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Biomedical subjects

T Maurer

Publications and source records attributed to T Maurer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Solution structure of leukemia inhibitory factor.

The solution structure of a murine-human chimera of leukemia inhibitory factor (LIF), a 180-residue cytokine with a molecular mass of 20 kDa, has been determined using multidimensional heteronuclear NMR techniques. The protein contains four alpha-helices, the relative orientations of which are well defined on the basis of long-range interhelical nuclear Overhauser effects. The helices are arranged in an up-up-down-down orientation, as found in other four-helix bundle cytokines, and the overall topology of the chimera is similar to that of the crystal structure of murine LIF (Robinson, R. C., Grey, L. M., Staunton, D., Vankelecom, H. Vernallis, A. B., Moreau, J. F., Stuart, D. I., Heath, J. K., and Jones, E. Y. (1994) Cell 77, 1101-1116). Differences between the structures are evident in the N-terminal region, where the peptide bond preceding Pro17 has a trans-conformation in solution but a cis-conformation in the crystal, and in the small antiparallel beta-sheet encompassing residues in the N terminus and the CD loop in the crystal structure, which is not apparent in solution. There are also minor differences in the extent of the helices. Other than at the N terminus, the main difference between the two structures occurs at the C-terminal end of the CD loop. As this loop is close to a receptor-binding site on LIF that makes a major contribution to high affinity binding to the LIF receptor alpha-chain, these differences between the solution and crystal structures should be taken into account in structural models of LIF receptor interactions.

Amino Acid Sequence↗
PubMed1998

Structural studies of histidine-containing phosphocarrier protein from Enterococcus faecalis.

Based on the complete sequential assignment of the 1H-NMR spectrum by multidimensional NMR techniques the secondary structure and the local geometry of the active site of histidine-containing phosphocarrier protein (HPr) from Enterococcus faecalis were elucidated. We present a comparative analysis of the active site in the seven known structures of HPr from different organisms determined by NMR or X-ray crystallography. In catalysis, HPr is phosphorylated at the ring N61 of His15. No general agreement exists in literature regarding the structure of the active-centre loop. In the crystal structure of HPr from E. faecalis, a torsion strain of the backbone at position 16 was observed, which was assumed to be important to the catalytic mechanism. Coupling constants were determined in order to calculate phi angles to establish whether there are strained torsion angles in HPr from E. faecalis in the solution state. The evaluation of data obtained indicate a stable and well-defined structure of HPr from E. faecalis, with an overall fold similar to that found in HPr from other bacteria. We find that in the active-site region there are relatively large variations in local geometry between the evaluated structures. In HPr from E. faecalis, a particularly detailed view of the phosphate-binding His15 and residues in close spatial proximity was obtained by determination of coupling constants obtained from the double-quantum-filtered COSY spectrum. Our data indicate that in aqueous solution, in the dominant conformational state there is no torsion strain of the backbone at position 16, as observed in the crystal state. The maximum population of a strained conformation in solution can be estimated to be smaller than 23%. The analysis of the data suggests that the active-centre loop is able to adopt different conformations in solution. A similar observation was made for HPr from E. faecalis phosphorylated at its regulatory site (Ser46). 31P-NMR shows that phosphorylated HPr exists in two conformational substates with nearly equal populations.

Bacterial Proteins↗
PubMed1998

Right-sided pulmonary aplasia: longitudinal lung function studies in two cases and comparison to results from term healthy neonates.

Agenesis of the right lung was diagnosed prenatally in two neonates born at 36 and 37 weeks, respectively. Computed tomographic scans and magnetic resonance imaging indicated that both cases had a Type 2 pulmonary agenesis, which was confirmed later by bronchoscopy. Both patients were clinically stable during the neonatal period. Serial pulmonary function tests revealed a decrease in specific respiratory system compliance (sCrs) in both neonates and a marked discrepancy between functional residual capacity measured by the nitrogen washout technique (FRCN2) and by plethysmography (FRCpleth) on follow-up. Early decrease of respiratory system compliance (Crs) and increase of respiratory system resistance (Rrs) in one infant preceded the onset of tracheal stenosis, which remained asymptomatic until the age of 8 weeks, when the infant developed acute respiratory failure requiring intubation and mechanical ventilation with high airway pressures. Aortopexy, implantation of a tissue expander into the right hemithorax, and laser ablation of fibrotic tissue at the site of tracheal stenosis were performed to achieve successful extubation. The second infant remained asymptomatic. Values for lung mechanics and volumes for both infants with pulmonary aplasia were as follows: Crs, 3.43 and 10.60 mL x kP(-1) x kg(-1); sCrs, 0.23 and 1.28 kpa(-1); Rrs, 11.1 and 7.4 kpa x s x L(-1); FRCN2, 14.9 and 10.2 mL x kg(-1); FRCpleth, 28.2 and 25.8 mL x kg(-1); FRCN2: FRCpleth ratio, 0.56 and 0.54 for patients 1 and 2, respectively. These values differed considerably from results of a control group of nine term healthy neonates (Crs, 10.0+/-1.8 mL x kPa(-1) x kg(-1); sCrs, 0.43+/-0.08 kpa(-1); Rrs, 5.10+/-0.55 kpa x s x L(-1); FRCN2, 24.0+/-2.5 mL x kg(-1); FRCpleth, 31.1+/-6.0 mL x kg(-1); FRCN2:FRCpleth ratio, 0.78+/-0.10). In conclusion, serial assessment of lung mechanics and pulmonary gas volumes detects airway obstruction early in neonates with unilateral lung agenesis. Bronchoscopy is recommended. Along with conventional surgical procedures, an expandable implant may improve management or prevent respiratory failure in selected cases.

Bronchoscopy↗
PubMed1998

Assessment of functional residual capacity using nitrogen washout and plethysmographic techniques in infants with and without bronchopulmonary dysplasia.

OBJECTIVE: In normal infants, functional residual capacity using plethysmography (FRCpleth) exceeds FRC(N2) (using nitrogen washout) and the within-subject difference FRC(pleth-N2) indicates the part of pulmonary gas volume not ventilated during tidal breathing. We postulated that infants with bronchopulmonary dysplasia (BPD) have an elevated FRC(pleth-N2). DESIGN: In a prospective study, FRC(pleth-N2) in healthy newborns (controls n = 17) was compared to that in neonates recovering from the respiratory distress syndrome without BPD (noBPD, studied at discharge, n = 13) and with BPD (BPD1 n = 14, studied at 36 post-conceptional weeks; BPD2 n = 16, at discharge). MEASUREMENTS AND RESULTS: Paired measurements, FRCpleth and FRC(N2), were performed using a plethysmograph (Jaeger, Germany) and an open-circuit nitrogen washout technique (SensorMedics 2600, USA). In comparison to the controls (5.2 ml/kg), FRC(pleth-N2)/kg in noBPD (12.7 ml/kg, p < 0.001), in BPD1 (24.9 ml/kg, p < 0.001) and in BPD2 (13.5 ml/kg, p < 0.001) was significantly higher. Compared with that of the controls FRCpleth was significantly increased in BPD1 (p < 0.001) and FRC(N2) was decreased in noBPD and both BPD groups. CONCLUSION: The FRC(pleth-N2) is a reliable indicator for pulmonary inhomogeneities in infants with respiratory diseases.

Breath Tests↗
PubMed1998

Relationship of coaching with performance in situational employment interviews.

This field study addressed the question of whether voluntary participation in interview coaching is related to performance in situational interviews. Promotional procedures in 4 different police and fire department jobs were involved, allowing replication in separate samples. In 3 of 4 jobs, when controlling for indicators of candidates' precoaching job knowledge and motivation to do well on the promotional procedures, attendance at a coaching session was significantly related to interview performance. Following a discussion of study limitations, an agenda for future research is discussed, including a proposed general model of coaching process and outcome variables.

Adult↗
PubMed1998

Improving primary care residents' proficiency in the diagnosis of skin cancer.

OBJECTIVE: To determine whether a brief, multicomponent intervention could improve the skin cancer diagnosis and evaluation planning performance of primary care residents to a level equivalent to that of dermatologists. PARTICIPANTS: Fifty-two primary care residents (26 in the control group and 26 in the intervention group) and 13 dermatologists completed a pretest and posttest. DESIGN: A randomized, controlled trial with pretest and posttest measurements of residents' ability to diagnose and make evaluation plans for lesions indicative of skin cancer. INTERVENTION: The intervention included face-to-face feedback sessions focusing on residents' performance deficiencies; an interactive seminar including slide presentations, case examples, and live demonstrations; and the Melanoma Prevention Kit including a booklet, magnifying tool, measuring tool, and skin color guide. MEASUREMENTS AND MAIN RESULTS: We compared the abilities of a control and an intervention group of primary care residents, and a group of dermatologists to diagnose and make evaluation plans for six categories of skin lesions including three types of skin cancer-malignant melanoma, squamous cell carcinoma, and basal cell carcinoma. At posttest, both the intervention and control group demonstrated improved performance, with the intervention group revealing significantly larger gains. The intervention group showed greater improvement than the control group across all six diagnostic categories (a gain of 13 percentage points vs 5, p < .05), and in evaluation planning for malignant melanoma (a gain of 46 percentage points vs 36, p < .05) and squamous cell carcinoma (a gain of 42 percentage points vs 21, p < .01). The intervention group performed as well as the dermatologists on five of the six skin cancer diagnosis and evaluation planning scores with the exception of the diagnosis of basal cell carcinoma. CONCLUSIONS: Primary care residents can diagnose and make evaluation plans for cancerous skin lesions, including malignant melanoma, at a level equivalent to that of dermatologists if they receive relevant, targeted education.

Clinical Competence↗
PubMed1998

Association of cutaneous and oral diseases in HIV-infected men.

OBJECTIVES: Mucocutaneous diseases are common in patients infected with human immunodeficiency virus (HIV). To identify cutaneous diseases for which HIV-infected people are at high risk, we sought those that are strongly associated with specific HIV-related oral lesions and with progression of HIV disease. DESIGN: A cross-sectional study of HIV-positive outpatients referred to a university stomatology clinic for diagnosis and treatment of oral diseases. Each subject underwent both complete oral and cutaneous examinations. RESULTS: Among 55 men, with a median age of 41 years and a median CD4 cell count of 125/microliter (range 0-950/microliter), 93% had active oral diseases or conditions, including candidiasis, hairy leukoplakia, ulcers, Kaposi's sarcoma (KS), and xerostomia, and 95% had skin conditions, including onychomycosis, dermatophytosis, seborrheic dermatitis, KS, folliculitis, xerosis, and molluscum contagiosum. Seborrheic dermatitis, xerosis, skin KS, and molluscum contagiosum were associated with oral HIV-sentinel lesions (oral candidiasis, hairy leukoplakia, and KS), with low CD4 cell counts, and with AIDS. CONCLUSION: Our results suggest that xerosis and seborrheic dermatitis may be early harbingers of HIV disease progression. Their roles as predictors warrant further study, based on their associations with low CD4 cell counts and AIDS and strong co-prevalence with one of the most common HIV-related oral lesions, oral candidiasis.

AIDS-Related Opportunistic Infections↗
PubMed1998

Ectopic hematopoietic bone marrow in the appendicular skeleton after trauma.

METHODS: Combined bone scanning and immunoscintigraphy (IS) with 99mTc-monoclonal antigranulocyte antibodies were performed in two patients with suspected reactivation of chronic osteomyelitis of the lower extremity. Because bone scanning and IS were strongly positive, both patients underwent surgical intervention. RESULTS: Macroscopic findings did not show purulent infection and microbiologic results remained negative, but histology revealed unexpected ectopic bone marrow, explaining the strong uptake on IS. One patient exhibited active hematopoietic bone marrow at the former fracture site of the tibial bone. The second patient presented with interspersed bone marrow in the cortical bone of the femoral diaphysis after several intramedullary surgical procedures. CONCLUSION: Unexpected ectopic hematopoietic marrow may occur in the appendicular skeleton after trauma and repeated surgical interventions. The bone marrow shows a physiologic uptake with IS and may be misinterpreted as granulocyte accumulation due to infection. This may lead to false-positive diagnosis in cases of suspected osteomyelitis.

Adult↗
PubMed1997

Chronic complicated osteomyelitis of the appendicular skeleton: diagnosis with technetium-99m labelled monoclonal antigranulocyte antibody-immunoscintigraphy.

Chronic post-traumatic osteomyelitis (OM) represents a particular challenge for nuclear medicine and radiology since clinical and biochemical parameters are frequently unreliable. The aim of this study was to investigate the value of combined bone scan (BS) and immunoscintigraphy (IS) with technetium-99m labelled monoclonal antigranulocyte antibody (MAB) in patients with suspected chronic OM of the appendicular skeleton. Twenty-four patients (17 females and 7 males) with suspected chronic post-traumatic OM were evaluated with three-phase BS/99mTc-MAB-IS. The final diagnosis was established by means of bone culture and histology in 19 cases and clinical follow-up in five cases. The studies were reviewed by two independent and experienced observers; the interobserver agreement was calculated by kappa statistics. The sensitivity, specificity and accuracy of BS alone were 92%, 18% and 58%, respectively. Combined BS/99mTc-MAB-IS had a sensitivity, specificity and accuracy of 84%, 72% and 79%, respectively. Of 24 studies, 11 were true-positive, two false-negative, eight true-negative and three false-positive. Two patients presented with unexpected ectopic haematopoietic bone marrow in the appendicular skeleton that caused false-positive results. A high degree of interobserver agreement was found (kappa=0. 85). It is concluded that combined BS/99mTc-MAB-IS represents a very sensitive and reproducible method with an acceptable specificity for the investigation of chronic OM. Problems may occur in the differentiation of low-grade OM from aseptic inflammation. Another problem is ectopic marrow that may occur in the appendicular skeleton due to a chronic inflammatory stimulus. A former intramedullary intervention in the femur with displacement of haematopoietic marrow may also lead to an ectopic location.

Bone and Bones↗
PubMed1997

Resonance assignments, secondary structure and topology of leukaemia inhibitory factor in solution.

The chemical shift assignments and secondary structure of a murine-human chimera, MH35, of leukaemia inhibitory factor (LIF), a 180-residue protein of molecular mass 20 kDa, have been determined from multidimensional heteronuclear NMR spectra acquired on a uniformly 13C, 15N-labelled sample. Secondary structure elements were defined on the basis of chemical shifts, NH-C alpha H coupling constants; medium-range NOEs and the location of slowly exchanging amide protons. The protein contains four alpha-helices, the relative orientations of which were determined on the basis of long-range, interhelical NOEs. The four helices are arranged in an up-up-down-down orientation, as found in other four-helical bundle cytokines. The overall topology of MH35-LIF is similar to that of the X-ray crystallographic structure for murine LIF [Robinson et al. (1994) Cell, 77, 1101-1116]. Differences between the X-ray structure and the solution structure are evident in the N-terminal tail, where the solution structure has a trans-Pro17 compared with the cis-Pro17 found in the crystal structure and the small antiparallel beta-sheet encompassing residues in the N-terminus and CD loop in the crystal structure is less stable.

Amino Acid Sequence↗
PubMed1996

Primary care physicians as gatekeepers in managed care. Primary care physicians' and dermatologists' skills at secondary prevention of skin cancer.

BACKGROUND AND DESIGN: This study determines (1) the readiness of primary care physicians (PCPs) to triage optimally lesions suspicious for skin cancer, (2) the difference in their abilities from those of dermatologists, and (3) whether accurate diagnosis after viewing slide images transfers to accurate diagnosis after viewing lesions on patients. Seventy-one primary care residents and 15 dermatologists and resident dermatologists diagnosed and selected a treatment/diagnostic plan for skin lesions suspicious for cancer. The lesions were shown on slides, computer images, and patients. Participants' performance was compared with biopsy results of all lesions. RESULTS: Dermatologists' scores were almost double those of primary care residents, and primary care residents' performance was positively associated with previous experience in dermatology. Primary care residents failed 50% of the time to diagnose correctly nonmelanoma skin cancer and malignant melanomas, and 33% of the time they failed to recommend biopsies for cancerous lesions. Primary care residents failed to diagnose malignant melanomas 40% of the time; dermatologists failed to do so 26% of the time. Both groups performed better using slide images compared with patients. CONCLUSIONS: Primary care residents may not be ready to assume a gatekeeper role for lesions suspicious for skin cancer. Because of the seriousness of missed diagnoses, especially of malignant melanomas, we need to improve the triage skills of PCPs. Future studies should evaluate whether primary care training allows sufficient time for PCPs to learn the necessary skills. Until we can show that PCPs are prepared to triage optimally, managed care plans should reduce the threshold for referrals to dermatologists of potential skin cancers.

Adult↗
PubMed1995

Eosinophilic folliculitis. The histologic spectrum.

We sought to define the light microscopic features of eosinophilic folliculitis as it occurs in human immunodeficiency virus (HIV)-infected individuals. The histologic findings of 52 biopsies from 50 patients were graded and compared with six biopsies of suppurative folliculitis from HIV-infected individuals. In all patients, clinical examination showed an eruption of pruritic follicular papules, and the folliculocentric nature of the disorder was confirmed histologically. Perifollicular infiltrates of lymphocytes and eosinophils were identified in all study biopsies, and there was also spongiosis of follicular epithelium. The inflammatory reaction was focused at the level of the follicular isthmus and the sebaceous duct. In all biopsies, lymphocytes and/or eosinophils were present within spongiotic follicular epithelium, but intrafollicular neutrophils were rare. Sebaceous glandular inflammation, eosinophilic pustule formation, and follicular rupture were present in less than half of the biopsies. Small numbers of microbes (bacteria, yeast, Demodex) were identified in 25% of the study biopsies in routine or special stains, but the organisms were away from areas of inflammation and were interpreted as nonpathogenic flora. The biopsies of suppurative folliculitis differed in that neutrophils and macrophages predominated in the infiltrate, microorganisms were readily identified in the inflammatory reaction, and the involved follicle was often ruptured. We believe that eosinophilic folliculitis is a unique HIV-associated dermatosis distinguishable from other folliculitides and papular dermatitides by clinical examination and light microscopy. We present our diagnostic approach.

Adult↗
PubMed1994

Guinea-pig contact sensitization assays.

After reviewing general aspects and the historical development of predictive animal skin sensitization tests, the recommended tests of the OECD and EC are discussed. Background information is given on the changes which occurred in the last 2 years. From the many factors known to influence induction and challenge of contact allergy in animals, the discussion is focused on the choice of induction concentration and the vehicle. The difference of general screening strategies in Europe and the USA is presented and discussed. The paper closes with a discussion on the importance of inhouse validation of the methods used for proper prediction of the sensitizing potential of chemicals and with remarks on predictive in vitro tests.

Allergens↗