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Biomedical subjects

E Jacobs

Publications and source records attributed to E Jacobs.

At least 109 records · Page 6Linked to original sources
PubMed1991

Effects of pentoxifylline on hemodynamics, oxygen transport, and tissue metabolism in experimental, severe hemorrhagic shock.

BACKGROUND AND METHODS: It is hypothesized that pentoxifylline may be beneficial during shock states by improving tissue oxygenation. To test this hypothesis, we examined the effect of pentoxifylline on hemodynamics, oxygen delivery (DO2), and tissue metabolism during severe hemorrhagic shock. We conducted a placebo-controlled, randomized trial using anesthetized, mechanically ventilated dogs in hemorrhagic shock maintained at a mean arterial pressure of 45 to 50 mm Hg. Six animals were treated with a 10-mg/kg bolus of iv pentoxifylline followed by a continuous infusion at 5 mg/kg.hr. The controls consisted of six animals treated with saline. RESULTS: There were no significant differences between the groups before treatment. During 150 mins of posttreatment, repeated measurements of the control and pentoxifylline groups showed no significant differences in heart rate (HR), cardiac output, systemic and pulmonary vascular resistances, DO2, or blood lactate concentration (repeated-measures analysis of variance). CONCLUSIONS: In this acute, nonresuscitated, canine hemorrhagic shock model, pentoxifylline did not act as a vasodilator, or have any significant effect on HR, cardiac output, oxygen transport, or lactic acidosis.

Animals↗
PubMed1991

Analysis of the Borrelia burgdorferi GeHo fla gene and antigenic characterization of its gene product.

The fla gene of Borrelia burgdorferi GeHo was analyzed and expressed in Escherichia coli. The structural gene encodes a flagellar protein of 336 amino acids. Comparative sequence analysis of the amino acid sequence revealed a high degree of sequence conservation with flagellins from both phylogenetically related and unrelated bacteria. The antigenic properties of the B. burgdorferi Fla protein were studied by synthesizing overlapping octapeptides, which were screened by using a battery of different monoclonal and polyclonal antibodies from various species directed against native and denatured flagellar proteins. No single species-independent immunodominant epitope could be located. However, immunoreactive oligopeptides clustered within the variable middle region (N-180 to I-260). This region could constitute a candidate antigen for more specific and sensitive serodiagnosis of Lyme borreliosis.

Amino Acid Sequence↗
PubMed1990

Prevalence of axis I and axis II disorders in women with late luteal phase dysphoric disorder.

The authors interviewed 78 female patients with late luteal phase dysphoric disorder and found a 78% lifetime prevalence of axis I disorders but only a 10% prevalence of axis II disorders. A prior depression was the predominant axis I disorder found, and 29% of parous patients had a prior postpartum depression. A comparison of Global Assessment Scale scores obtained at both the follicular and luteal phases of the menstrual cycle confirmed luteal increases in symptoms and role impairment.

Adult↗
PubMed1990

A bispecific monoclonal antibody against methotrexate and a human tumour associated antigen augments cytotoxicity of methotrexate-carrier conjugate.

A bispecific monoclonal antibody, reactive with methotrexate (MTX) and a tumour associated antigen (gp72) has been produced by fusing spleen cells from MTX immunised mice with 791T/36/3 (anti-gp72) hybridoma. The hybrid antibody was purified from anti-MTX and anti-gp72 antibodies present in the hybridoma culture supernatant by combinations of affinity chromatography on a MTX-agarose immunoabsorbent and stepwise acid elution from Sepharose-Protein A. A particular feature of the present antibody is that it reacts with conjugated MTX; this would allow in vivo targeting of conjugates, increasing many fold the number of molecules of drug carried or localising to pre-targeted antibody. Dual binding between tumour cell surface antigen and MTX was demonstrated by the ability of the hybrid antibody to bridge between tumour cells and MTX as MTX-HSA conjugate, reaction here being detected by flow cytofluorimetry. Purified hybrid antibody specifically enhanced the in vitro cytotoxicity of MTX-HSA for gp72 positive tumour cells.

Antibodies, Monoclonal↗
PubMed1990

C595--a monoclonal antibody against the protein core of human urinary epithelial mucin commonly expressed in breast carcinomas.

Urinary mucins which express determinants for the anti-breast carcinoma monoclonal antibody, NCRC-11 (IgM), closely resemble the mammary mucins found in milk fat globules and carcinomas. An IgG3 monoclonal antibody, C595, was prepared against urinary mucins isolated on a NCRC-11 antibody affinity column, and this 'second generation' antibody was shown to have a very similar pattern of reactivity to the original NCRC-11 antibody. By immunohistology, the profile of reactivity of both antibodies with tumour and normal tissue specimens was virtually identical. Both antibodies reacted with epithelial mucins isolated from breast tumours or normal urine using an NCRC-11 antibody affinity column, although the antibodies were unreactive with other antigen preparations. Heterologous immunoradiometric assays ('sandwich' tests) confirmed that NCRC-11 and C595 epitopes were co-expressed on the same molecule. C595 antibodies inhibited the binding of radiolabelled NCRC-11 antibodies to antigen, suggesting that the two epitopes were in close topographical proximity. The protein core of the mammary mucins has recently been shown to consist predominantly of a repeated 20 amino acid sequence (Gendler et al., 1988). Peptides with this complete sequence and small fragments were synthesised, and the C595 antibody was found to recognise an epitope within this repeat. The ability to identify and synthesise monoclonal antibody-defined determinants, as well as those in the adjacent or overlapping sequences within the protein core of epithelial mucins, is viewed as a strategy for facilitating the production of antibodies of new and novel specificity to complement the panels of existing anti-breast cancer reagents.

Antibodies, Monoclonal↗
PubMed1990

Topological mapping of the P1-adhesin of Mycoplasma pneumoniae with adherence-inhibiting monoclonal antibodies.

Five adherence-inhibiting monoclonal antibodies (mAbs) were used for topological mapping of the binding sites of the 169 kDa membrane-integrated adhesin of Mycoplasma pneumoniae. Antibody binding sites were characterized using overlapping synthetic octapeptides. Three regions of the protein seem to be involved in adherence: the N-terminal region [N-reg, epitopes beginning at amino acid (aa) 1 to aa 14 and aa 231 to aa 238, respectively]; a domain (D1) approximately in the middle of the molecule (beginning at aa 851 to aa 858 and aa 921 to aa 928); and a domain (D2) closer to the C-terminus (beginning at aa 1303 to aa 1310, aa 1391 to aa 1398 and aa 1407 to aa 1414). Each of the mAbs P1.26 and P1.62 reacted with two primary amino acid sequences. Both antibodies bound to the D1 region, but mAb P1.62 showed additional binding to a sequence (aa 231 to aa 238) near the N-terminus, and mAb P1.26 reacted with a second epitope in the D2 domain (aa 1303 to aa 1310). Such dual binding by the two antibodies suggests that in the native protein the epitopes are composed of two sequences which are located on two different sites of the molecule (D1/N-reg and D1/D2, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesins, Bacterial↗
PubMed1990

A B cell-, T cell-linked epitope located on the adhesin of Mycoplasma pneumoniae.

The identification of specific T cell and B cell epitopes of the P1 protein, which functions as an adhesin and as a major antigen of Mycoplasma pneumoniae, has become of central interest for the design of synthetic vaccines. Here we report the isolation from guinea pigs infected intranasally with M. pneumoniae of hilar and bronchial T lymphocytes which proliferated after in vitro stimulation with sonicated M. pneumoniae whole-cell antigen and with the isolated P1 protein. For more detailed information on T cell epitopes, a 51-amino-acid region (histidine 821 to glycine 871; numbered from the NH2-terminal end) of the P1 protein was analyzed for a T cell epitope. An octapeptide, S-G-S-R-S-F-L-P (starting at amino acid 845), stimulated in vitro lymphocytes of bronchial washings and of hilar lymph nodes. Furthermore, this T cell-stimulating amino acid sequence was located at the C-terminal end of a B cell epitope with the sequence T-N-T (starting at amino acid 842).

Adhesins, Bacterial↗
PubMed1990

Immunodominant epitopes of the adhesin of Mycoplasma pneumoniae.

Overlapping octapeptides from the amino acid sequence of the adherence protein of Mycoplasma pneumoniae were synthesized and used as the antigen in an enzyme-linked immunosorbent assay with serum samples from M. pneumoniae-infected patients. Of a sequence of 338 amino acids positioned between leucine 801 and leucine 1139, only two regions with immunodominant continuous epitopes were detected. The immunoglobulin G and immunoglobulin M antibodies of child and adult patients reacted especially with the NH2-(810)-W-I-G-N-G-Y-R-Y peptide but also reacted with the NH2-(1124)-F-T-D-F-V-K-P-R peptide.

Adhesins, Bacterial↗
PubMed1990

TEC1, a gene involved in the activation of Ty1 and Ty1-mediated gene expression in Saccharomyces cerevisiae: cloning and molecular analysis.

Ty and Ty-mediated gene expression observed in haploid cells of Saccharomyces cerevisiae depends on several determinants, some of which are required for the expression of haploid-specific genes. We report here the cloning and molecular analysis of TEC1. TEC1 encodes a 486-amino-acid protein that is a trans-acting factor required for full Ty1 expression and Ty1-mediated gene activation. However, mutation or deletion of the TEC1 gene had little effect on total Ty2 transcript levels. Our analysis provides clear evidence that TEC1 is not involved in mating or sporulation processes. Unlike most of the proteins involved in Ty and adjacent gene expression, the product of TEC1 has no known cellular function. Although there was no mating-type effect on TEC1 expression, our results indicate that the TEC1 and the a/alpha diploid controls on Ty1 expression are probably not cumulative.

Alleles↗
PubMed1990

How family spending has changed in the U.S.

Since the Monthly Labor Review began, the proportion of family expenditures allocated for food has dropped by half, the incidence of homeownership has doubled, and spending for transportation, medical care, and recreation has increased significantly.

Data Collection↗
PubMed1989

Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cells.

The unprocessed Gag precursor from HIV-1, when expressed in recombinant baculovirus-infected insect cells, is targeted to the plasma membrane and assembles in 100-120 nm particles budding from the cell surface. This process mimics HIV immature particle formation and is dependent on myristoylation of the N-terminal glycine, as deletion of the latter results in particle accumulation in the cytoplasm and, interestingly, in the nucleus, pointing to a potential role of this non-fatty-acid-acylated species in the viral life cycle. Inclusion of the pol gene in the construct results in efficient processing of Pr55gag and a pronounced decrease in particle formation. Deletion of the C terminus (p16) of the Gag precursor, including the finger domains, abolishes particle assembly, but membrane targeting and evagination still occur. Heterologous expression in insect cells may prove very useful for the study of the molecular events leading to retroviral particle morphogenesis.

Animals↗
PubMed1989

Simultaneous synthesis and assembly of various hepatitis B surface proteins in Saccharomyces cerevisiae.

Yeast transposon of class-1-based vectors, allowing integration at a series of chromosomal loci by homologous recombination with resident transposons, were constructed. Using such vectors, we have introduced several copies of an expression cassette encoding the major hepatitis B surface protein as well as expression cassettes encoding the middle (M) or/and the large (L) surface protein into Saccharomyces cerevisiae. In extracts of such strains, coassembly of the different proteins into a single lipoprotein structure is observed. This was demonstrated by immunoprecipitation of the major protein using monoclonal antibodies directed specifically against epitopes that are present only on the M or the L protein. These results show that hepatitis B surface antigen envelope proteins synthesized in yeast are able to assemble into structures composed of different polypeptides. This opens the possibility of producing in yeast a variety of particles carrying well-defined amounts of preS epitopes on their surface. Also, one can envisage the production of mixed particles containing different foreign epitopes on their surface, in defined relative abundance, which could be useful for vaccine applications.

Blotting, Southern↗
PubMed1989

The HIV-1 Gag precursor Pr55gag synthesized in yeast is myristoylated and targeted to the plasma membrane.

Myristoylation of the Pr65gag protein from Moloney murine leukemia virus has been shown to be essential for virus particle formation [Rein et al., Proc. Natl. Acad. Sci. USA 83 (1986) 7246-7250], and by analogy, myristoylation of the human immunodeficiency virus (HIV) Gag precursor could possibly play a similar role. We have investigated the expression and myristoylation of the complete HIV Gag precursor Pr55gag in yeast, the subcellular localization of that protein, and the contribution of the myristoyl-glycine residue to this localization. Immunogold labelling of myristoylated Pr55gage with antibodies directed against HIV Gag products was apparent in the vicinity of the plasma membrane. On the contrary, non-myristoylated derivatives of Pr55gag were only detected in relatively well-defined regions of the cytoplasm. These results show that targeting and accumulation of the HIV Gag precursor, Pr55gag, at the plasma membrane occurs in yeast in the absence of other viral components and requires the N-myristoyl-glycine residue.

Amino Acid Sequence↗
PubMed1989

The GAG precursor of simian immunodeficiency virus assembles into virus-like particles.

To examine the potential role of the GAG precursor polyprotein in morphogenesis and assembly of the simian immunodeficiency virus (SIV), we have expressed the gag gene of SIVMac using a baculovirus expression vector. Infection of insect cells with recombinant virus containing the entire gag gene results in high expression of the GAG precursor protein, Pr57gag. The recombinant protein is myristylated and is released in the culture supernatant in an insoluble particulate form. A point mutation in the N-terminal glycine codon (Gly----Ala) inhibits myristylation. This mutated product is highly expressed but is not found in the culture supernatant. Electron microscopy and immunogold labelling of infected cells show that the native Pr57gag protein assembles into 100-120 nm virus-like particles that bud from the cell plasma membrane and are released in the culture supernatant. The unmyristylated protein also assembles into particulate structures which only accumulate inside the cells. These results demonstrate that the unprocessed GAG precursor of SIV can spontaneously assemble into particles in the absence of other viral proteins. Myristylation of the Pr57gag precursor is necessary for its association with the cell plasma membrane, for budding and for extracellular release.

Animals↗
PubMed1989

Seroepidemiological study of the immune response to Campylobacter pylori in potential risk groups.

To gain more understanding of the epidemiology of Campylobacter pylori infection, the immune response to the organism was studied in the following selected potential risk groups: endoscopy staff (n = 45), dental staff (n = 58), orphanage children (n = 24), psychiatric patients (n = 58), and family contacts of Campylobacter pylori-infected patients (n = 55). The frequency of an IgG and IgA antibody response in the different groups was determined by the immunoblot method and compared with that in an appropriate control group (n = 189). The frequency of a positive antibody response was dependent on age (p less than 0.0001) but not on sex. When results were corrected for age by logistic regression analysis, all groups, with the exception of dental staff and orphanage children, revealed a significantly raised frequency of an IgA and combined IgG/IgA immune response compared to controls. There was not a significant difference for the IgG response, except in orphanage children. It is concluded that endoscopy staff, family contacts of Campylobacter pylori-infected patients and people living in closed communities such as psychiatric patients and orphanage children must be considered as risk groups for Campylobacter pylori infection. The findings support the notion that person-to-person spread and a common source are the predominant modes of transmission of Campylobacter pylori in addition to endoscopes.

Adolescent↗
PubMed1989

Precise measurement of vertebral bone density using computed tomography without the use of an external reference phantom.

Bone density measurement by quantitative computed tomography (QCT) commonly uses an external reference phantom to decrease scan-to-scan and scanner-to-scanner variability. However, the peripheral location of these phantoms and other phantom variables is also responsible for a measurable degradation in accuracy and precision. Due to non-uniform artifacts such as beam hardening, scatter, and volume averaging, the ideal reference phantom should be as close to the target tissue as possible. This investigation developed and tested a computer program that uses paraspinal muscle and fat tissue as internal reference standards in an effort to eliminate the need for an external phantom. Because of their proximity, these internal reference tissues can be assumed to reflect more accurately the local changes in the x-ray spectra and scatter distribution at the target tissue. A user interactive computerized histogram plotting technique enabled the derivation of reproducible CT numbers for muscle, fat, and trabecular bone. Preliminary results indicate that the use of internal reference tissues with the histogram technique may improve reproducibility of scan-to-scan measurements as well as inter-scanner precision. Reproducibility studies on 165 images with intentional region-of-interest (ROI) mispositioning of 1.5, 2.5, or 3.5 mm yielded a precision of better than 1% for normals and 1% to 2% for osteoporotic patients--a twofold improvement over the precision from similar tests using the standard technique with an external reference phantom. Such improvements in precision are essential for QCT to be clinically useful as a noninvasive modality for measurement of the very small annual changes in bone mineral density.

Bone Density↗