the virus. We generated a monovalent plasmid DNA and demonstrated the expression of HIV-1 clade B subtype NL4-3 gp120 and gp160 in comparison to a multivalent plasmid DNA encoding for a variety of V3-variants. In contrast to the membrane-anchored gp160, preliminary data demonstrate the monovariant gp120 is expressed in and presented on a human dendritic cell (DC) line, due to a HIVenv-specific re-stimulation of naïve T-cells detected by IFNgamma-ELISPOT assay.

AIDS Vaccines↗

PubMed2004

Saddle index properties, singular topology, and its relation to thermodynamic singularities for a phi4 mean-field model.

We investigate the potential energy surface of a phi(4) model with infinite range interactions. All stationary points can be uniquely characterized by three real numbers alpha(+) , alpha(0) , alpha(-) with alpha(+) + alpha(0) + alpha(-) =1 , provided that the interaction strength mu is smaller than a critical value. The saddle index n(s) is equal to alpha(0) and its distribution function has a maximum at n(max)(s) =1/3 . The density p (e) of stationary points with energy per particle e , as well as the Euler characteristic chi (e) , are singular at a critical energy e(c) (mu) , if the external field H is zero. However, e(c) (mu) not equal upsilon(c) (mu) , where upsilon(c) (mu) is the mean potential energy per particle at the thermodynamic phase transition point T(c) . This proves that previous claims that the topological and thermodynamic transition points coincide is not valid, in general. Both types of singularities disappear for H not equal 0 . The average saddle index n (s) as function of e decreases monotonically with e and vanishes at the ground state energy, only. In contrast, the saddle index n(s) as function of the average energy e ( n(s) ) is given by n(s) ( e ) =1+4 e (for H=0 ) that vanishes at e =-1/4> upsilon(0) , the ground state energy.

Journal Article↗

PubMed2003

Efficacy and safety of DALI LDL-apheresis at high blood flow rates: a prospective multicenter study.

Direct adsorption of lipids (DALI) is the first LDL-apheresis method compatible with whole blood. Usually, the blood flow rate is adjusted at 60-80 ml/min, which results in session times of about 2 hr. The present study was performed to test the safety and efficacy of low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] removal by DALI at high blood flow rates in order to reduce treatment time. Thirteen chronic DALI patients in seven centers suffering from hypercholesterolemia (LDL-C 162 +/- 42 mg/dl at baseline) and coronary artery disease were treated on a weekly or biweekly basis by DALI apheresis. The blood flow rate QB was held constant for at least two sessions, respectively, and was increased from 60 to 80, 120, 160, 200, and 240 ml/min. All patients had pre-existing av-fistulas. The anticoagulation was performed by a heparin bolus plus ACD-A at a ratio of citrate:blood ranging from 1:20 to 1:90. Clinically, the sessions were well tolerated and only 26/201 sessions (12%) of the treatments were fraught with minor adverse events. Acute LDL-C reductions (derived from LDL-C levels determined by lipoprotein electrophoresis) averaged 72/66/60/53/50/48% for QB=60/80/120/160/200/240 ml/min. Lp(a) reductions were 68/67/62/60/58/56%, whereas HDL-C losses were < or =10%. Routine blood chemistries and blood cell counts remained in the normal range. Treatment times averaged 142/83/45 min at Qb=60/120/240 ml/min. On average, DALI LDL-apheresis could be performed safely and effectively at high blood flow rates up to at least 120 ml/min in patients with good blood access, which significantly reduced treatment time from 142 to 83 min (-42%).

Adsorption↗

PubMed2002

Dynamical precursor of nematic order in a dense fluid of hard ellipsoids of revolution.

We investigate hard ellipsoids of revolution in a parameter regime where no long range nematic order is present but already finite-size domains are formed which show orientational order. Domain formation leads to a substantial slowing down of a collective rotational mode which separates well from the usual microscopic frequency regime. A dynamic coupling of this particular mode into all other modes provides a general mechanism which explains an excess peak in spectra of molecular fluids. Using molecular dynamics simulation on up to 4096 particles and on solving the molecular mode coupling equation we investigate dynamic properties of the peak and prove its orientational origin.

Journal Article↗

PubMed2001

Microscopic dynamics of molecular liquids and glasses: role of orientations and translation-rotation coupling.

We investigate the dynamics of a fluid of dipolar hard spheres in its liquid and glassy phases, with emphasis on the microscopic time or frequency regime. This system shows rather different glass transition scenarios related to its rich equilibrium behavior, which ranges from a simple hard sphere fluid to long range ferroelectric orientational order. In the liquid phase close to the ideal glass transition line and in the glassy regime a medium range orientational order occurs leading to a softening of an orientational mode. To investigate the role of this mode we use the molecular mode-coupling equations to calculate the spectra straight phi"lm(q,omega) and chi"lm(q,omega). In the center of mass spectra straight phi"00(q,omega) and chi"00(q,omega) we found, besides a high frequency peak at omega(hf), a peak at omega(op), about one decade below omega(hf) x omega(op) has almost no q dependence and exhibits an "isotope" effect omega(op) proportional to I(-1/2), with I the moment of inertia. We give evidence that the existence of this peak is related to the occurrence of medium range orientational order. It is shown that some of these features also exist for schematic mode coupling models.

Journal Article↗

PubMed2001

Non-cytolytic inhibition of hepatitis B virus replication in human hepatocytes.

BACKGROUND/AIMS: Interferon-gamma (IFN-gamma) has been shown to abolish hepatitis B virus (HBV) gene expression and replication in HBV transgenic mice without destroying infected hepatocytes. We investigated the characteristics of IFN-gamma induced non-cytolytic inhibition of viral replication in human HBV infection. METHODS: We used an in vitro model where lymphocytes from 15 HBsAg positive patients were co-cultured with transfected hepatocytes supporting HBV replication. The effector and target cells were separated by a membrane, which allowed transfer of soluble factors only, to determine whether IFN-gamma produced from antigen-specific CD4+ T cells or mitogen stimulated lymphocytes inhibits HBV replication. RESULTS: IFN-gamma produced following lymphocyte stimulation reduced cytoplasmic HBV DNA in the target cells. The degree of HBV DNA reduction correlated with the level of IFN-gamma in the supernatants. Further investigations using naturally infected human hepatocytes confirmed that recombinant IFN-gamma reduces HBV DNA and HBV RNA in these cells as well, in parallel with the induction of cellular interferon-responsive genes. This antiviral effect was without significant cytotoxicity and was more pronounced in hepatocytes from patients with low HBV replication. CONCLUSIONS: These results provide direct evidence that IFN-gamma can inhibit both HBV transcription and replication in human hepatocytes without cell lysis.

Adult↗

PubMed2000

Test of molecular mode coupling theory for general rigid molecules

We report recent progress on the test of mode coupling theory for molecular liquids (MMCT) for molecules of arbitrary shape. The MMCT equations in the long time limit are solved for supercooled water including all molecular degrees of freedom. In contrast to our earlier treatment of water as a linear molecule, we find that the glass-transition temperature T(c) is overestimated by the theory as was found in the case of simple liquids. The nonergodicity parameters are calculated from the "full" set of MMCT equations truncated at l(co)=2. These results are compared (i) with the nonergodicity parameters from MMCT with l(co)=2 in the "dipole" approximation n=n(')=0 and the diagonalization approximation n=n(')=0, l=l(') and (ii) with the corresponding results from a MD simulation. This work supports the possibility that a reduction to the most prominent correlators may constitute a valid approximation for solving the MMCT equations for rigid molecules.

Journal Article↗

PubMed2000

Molecular correlations in a supercooled liquid

We present static and dynamic properties of molecular correlation functions S(lmn,l(')m(')n('))(q-->,t) in a simulated supercooled liquid of water molecules, as a preliminary effort in the direction of solving the molecular mode-coupling theory (MMCT) equations for supercooled molecular liquids. The temperature and time dependence of various molecular correlation functions, calculated from 250 ns long molecular dynamics simulations, show the characteristic patterns predicted by MMCT and shed light on the driving mechanism responsible for the slowing down of the molecular dynamics. We also discuss the symmetry properties of the molecular correlation functions that can be predicted on the basis of the C(2v) symmetry of the molecule. Analysis of the molecular dynamics results for the static correlators S(lmn,l(')m(')n('))(q-->) reveals that additional relationships between correlators with different signs of n and n(') exist. We prove that for molecules with C(rv) symmetry this unexpected result becomes exact at least for high temperatures.

Journal Article↗

PubMed2000

Ideal glass transitions for hard ellipsoids

For hard ellipsoids of revolution we calculate the phase diagram for the idealized glass transition. Our equations cover the glass physics in the full phase space, for all packing fractions and all aspect ratios X0. With increasing aspect ratio we find the idealized glass transition to become primarily driven by orientational degrees of freedom. For needlelike or platelike systems the transition is strongly influenced by a precursor of a nematic instability. We obtain three types of glass transition line. The first one (straight phi((B))(c)) corresponds to the conventional glass transition for spherical particles which is driven by the cage effect. At the second one (straight phi((B'))(c)), which occurs for rather nonspherical particles, a glass phase is formed that consists of domains. Within each domain there is a nematic order where the center of mass motion is quasiergodic, whereas the interdomain orientations build an orientational glass. The third glass transition line (straight phi((A))(c)) occurs for nearly spherical ellipsoids where the orientational degrees of freedom with odd parity, e.g., 180 degrees flips, freeze independently from the positions.

Journal Article↗

PubMed2000

Molecular mode-coupling theory applied to a liquid of diatomic molecules

We study the molecular mode-coupling theory for a liquid of diatomic molecules. The equations for the critical tensorial nonergodicity parameters F(m)(ll('))(q) and the critical amplitudes of the beta relaxation H(m)(ll('))(q) are solved up to a cutoff l(co)=2 without any further approximations. Here l,m are indices of spherical harmonics. Contrary to previous studies, where additional approximations were applied, we find in agreement with simulations that all molecular degrees of freedom vitrify at a single temperature T(c). The theoretical results for the nonergodicity parameters and the critical amplitudes are compared with those from simulations. The qualitative agreement is good for all molecular degrees of freedom. To study the influence of the cutoff on the nonergodicity parameter, we also calculate the nonergodicity parameters for an upper cutoff l(co)=4. In addition, we also propose a method for the calculation of the critical nonergodicity parameter from the liquid side of transition.

Journal Article↗

PubMed2000

Inhibition of cholesteryl ester transfer protein by substituted dithiobisnicotinic acid dimethyl ester: involvement Of a critical cysteine.

SC-71952, a substituted analog of dithiobisnicotinic acid dimethyl ester, was identified as a potent inhibitor of cholesteryl ester transfer protein (CETP). When tested in an in vitro assay, the concentration of SC-71952 required for half-maximal inhibition was 1 microm. The potency of SC-71952 was enhanced 200-fold by preincubation of the inhibitor with CETP, and was decreased 50-fold by treatment with dithiothreitol. Analogs of SC-71952 that did not contain a disulfide linkage were less potent, did not display time dependency, and were not affected by dithiothreitol treatment. Kinetic and biochemical characterization of the inhibitory process of CETP by SC-71952 suggested that the inhibitor initially binds rapidly and reversibly to a hydrophobic site on CETP. With time, the bound inhibitor irreversibly inactivates CETP, presumably by reacting with one of the free cysteines of CETP. Liquid chromatography/mass spectroscopy (LC/MS) analyses of tryptic digests of untreated or SC-71952-inactivated CETP was used to identify which cysteine(s) were potentially involved in the time-dependent, irreversible component of inactivation by the inhibitor. One disulfide bond, Cys143-Cys184, was unaffected by treatment with the inhibitor. Inactivation of CETP by SC-71952 correlated with a progressive decrease in the abundance of free Cys-13 and Cys-333. Conversion of Cys-13 to alanine had no effect on the rapid reversible component of inactivation by SC-71952. However, it abolished the time-dependent enhancement in potency seen with the inhibitor when using wild-type CETP. These data indicate that Cys-13 is critical for the irreversible inactivation of CETP by SC-71952 and provides support for the structural model that places Cys-13 near the neutral lipid-binding site of CETP.

Amino Acid Substitution↗

PubMed1999

Molecular mode-coupling theory for supercooled liquids: application to water.

We present mode-coupling equations for the description of the slow dynamics observed in supercooled molecular liquids close to the glass transition. The mode-coupling theory (MCT) originally formulated to study the slow relaxation in simple atomic liquids, and then extended to the analysis of liquids composed by linear molecules, is here generalized to systems of arbitrarily shaped, rigid molecules. We compare the predictions of the theory for the q-vector dependence of the molecular nonergodicity parameters, calculated by solving numerically the molecular MCT equations in two different approximation schemes, with "exact" results calculated from a molecular dynamics simulation of supercooled water. The agreement between theory and simulation data supports the view that MCT succeeds in describing the dynamics of supercooled molecular liquids, even for network forming ones.

Journal Article↗

PubMed1999

Multiparticle breathers for a chain with double-quadratic on-site potential.

We investigate the existence and properties of multiparticle breathers for a one-dimensional model with harmonic nearest neighbor interactions where a group of r particles (r=1,2,3, ...) perform interwell oscillations between both wells of a double-quadratic on-site potential. We find two types of such breathers. For the first type the breather frequency Omega is within the single-particle oscillator spectrum, and the "residence" time of each breather particle in the left and right well is about the same. For the second breather Omega is below that spectrum, and the ratio tau(L)/tau(R) of the residence time in the left and right wells is different from zero, and takes approximately rational values like 1/4,1/3,2/3,3/4, etc. This second type of breather occurs for two and more breather particles only.

Journal Article↗

PubMed1999

Neutron scattering and molecular correlations in a supercooled liquid.

We show that the intermediate scattering function S(n)(q,t) for neutron scattering (ns) can be expanded naturally with respect to a set of molecular correlation functions that give a complete description of the translational and orientational two-point correlations in the liquid. The general properties of this expansion are discussed with special focus on the q dependence, and hints for a (partial) determination of the molecular correlation functions from neutron scattering results are given. The resulting representation of the static structure factor S(n)(q) is studied in detail for a model system using data from a molecular dynamics simulation of a supercooled liquid of rigid diatomic molecules. The comparison between the exact result for S(n)(q) and different approximations that result from a truncation of the series representation demonstrates its good convergence for the given model system. On the other hand it shows explicitly that the coupling between translational and orientational degrees of freedom of each molecule and rotational motion of different molecules cannot be neglected in the supercooled regime. Further we report the existence of a prepeak in the ns static structure factor of the examined fragile glass former, demonstrating that prepeaks can occur even in the most simple molecular liquids. Besides examining the dependence of the prepeak on the scattering length and the temperature we use the expansion of S(n)(q) into molecular correlation functions to point out the intermediate range orientational order as its principle origin.

Journal Article↗

PubMed1998

The high-risk sexual practices of crack-smoking sex workers recruited from the streets of three American cities. The Multicenter Crack Cocaine and HIV Infection Study Team.

BACKGROUND AND OBJECTIVES: Small ethnographic and clinic-based studies indicate that crack-smoking sex workers are at high risk for human immunodeficiency virus (HIV) and sexually transmitted diseases (STD). STUDY GOALS: To examine the prevalence of risky sexual behaviors and HIV and STD in a large sample of street-recruited crack-smoking sex workers. STUDY DESIGN: From 1991 to 1992, 419 crack-smoking sex workers were recruited from urban neighborhoods, interviewed, and serologically tested. RESULTS: Many female and male sex workers reported sex with injectors (30% to 41%) or HIV-infected persons (8% to 19%), past STD (73% to 93%), and inconsistent condom use (> 50% for all types of sex). Sex workers who worked in crack houses or vacant lots, were paid with crack, or injected drugs had the riskiest sex practices. Most sex workers initiated sex work before they first smoked crack. More than 25% were infected with HIV (27.9%), syphilis (37.5%), or herpes simplex virus type 2 (66.8%). CONCLUSIONS: Interventions to prevent HIV/STD transmission among crack-smoking sex workers are urgently needed.

Adult↗

PubMed1998

Cardiac syncope due to transient coronary artery occlusion: the role of percutaneous angioplasty.

A case of cardiac syncope is presented, associated with single vessel coronary disease. The mechanism of the syncope would appear to be a ventricular arrhythmia with transmural myocardial ischaemia due to transient occlusion of the diseased coronary artery. The symptoms and electrocardiographic abnormalities were reproduced and subsequently abolished by percutaneous coronary angioplasty.

Angina Pectoris, Variant↗

PubMed1998

Partner violence and sexual HIV-risk behaviors among women in an inner-city emergency department.

This study examines the relationship between partner violence and sexual risk behaviors in a sample of predominantly Latina and African American women who sought medical care from a New York City hospital emergency department. Eligibility criteria selected women between the ages of 18 and 55, who were sexually active in the past 90 days, and were triaged to nonemergency care. The interview addressed demographics, partner violence, childhood abuse, sexual behavior, and drug and alcohol use. Multiple logistic regression analysis was used to assess the association between partner violence and history of having a sexually transmitted disease (STD) and of having sex with a risky partner. Nearly one half of the 143 respondents (46.1%, n = 66) reported that they had experienced physical, sexual, or life-threatening abuse by a boyfriend or spouse in the past and 17.5% reported that abuse had occurred within the past year. In the univariate analyses, abused women were more likely than nonabused women to report having had an STD; engaging in sex with a risky partner; having more than one sexual partner; and being tested for HIV. After controlling for confounding variables, abused women were almost five times more likely than their counterparts to have reported an STD and four times more likely to engage in sex with a risky sexual partner. The relationship between partner violence and sexual risk behaviors among women seeking treatment in an emergency department suggests the need for the development of HIV-risk reduction strategies that address the needs of women in abusive relationships.

Adolescent↗

PubMed1998

Hmong/medicine interactions: improving cross-cultural health care.

BACKGROUND AND OBJECTIVES: There are now more than 100,000 Hmong (Southeast Asian) refugees in the United States. This study examined interactions between Hmong patients and their health care providers and identified specific factors that either enable or obstruct health care delivery. METHODS: We used semistructured interview techniques to investigate patients' and providers' experiences, looking for attitudes, ideas, or behaviors that could be modified to improve health care delivery. Interviews with 23 Hmong patients, 18 health care providers, and six translators were audiotaped, transcribed, and analyzed by a multidisciplinary team. Methods included text analysis, theme identification, rank ordering, participant observation, immersion-crystallization, and open-ended discussion. RESULTS: Hmong patients and their US-trained health care providers have different health belief systems. Both linguistic and cultural translation were seen as problematic. Additionally, an overwhelming number of patients identified kindness, caring, and a positive attitude as important provider characteristics. Providers noted difficulties in understanding Hmong conceptions of acute versus chronic diseases, illness prevention, and pain, both physical and psychological. Many respondents gave suggestions for improvement: 1) learn more about each other's cultures, 2) be patient, kind, and positive, 3) avoid negative statements or predictions, 4) improve translation quality, 5) explain medical terms using visual aids, 6) respect Hmong family-centered decision making, 7) increase the time allotted for translated clinical encounters, and 8) train Hmong health care providers. CONCLUSIONS: Many basic issues in relations between clinicians and Hmong patients must be addressed to improve health care communication.

Asia, Southeastern↗