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Biomedical subjects

J Neumann

Publications and source records attributed to J Neumann.

At least 379 records · Page 21Linked to original sources
PubMedDate not supplied

Protein phosphorylation in isolated trabeculae from nonfailing and failing human hearts.

Disturbances in the cAMP production during beta-adrenergic stimulation and alterations of Ca2+ transport controlling proteins and their regulation in the sarcoplasmic reticulum might be involved in the pathogenesis of the failing human heart. Thus, we investigated the cAMP-mediated phosphorylation of phospholamban, troponin I and C-protein in electrically driven, intact isolated trabeculae carneae from nonfailing and failing (NYHA IV) human hearts in parallel to contractile properties on the same tissue samples. The increase in force of contraction induced by isoproterenol (0.2 microM) or pimobendan (100 microM), a phosphodiesterase inhibitor, was diminished in the failing human hearts compared to nonfailing hearts by 49% and 36%, respectively. Concomitantly the isoproterenol-induced phosphorylation (pmol P/mg homogenate protein) of phospholamban, troponin I and C-protein was reduced from 13.0 +/- 2.4 (n = 4), 30.5 +/- 1.5 (n = 5) and 11.0 +/- 1.3 (n = 5) in the nonfailing heart to 5.2 +/- 0.6 (n = 13), 14.6 +/- 2.2 (n = 16) and 7.1 +/- 1.0 (n = 6) in the failing human heart, respectively. Pimobendan changed the phosphorylation state of these proteins similar to isoproterenol. The fact that combined addition of both agents or dibuturyl cAMP (1 mM) alone restored the phosphorylation capacity as observed in the control groups indicates that i) a reduced cAMP generation is related to the reduced phosphorylation of regulatory phosphoproteins located in the sarcoplasmic reticulum and contractile apparatus e.g. phospholamban, troponin I and C-protein, that ii) there is a relationship between protein phosphorylation state and contractile activity and that iii) no changes in the respective content of phosphoproteins are involved in the limitation of cAMP-mediated inotopic activity in the failing human heart.

Adolescent↗
PubMedDate not supplied

Clinical relevance of low levels of preformed alloantibodies detected by flow cytometry in the first year post-kidney transplantation.

OBJECTIVE: To determine the prevalence of transplants performed with a false-negative cytotoxicity cross-match and to analyze the clinical relevance of alloantibodies (Ab) detected only by flow cytometry (flow). METHODS: We studied 66 patients undergoing kidney transplantation from a cadaveric donor. All patients had a simultaneous negative T+AHG+DTT and B+DTT. Pretransplant sera were retrospectively analyzed by flow cytometry according to an Emory University protocol: (1) T+ and B-: Ab anti-class I; (2) T- and B+: anti-class II; (3) T+B+: anti-class I + II. Chi-square, Fisher exact, Student t test, and Kaplan Meier analyses were employed with significance assigned at P < or = .05. RESULTS: The overall incidence of false-negative cytotoxicity was 33.3% (22/66), namely, 6.1% (n = 4) anti-class I; 9.1% (n = 6) anti-class II; and 18.2% (n = 12) anti-class I + II. Primary nonfunctioning grafts occurred in 6.8% (3/44) and 13.6% (3/22) negative and positive flow patients (two anti-class I + II and one class II; P = .39). The incidence of graft loss in the first year was respectively, 13.6% (6/44) and 18.2% (4/22; two anti-class II and two anti-class I + II; P = .72). Compared to flow-negative grafts, creatinine levels were significantly higher among flow-positive patients at 8 and 12 weeks. One-year graft survivals were 86.4% among negative versus 81.8% for the positive group (P = .67). CONCLUSIONS: We observed that 33% of kidney transplant recipients had low levels of alloantibodies detected only by flow. This single factor was associated with the worst graft function in the first trimester with a suggestion of a higher risk for non-functioning graft.

Cadaver↗
PubMedDate not supplied

Immunoglobulin G-positive in B-cell cross-match decreases kidney allograft survival.

We retrospectively studied all 1149 transplants performed at our center between 1993 and 2003 to determine the incidence and clinical effect of pretransplant B-positive cross-match on kidney graft survival. The patients were divided in two groups: B-negative (n = 1102) and B-positive in current sera (n = 47; 4.1%). AB-positive test was more frequent among regrafted patients (14% vs 3%; P = .00). Demographic data were not different between the groups. The overall rate of graft loss was similar (26% vs 24%, respectively; P = .86). However, early nonsurgical graft losses were more frequent among B-positive patients (46% vs 20%, respectively; P = .04). IgM was the most frequent immunoglobulin in the B-positive group (76% IgM and 24% IgG). There was no significant difference between B-negative and B-positive groups in the 1-, 5-, and 10-year graft survival rates (87% vs 83%, 73% vs 78%, 64% vs 66%, respectively; P = .87). The graft survival was significantly reduced comparing an IgG anti-B cell to the B-negative group (P = .03) as well as IgG compared to IgM (P = .004). In conclusion, only B-positive cross-match due to IgG decreased graft survival. Even though it is an uncommon situation (0.9%), this study stressed the clinical value of the B-cell cross-match as a tool to identify patients with a higher immunological risk.

B-Lymphocytes↗
PubMedDate not supplied

Antigenemia for cytomegalovirus in renal transplantation: choosing a cutoff for the diagnosis criteria in cytomegalovirus disease.

Cytomegalovirus (CMV) infection is a frequent complication in transplant recipients, causing a high level of morbidity and mortality. We studied 203 consecutive renal transplant recipients performed between January 2000 and December 2001. Patients underwent weekly measurements of CMV pp65 antigen to assess CMV activity from the 4th to the 12th week posttransplantation. The results were reported as number of cells positive for the pp65 antigen among 10(5) granulocytes. In order to define a best cutoff to diagnose CMV disease with desirable sensitivity and specificity, we used a receiver operator characteristics (ROC) curve. The cutoff of four positive cells corresponded to a sensitivity of 93% and specificity of 60% (AUC = 0.87) for the diagnosis of CMV disease. The chosen cutoff for starting antiviral treatment was 10 cells, since this was associated with a sensitivity of 92% and specificity of 70% (AUC = 0.90). In conclusion, the highly sensitive cutoff points for the diagnosis of antigenemia was four cells and 10 cells for initiation of antiviral therapy.

Antigens, Viral↗
PubMedDate not supplied

Detection of the acoustic reflex below 80 dB HL.

A new method for detecting the acoustic reflex that utilizes standard otoacoustic emissions recording techniques is introduced and discussed. Two successive identical tone bursts of 100 ms duration and 10 ms interstimulus interval are presented in the occluded ear canal at a repetition rate of one per second. If the acoustic reflex is elicited, the contraction of the stapedius muscle is delayed with respect to the onset of the first stimulus. Hence, the acoustic compliance in the ear canal decreases primarily during the second stimulus. The difference of the microphone signals produced by the two stimuli is computed and averaged across a certain number of repetitions of the sequence. The presentation level is increased until this difference is larger than -40 dB (with respect to the stimulus level) and if its signal-to-noise ratio exceeds 20 dB. For normal-hearing subjects, the acoustic reflex threshold measured with this method is on average 8 dB lower than in a standard clinical setup. In 5 out of the 10 tested hearing-impaired subjects, the new method could detect an acoustic reflex at one or more frequencies where no reflex was detected in the clinical setup.

Adult↗
PubMedDate not supplied

Comparative study of adenoviruses with monoclonal antibodies.

The obtainment of monoclonal antibodies for adenovirus species 4(Ad4) is described. The specificities of selected monoclonal antibodies were determined by means of viral neutralization test in cell culture, immunofluorescence and Enzyme-Linked Immunosorbent Assay (ELISA), in the presence of the following species of human adenovirus: 1, 2, 5 (subgenus C), 4 (subgenus E), 7 and 16 (subgenus B) and 9 (subgenus D). Two monoclonal antibodies species specific to adenovirus 4 (1CIII and 3DIII) and one monoclonal antibody that cross reacted with adenovirus species 4 and 7 (2HIII) were obtained.

Adenoviruses, Human↗