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Biomedical subjects

E Jacobs

Publications and source records attributed to E Jacobs.

At least 73 records · Page 4Linked to original sources
PubMed1995

Intraperitoneal micro-organisms and the severity of peritonitis.

OBJECTIVE: To find out if there was any correlation between the type or number of pathogenic bacteria in peritoneal exudate, the values of various prognostic scores, the inflammatory response, and the outcome, in patients with peritonitis. DESIGN: Prospective open study. SETTING: University hospital, Germany. SUBJECTS: 51 Consecutive patients with secondary peritonitis. INTERVENTIONS: Laparotomy within 12 hours of admission or within 8 hours of diagnosis in 9 patients with postoperative peritonitis. MAIN OUTCOME MEASURES: Correlation between the severity of the disease (APACHE II score, Septic Severity Score, Mannheim Peritonitis Index, Peritonitis Index Altona II, and outcome), the intraperitoneal and the systemic inflammatory response, intraperitoneal and systemic endotoxin concentrations, and type and number of micro-organisms grown from peritoneal fluid. RESULTS: Intra-abdominal microbiological findings did not correlate with severity of illness judged by the scoring systems, the later incidence of infective complications, or the final outcome. The presence of intra-abdominal microbes was associated with signs of a systemic inflammatory response (median activation index 3 (range 1-3) compared with 2 (range 1-3)), the length of history (median 52 hours (range 3-72) compared with 16 hours (range 3-56), and local and systemic concentrations of endotoxin (peritoneal exudate: median 4800 EU/ml (range 0.06-136674) compared with 220 EU/ml (range 0.00-1800); plasma: median 0.05 EU/ml (range 0.00-1.32) compared with 0.04 EU/ml (range 0.00-0.13)). The sensitivity of the organisms to the antibiotics given (cefuroxime and metronidazole) did not influence the incidence of later infective complications or the outcome. CONCLUSIONS: These results do not suggest micro-organisms invading the peritoneal cavity and respective antibiotic treatment to be major determinants of the clinical course of peritonitis.

APACHE↗
PubMed1995

Effects of peritonitis exudates on chemotaxis and phagocytosis of human neutrophils.

OBJECTIVE: To elucidate the in vitro effects of peritoneal exudate in patients with peritonitis on the functions of normal neutrophils (chemotaxis and phagocytosis) and to correlate these findings with constituents of the exudate, severity of disease, and clinical course. DESIGN: Open study. SETTING: University hospital, Germany. SUBJECTS: Fifty consecutive patients with secondary peritonitis and healthy volunteers. INTERVENTIONS: Samples of peritoneal exudate were taken during operation and tested for their ability to stimulate or inhibit chemotaxis and phagocytosis of polymorphonuclear neutrophils (PMN). MAIN OUTCOME MEASURES: Correlation between chemotaxis and phagocytosis and concentrations of constituents of peritoneal exudate. RESULTS: Mean (SD) exudate-induced chemotaxis was 102.5 (22.8) microns compared with 62.3 (4) in the buffer control and 116 (17) in the 1 ng/ml C5a buffer control. The mean (SD) phagocytic index (uptake of zymosan and Candida albicans) was 68.8 (28.1) % of the respective serum control. There were correlations between chemotaxis and concentrations of C3a, endotoxin, and white cell count in the exudates; between phagocytosis and concentrations of C3a, IgG, IgM, protein and granulocyte elastase activity (GE and GE-alpha 1 proteinase inhibitor complex) in the peritoneal exudate; concentrations of endotoxin, and tumour necrosis factor alpha (TNF alpha), and granulocyte elastase activity in the exudate; and concentrations of C3a, IgG, IgM, and fibrinopeptide A in the exudate. There were no differences in chemotaxis and phagocytosis between patients who survived and those who died, and only the APACHE II score, the Sepsis Severity Score and the Mannheim Peritonitis Index correlated with mortality. CONCLUSION: It is still not clear whether other constituents of the exudate, variable conditions of resorption, inflammatory conditions within the peritoneal lining, or the individual patient's capacity to limit the systemic response, may have a critical role.

APACHE↗
PubMed1994

Involvement of SRE element of Ty1 transposon in TEC1-dependent transcriptional activation.

Some Ty1 transposable element insertion mutations of Saccharomyces cerevisiae activate transcription of adjacent genes in a cell-type dependent manner. This activation requires at least STE12 and TEC1 gene products. The binding site for the STE12 protein is located in the sterile responsive element (SRE), which is just downstream the 5' LTR of Ty1 and contains one copy of the pheromone response element (PRE). This report defines the sequences in Ty1 required for TEC1-dependent activation using a TDH3::lacZ reporter gene in which the UAS was replaced by different portions of a Ty1 or Ty2 element. The Ty1 SRE seems to be sufficient to ensure the TEC1 and STE12-mediated activation whereas Ty2 SRE can activate the expression of the adjacent genes in the absence of both proteins. Adjacent to the PRE element, there is a region (PAE) with extensive sequence divergence in Ty1 and Ty2 SREs. Swapping experiments between Ty1 and Ty2 sequences show that Ty1 PAE is required for the activation of adjacent gene expression in a TEC1 and STE12-dependent manner. The use of a LexA::TEC1 construct indicates that the chimeric protein has no activation ability suggesting that TEC1 could act in conjunction with another factor.

Base Sequence↗
PubMed1994

Production of monoclonal antibodies recognising the peptide core of MUC2 intestinal mucin.

A peptide based on the tandem repeat sequence of MUC2 mucin was used to produce a series of monoclonal antibodies (MAb). The fine specificity of these antibodies and their implications for MUC2 expression are presented. Three of the MAbs, 996/1, 996/7 and 995/25, were specific to the MUC2p and failed to bind to peptides based on the MUC1,3,4 tandem repeat sequences whereas three others, 994/152, 994/91 and 996/36, cross reacted with the MUC2p and the MUC3 tandem repeat peptide but not the MUC1 and MUC4 peptides. An antigen, affinity purified from a colorectal tumour on one of the MUC2p-specific MAbs, 996/1, was shown to be a high molecular weight polydisperse, mucin-like antigen. Two of the MAbs, 996/1 and 994/152, recognised MUC2 in tissue sections, although the fine specificity varied between the two MAbs, with 994/152 strongly staining gastric, ileum and kidney epithelia, and MAb 996/1 intensely staining colon, liver and prostate tissues. These antibodies also stained a colorectal cell line, and MAb 994/152 also stained a gastric and an ovarian cell line. Six of the MAbs were used to stain colorectal tumour and adjacent 'normal' colonic mucosa sections. All six stained normal mucosa, but only two of the MAbs, 996/1 and 994/91, stained tumour tissue. The staining probably reflects exposure of cryptic epitopes due to varying levels of glycosylation in different tissues. These anti-MUC2p MAbs may help in determining the normal role of MUC2 mucin and how it is subverted in malignancy.

Amino Acid Sequence↗
PubMed1994

Isolation and characterization of Saccharomyces cerevisiae mRNA transport-defective (mtr) mutants.

To understand the mechanisms of mRNA transport in eukaryotes, we have isolated Saccharomyces cerevisiae temperature-sensitive (ts) mutants which accumulate poly(A)+ RNA in the nucleus at the restrictive temperature. A total of 21 recessive mutants were isolated and classified into 16 complementation groups. Backcrossed mRNA transport-defective strains from each complementation group have been analyzed. A strain which is ts for heat shock transcription factor was also analyzed since it also shows nuclear accumulation of poly(A)+ RNA at 37 degrees C. At 37 degrees C the mRNA of each mutant is characterized by atypically long polyA tails. Unlike ts pre-mRNA splicing mutants, these strains do not interrupt splicing of pre-mRNA at 37 degrees C; however four strains accumulate oversized RNA polymerase II transcripts. Some show inhibition of rRNA processing and a further subset of these strains is also characterized by inhibition of tRNA maturation. Several strains accumulate nuclear proteins in the cytoplasm when incubated at semipermissive temperature. Remarkably, many strains exhibit nucleolar fragmentation or enlargement at the restrictive temperature. Most strains show dramatic ultrastructural alterations of the nucleoplasm or nuclear membrane. Distinct mutants accumulate poly(A)+ RNA in characteristic patterns in the nucleus.

Biological Transport↗
PubMed1994

A comparative study of intravenous versus intralymphatic interleukin-2, with assessment of effects of interleukin-2 on both peripheral blood and thoracic-duct lymph.

Recombinant human interleukin-2 (IL-2) was administered by the intravenous (i.v.) or intralymphatic (i.l.) route to 14 patients with advanced malignancy. IL-2 was given in doses of 600,000 IU/kg or 1,050,000 IU/kg daily x 5. Thoracic duct (TD) catheters were placed, and both TD lymphocytes (TDL) and peripheral blood lymphocytes (PBL) were studied. Five of eight patients at the 600,000 IU/kg dose experienced grade III toxicity as did five of six patients at the 1,050,000 IU/kg dose. Two episodes of grade IV toxicity were seen at the higher dose. The i.l. and i.v. routes had a similar toxicity profile excepting lymphangitis/pedal infection, seen only with i.l. administration. One partial response was seen in a patient with renal cell carcinoma. Lymphopenia was seen early in therapy, with lymphocytosis by day 6. Lymphoid yield of the TD catheter fell early in therapy, then increased over baseline by the end of treatment. Intralymphatic administration resulted in a prolonged serum t1/2 and lower serum levels than did i.v. administration, but resulted in higher TD levels. Antibodies against IL-2 were ubiquitous but had no clear effects. Lymphocyte trafficking studies suggested that IL-2 affected lymphocyte redistribution to liver, spleen, bone marrow, and lymph nodes. NK activity and phenotype and LAK activity increased in response to IL-2, with no advantage for TDL. Tumor necrosis factor-alpha and gamma-interferon levels increased sporadically with treatment. The i.l. route offered no advantage over the i.v. route, and TDL offered no advantage over PBL.

Adult↗
PubMed1994

Cytokine gene expression in the lungs of BALB/c mice during primary and secondary intranasal infection with Mycoplasma pneumoniae.

Cytokine gene expression was determined in vivo in the lungs and spleens of Mycoplasma pneumoniae-infected BALB/c mice by means of qualitative and semiquantitative PCR-mediated mRNA amplification. During the acute phase of both primary and secondary infections, cytokines commonly associated with innate resistance, TNF alpha, IFN gamma, IL-1 beta and IL-6, were expressed. In contrast, early expression of the genes for IL-2 and IL-2 receptor was detected only during reinfection. Expression was greater in the lungs than in the spleen, attesting to the rapid accumulation of lymphocytes at the infected site. Interestingly, IL-2 mRNA expression declined rapidly and was no longer detectable after 24 h, whereas IL-10 mRNA levels rose sharply during the same period. During reinfection, mRNAs for TNF alpha and IL-6 were 10-fold and for IFN gamma about 50-fold higher than during primary challenge. The results suggest that the pathogenesis of M. pneumoniae diseases may be associated with elevated expression of proinflammatory cytokines.

Acute Disease↗
PubMed1994

Characterization of a highly structured domain in Tbp2 from Neisseria meningitidis involved in binding to human transferrin.

The binding of iron-loaded human transferrin at the surface of Neisseria meningitidis is mediated by two polypeptides, Tbp1 and Tbp2. Predicted Tbp amino acid sequences from N. meningitidis strains are highly divergent. This variability is particularly pronounced throughout the Tbp2 polypeptide. In this study, a highly structured and extremely stable Tbp2 domain of about 270 to 290 amino acids which is involved in the binding to transferrin and whose position is well conserved has been characterized. The conservation of such a remarkable structure in a very divergent protein domain (there is only 43% amino acid identity within this region) suggests that is plays an essential biological role and raises a number of questions regarding tbp2 evolution.

Amino Acid Sequence↗
PubMed1994

Continuous measurements of changes in pulmonary capillary surface area with 201Tl infusions.

The impact of physiological and pathological processes on metabolism and transport of a variety of substances traversing the pulmonary vasculature depends in part on the capillary surface area available for exchange, and a reliable method for detecting changes in this parameter is needed. In this study, a continuous-infusion approach was used to investigate the response of the pulmonary capillary surface area to increases in flow and left atrial pressure. Isolated rat lungs were perfused with an acellular perfusion solution containing 125I-labeled albumin (an intravascular indicator) and 201Tl, a K+ analogue which is concentrated within lung cells. The extraction of 201Tl from the perfusate was 61% greater at low flow (8.5 ml/min) than at high flow (26 ml/min), and rapid changes in extraction were observed when flow was altered. In contrast, the permeability-surface area product was 76% greater when lungs were perfused at high flow than at low flow, suggesting comparable increases in pulmonary capillary surface area in these zone 2 lungs (airway pressure = 5 cmH2O, left atrial pressure < 0 cmH2O). In a second group of experiments, increases in left atrial pressure to 14 cmH2O (zone 3 lungs) at a constant flow of 8.5 ml/min increased the permeability-surface area product by only 18% despite increases in average intravascular pressure that were at least as high as those associated with high perfusion rates. 201Tl infusions provide a useful method for detecting and quantifying changes in pulmonary capillary surface area.

Animals↗
PubMed1994

Flushing with autologous blood improves intraoperative hemodynamic stability and early graft function in clinical hepatic transplantation.

Hemodynamic instability and hyperkalemia are common after reperfusion and may cause ischemic damage on the hepatic allograft. Two techniques for flushing hepatic grafts before reperfusion were studied to evaluate their effects on intraoperative hemodynamic and metabolic status and on early graft function in 83 consecutive adult hepatic transplantations. In the first 41 patients (group 1), the hepatic grafts were rinsed with 500 milliliters of lactated Ringer's solution (LR). In the subsequent 42 patients (group 2), in addition to LR rinse, the first 500 milliliters of portal blood to flush and reperfuse the liver were drained through the cannula inserted into the donor vena cava before unclamping the vena cava. After reperfusion, the mean arterial pressure decreased 30 +/- 4 percent in group 1 versus 17 +/- 2 percent in group 2 (p < 0.02), and serum K+ increased by 1.9 +/- 0.2 in group 1 versus 0.8 +/- 0.2 milliequivalents per liter in group 2 (p < 0.01). Hyperkalemic cardiac arrest was only seen in two patients in group 1. The K+ concentration in the first 100 milliliters of discarded blood was found to be 40 +/- 2 milliequivalents per liter. The 500 milliliters of discarded blood contained 8.3 +/- 0.4 milliequivalents, which was correlated with graft liver weight (p < 0.001). Early graft function, as measured by serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, total bilirubin and prothrombin time on postoperative day No. 2, was significantly better in group 2 than in group 1 (p < 0.05). The six-month graft and patient survival rates in group 1 were 66 and 75 percent, versus 90 and 95 percent in group 2 (p < 0.01 and p < 0.02, respectively). Further flushing with 500 milliliters of autologous portal blood resulted in smaller intraoperative shifts in serum K+, greater hemodynamic stability, better graft function and improved graft and patient survival.

Adult↗
PubMed1993

Cloning and characterization of Neisseria meningitidis genes encoding the transferrin-binding proteins Tbp1 and Tbp2.

Genes tbp1 and tbp2, encoding the transferrin-binding proteins Tbp1 and Tbp2, have been isolated from two strains of Neisseria meningitidis. The tbp2 and tbp1 open reading frames are tandemly arranged in the genome with an 87-bp intergenic region, and the DNA region upstream from the tbp2-coding sequence contains domains homologous to Escherichia coli promoter consensus motives. Nucleotide sequence analysis suggests the existence of a Tbp1 precursor carrying an N-terminal signal peptide with a peptidase I cleavage site and of a Tbp2 precursor with N-terminal homology to lipoproteins, including a peptidase II cleavage site. Comparison of the Tbp1 deduced amino acid (aa) sequences from both strains showed about 76% aa homology, while those of Tbp2 revealed only about 47% aa homology. These comparisons should be extended to other Neisseria strains in order to evaluate further this genetic divergence further.

Amino Acid Sequence↗
PubMed1993

Characterization of the cellular response of spleen cells in BALB/c mice inoculated with Mycoplasma pneumoniae or the P1 protein.

BALB/c mice were intranasally infected or intraperitoneally inoculated with Mycoplasma pneumoniae whole cells or were immunized with the isolated adhesin (P1 protein). Spleen cells were isolated and tested in vitro for proliferation activity after stimulation with the P1 protein and sonicated M. pneumoniae whole antigen preparations. In frequency analysis experiments the P1 protein-specific proliferative response of spleen lymphocytes increased from 1/11494 in mice immunized once to 1/3246 in eightfold-inoculated mice, demonstrating that the P1 protein is a prominent immunogen of M. pneumoniae cells. Depletion experiments showed that T and B cells are activated in a 2:1 relation. Fluorescence-activated cells sorting analysis revealed a shift of the CD4/CD8 ratio from 2:1 in control mice up to 3:1 in M. pneumoniae-, and to 3.4:1 in P1 protein-immunized mice, as well as an increase in interleukin 2 receptor-bearing cells and macrophage cell populations. The results indicate that this animal model is appropriate to study host-M. pneumoniae interactions and vaccination schedules.

Adhesins, Bacterial↗
PubMed1993

Identification of Chlamydia pneumoniae-specific protein antigens in immunoblots.

The immunoblot patterns of 248 sera, all examined previously by the microimmunofluorescence test (MIF) for species-specific Chlamydia antibodies, were analyzed. Predominant specific antibody activity was directed to the 54 kDa protein of Chlamydia pneumoniae, which was recognized by 93% of sera positive for Chlamydia pneumoniae by MIF but by only 2% of sera positive for Chlamydia trachomatis and negative for Chlamydia pneumoniae and by 3% of sera negative for both Chlamydia pneumoniae and Chlamydia trachomatis. This antigen appears to be specific for Chlamydia pneumoniae. Other Chlamydia pneumoniae-specific protein antigens were recognized far less frequently. Absorption analysis indicated that the 54 kDa protein is located on the surface of the Chlamydia pneumoniae elementary bodies.

Antigens, Bacterial↗
PubMed1993

Evaluation of an antigen-capture enzyme immunoassay for rapid diagnosis of Mycoplasma pneumoniae infection.

A new enzyme immunoassay (EIA; Enzygost) for rapid detection of Mycoplasma pneumoniae antigen was evaluated in 51 young adults with acute respiratory infection. The EIA results using sputa and nasopharyngeal aspirates were compared with those of serological antibody tests, culture and a DNA probe. In sputum the sensitivity of the EIA ranged from 40% to 81% and the specificity from 64% to 100%, depending on the reference method. In nasopharyngeal aspirates the sensitivity was well below 20%, but the test was nearly 100% specific.

Acute Disease↗
PubMed1993

Development of second generation monoclonal antibodies recognising Lewisy/b antigen by anti-idiotypic immunisation.

Five new monoclonal antibodies (Mabs) recognising the Lewisy/b hapten of the IgG isotype have been produced following immunisation with rat anti-idiotypic antiserum to C14, an IgM Lewisy/b hapten Mab and boosting with C14gp200 antigen. They have the same fine specificity as the original Mab binding to a cell surface and secreted antigen preferentially expressed by colorectal tumour cells.

Animals↗
PubMed1993

Serological diagnosis of Mycoplasma pneumoniae infections: a critical review of current procedures.

Respiratory diseases due to Mycoplasma pneumoniae are still confirmed with serological methods, although during the acute phase of M. pneumoniae disease indicative parameters are frequently negative. This result is true not only for serodiagnosis based on tests for the presence of cold hemagglutinin (the first but unspecific acute-phase parameter; these are positive in only about 50% of cases) but also for serodiagnosis based on CF tests, particle agglutination tests, or even enzyme-linked immunoassays that test for "early" IgM antibodies. Whereas the sensitivity of the different tests is difficult to improve, advances in specificity were obtained with use of more defined protein antigen preparations of M. pneumoniae cells. Even more problematic than negative titers in the first serum samples and delayed positive titers in the convalescent-phase sera are false-negative results with sera from immunocompromised patients, which limit the value of serological approaches for diagnosis of M. pneumoniae infections in particular risk groups. This review summarizes the use and the limitations of various serological approaches but also refers to alternative methods that are suitable for diagnosis of acute-phase M. pneumoniae disease or cases in which seroconversion has not occurred.

AIDS-Related Opportunistic Infections↗