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Biomedical subjects

I Wagner

Publications and source records attributed to I Wagner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Autocatalytic processing of the ATP-dependent PIM1 protease: crucial function of a pro-region for sorting to mitochondria.

The biogenesis of the ATP-dependent PIM1 protease of mitochondria was studied by mutational analysis. The ATPase and proteolytic activities of PIM1 were shown to be essential for mitochondrial function. A proteolytically inactive mutant form of PIM1 protease accumulated as a pro-form in mitochondria, revealing a two-step processing of PIM1: the matrix targeting signal is removed by the mitochondrial processing peptidase and then a pro-region of 61 amino acids is cleaved off in an autocatalytic reaction. This latter process depended on the ATP-dependent assembly of PIM1 protease subunits and can occur by an intermolecular and, most probably, also an intramolecular pathway. The respiratory competence of cells harboring mutant PIM1 protease lacking the pro-region was strongly impaired. Subcellular fractionation revealed a cytosolic localization of mutant PIM1 protease. This demonstrates the requirement for the propeptide for efficient sorting of PIM1 protease to mitochondria.

ATP-Dependent Proteases↗
PubMed1996

[Treatment by CO2 broncho-laser for acquired tracheobronchial stenosis in children with bronchopulmonary dysplasia].

OBJECTIVE: Evaluation of carbon dioxide (CO2) broncholaser for treating acquired proximal tracheo-bronchial stenosis in children with bronchopulmonary dysplasia. DESIGN: Retrospective study from June 1987 through August 1995, with 39 months follow-up. PATIENTS AND METHODS: During the study, 65 children were treated for bronchopulmonary dysplasia. Eight of those (average age: 42.6 months) had symptomatic tracheo-bronchial stenosis; they were treated with CO2 broncholaser and represented 23.5% of all broncholaser applications. All patients presented multiple lesions. Ten symptomatic well-organized lesions (obstructive bridles or diaphragms), all accessible to broncholaser, were treated. Broncholaser was the primary treatment used, except in one case where it was used following balloon dilatation failure. An adaptable rigid fibroscope combined with a CO2 Sharplan laser was used. All interventions were performed under general anesthesia. RESULTS: Lesions not reaching the trachea's bifurcation (eight cases) disappeared following one laser session with significant clinical improvement. Lesions extending to the trachea's bifurcation (two cases) only showed partial improvement despite three laser sessions. The results remained stable throughout the follow-up period. There were no major complications. CONCLUSIONS: Broncholaser is a safe and efficient method of treating stenoses occurring in patients with bronchopulmonary dysplasias. Obstructive lesions (such as bridles or diaphragms) and those which do not reach the trachea's bifurcation, give the best results.

Bronchi↗
PubMed1996

Sperm chromatin anomalies can influence decondensation after intracytoplasmic sperm injection.

In this study we investigated whether morphology and chromatin anomalies in human spermatozoa can influence fertilization after intracytoplasmic sperm injection (ICSI). We examined unfertilized oocytes, using the fluorochrome Hoechst 33342, to determine whether a relationship exists between failure of fertilization and sperm chromatin quality. Sperm chromatin packaging quality was assessed using the chromomycin A3 (CMA3) fluorochrome, and the presence of DNA damage in spermatozoa, using in-situ nick translation, Normal males present sperm parameters with a normal morphology of > 20%, CMA3 fluorescence of < 30% and exhibit endogenous nicks in < 10% of their spermatozoa. When patients were separated according to these values no difference was observed in their fertilization rates after ICSI. When the unfertilized ICSI oocytes were examined, we found that patients with CMA3 fluorescence of <30% and nicks in < 10% of their spermatozoa had only 17.5 and 21.6% respectively of their unfertilized oocytes containing spermatozoa that remained condensed. In contrast, patients with higher CMA3 and nick values had a significantly higher number, 41.2 and 48.9%, of their unfertilized oocytes containing condensed spermatozoa. sperm morphology did not show any such pattern. The percentage of spermatozoa which had initiated decondensation in unfertilized oocytes was not influenced by morphology, CMA3 fluorescence or nicks. In light of these results we postulate that poor chromatin packaging and/or damaged DNA may contribute to failure of sperm decondensation after ICSI and result in failure of fertilization.

Adult↗
PubMed1996

[Surgery of primary malignant melanomas of the mucosa of the nasal fossa and facial sinuses].

A retrospective analysis of 22 patients with primary malignant melanoma of the nasal fossa and/or paranasal sinuses consecutively managed with surgery at our department from 1975 to 1993 was conducted. Fifteen patients had negative margins of resection. Neoadjuvant chemotherapy and post-operative radiation therapy was associated in 4 and 5 of these 15 patients, respectively. Four patients had positive margins. Adjunctive treatment was chemotherapy and postoperative radiation therapy in 2 and 3 of these 4 patients, respectively. The remaining 3 patients were managed with palliative treatment (debulking surgery and chemotherapy). No patients were lost to follow up. A 3-year follow-up was always achieved. In patients in whom surgical resection achieved negative margins, the 5-year actuarial survival, and local control estimate was 17.9%, and 26.9%, respectively. None of the variables under analysis were statistically related to local recurrence or survival. Death always occurred within 24 months from initial diagnosis in all 7 patients but one in whom surgical resection with negative margins was not achieved or debulking surgery was performed.

Aged↗
PubMed1995

Cardiac troponin I release correlates with myocardial infarction size.

Cardiac troponin I, creatine kinase, and creatine kinase MB activity were tested in serial blood samples from 15 patients with first-time Q wave acute myocardial infarction (2 anterior and 13 inferior wall infarctions). All patients received intravenous thrombolytic therapy. Cardiac troponin I and creatine kinase MB activity were compared with scintigraphic estimates of myocardial scar (single photon emission computed tomography [SPECT] with 99mTechnetium-isonitrile [Tc-sestamibi]) on late images at rest about 5 weeks after myocardial infarction. Scintigraphic defect sizes ranged from 3.2 to 41.2% (median: 27.3%) of left ventricle. Cardiac troponin I increased and peaked in parallel with creatine kinase MB activity, and the peak values correlated with each other (r = 0.76, p = 0.002). Troponin I stayed increased for several days longer than creatine kinase and creatine kinase MB activity. It could be detected at least until the 4th day after admission. Significant correlation coefficients were found between 99mTc-isonitrile defect sizes and areas under cardiac troponin I curves (r = 0.53, p = 0.042) and between 99mTc-isonitrile defect sizes and cumulative creatine kinase MB activity release (r = 0.64, p = 0.01). Animal studies have already shown a very close correlation between histologic infarct size and SPECT 99mTc-isonitrile defect size. Therefore, our results indicate that cardiac troponin I release in patients with acute myocardial infarction is also correlated with infarct size.

Aged↗
PubMed1994

Molecular chaperones cooperate with PIM1 protease in the degradation of misfolded proteins in mitochondria.

ATP dependent proteolytic degradation of misfolded proteins in the mitochondrial matrix is mediated by the PIM1 protease and depends on the molecular chaperone proteins mt-hsp70 and Mdj1p. Chaperone function is essential to maintain misfolded proteins in a soluble state, a prerequisite for their degradation by PIM1 protease. In the absence of functional mt-hsp70 or Mdj1p misfolded proteins either remain associated with mt-hsp70 or form aggregates and thereby are no longer substrates for PIM1 protease. Mdj1p is shown to regulate the ATP dependent association of an unfolded polypeptide chain with mt-hsp70 affecting binding to as well as release from mt-hsp70. These findings establish a central role of molecular chaperone proteins in the degradation of misfolded proteins by PIM1 protease and thereby demonstrate a functional interrelation between components of the folding machinery and the proteolytic system within mitochondria.

ATP-Dependent Proteases↗
PubMed1994

Different time courses of cardiac contractile proteins after acute myocardial infarction.

For the first time we have compared time courses of cardiac myosin light chain-1 (MLC-1), beta-type myosin heavy chain (MHC), troponin T (TnT), myoglobin, creatine kinase (CK) and CKMB in the same patients with acute myocardial infarction (AMI). Blood samples were serially collected in 23 patients with first-time AMI. All but 3 patients received intravenous thrombolytic treatment. TnT and MLC-1 time courses were biphasic in most patients and showed two distinct peaks in 13 and 8 patients, respectively. MHC time courses were usually monophasic. Only 1 patient showed a biphasic MHC time course with two distinct peak values. Although MHC and MLC were lower by about the fourth day after onset of AMI in early reperfused patients, reperfusion did not qualitatively alter MLC and MHC release (no significant influence on the first appearance in blood or on time to peak). MLC and MHC peaks correlated closely (r = 0.75, P = 0.0001), whereas TnT peaks were correlated less closely with MLC or MHC peaks (r = 0.58 each, P < 0.007). Peak values of all cardiac contractile proteins correlated closely and significantly with CKMB peaks (0.75 < or = r < or = 0.81, P < or = 0.0006). Myoglobin was the first marker to increase in blood after AMI and showed the earliest peaks, whereas MHC increased latest showing the latest peaks. TnT increased significantly (P = 0.0001) earlier than MLC and MHC. These results can be explained by the impact of the intracellular compartmentation of a cardiac protein on the rapidity with which it is released after AMI.

Adult↗
PubMed1994

Concentration time courses of troponin and myosin subunits after acute myocardial infarction.

BACKGROUND: As a result of the limited sensitivity and specificity of creatine kinase and lactate dehydrogenase (LDH) as well as their isoenzymes, there is increasing interest in the use of cardiac contractile proteins for the diagnosis of acute myocardial infarction (AMI) and myocardial damage. METHODS: This study compared the release of creatine kinase, creatine kinase MB, myoglobin, cardiac troponin I (cTnI), cardiac troponin T (cTnT), cardiac myosin light chain-1 (cMLC-1), and beta-type myosin heavy chains (bMHC) in serial blood samples from 13 patients (10 men, three women; median age 54 years, range 40-74 years) with first-time AMI (11 Q-wave, two non-Q-wave AMI; three anterior and 10 inferior wall AMI). All but one patient received intravenous thrombolytic treatment. RESULTS: Myoglobin was the first marker to increase in blood after AMI and showed the earliest peak levels, whereas bMHC increased latest, showing the latest peak levels. cTnI and cTnT increased significantly earlier than cMLC-1 and bMHC. cTnI and cTnT increased and reached peak levels parallel to each other, but the latter tended to stay increased longer. cTnT time courses were biphasic in the majority of AMI patients, unlike cTnI time courses. cMLC-1 release was mostly biphasic. cMLC-1 allows diagnosis during the acute phase as well as several days after the onset of AMI. The time courses of bMHC were usually monophasic. Its delayed appearance makes it useful for the diagnosis of remote infarction. In contrast to cTnI and cTnT, cMLC-1 and bMHC time courses were not significantly influenced by early reperfusion. CONCLUSION: Our results demonstrate the impact of the intracellular compartmentation of an intramyocardial protein (cytosolic, structurally bound, or structurally bound with soluble pool) on its concentration time course after AMI, particularly on the rapidity of its release.

Adult↗
PubMed1994

[Loudness scaling. A procedure for quantitative recruitment detection].

Direct loudness scaling has been known as an audiological tool for about four decades. Although numerous publications have shown its clinical importance, loudness scaling has not been used in audiology and hearing aid fitting until now. This might be due to the lack of audiometers equipped with loudness scaling devices as well as missing evidence for its clinical applicability. In this study normal data for a single-step direct scaling procedure were established and loudness determinations of 105 patients with sensorineural hearing losses collected. The results show that normal level loudness functions exhibit very similar shapes for narrow band stimulation in the frequency range of 500 to 4000 Hz. However, loudness scaling is affected by the gender of the subjects: females scale systematically louder than do males. In hearing-impaired subjects the slopes of the level loudness functions tend to decrease with increasing hearing loss, indicating negative recruitment. This holds particularly true in the high-frequency range, e.g. at 4000 Hz. Our long-term experience with single-step direct loudness scaling has proven its clinical feasibility in typical patients of an audiology unit. Loudness scaling will prove useful for the localization of hearing impairments, as it can be employed as a quantitative indicator of recruitment without any restrictive preconditions. In addition, it allows the evaluation of hearing aids and cochlear implants by frequency-specific gain measurement.

Audiometry, Pure-Tone↗
PubMed1993

IVF treatment of moderate male factor infertility: a comparison of mini-Percoll, partial zona dissection and sub-zonal sperm insertion techniques.

In this study we examined various techniques of in-vitro fertilization (IVF) for treating couples in whom the male had subnormal semen parameters. We compared two sperm preparation methods (mini-Percoll and conventional swim-up) for efficiency of recovery after preparation and for fertilization rates after IVF, and compared the suitability of partial zona dissection (PZD) and sub-zonal sperm insertion (SUZI) to patients with different types of male factor infertility. The mini-Percoll technique allowed the recovery of significantly more motile spermatozoa from the same semen sample compared to the swim-up method. More oocytes were fertilized after spermatozoa were prepared by the mini-Percoll technique. An increased number of spermatozoa recovered from an ejaculate led to an improvement in the quality of spermatozoa in the insemination droplet. Subsequently, when using the PZD technique, the fertilization rate increased when there was a higher number of spermatozoa in the patient's ejaculate. When comparing the two micromanipulation techniques, SUZI provided patients with oligoasthenzoospermia (i.e. < 10 x 10(6) spermatozoa/ml and 40% motility) with a higher chance of obtaining 2-pronculeate eggs.

Colloids↗
PubMed1993

Cardiac troponin T release in acute myocardial infarction is associated with scintigraphic estimates of myocardial scar.

BACKGROUND: This study compared clinical-chemical estimates of infarct size with scintigraphic estimates of myocardial scar in patients with first-time acute myocardial infarction (AMI). METHODS: Levels of the cardiac isoform of the contractile protein troponin T (TnT), of creatine kinase (CK), and of the isoenzyme MB of CK (CK MB) were tested in serially drawn blood samples from 21 patients (two females and 19 males; median age, 55 years). Of these 21 patients, five had anterior- and 16 had inferior-wall AMI; all patients received intravenous thrombolytic therapy. Single-photon emission computed tomography (SPECT) with technetium-99m-isonitrile (Tc-sestamibi) was performed at rest after the onset of AMI (median time, 5 weeks). Scintigraphic defects were calculated using "bull's-eye" polar coordinate maps. All patients had an uncomplicated course between discharge and myocardial scintigraphy. RESULTS: Scintigraphic defect sizes ranged from 3.2% to 47.8% of the left ventricle (median, 27.3%). Cardiac TnT and CK MB release correlated closely with each other and with scintigraphic estimates of myocardial scar. Significant correlates were found between cardiac TnT and CK MB peak values (r = 0.87, P = 0.0001), CK MB peaks and Tc-sestamibi defect sizes (r = 0.73, P = 0.0014), and TnT peaks and scintigraphic defect sizes (r = 0.73, P = 0.0011). CONCLUSIONS: Because animal studies have already shown a very close correlation between histologic infarct size and SPECT Tc-sestamibi defect size, our results indicate that cardiac TnT is a useful marker to assess infarct size noninvasively in man.

Adult↗
PubMed1992

Pleural liposarcoma presenting with respiratory distress and suspected diaphragmatic hernia.

A young woman with a history of diaphragmatic hernia presented to the hospital in respiratory distress and in premature labor. Her admission chest roentgenogram showed opacification of the left hemithorax, and her arterial blood gas analysis revealed hypoxemia. Emergency cesarean section and exploratory left thoracotomy were carried out; a large tumor occupied the left side of the chest, and pneumonectomy was performed. No diaphragmatic hernia was present. A pathologic diagnosis of primary liposarcoma was made.

Adult↗
PubMed1992

Early diagnosis of acute myocardial infarction by a newly developed rapid immunoturbidimetric assay for myoglobin.

OBJECTIVE: To evaluate a rapid immunoturbidimetric assay for myoglobin and to investigate its clinical usefulness in the early detection of acute myocardial infarction. DESIGN: Prospective study. Immunoturbidimetrically determined myoglobin concentrations were compared with radioimmunoassay results obtained with the same blood samples. The diagnostic performance of myoglobin determination was compared with creatine kinase and creatine kinase MB activity (current standard of routine diagnosis). SETTINGS: Part 1: coronary care unit. Part 2: emergency room in a university hospital. PATIENTS: Part 1:30 patients with acute myocardial infarction admitted not later than four hours (median two hours) after the onset of symptoms. Part 2: 126 patients admitted to the emergency room with chest pain not caused by trauma (51 cases of acute myocardial infarction, 51 cases of angina pectoris, and 24 cases of chest pain not related to coronary artery disease). INTERVENTIONS: Part 1: routine treatment including intravenous thrombolytic treatment (28 patients). Part 2: routine emergency treatment without thrombolytic treatment. MAIN OUTCOME MEASURES: The analytical quality of the immunoturbidimetric myoglobin assay and a comparison between the myoglobin assay and creatine kinase and creatine kinase MB for diagnostic sensitivity and performance. RESULTS: The immunoturbidimetric myoglobin assay was fast and convenient and gave myoglobin determinations of high analytical quality. The concentration of myoglobin increased, peaked, and returned to the reference range significantly earlier than creatine kinase (p < or = 0.0001) and creatine kinase MB (p < or = 0.0002). Before thrombolytic therapy was started the diagnostic sensitivity of myoglobin was significantly higher than that of creatine kinase MB activity 0-6 h after the onset of chest pain and significantly higher (0.82 v 0.29) than creatine kinase 2-4 h after the onset of chest pain. In almost all patients (92%) plasma myoglobin concentrations were increased 4-6 h after the onset of chest pain. CONCLUSION: Myoglobin was more sensitive in detecting early myocardial infarction than creatine kinase and creatine kinase MB activity. Immunoturbidimetric myoglobin measurements could be useful in the early evaluation of patients with suspected myocardial infarction because this assay takes less than two minutes.

Clinical Enzyme Tests↗
PubMed1991

Early detection of acute myocardial infarction by measurement of mass concentration of creatine kinase-MB.

The diagnostic sensitivity and performance of immunoenzymometric measurements of creatine kinase (CK)-MB mass concentrations in the early diagnosis of acute myocardial infarction (AMI) were examined and compared with the sensitivities and performances of CK and CK-MB activity, in the context of simultaneous measurements of CK, CK-MB activity, and CK-MB mass concentrations in serially drawn blood samples obtained immediately from 36 patients with AMI and 126 patients with chest pain on admission to the emergency room of the department of internal medicine. In the 36 patients with AMI, who were all admitted no later than 4 hours after the onset of chest pain, pathologic increase occurred significantly earlier in CK-MB mass than in both CK and CK-MB activity, with a median difference of 1 hour each. In patients coming to the emergency room (51 with AMI, 51 with angina pectoris and 24 with chest pain not related to coronary artery disease), CK-MB mass was the best diagnostic measurement for AMI of all markers tested (significantly higher efficiency, Youden index and likelihood ratio than both CK and CK-MB activity). Before initiating thrombolytic therapy, the sensitivity of CK-MB mass is significantly higher than CK-MB activity during the 0- to 6-hour period and significantly higher than CK activity during the 2- to 4-hour period after the onset of chest pain. Consequently, it is often possible to diagnose an AMI on the basis of increased CK-MB mass concentrations even at a time when CK and CK-MB activities are still within the reference interval.

Adult↗