PubMed HealthSearch

Biomedical subjects

J Gabriel

Publications and source records attributed to J Gabriel.

At least 19 recordsLinked to original sources

Inactivation of a common epitope responsible for the induction of antibody-dependent enhancement of HIV.

BACKGROUND: The primary antigenic domain responsible for complement-mediated antibody-dependent enhancement (C'-ADE) of HIV and simian immunodeficiency virus resides in the principal immunodominant sequence of the transmembrane protein. OBJECTIVE: To identify whether there are amino-acid residues common to the epitopes of the known enhancing human monoclonal antibodies (MAb), and to provide a structural model for this functional region present on the HIV envelope. Since our model predicts that this region is involved in the association of gp120 with gp41, this association was monitored for each mutant. DESIGN: The binding of enhancing human MAb to point and deletion mutations within the enhancing domain was analyzed by two methods. The first analyzed binding to mutants expressed in COS cells: the second quantified the binding of four enhancing human MAb to each mutant gp160 versus wild-type control by enzyme-linked immunosorbent assay (ELISA). METHODS: Site-directed mutagenesis was used to produce specific deletions and point mutants, which were expressed in COS cells. Binding of MAb 50-69 and V3-loop MAb 5F7 were visualized in the wild-type and each of the mutant constructs by immunohistochemistry. Quantitative evaluation of enhancing human MAb binding to each mutant versus wild-type was performed by ELISA. A model for the enhancing domain and its relationship to gp120 association with gp41 was provided by molecular dynamics and ligand docking methods. RESULTS: All available enhancing human MAb known to bind to the principal immunodominant region of gp41 were unable to bind to deletions involving the disulfide loop, which in our molecular model provided the primary association site between gp120 and gp41. Point mutations in the loop blocked this association, but had a quantitatively smaller effect on the binding of the enhancing human MAb. A conservative W596Y mutation completely blocked the binding of all human MAb, but had no effect on gp120-gp41 association. CONCLUSIONS: A variety of mutations within the primary C'-ADE domain inhibit binding of enhancing human MAb as well as blocking the association of gp120 and gp41. A conservative W596Y mutation blocks binding of all enhancing human MAb with retention of gp120-gp41 association. These data are important to the design of vaccines in which the primary enhancing epitope is disarmed to prevent the subsequent induction of an amnestic response that could lead to viral enhancement of infection. The retention of the gp120-gp41 association is postulated to yield an immunogen similar to natural infection for both subunit and genetic vaccines.

Amino Acid Sequence

Antifungal effects of new heterocyclic compounds, 6H-pyrimido[2,1-a]isoindole derivatives.

Minimal inhibitory concentrations for 10 new condensed isoindole derivatives were established by the agar diffusion method. Benzo[b]-6H-pyrimido[2,1-a]isoindole-4-one exhibited a broad antifungal effect; the observed MIC (mg/L) were 7 (K. lactis), 8 (C. pseudotropicalis), 17 (W. fluorescens), 22 (E. magnusii), 31 (P. membranaefaciens), 32 (S. alluvius) and 32 (S. cerevisiae). The compound also inhibited the growth of B. subtilis (MIC 9 mg/L). No effect on the growth of E. coli was found.

Antifungal Agents

[Initial applications of a new trochar system for non-laparoscopic intraluminal surgery].

Instruments that have been used in flexible endoscopy have always been confined to the working channel of the endoscope. We have therefore developed a device that allows transabdominal manipulation in the stomach under gastroscopic control with a device similar to a percutaneous endoscopic gastrostomy (PEG). For the first clinical application of this device it was used in order to perform pseudocystogastrostomy in patients with pancreatic pseudocysts.

Drainage

Ammonia mediates communication between yeast colonies.

Under certain growth conditions unicellular organisms behave as highly organized multicellular structures. For example, the fruiting bodies of myxobacteria and of the slime mould Dictyostelium discoideum form structures composed of non-dividing motile cells. Although non-motile, yeasts can create organized structures, colonies in which cells communicate and act in a coordinated fashion. Colony morphologies are characteristic for different species and strains. Here we describe that, in addition to short-range intracolony cell-cell communication, yeasts exhibit long-distance signals between neighbouring colonies. The volatile alkaline compound ammonia, transmitted by yeast colonies in pulses, has been identified as a substance mediating the intercolony signal. The first alkaline pulse produced by neighbouring colonies is non-directed and is followed by acidification of the medium. The second pulse seems to be enhanced and is oriented towards the neighbour colony. Ammonia signalling results in growth inhibition of the facing parts of both colonies. This phenomenon is observed in different yeast genera. The presence of amino acids in the medium is required for ammonia production. Colonies derived from the yeast Saccharomyces cerevisiae shr3 mutant, defective in localization of amino-acid permeases, do not produce detectable amounts of ammonia and do not exhibit asymmetric growth inhibition.

Amino Acids

Gender differences in the frequency of schizophrenic subtypes in unselected hospitalized patients.

The phenotypic expression of the subtypes of schizophrenic disorders was studied in relationship to their relative frequency and the gender composition within each subtype using 374 successive DSM-III-R diagnosed schizophrenic patients. Two hundred and twenty-six of them were first admissions to a hospital. They were all diagnosed independently by three reviewers. While in the paranoid, the undifferentiated and the disorganized subtypes there was no significant difference between men and women, in the residual and the catatonic subtypes the frequency of men was more than three times greater than that of women. Among the 226 first admissions the frequency of the residual subtype was significantly lower than in the multiple admissions. The preponderance of male schizophrenic patients within the residual subtype indicates that they end up into this subtype, more frequently than women schizophrenic patients, whereas the greater preponderance of men in the catatonic subtype appears to reflect an intrinsic characteristic of this subtype.

Analysis of Variance

High-performance liquid chromatographic study of the aromatic nitrile metabolism in soil bacteria.

Simultaneous HPLC determination of bromoxynil, ioxynil and dichlobenil, three arylnitrile herbicides, and their metabolic products in soil extracts and microbiological media is described. Limits of detection (LODs) ranged from 0.56 to 3.97 ppb. Slight modification of the mobile phase composition allowed determination of 13 other aromatic nitriles. Assay of aromatic nitrile hydratase, amidase or nitrilase activities is possible by the method developed.

Benzamides

A comparative immunocytochemical study using an antiserum against a synthetic analogue of the corpora cardiaca peptide Pea-CAH-I (MI, neurohormone D) of Periplaneta americana.

An antiserum against the octapeptide Pea-CAH-I, a member of the adipokinetic hormone/red pigment-concentrating hormone family, has been produced for immunocytochemical staining in insects and various other invertebrate species. The anti-Pea-CAH-I serum stains the glandular corpora cardiaca cells of those insect species that synthesize identical or structurally similar peptides. In the corpora cardiaca of species producing peptides with a different C-terminus, these cells remain unstained. Pea-CAH-I-like immunoreactivity has also been found in neurons of the central nervous system of all invertebrate orders studied. The antiserum recognizes the C-terminal sequence Pro-Asn-Trp-NH2 of the Pea-CAH-I molecule as established by enzyme immunoassay. The widespread Pea-CAH-I-like immunoreactivity in all nervous systems of the studied animals probably does not reflect the presence of Pea-CAH-I but the occurrence of peptides carrying similar epitopes.

Amino Acid Sequence

Induction of mucosal anti-HIV antibodies by facilitated transfection of airway epithelium with lipospermine/DNA complexes.

BACKGROUND: Expression of microbial protein sequences in eukaryotic cells transfected by transcriptional/translational permissive cDNA constructs can induce systemic humoral and cellular responses in vivo. Two methods of in vivo transfection have been described to date. One method uses large quantities of naked DNA injected into skeletal muscle. The second method uses relatively small quantities of DNA complexed to gold particles for bollistic penetration of the plasma membrane of keratinocytes. The major disadvantage of the bolistic method is that instrumentation is required which is not generally available. OBJECTIVES: The objectives of this study were to determine whether the use of DNA complexed with a cationic lipopolyamine could reduce the quantity of DNA required to induce systemic humoral responses following muscle transfection and whether similar DNA/lipopolyamine complexes could induce mucosal humoral responses following airway exposure. STUDY DESIGN: Balb/c mice were exposed by nasal aerosol or intramuscular inoculation to a mammalian transcriptional/translational permissive DNA construct containing the entire sequence for the HIV-1 envelope polyprotein. Experimental animals were further segregated by the number of exposures at 3-week intervals and whether the DNA was complexed to dioctadecylamidoglycylspermine (DOGS) at a 5:1 molar charge ratio of DOGS/DNA. RESULTS: DOGS facilitated in vivo transfection of mouse muscle reduced the quantity of DNA required for a systemic humoral response to surface expressed HIV-envelope proteins by one order of magnitude. Exposure of airway mucosa to both 10 micrograms and 1 microgram quantities of DNA complexed to DOGS produced systemic humoral responses to HIV-envelope as well as mucosal antibodies in pulmonary and colonic epithelia. Molecular modeling of DOGS/DNA complexes at the 5:1 charge ratio used in this study indicates that the DNA component is not exposed to aqueous solvents and may be relatively resistant to degradation under common biological environments. CONCLUSION: Facilitated transfer of DNA by DOGS to transcriptional/translational competent cells offers several distinct advantages to the use of DNA alone. Since significantly smaller amounts of DNA are required, the potential for the induction of antibodies against DNA itself lessens the likelihood for the development of a lupus-like syndrome. More importantly, however, is the apparent ability to transfect mucosal cells which results in the development of specific mucosal immune responses. This procedure may allow the development of general methods for the induction of mucosal immunity at the level of entry for mucosal pathogens without the disadvantages inherent in live attenuated vectors.

Animals

Age at onset in subtypes of schizophrenic disorders.

Age at onset and sex differences in the age at onset were investigated in the schizophrenic subtypes of 200 patients. Significant differences in the age at onset were observed among these subtypes; the disorganized subtype demonstrated the earliest and the paranoid the latest onset. The mean age at onset of all female patients was significantly greater than that of the male. Specifically, in the paranoid subtype the onset for men occurred earlier than for women. Conversely, in the disorganized subtype the disorder appeared earlier in women. There was no significant sex difference in the age at onset in the undifferentiated and the residual subtypes. In the paranoid subtype most men developed the disease before age 30 (72%), whereas women had an even distribution of the onset before and after 30. Ninety-six patients admitted for the first time demonstrated findings similar to those of the total sample. The data provide additional information on the phenotypic expression of the subtypes of schizophrenic disorders and indicate the necessity for further demographic and genetic studies to delineate the underlying defect.

Adolescent

Anniversary reaction as seasonal mood disorder.

We describe the case of a patient who, after a traumatic experience at the age of 12, had a series of anniversary depressive episodes at 16, 17, 18 and 19 years of age, followed by a series of anniversary manic episodes at the ages of 21, 23, 24, 25 and 26 years. All of these episodes occurred almost always a few days before or after the date of the accident and only when the patient was residing in his home town, the place of the traumatic event. The case fulfills the DSM-III-R criteria for seasonal mood disorder, but differs from previously described cases in that: (a) both depressive and manic episodes developed at the same time of the year, and (b) the illness was precipitated by psychosocial factors rather than climatic conditions.

Adjustment Disorders

[Antibiotic activity of cortalcerone and its 7-diphenylhydrazone derivative].

The present paper investigates the antibiotic properties of the novel antifungal antibiotic agent cortalceron and its semisynthetic derivative cortalceron 7-diphenylhydrazone. The MIC values were assayed by the agar diffusion method. Cortalceron was found to weakly inhibit the growth of E. coli and B. subtilis. The growth of yeast was not influenced. On i.v. administration to mice [correction of rats], the agent produced breathing disorders and convulsions which later disappeared. The diphenylhydrazine derivative of cortalceron inhibited the growth of most yeasts tested as well.

Animals

Inferences concerning crossbridges from work on insect muscle.

This paper presents a number of separate results concerning crossbridge attachment: [1] X-ray diffraction from live bumble bee flight muscle shows a set of layer lines distinct from that of relaxed Lethocerus, in which the apparent myosin helix is shorter than that of the actin. [2] Rigor crossbridges of Lethocerus are not rotatable by stretch. [3] Rabbit and Lethocerus fibres in rigor relaxed by ATP at -35 degrees C show evidence of non-rigor crossbridge attachment.

Animals

Pyranosone dehydratase from the basidiomycete Phanerochaete chrysosporium: improved purification, and identification of 6-deoxy-D-glucosone and D-xylosone reaction products.

Pyranose oxidase and pyranosone dehydratase (aldos-2-ulose dehydratase), enzymes which convert in coupled reactions D-glucose to beta-pyrone cortalcerone, peaked coincidently during idiophasic growth of Phanerochaete chrysosporium under agitated conditions. The enzymes were purified from mycelial extracts of the fungus and separated from each other by hydrophobic interaction chromatography on Phenyl-Sepharose and Phenyl-Superose. Two pyranosone dehydratase activity peaks, PD I and PD II, were resolved. The major PD I fraction, consisting about 74% of the total dehydratase activity, was further purified by anion exchange chromatography on Mono Q to yield apparently pure enzyme as judged by SDS-PAGE and gel filtration on Superose 12. Isoelectric focusing indicated microheterogeneity of the protein by the presence of at least five protein bands with pI 5.1-5.3. PD II had a pI of 5.75. Overall PD I purification was 60.7-fold with 50% yield. The enzyme acted on several osones (glycosuloses), with the preferred substrate being D-glucosone. D-Xylosone and 6-deoxy-D-glucosone were dehydrated at C-3-C-4 to give the corresponding 5-hydroxy-2,3-dioxoalcanals (4-deoxy-2,3-glycosdiuloses), new enzymatically produced sugar derivatives. The latter labile compounds were trapped as diphenylhydrazine or o-phenylenediamine derivatives and spectroscopically identified. The analogous D-glucosone dehydration product did not accumulate due to its further transformation. pH optimum of PD I activity was 6.0 and its pH stability was optimal at pH 7-11. The enzyme was sensitive to Me2+ chelating agents and some heavy metal ions (Hg2+, Cu2+).

Basidiomycota