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Biomedical subjects

J Hess

Publications and source records attributed to J Hess.

At least 109 records · Page 6Linked to original sources

The gene cluster inlC2DE of Listeria monocytogenes contains additional new internalin genes and is important for virulence in mice.

In this work we identified and characterized a gene cluster containing three internalin genes of Listeria monocytogenes EGD. These genes, termed inlG, inlH and inlE, encode proteins of 490, 548 and 499 amino acids, respectively, which belong to the family of large, cell wall-bound internalins. The inlGHE gene cluster is flanked by two listerial house-keeping genes encoding proteins homologous to the 6-phospho-beta-glucosidase and the succinyl-diaminopimelate desuccinylase of E. coli. A similar internalin gene cluster, inlC2DE, localised to the same position on the L. monocytogenes EGD chromosome was recently described in a different isolate (Dramsi S, Dehoux P, Lebrun M, Goossens PL, Cossart P (1997) Infect Immun 65: 1615-1625). Sequence comparison of the two inl gene clusters indicates that inlG is a new internalin gene, while inlH was generated by a site-specific recombination, leading to an in-frame deletion which removed the 3'-terminal end of inlC2 and the 5'-terminal part of inlD. The third gene of the inlGHE cluster, inlE, is almost identical to the previously reported inlE gene. Our data show that the inlGHE gene cluster is probably transcribed from a major PrfA-independent promoter located upstream of inlG. PCR analysis revealed the presence of the newly identified inl genes inlG and inlH in most L. monocytogenes isolates tested. A mutant which has lost inlG, inlH and inlE by an in-frame deletion exhibited, after oral infection of mice, a significant loss in virulence and shows drastically reduced numbers of viable bacteria in both liver and spleen when compared to the wild-type strain.

Amino Acid Sequence↗

Heparin as a risk factor for perigraft seroma complicating the modified Blalock-Taussig shunt.

OBJECTIVE: The purpose of this study was to determine the risk factors associated with the occurrence of perigraft seromas complicating systemic-to-pulmonary polytetrafluoroethylene grafts. METHODS: Clinical and perioperative variables were reexamined, blinded for the outcome variable perigraft seroma, in 60 patients undergoing 67 consecutive graft procedures in a 3.5-year period. RESULTS: Eight cases of perigraft seroma were diagnosed in six patients. Univariate analysis revealed age (p = 0.02), a diagnosis of pulmonary atresia with ventricular septal defect and systemic-pulmonary collaterals (p = 0.001), reimplantation of collaterals during the procedure (p < 0.001), and intravenous heparin administered after operation (p < 0.0001) as risk factors for symptomatic perigraft seroma. Multivariable analysis defined heparin as the only significant factor associated with symptomatic perigraft seroma. Consolidation of the upper lobe on chest radiograph, ipsilateral to the shunt, directly after operation (p = 0.01), but especially 8 to 10 days after operation (p < 0.0001), or the need for prolonged drainage of pleural fluid (p < 0.0001) were correlated with the occurrence of perigraft seroma. Perigraft seroma led to four early rethoracotomies in three patients and to accelerated corrective surgery in three cases. Consolidation and absent perfusion of lung segments persisted in two patients. CONCLUSIONS: Our data suggest that the use of heparin leads to an increased risk of perigraft seroma, complicating systemic-pulmonary polytetrafluoroethylene grafts. Prolonged pleural drainage and/or postoperative consolidation of the upper lobe indicate the development of symptomatic perigraft seroma. Treatment is controversial and results are unpredictable. Expectative management seems to be justified so long as permitted by the clinical condition.

Anastomosis, Surgical↗

Myocardial blood flow and coronary flow reserve late after anatomical correction of transposition of the great arteries.

OBJECTIVES: Myocardial blood flow (MBF) in children late after arterial switch operation (ASO) was investigated quantitatively by positron emission tomography (PET). BACKGROUND: In children with transposition of the great arteries (TGA), ASO is widely accepted as the management of choice. The long-term patency of coronary arteries after surgical transfer to the neo-aorta, however, remains a concern. METHODS: Twenty-two normally developed, symptom-free children were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilation 10+/-1 years after ASO. A subgroup of 15 children (9+/-1 years; group A) had simple TGA and underwent ASO within 20 days after birth while 7 (13+/-3 years; group B) had complex TGA and underwent ASO and correction of associated anomalies later after birth. Ten young, healthy adults (26+/-6 years) served as the control group. RESULTS: Resting MBF was not different between groups. After correction for the rate-pressure product as an index of cardiac work, younger children of group A had significantly higher MBF at rest compared to healthy adults (102+/-29 vs. 77+/-6 ml/100 g/min; p = 0.012) while flow in group B was not different from the other groups (85+/-22 ml/100 g/min; p = NS). Hyperemic blood flows were significantly lower in both groups after ASO compared to normals (290+/-42 ml/100 g/min for group A, 240+/-28 for group B, 340+/-57 for normals; p < 0.01); thus, coronary flow reserve was significantly lower in both groups after ASO compared to healthy adults (3.0+/-0.6 for group A, 2.9+/-0.6 for group B, 4.6+/-0.9 for normals; p < 0.01). CONCLUSIONS: Blood flow measurements suggest decreased coronary reserve in the absence of ischemic symptoms in children late after arterial switch repair of TGA. The global impairment of stress flow dynamics may indicate altered vasoreactivity; however, the prognostic significance of these findings needs to be determined.

Adolescent↗

Application of differential cDNA screening techniques to the identification of unique gene expression in tumours and lymphocytes.

Development, differentiation and cell death in all organisms are mediated by tightly regulated programs of differential gene expression. Furthermore, changes in gene expression profiles are responsible for tumour formation and tumour progression, as well as for many other human diseases. Thus, the definition of distinct patterns of gene expression is not only essential for understanding complex biological processes but also leads to the identification of novel targets for therapy of various diseases.

DNA, Complementary↗

Delivery of antigen-encoding plasmid DNA into the cytosol of macrophages by attenuated suicide Listeria monocytogenes.

Eukaryotic expression vectors can be delivered to macrophages using attenuated self-destructing Listeria monocytogenes. L. monocytogenes cells are preferentially lysed in the host cell macrophage cytosol by the production of a PactA-dependent Listeria-specific phage lysin. Efficient expression of the cloned reporter genes by the macrophages and subsequent antigen presentation were achieved after the delivery of eukaryotic expression vectors by the attenuated suicide L. monocytogenes strain. After delivery by L. monocytogenes plasmid DNAs were found to integrate into the macrophage cell's genome at a frequency of about 10(-7).

Animals↗

Haemophilia and advanced fibrin sealant technologies.

Fibrin sealant, which consists mainly of fibrinogen and thrombin, provides rapid haemostasis as well as tissue sealing and adhesion. Commercial, viral-inactivated products are available in Europe, Canada, and Japan. Liquid fibrin sealant (LFS) has been used clinically in haemophiliacs to perform dental procedures, orthopedic surgeries, non-orthopaedic surgeries, and circumcisions. LFS use is expected to increase as commercial products will soon be available in the US. Recombinant sources and transgenic animal bioreactor systems will replace plasma-derived products and become the predominant sources for this product in the next decade. Other areas of innovation include the development of fibrin sealant bandages or dressings, expandable foams, and spray powders which will provide the haemophiliac the ability to rapidly attain control of traumatic haemorrhages prior to hospital treatment with a significant reduction in the use of i.v. clotting factors. Fibrin sealant products have the potential to provide life-saving control of haemorrhage, reduction in factor dependency, lower viral exposure risk, and medical care cost reduction.

Drug Contamination↗

A novel PrfA-regulated chromosomal locus, which is specific for Listeria ivanovii, encodes two small, secreted internalins and contributes to virulence in mice.

Several large, cell wall-associated internalins and one small, secreted internalin (InlC) have been described previously in Listeria monocytogenes. Using degenerate primers derived from sequenced peptides of an L. ivanovii major secreted protein, we identified a new 4.25 kb internalin locus of L. ivanovii, termed i-inlFE. The two proteins encoded by this locus, i-InlE and i-InlF, belong to the group of small, secreted internalins. Southern blot analyses show that the i-inlFE locus does not occur in L. monocytogenes. These data also indicate that six genes encoding small, secreted internalins are present in L. ivanovii, in contrast to L. monocytogenes, in which inlC encodes the only small internalin. The mature i-InlE protein (198 amino acids) is secreted in large amounts into the brain-heart infusion (BHI) culture medium in the stationary growth phase. In minimum essential medium (MEM), which has been used previously to induce PrfA-dependent gene transcription, i-inlE mRNA and i-InlE protein are expressed at high levels. As shown by Northern blot analysis and primer extension, transcription of the tandemly arranged i-inlF and i-inlE genes is dependent on the virulence regulator PrfA, and characteristic palindromic sequences ('PrfA-boxes') were identified in the promoter regions of i-inlF and i-inlE. Non-polar i-inlE and i-inlF deletion mutants and an i-inlFE double deletion mutant were constructed and tested in the mouse infection model. After intravenous infection, all three mutants entirely failed to kill C57BL/6 mice even at high infectious doses of 109 bacteria per mouse, whereas the LD50 for the parental strain was determined as 4 x 107 bacteria per mouse. These data suggest an important role for i-InlE and i-InlF in L. ivanovii virulence.

Amino Acid Sequence↗

Psychopathology in young adults with congenital heart disease. Follow-up results.

AIMS: The aim of the present study was to assess the occurrence of a wide range of behavioural and emotional problems long-term (> 9 years) after surgical correction for congenital heart disease in infancy and childhood. METHODS: The problem scores on the Young Adult Self-Report of 166 19-25-year-old adults with congenital heart disease were compared with those of subjects of similar age from the general population. RESULTS: On most Young Adult Self-Report scales no differences were found between the mean problem scores of the congenital heart disease-adults and reference peers. On only two Young Adult Self-Report scales (i.e. Somatic Complaints and Strange) and the total problem score were significant though small differences found between the mean problem scores of the congenital heart disease adults and reference peers. No significant relationship was found between cardiac diagnosis and problem behaviours in congenital heart disease adults. No relationship was found between IQ scores and problem behaviours in congenital heart disease adults. CONCLUSION: Overall, it can be concluded that the results of the congenital heart disease adults were not unfavourable, since the differences in mean (total) problem scores between the congenital heart disease sample and reference group were small and limited to only two specific problem areas.

Adult↗

Prediction of behavioural and emotional problems in children and adolescents with operated congenital heart disease.

AIMS: The aim of the present study was to determine which medical variables were predictors of long-term behavioural/emotional outcome after surgical correction for congenital heart disease in infancy and childhood. METHODS: The Child Behavior Checklist (CBCL) was used to predict parent-reported behavioural/emotional problems in 125 10-15 year-old congenital heart disease children from: (1) biographical status (2) medical history (3) heart surgery (4) short-term post-operative course and (5) number of heart operations and (6) extra cardiac concomitant anomalies. RESULTS: Higher CBCL total problem scores at follow-up were associated with a greater number of heart operations and deep hypothermic circulatory arrest (< 22 degrees). 'Internalizing problems' were associated with a greater number of heart operations, deep hypothermic circulatory arrest, a short gestational age, low systemic oxygen saturation, and older age at surgical repair. 'Externalizing problems' were associated with a greater number of heart operations only. CONCLUSION: Several medical variables were significant predictors and can be used to identify those congenital heart disease children who are at risk of long-term behavioural/emotional maladjustment.

Adolescent↗

Screening for congenital heart malformation in child health centres.

BACKGROUND: Although screening for congenital heart malformations is part of the child health care programme in several countries, there are very few published evaluations of these activities. This report is concerned with the evaluation of this screening at the Dutch Child Health Centres (CHC). METHODS: All consecutive patients, aged between 32 days and 4 years, presented at the Sophia Children's Hospital Rotterdam throughout a period of 2 years, with a congenital heart malformation were included in this study. Paediatric cardiologists established whether or not these patients were diagnosed after haemodynamic complications had already developed (diagnosed 'too late'). Parents and CHC-physicians were interviewed in order to establish the screening and detection history. Test properties were established for all patients with a congenital heart malformation (n = 290), intended effects of screening were established in patients with clinically significant malformations (n = 82). RESULTS: The sensitivity of the actual screening programme was 0.57 (95% CI : 0.51-0.62), the specificity 0.985 (95% CI : 0.981-0.990) and the predictive value of a positive test result 0.13 (95% CI: 0.10-0.19). Sensitivity in a subpopulation of patients adequately screened was 0.89 (95% CI: 0.74-0.96). Adequately screened patients were less likely to be diagnosed 'too late' than inadequately screened patients (odds ratio [OR] = 0.20, 95% CI: 0.04-1.05). The actual risk of being diagnosed 'too late' in the study-population (48%) was only slightly less than the estimated risk for patients not exposed to CHC-screening (58%, 95% CI: 43%-72%). Adequately screened patients however were at considerably less risk (17%, 95% CI: 4%-48%). CONCLUSION: Screening for congenital heart malformations in CHC contributes to the timely detection of these disorders. The actual yield, however, is far from optimal, and the screening programme should be improved.

Child Health Services↗

A review of regional blocks for the foot.

The blocking of the posterior tibial, sural, saphenous, superficial peroneal, and the deep peroneal nerves with possible alternative approaches is discussed. Digital blocks, Mayo blocks, and intravenous regional anesthesia are also discussed. The placement of the tourniquet above the ankle but below the calf muscles will avoid deep muscle pain. Lidocaine and bupivacaine cause vasodilatation in the foot.

Anesthesia, Conduction↗

Clinical outcome and left ventricular function after pulmonary autograft implantation in children.

BACKGROUND: Aortic root replacement with a pulmonary autograft is an alternative treatment for children with aortic valve or root disease, or both. METHODS: Twenty-six patients (18 boys and 8 girls) with a mean age of 10.9 years (range, 0.3 to 16.9 years) underwent this procedures in a 7-year period. The mean follow-up period was 3.2 years (range, 0.2 to 7.5 years). RESULTS: During follow-up 3 patients died and one autograft was replaced with a mechanical valve. The actuarial survival and actuarial event-free survival rates were 87% and 79%, respectively, at both 5 and 7 years. None of the surviving patients had complaints, and all have done well and are living normal lives. Electrocardiographic signs of myocardial ischemia and left ventricular hypertrophy were not present. Echocardiography showed autograft valve regurgitation to be absent or trivial (n = 17) or mild (n = 5). Stenosis was not present. Increasing autograft annulus diameters were noted during follow-up, but this was not related to the severity of autograft regurgitation. Left ventricular dimensions and function were within normal limits later than 1 year after the operation. Only 2 patients had a moderate pulmonary stenosis without right ventricular hypertrophy. CONCLUSIONS: The surgical results, clinical outcome, valve function, and left ventricular function in our patients have been good. This procedure is recommended as a method of aortic valve replacement in children.

Actuarial Analysis↗

Identification of target genes of the lymphoid-specific transcription factor Oct2.

The Oct2 transcription factor is expressed predominantly in B lymphocytes and plays an essential role during the terminal phase of B cell differentiation. The regulatory regions of several genes specifically expressed in B cells contain functional binding sites for Oct2. Nevertheless, none of the genes originally thought to be regulated by Oct2 were affected in their expression in Oct2-deficient B cells. In an attempt to find such elusive Oct2 target genes and to understand the molecular function of Oct2 in B cell development, we isolated cDNAs for Oct2 target genes. So far, we have identified five potential targets for Oct2: the membrane glycoprotein CD36, the cysteine-rich secreted protein 3 (CRISP-3), a mouse homolog of the human monocyte/neutrophil elastase inhibitor (mEI) and two unknown cDNA sequences Nov1 and Nov2. These target genes show quite distinct expression patterns demonstrating that transcription factors in addition to Oct2 are involved in their regulation. Whereas CD36 and mEI were expressed in all hematopoetic cell lines containing Oct2,. CRISP-3 is pre-B cell-specific, Nov1 is plasma B cell-specific and Nov2 is B cell-specifically expressed.

Animals↗

Pulmonary hypertension and systemic vasoconstriction may offset the benefits of acellular hemoglobin blood substitutes.

OBJECTIVE: We tested the hypothesis that the pharmacologic properties of a small volume of alpha alpha-cross-linked hemoglobin (alpha alpha Hb) could effectively resuscitate pigs subjected to hemorrhage. METHODS: Fourteen pigs hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg for 60 minutes were treated with a 4-mL/kg 2-minute infusion of 10 g/dL alpha alpha Hb or 7 g/dL human serum albumin, an oncotically matched control solution. RESULTS: The removal of blood (17 +/- 1.5 mL/kg) caused the typical physiologic responses to hemorrhagic hypovolemia. Infusion of alpha alpha Hb restored mean arterial pressure and coronary perfusion pressure, but cardiac output and mixed venous O2 saturation did not improve significantly. Pulmonary arterial pressure and pulmonary vascular resistance increased markedly and were higher than baseline levels after alpha alpha Hb. Infusion of human serum albumin produced only minor hemodynamic changes. Brain blood flow did improve to baseline values after alpha alpha Hb, but was the only tissue to do so. In the human serum albumin group, superior mesenteric artery blood flow recovered to baseline values, whereas brain blood flow did not. Blood flows to other tissues were similar in both groups. CONCLUSION: Small-volume infusion of alpha alpha Hb restored mean arterial pressure and brain blood flow, but pulmonary hypertension and low peripheral perfusion may offset benefits for trauma patients.

Albumins↗