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U Esser

Publications and source records attributed to U Esser.

17 recordsLinked to original sources

Molecular function of the CD4 D1 domain in coreceptor-mediated entry by HIV type 1.

The surface molecule CD4 plays a key role in initiating cellular entry by the human immunodeficiency virus type 1 (HIV-1), and it is now recognized as acting synergistically with select chemokine receptors (coreceptors) in the infection process. The present study was undertaken to determine whether the extracellular region of CD4 is sufficient to induce fusion of HIV-1 virions with target cells in the absence of its anchoring function. Using pseudotype reporter viruses to quantitate infection, soluble CD4 (sCD4) was tested for its ability to induce fusion by viruses utilizing CCR5 as their coreceptor. We found that sCD4 was competent to replace membrane-bound CD4 to trigger infection mediated by several HIV-1 envelopes. Furthermore, in a comparison of the envelopes of HIV-1 NL4-3 and a chimera containing the gp120 V3 loop of Ba-L, the V3 region was found to be one factor affecting susceptibility to induction by sCD4. In addition, using truncated and mutant derivatives of sCD4, the amino-terminal D1 domain of CD4 was found to be necessary and sufficient for induction of fusion and to require an intact gp120-binding site for this activity. These results delineate determinants on CD4 and gp120 required for fusion induction in collaboration with a coreceptor, and suggest a mechanism whereby CD4 may contribute to viral infection in trans.

CD4 Antigens↗

A trans-receptor mechanism for infection of CD4-negative cells by human immunodeficiency virus type 1.

Chemokine receptors, particularly CCR5 and CXCR4, act as essential coreceptors in concert with CD4 for cellular entry by human immunodeficiency virus type 1 (HIV-1; reviewed in [1]). But infection of CD4(-) cells has also been encountered in various tissues in vivo, including astrocytes, neurons and microvascular endothelial cells of the brain [2] [3] [4] [5] [6], epithelial cells [5] [7], CD4(-) lymphocytes and thymocytes [8] [9], and cardiomyocytes [10]. Here, we present evidence for the infection of CD4(-) cell lines bearing coreceptors by well-known HIV-1 strains when co-cultured with CD4(+) cells. This process requires contact between the coreceptor-bearing and CD4(+) cells and supports the full viral replication cycle within the coreceptor-bearing target cell. Furthermore, CD4 provided in trans facilitates infection of primary human cells, such as brain-derived astrocytes. Although the pathobiological significance of infection of CD4(-) cells in vivo remains to be elucidated, this trans-receptor mechanism may facilitate generation of hidden reservoirs of latent virus that confound antiviral therapies and that contribute to specific AIDS-associated clinical syndromes.

CD4 Antigens↗

Rabbit cells expressing human CD4 and human CCR5 are highly permissive for human immunodeficiency virus type 1 infection.

To evaluate the feasibility of using transgenic rabbits expressing CCR5 and CD4 as a small-animal model of human immunodeficiency virus type 1 (HIV) disease, we examined whether the expression of the human chemokine receptor (CCR5) and human CD4 would render a rabbit cell line (SIRC) permissive to HIV replication. Histologically, SIRC cells expressing CD4 and CCR5 formed multinucleated cells (syncytia) upon exposure to BaL, a macrophagetropic strain of HIV that uses CCR5 for cell entry. Intracellular viral capsid p24 staining showed abundant viral gene expression in BaL-infected SIRC cells expressing CD4 and CCR5. In contrast, neither SIRC cells expressing CD4 alone nor murine 3T3 cells expressing CCR5 and CD4 exhibited significant expression of p24. These stably transfected rabbit cells were also highly permissive for the production of virions upon infection by two other CCR5-dependent strains (JR-CSF and YU-2) but not by a CXCR4-dependent strain (NL4-3). The functional integrity of these virions was demonstrated by the successful infection of human peripheral blood mononuclear cells (PBMC) with viral stocks prepared from these transfected rabbit cells. Furthermore, primary rabbit PBMC were found to be permissive for production of infectious virions after circumventing the cellular entry step. These results suggest that a transgenic rabbit model for the study of HIV disease may be feasible.

Animals↗

Effect of moderate exercise on insulin sensitivity and substrate metabolism during post-exercise recovery in cirrhosis.

We examined whether a single bout of moderate exercise has a beneficial effect on insulin sensitivity and fuel homeostasis in cirrhosis. Clinically stable cirrhotic patients and age-, sex-, and weight-matched controls participated in insulin clamp studies (either euglycemic hyperinsulinemic or hyperglycemic hyperinsulinemic) in combination with indirect calorimetry and [6,6-2H2]glucose. Three to seven days later, studies were repeated following a single bout of exercise (30 minutes of treadmill exercise at 60% of maximal aerobic capacity). After an overnight fast, following exercise, both cirrhotic and control individuals showed a shift in fuel utilization to enhanced lipid oxidation, decreased glucose oxidation, and increased nonoxidative glucose disposal rates (i.e., glycogen synthesis in muscle) when compared with pre-exercise rates but differences were statistically significant only in the patient group. During euglycemic hyperinsulinemia, insulin-mediated glucose disposal was significantly reduced in cirrhotic patients (3.43 +/- 0.26 vs. 7.36 +/- 0.48 mg/kg/min, P < .01). Following exercise, glucose uptake increased significantly in cirrhotic patients when compared with pre-exercise levels (P < .05) but remained unchanged in the control group. The increase in total body glucose disposal in cirrhotic patients was entirely accounted for by an increase in nonoxidative glucose disposal (0.81 +/- 0.20 vs. 0.51 +/- 0.15 mg/kg/min, P < .05). During combined hyperglycemia/hyperinsulinemia, however, insulin sensitivity was unaffected by exercise in both patients and control individuals. In summary, in cirrhotic patients, a single bout of moderate exercise 1) causes a shift in substrate utilization with an increase in lipid oxidation in the postexercise period that is significantly more pronounced than in controls, and 2) increases insulin sensitivity only during euglycemia but not during the more physiological condition of hyperglycemia. Single bouts of moderate exercise therefore may not have a beneficial effect on the metabolic status of patients with chronic liver disease.

Adult↗

[Abscess of the skull base--therapy and reconstruction after zygoma resection].

Abscesses of the base of skull, if not correctly managed, can lead to the intracranial spread of infection - a life-threatening complication. Infection can spread from the upper and lower molar teeth through the retromaxillary area or the parapharyngeal space to reach the temporal, infratemporal or pterygopalatine fossa. Our recommended treatment of abscesses in these fossae is wide abscess incision together with resection of the midsection of the zygomatic arch ("Partsch method"). Two case reports are included. The first report is of a patient with cerebral abscess caused by an oral infection. The second report is of a case in which zygomatic arch reconstruction was necessary after its partial resection for abscess treatment. A new alloplastic bone-substitute material made from coral was used in the reconstruction.

Actinomycosis↗

[Management of panfacial fractures--also an intubation problem].

Conventional oro- or nasotracheal intubation represents an obstacle in cases of panfacial fractures or elective operations of the facial skeleton above the Le Fort I level because of the intermaxillary fixation that often becomes necessary. Until recently, protection of the airway required tracheotomy with its well-known disadvantages of the usual intubations, which could compromise surgical strategies. A useful alternative method for protecting the airway involves the submental route for intubation and was first described in 1986 by Altemir. We present our experience with submandibular transmylohoid intubation in 14 patients. The technique is relatively simple and includes only a small risk potential. The cosmetic result of the extraoral incision required is good to excellent.

Chin↗

Characterization of the genes coding for the F1F0 subunits of the sodium dependent ATPase of Propionigenium modestum.

The DNA coding for the eight structural genes and uncI of the sodium dependent ATPase of Propionigenium modestum has been cloned and sequenced. Based on sequence homology, the genes were determined to appear in the order uncBEFHAGDC as in several other bacterial species. Minicell experiments revealed that plasmids containing the P. modestum DNA expressed those ATPase polypeptides in Escherichia coli. These were very similar in molecular mass to those obtained from the purified ATPase of P. modestum. No membrane-bound ATPase activity was observed in E. coli unc deletion strains containing the P. modestum ATPase genes. Amino acid alignments which were done with the Fo subunits revealed only a few conservative changes in the highly conserved regions of the polypeptides.

Adenosine Triphosphatases↗

Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics.

To test models of T-cell recognition, mice transgenic for T-cell receptor alpha or beta chain have been immunized with variant peptides that force changes in the resulting T-cell response. In particular, charge substitutions on the peptide often elicit reciprocal charges in the junctional (CDR3) sequences of T-cell receptor V alpha or V beta chains, indicating direct T-cell receptor-peptide contact, and allowing derivation of a topology for the T-cell receptor-MHC interaction. At one position on the peptide, variants transformed a homogeneous V beta response into a very heterogeneous one.

Amino Acid Sequence↗

Characterization of the H(+)-pumping F1F0 ATPase of Vibrio alginolyticus.

The F1F0 ATPase of Vibrio alginolyticus was cloned from a chromosomal lambda library. The unc operon, which contains the structural genes for the ATPase, was sequenced and shown to have a gene organization of uncIBEFHAGDC. The sequence of each subunit was compared with those of other eubacterial ATPases. The V. alginolyticus unc genes exhibited greater similarity to the Escherichia coli unc genes than to any of the other bacterial unc genes for which the sequence is available. The ATPase was expressed in an E. coli unc deletion strain, and the ATP hydrolytic activity was characterized. It has a pH optimum of 7.6 and is stimulated by the addition of Triton X-100 or any of a variety of salts. The recombinant F1F0 was purified 30.4-fold and reconstituted into proteoliposomes. This enzyme catalyzed the pumping of protons coupled to ATP hydrolysis as measured in fluorescence quenching experiments but would not pump Na+ ions under similar conditions.

Amino Acid Sequence↗

Evaluation of advanced silica packings for the separation of biopolymers by high-performance liquid chromatography. VI. Design, chromatographic performance and application of non-porous silica-based anion exchangers.

The linear solvent strength model of Snyder was applied to describe fast protein separations on 2.1-micron non-porous, silica-based strong anion exchangers. It was demonstrated on short columns packed with these anion exchangers that (i) a substantially higher resolution of proteins and nucleotides was obtained at gradient times of less than 5 min than on porous anion exchangers; (ii) the low external surface area of the non-porous anion exchanger is not a critical parameter in analytical separations and (iii) microgram-amounts of enzymes of high purity and full biological activity were isolated.

Biopolymers↗