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Biomedical subjects

J Muller

Publications and source records attributed to J Muller.

At least 37 records · Page 2Linked to original sources

Spectroscopic evidence for the tricapped trigonal prism structure of semiconductor clusters

We have obtained photoelectron spectra (PES) for silicon cluster anions with up to 20 atoms. Efficient cooling of species in the source has allowed us to resolve multiple features in the PES for all sizes studied. Spectra for an extensive set of low-energy Si(-)(n) isomers found by a global search have been simulated using density functional theory and pseudopotentials. Except for n = 12, calculations for Si(-)(n) ground states agree with the measurements. This does not hold for other plausible geometries. Hence PES data validate the tricapped trigonal prism morphologies for medium-sized Si clusters.

Journal Article↗

Effect of different promoters on immune responses elicited by HIV-1 gag/env multigenic DNA vaccine in Macaca mulatta and Macaca nemestrina.

pCMV-NL(Deltapol) and pAKV-NL(Deltapol) expressed human immunodeficiency virus type 1 (HIV-1) gag and env under the regulation of the human cytomegalovirus (CMV) immediate-early (IE) promoter/enhancer and the endogenous AKV murine leukemia viral long terminal repeat (LTR), respectively. Analysis of the immune responses elicited by direct DNA injection of pCMV-NL(Deltapol) and pAKV-NL(Deltapol) in macaques indicated that generation of the humoral and T-cell proliferative responses correlated directly with the promoter strength of the vaccine DNAs. In Macaca mulatta, pCMV-NL(Deltapol) generated stronger humoral responses and T-cell proliferative responses to Gag and Env using less DNA and fewer number of injections than pAKV-NL(Deltapol). Similarly, in Macaca nemestrina pCMV-NL(Deltapol) elicited high humoral responses, which persisted long-term and were boostable. Injection of large amounts of pAKV-NL(Deltapol), in general, failed to produce antibody levels comparable to pCMV-NL(Deltapol). However, injection of a control animal with large amounts of vector DNA produced a generalized enzyme-linked immunosorbent assay (ELISA) reactivity to HIV-1. The results indicated that generation of high immune responses to HIV-1 cannot be achieved by increasing the vaccine DNA dose and may require high protein expression from the DNA by including a strong promoter or by the use of other boosting agents. Furthermore, safety concerns may arise with increasing the DNA dose that could need additional investigation.

3T3 Cells↗

Direct observation of the dynamics of electronic excitations in molecules and small clusters

Femtosecond time-resolved photoelectron spectroscopy is applied to study relaxation paths of excited states of mass-selected negatively charged clusters. As a first example, the lifetime of an excited state of the carbon trimer anion is measured directly. In addition, the mechanism of the decay, i.e., the configurations of the participating electronic states, is determined from the photoelectron spectra. In general, this method can be used to study all kinds of electronic excitation and relaxation processes in mass-selected nanoparticles.

Journal Article↗

Pnictides as symmetrically bridging ligands in novel neutral complexes

The reaction of [LWCl] (3) [L = N(CH2CH2NiPr)3] with LiE(SiMe3)2 (E = P, As, Sb) yields the novel, neutral pnictido-bridged complexes [LW = E = WL] (5-7). By following the reaction, which starts from the LiP-(SiMe3)2 derivative, by 31P NMR spectroscopy, the formation of an intermediate with a terminal pnictido ligand can be ruled out. The paramagnetic complexes 5-7 are comprehensively spectroscopically characterised. The X-ray structure analysis of the heterocumulenes 5-7 reveals a linear structure in which the two W-"tren" units bind to the central pnictido atom in a staggered conformation ["tren" = tren-based ligand; tren = tris(2-aminoethyl)-amine. When N2 is used as the inert gas in the synthesis of the starting material [N(CH2CH2NNp)3WCl] [Np = CH2C-(CH3)3], the complex [[N(CH2CH2NNp)3]W2(mu, eta 1: eta 1-N2)] (4) is formed as a side product. Complex 4 possesses a hydrazido(4-) (N2(4-)) ligand connected by two tungsten-"tren" moieties.

Journal Article↗

Bilateral effect of a unilateral occlusal splint on the expression of myosin heavy-chain isoforms in rat deep masseter muscle.

Many studies have shown that various myosin isoforms are involved in muscle contraction. A search for specific antibodies directed against the myosin heavy chain (MHC) resulted in the identification of at least two main classes, referred to as MHC type I and type II. In this study, immunohistology and gel electrophoresis were used to determine the proportion of MHC isoforms in rat deep masseter muscle at different times after the insertion of an unilateral occlusal splint. An increasing proportion of MHC type I isoforms was found in both deep masseters soon after splinting, and this trend continued until 7 days after splint insertion. The type I fibres were clearly distributed on either side of the central axis of the muscle. At 15 days, a significant decrease in the percentage of the type IIb MHC isoform was observed on the occlusal splint side compared to the contralateral side. After 30 days of unilateral splinting, the proportion of type IIb fibres on the splint side returned to baseline whereas on the contralateral side there was an increase in the proportion of this type. The results suggest an initial adaptation after the unilateral occlusal disturbance in which muscles of both sides react in the same way; later, the muscles of each side adapt their expression of MHC isoforms according to altered functional demand.

Adaptation, Physiological↗

Urinary choloyl-PABA excretion in diagnosing small intestinal bacterial overgrowth: evaluation of a new noninvasive method.

The synthetic substrate cholyl-PABA, developed by conjugating cholic acid with paraaminobenzoic acid, is hydrolyzed by the bacterial enzyme cholyl hydrolase to release free PABA. This study aimed to evaluate whether quantitating urinary excretion of PABA after oral administration of cholyl-PABA can detect small intestinal bacterial overgrowth. In the first phase, investigations were performed on 10 healthy volunteers to study the dynamics of urinary excretion of PABA and any adverse reactions after oral administration of 1.2 g of cholyl-PABA. Another 10 healthy volunteers and 25 adult patients with various gastrointestinal disorders participated in the second phase, where the urinary cholyl-PABA test was compared to the [14C]xylose breath test (XBT). The upper limit of normal levels of urinary PABA excretion at the end of 4 h was 1.1% of the administered dose of cholyl-PABA. The urinary PABA excretion after 4 hr [median (range), in percentage] in the XBT-positive group was 1.6 (0.6-35.0), which was significantly higher than those in the XBT-negative group [0.7 (0.4-1.8)] and the healthy controls [0.7 (0.2-1.1)]. The agreement between the XBT and the urinary cholyl-PABA test was 85.7% (P < 0.01). No adverse effect was noted. In conclusion, the urinary cholyl-PABA test offers a simple, safe, noninvasive, and rapid method for diagnosing small intestinal bacterial overgrowth and warrants further clinical evaluation.

4-Aminobenzoic Acid↗

HIV-1 infects and alters immune function of a monocyte subset expressing low CD14 surface phenotype.

Monocytes represent a leukocyte subset that express high levels of CD14 on their surface (CD14-high). These cells play a critical role in the pathogenesis of HIV-1 infection. In the present study, we have identified a monocyte subset expressing an extremely low level of CD14 (CD14-low), and examined their susceptibility to HIV-1 infection. Phenotypic analysis by flow cytometry of these cells revealed a low level of CD4, but the absence of CD3, CD14, CD19, and CD83 surface markers. Both CD14-low and CD14-high cell populations expressed CD13 and CD33 markers on their surface, suggesting these cells to be of myeloid origin. Morphologically, CD14-low cells were indistinguishable from CD14-high cells. CD14-low cells were susceptible to infection with a monocytotropic strain of HIV-1 (HIVADA). However, like CD14-high monocytes, CD14-low cells could not be productively infected with a T cell tropic strain of HIV-1 (H9/HTLV(IIIB)). Similar to CD14-high monocytes, CD14-low cells were capable of inducing antigen-stimulated CD4+ T-cell proliferation. HIV-1 infection substantially reduced their ability to induce antigen-stimulated T-cell proliferation. These data indicate that CD14-low cells belong to the monocyte lineage and may play an important role in the immunopathogenesis of HIV-1 infection.

Antigen Presentation↗

BBID: the biological biochemical image database.

The Biological Biochemical Image Database is a WWW accessible relational database of archived images from research articles that describe regulatory pathways of higher eukaryotes. Pathway information is annotated and can be queried in the study of complex gene expression. In this way, complex regulatory pathways can be tested empirically in an efficient manner in the context of large-scale gene-expression systems.

Computer Graphics↗

A randomized, double-blind, placebo-controlled, dose-ranging study to compare the efficacy and safety of three doses of botulinum toxin type A (Dysport) with placebo in upper limb spasticity after stroke.

BACKGROUND AND PURPOSE: We sought to define an effective and safe dose of botulinum toxin type A (Dysport) for the treatment of upper limb muscle spasticity due to stroke. METHODS: This was a prospective, randomized, double-blind, placebo-controlled, dose-ranging study. Patients received either a placebo or 1 of 3 doses of Dysport (500, 1000, 1500 U) into 5 muscles of the affected arm. Efficacy was assessed periodically by the Modified Ashworth Scale and a battery of functional outcome measures. RESULTS: Eighty-three patients were recruited, and 82 completed the study. The 4 study groups were comparable at baseline with respect to their demographic characteristics and severity of spasticity. All doses of Dysport studied showed a significant reduction from baseline of muscle tone compared with placebo. However, the effect on functional disability was not statistically significant and was best at a dose of 1000 U. There were no statistically significant differences between the groups in the incidence of adverse events. CONCLUSIONS: The present study suggests that treatment with Dysport reduces muscle tone in patients with poststroke upper limb spasticity. Treatment was effective at doses of Dysport of 500, 1000, and 1500 U. The optimal dose for treatment of patients with residual voluntary movements in the upper limb appears to be 1000 U. Dysport is safe in the doses used in this study.

Arm↗

Intramyocardial electrogram recordings (IMEG) for diagnosis of cellular and humoral mediated cardiac allograft rejection.

OBJECTIVE: The purpose of this study was to prove the reliability of intramyocardial electrogram (IMEG) recordings for diagnosis and treatment monitoring of (1) cellular and (2) humoral mediated allograft rejection after heart transplantation. MATERIAL AND METHODS: Fifteen beagle dogs underwent heterotopic neck-heart transplantation. Eight of them were previously sensitized through several skin transplantations. IMEG recordings were performed daily. Donor-specific antibodies (IgG, IgM) were determinated in serum daily. Transmyocardial biopsies were performed every two days. RESULTS: In the sensitized group (group I) accelerated rejection occurred under triple drug immunosuppression with cyclosporine A, azathioprine, and cortisone on the fifth postoperative day (range: 4th-5th). All episodes were detected through IMEG diagnosis. In each case rejection could be treated successfully. In the cellular mediated group (group II), the average sensitivity for rejection diagnosis of a single lead was 24% for the unipolar and 42% for the bipolar leads. When the voltages of different leads were summed up the sensitivity rose to 36% (3 unipolar), 81% (3 bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 hours. CONCLUSION: The IMEG detects cellular and humoral mediated rejection early and with high reliability. The rejection-related changes of grade 2/3a rejection in IMEG seem to follow a Ofocal patternO similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance diagnostic reliability.

Animals↗

Rubella virus-induced apoptosis varies among cell lines and is modulated by Bcl-XL and caspase inhibitors.

Rubella virus (RV) causes multisystem birth defects in the fetuses of infected women. To investigate the cellular basis of this pathology, we examined the cytopathic effect of RV in three permissive cell lines: Vero 76, RK13, and BHK21. Electron microscopy and the TUNEL assay showed that the cytopathic effect resulted from RV-induced programmed cell death (apoptosis) in all three cell lines, but the extent of apoptosis varied among these cells. At 48 h postinfection, the RK13 cell line showed the greatest number of apoptotic cells, the Vero 76 cell line was approximately 3-fold less, and BHK21 had very few. An increased multiplicity of infection and longer time postinfection were required for the BHK21 cell line to reach the level of apoptotic cells in Vero 76 at 48 h. Purified RV induced apoptosis in a dose-dependent fashion, but not UV-inactivated RV or virus-depleted culture supernatant. Specific inhibitors of the apoptosis-specific proteases caspases reduced RV-induced apoptosis and led to higher levels of RV components in infected cells. To address the role of regulatory proteins in RV-induced apoptosis, the antiapoptotic gene Bcl-2 or Bcl-XL was transfected into RK13 cells. Although a high level of Bcl-2 family proteins was expressed, no protection was observed from apoptosis induced by RV, Sindbis virus, or staurosporine in RK13 cells. In BHK21 cells, however, increased expression of Bcl-XL protected cells from apoptosis. The observed variability in apoptotic response to RV of these cell lines demonstrates that programmed cell death is dependent on the unique properties of each cell and may be indicative of how selective organ damage occurs in a congenital rubella syndrome fetus.

Animals↗

Loss of retrovirus production in JB/RH melanoma cells transfected with H-2Kb and TAP-1 genes.

JB/RH1 melanoma cells, as well as other melanomas of C57BL/6 mice (B16 and JB/MS), express a common melanoma-associated antigen (MAA) encoded by an ecotropic melanoma-associated retrovirus (MelARV). JB/RH1 cells do not express the H-2Kb molecules due to down-regulation of the H-2Kb and TAP-1 genes. When JB/RH1 cells were transfected with the H-2Kb and cotransfected with the TAP-1 gene, it resulted in the appearance of H-2Kb molecules and an increase in their immunogenicity, albeit they lost expression of retrovirus-encoded MAA recognized by MM2-9B6 mAb. Loss of MAA was found to result from a complete and stable elimination of ecotropic MelARV production in the H-2Kb/TAP-1-transfected JB/RH1 cells. Northern blot analysis showed no differences in ecotropic retroviral messages in MelARV-producing and -nonproducing melanoma cells, suggesting that loss of MelARV production was not due to down-regulation of MelARV transcription. Southern blot analysis revealed several rearrangements in the proviral DNA of H-2Kb-positive JB/RH1 melanoma cells. Sequence analysis of the ecotropic proviral DNA from these cells showed numerous nucleotide substitutions, some of which resulted in the appearance of a novel intraviral PstI restriction site and the loss of a HindIII restriction site in the pol region. PCR amplification of the proviral DNAs indicates that an ecotropic provirus found in the H-2Kb-positive cells is novel and does not preexist in the parental H-2Kb-negative melanoma cells. Conversely, the ecotropic provirus of the parental JB/RH1 cells was not amplifable from the H-2Kb-positive cells. Our data indicate that stable loss of retroviral production in the H-2Kb/TAP-1-transfected melanoma cells is probably due to the induction of recombination between a productive ecotropic MelARV and a defective nonecotropic provirus leading to the generation of a defective ecotropic provirus and the loss of MelARV production and expression of the retrovirus-encoded MAA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Increased winter mortality from acute myocardial infarction and stroke: the effect of age.

OBJECTIVES: We examined seasonal variations in mortality from acute myocardial infarction (AMI) and stroke by age using 300,000 deaths in the Canadian Mortality Database for the years 1980 to 1982 and 1990 to 1992. BACKGROUND: The effect of age on environmental determinants of AMI and stroke is not well understood. METHODS: Seasonal variations were analyzed by month and for the four seasons (winter beginning in December). A chi-square test was used to test for homogeneity at p < 0.01, and relative risk ratios (RRs) for high and low periods were determined in relation to the overall mean. For each of four age subgroups, the magnitude of the seasonal variation was reported as the difference in mortality between the highest and lowest frequency seasons. RESULTS: By month, AMI deaths were highest in January (RR = 1.090) and lowest in September (RR = 0.904), a relative risk difference of 18.6%. The seasonal mortality variation in AMI deaths (winter vs. summer) increased with increasing age: 5.8% for <65, 8.3% for 65 to 74, 13.4% for 75 to 84 and 15.8% for >85 years (p < 0.005 for trend). Stroke mortality peaked in January (RR = 1.113) and had a trough in September (RR = 0.914), a relative risk difference of 19.9%. The seasonal variation in stroke mortality also increased with age. Seasonal variations were not seen in those aged <65 years, compared with 11.6% for 65 to 74, 15.2% for 75 to 84 and 19.3% for >85 years (p < 0.005 for trend). CONCLUSIONS: The elderly demonstrate a greater winter increase in AMI and stroke mortality than younger individuals. An understanding of these seasonal patterns may provide novel avenues for research in cardiovascular disease prevention.

Age Factors↗

Sensitive assays for isolation and detection of simian foamy retroviruses.

Simian foamy viruses (SFVs) are highly prevalent in a variety of nonhuman primate species ranging from prosimians to apes. SFVs possess a broad host range, and human infections can occur by cross-species transfer (W. Heneine et al., Nat. Med. 4:403-407, 1998). Retrovirus screening of potential sources of infection, such as laboratory research animals and simian-derived biological products, could minimize human exposure to SFVs by reducing the risk of potential retrovirus infection in humans. We describe a variety of sensitive assays for SFV isolation and detection which were developed with a prototype strain of SFV serotype 2. The Mus dunni cell line (M. R. Lander and S. K. Chattopadhyay, J. Virol. 52:695-698, 1984) was found to be highly sensitive for SFV production on the basis of various general and specific retrovirus detection assays such as reverse transcriptase assay, transmission electron microscopy, immunofluorescence assay, and Western blotting. A highly sensitive PCR assay was developed on the basis of the sequences in primary SFV isolates obtained from pig-tailed macaques (Macaca nemestrina) and rhesus macaques (Macaca mulatta). Analysis of naturally occurring SFV infection in macaques indicated that analysis by a combination of assays, including both highly sensitive, specific assays and less sensitive, broadly reactive assays, is important for evaluation of retrovirus infection.

Animals↗