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Biomedical subjects

J Schreiber

Publications and source records attributed to J Schreiber.

At least 37 records · Page 2Linked to original sources

Interstitial lung disease induced by endogenous Candida albicans.

We report on a 64-year old woman with an interstitial lung disease which had characteristics of hypersensitivity pneumonitis. Severe febrile attacks with impairment of ventilation and diffuse poorly defined radiodensities and ground glass opacities on chest x-ray occured repeatedly. Laboratory data showed hypoxemia, leukopenia and circulating Candida albicans (C.a.)-antigen. Bronchoalveolar lavage revealed an increase in neutrophils. Transbronchial biopsies showed lymphocytic alveolitis, bronchiolitis obliterans and epitheloid cell granulomas. IgG and IgA and the lymphocyte proliferation assay were positive with C.a.-antigen. C.a. was detected in the feces. Intradermal skin test with C.a. showed a positive immediate and late phase reaction and inhalative provocation test with C.a.-antigen was positive. After antimycotic treatment the symptoms resolved completely and long-lasting. We conclude that the disease was induced by C.a.-antigen reaching the lungs from the intestinal tract via the bloodstream.

Antifungal Agents↗

Reproducibility of HTS-SQUID magnetocardiography in an unshielded clinical environment.

A new technology has been developed which measures the magnetic field of the human heart (magnetocardiogram, MCG) by using high temperature superconducting (HTS) sensors. These sensors can be operated at the temperature of liquid nitrogen without electromagnetic shielding. We tested the reproducibility of HTS-MCG measurements in healthy volunteers. Unshielded HTS-MCG measurements were performed in 18 healthy volunteers in left precordial position in two separate sessions in a clinical environment. The heart cycles of 10 min were averaged, smoothed, the baselines were adjusted, and the data were standardized to the respective areas under the curves (AUC) of the absolute values of the QRST amplitudes. The QRS complexes and the ST-T intervals were used to assess the reproducibility of the two measurements. Ratios (R(QRS), R(STT)) were calculated by dividing the AUC of the first measurement by the ones of the second measurement. The linear correlation coefficients (CORR(QRS), CORR(STT)) of the time intervals of the two measurements were calculated, too. The HTS-MCG signal was completely concealed by the high noise level in the raw data. The averaging and smoothing algorithms unmasked the QRS complex and the ST segment. A high reproducibility was found for the QRS complex (R(QRS)=1.2+/-0.3, CORR(QRS)=0.96+/-0.06). Similarly to the shape of the ECG it was characterized by three bends, the Q, R, and S waves. In the ST-T interval, the reproducibility was considerably lower (R(STT)=0.9+/-0.2, CORR(STT)=0.66+/-0.28). In contrast to the shape of the ECG, a baseline deflection after the T wave which may belong to U wave activity was found in a number of volunteers. HTS-MCG devices can be operated in a clinical environment without shielding. Whereas the reproducibility was found to be high for the depolarization interval, it was considerably lower for the ST segment and for the T wave. Therefore, before clinically applying HTS-MCG systems to the detection of repolarization abnormalities in acute coronary syndromes, further technical development of the systems is necessary to improve the signal-to-noise ratio.

Adult↗

Differential mediator release from basophils of allergic and non-allergic asthmatic patients after stimulation with anti-IgE and C5a.

The differentiation between allergic and non-allergic asthma is a common and important challenge for the clinician. Until now, no in vitro diagnostic characteristics have been described to distinguish between these types. To examine the diagnostic value of a basophil stimulation test, we compared anti-IgE- and C5a-induced mediator release from peripheral blood leucocytes in different types of bronchial asthma. Peripheral blood leucocytes (PBL) from 10 aspirin-sensitive asthmatics (ASA), 12 non-allergic asthmatics without aspirin intolerance (NAA), seven allergic asthmatics (AA), and nine healthy controls were prepared by dextran sedimentation. After priming with interleukin-3 (IL-3) PBL were stimulated with anti-IgE and C5a, and the release of histamine (HR) and sulfidoleukotrienes (LTR) in the supernatant was compared. Additionally, purified leucocyte fractions were studied to determine the cellular source of mediator release. Upon stimulation with anti-IgE LTR was slightly, but not significantly, lower in ASA and NAA compared to AA and controls. In contrast, C5a-triggered LTR was significantly higher in ASA (14.4 +/- 12.88 pg/105 cells) and NAA (22.9 +/- 22.61 pg/105 cells) than in AA (9.6 +/- 3.29 pg/105 cells) and controls (7.5 +/- 7.19 pg/105 cells) (P < 0.05). This difference between ASA and NAA vs. AA and controls was even more pronounced when determining the quotient C5a-/anti-IgE-induced LTR (P < 0.001). At an optimal cut-off point of 1.0, calculated by relative operating characteristics (ROC) analysis, the positive predictive value for a donor to belong to ASA or NAA was 0.94. No significant differences could be found in HR between the asthmatic patient groups and healthy controls in either condition. As cellular source of LTR and HR the basophil could be determined. Determination of anti-IgE- and C5a-induced LTR from basophils allows us to discriminate between allergic and non-allergic asthmatic patients. For diagnostic purposes the quotient C5a-/anti-IgE-induced LTR is more significant than considering a single parameter. ASA cannot be distinguished from NAA.

Adolescent↗

[Non-tubercular mycobacterial infection of the lungs due to Mycobacterium smegmatis].

Nontuberculous mycobacteriosis due to M. smegmatis is a rarity. We report on the case of a 51 year old male HIV-seronegative patient without predisposing bronchopulmonary disease, but with a state after gastrectomy and splenectomy who developed unproductive cough, night sweat and weight loss. The chest radiograph and thoracic CT showed wide-spread bilateral patchy infiltrations. Histological examination of transbronchial biopsies revealed chronic carnificating pneumonia. A perhoracic fine-needle biopsy showed caseating epitheloid cell granulomas with acid fast bacilli. These were identified as M. smegmatis by PCR with subsequent sequencing. Acid fast bacilli could not be detected microscopically neither in sputum nor in bronchial secretions, however M. smegmatis has been repeatedly detected by culture in these materials. In neither material tubercle bacilli have been detected by nucleic acid amplification (NAT) or culture. Immunologic investigations revealed a reduced number of CD4+ lymphocytes and a reduction of interferon alpha- and -gamma-synthesis by peripheral blood mononuclear cells. Treatment with Rifabutin, Ethambutol, Clarithromycin and Ofloxacin resulted in complete clinical and roentgenological resolution.

CD4-Positive T-Lymphocytes↗

[Primary pulmonary manifestation of extramedullary acute myelocytic leukemia].

We report on a 49 year old female with primary extra-medullary manifestation of a acute myeloid leukemia in the lungs without leukemic signs. The disease was diagnosed by detection of leukemic blast cells in bronchoalveolar lavage. Chemotherapy with the TAD-VP-scheme resulted in partial remission. The patient died in systemic early relapse. To our knowledge this is the first description of primary isolated extra-medullary manifestation of a acute myeloid leukemia in the lungs.

Antineoplastic Combined Chemotherapy Protocols↗

Temporal characteristics of slot machine play in recreational gamblers.

The present study examined the temporal characteristics of play exhibited by recreational slot machine players. 12 women (M = 24 yr., range 22-28) played a computerized version of a slot machine with probability of payoff, i.e., a winning spin, ranging from .2 to .6. Intertrial intervals or the time between the termination of one trial to the initiation of the next trial varied within subjects as a function of wins and losses. Winning trials were associated with larger intertrial intervals and losing trials with smaller intertrial intervals for 10 of the 12 women. No differences were found across probability levels between subjects. Results are discussed in terms of the post-reinforcement pause that occurs on specific schedules of reinforcement.

Adult↗

Genome-wide location and function of DNA binding proteins.

Understanding how DNA binding proteins control global gene expression and chromosomal maintenance requires knowledge of the chromosomal locations at which these proteins function in vivo. We developed a microarray method that reveals the genome-wide location of DNA-bound proteins and used this method to monitor binding of gene-specific transcription activators in yeast. A combination of location and expression profiles was used to identify genes whose expression is directly controlled by Gal4 and Ste12 as cells respond to changes in carbon source and mating pheromone, respectively. The results identify pathways that are coordinately regulated by each of the two activators and reveal previously unknown functions for Gal4 and Ste12. Genome-wide location analysis will facilitate investigation of gene regulatory networks, gene function, and genome maintenance.

Binding Sites↗

Hypersensitivity alveolitis induced by endogenous candida species

We report the case of a 64-year old woman with severe attacks of allergic alveolitis occurring frequently independent of a concrete place. These attacks were regularely preceded by diarrhoe. Laboratory data showed marked leukopenia and circulating Candida albicans (C.a.)-antigen. Bronchoalveolar lavage revealed an increase in neutrophils (13%). Transbronchial biopsies showed focal alveolitis and focal septal fibrosis with bronchiolitis obliterans and an epitheloid cell granuloma. Immunohistochemical examination revealed C.a.-antigen in alveolar macrophages. In the faeces a high amount of C.a. and C. glabrata was detected. In serum IgG and IgA were positive against C.a., IgE against C.a. was negative. Lymphocyte proliferation assay with C.a.-antigen was positive. Intradermal skin test with C.a. showed positive immediate and late phase reaction. Furthermore inhalation challenge with C.a.-antigen was positive. A febrile reaction with chills, dyspnea and hypoxemia and leukocytosis in peripheral blood occured after 6 hours. Lung function showed a predominantly obstructive impairment of ventilation. An extensive search for other IgG- or IgE-mediated allergies (other fungi, environmental or food allergens) was completely negative. Investigation of the gastrointestinal tract did not show any abnormality exept the detection of lactose intolerance. There was no fungal growth in the patients flat. After initiation of antimycotic treatment the symptoms resolved completely. - We conclude that the disease was induced by C.a.-antigen reaching the lungs from the intestinal tract via the bloodstream. It is still a matter of debate whether an additional factor is necessary for the antigen to penetrate the intestinal mucosa.

Journal Article↗

Protein stability and domain topology determine the transcriptional activity of the mammalian glial cells missing homolog, GCMb.

The glial cells missing (GCM) family of transcription factors consists of Drosophila GCM and the mammalian proteins GCMa and GCMb. They are expressed in a highly restricted manner during development and are known or assumed to be important regulators of developmental fate decisions. As the biochemical properties of GCMb have not been studied so far, we have undertaken a detailed structure-function analysis of the mouse GCMb (mGCMb) protein. DNA-binding specificity was very similar to that of other GCM proteins. Nevertheless, mGCMb was only a weak transcriptional activator in a number of different tissue culture systems. Interestingly, this was not due to an intrinsic absence of transactivation potential. In effect, we were able to identify two separate transactivation domains within mGCMb, one carboxyl-terminally adjacent to the DNA-binding domain and the second within the extreme carboxyl terminus. Activity of both transactivation domains was, however, modulated by an inhibitory region unique to mGCMb and located between the two transactivation domains. Furthermore, pulse-chase experiments proved that the mGCMb protein has a half-life approximately four times shorter than mGCMa. Introduction of the above mentioned inhibitory domain of mGCMb into mGCMa shortened the half-life of mGCMa to a value typical of mGCMb with a concomitant reduction in transactivation potential. Given the strong correlation between protein stability and transactivation potential, functional differences between the two mammalian GCM homologs are likely due to differences in stability with a single inhibitory region in mGCMb being involved in the reduction of both.

Amino Acid Sequence↗

[Studies on the stabilization of the cornea in rabbits].

BACKGROUND: The mechanical stabilization of the cornea in keratoconus may delay progression of this disease. The cross-linking techniques optimized in corneas of enucleated porcine eyes were investigated under in vivo conditions in rabbits to estimate the biocompatibility and duration of the stiffening effect. METHODS: Twenty-eight rabbits were treated monocularly, the fellow eye serving as control. The epithelium was mechanically removed and 19 eyes were treated with riboflavin plus ultraviolet irradiation (365 nm, 2 mW/cm2) for 45 min and 9 eyes with 0.075% glutaraldehyde for 20 min. After treatment, the eyelids were sutured for 3 days. The healing process was controlled by slit-lamp examination and photographically documented. After 1 month, 20 animals and after 3 months 8 animals were sacrificed, the eyes enucleated, and the stress-strain relation of the corneas measured and compared to the fellow eye. RESULTS: The epithelium was closed after 4-5 days. The transparency of the corneas remained clear during follow-up, and there were no signs of inflammatory reaction. Stress for a strain of 6% was higher in the treated corneas by a factor of 1.3 +/- 0.66 (P = 0.319) in the glutaraldehyde group and by a factor of 1.6 +/- 0.75 (P = 0.0408) in the riboflavin group at 1 month, and by 1.3 +/- 0.48 (P = 0.07) at 3 months after treatment. CONCLUSIONS: The cross-linking technique using riboflavin plus UV irradiation is suitable for at least temporarily stiffening the cornea in vivo and seems to be a promising method for conservative treatment of keratectasia.

Animals↗

A chart review of the ordering and documentation of urine toxicology screens in a cancer center: do they influence patient management?

Urine toxicology screens (UTSs) may be useful in the diagnosis or monitoring of patients with established or suspected substance abuse. In the medically ill, including those with cancer, the test may help clinicians manage therapy with controlled prescription drugs. To describe the current use of UTSs in a cancer center, the medical records of 111 patients who underwent UTS were reviewed. These 111 patients were randomly selected from a group of 215 patients who underwent screening between January 1, 1990 and December 31, 1994 (a period during which over 80,000 admissions occurred). Fifty-six of the 111 patients had evidence of one or more illicit drugs, a prescription medication that had not been ordered, or alcohol; 50 patients had negative screens. The likelihood of a positive UTS was higher if the patient had human immunodeficiency virus (HIV) infection (100% versus 46.6%) or was undergoing treatment for chronic nonmalignant pain (100% versus 43.9%). Documentation of the UTS in the medical record was infrequent: 37.8% of the charts listed no reason for obtaining the test and the ordering physician could not be identified in 29% of the records. Eighty-nine percent of the records did not contain a subsequent mention of the result of the UTS. The result was more likely to lead to a documented outcome when it was positive rather than negative (14.3% versus 0%). These results suggest that UTSs are used infrequently in the tertiary care oncology center. The documentation surrounding the ordering and subsequent use of the test in patient management is unsystematic. The appropriate use and documentation of UTSs, like substance abuse issues in general, should be a focus of staff education and quality improvement efforts.

Adult↗

Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa.

The GCM family of transcription factors consists of Drosophila melanogaster GCM, an important regulator of gliogenesis in the fly, and its two mammalian homologs, GCMa and GCMb. To clarify the function of these mammalian homologs, we deleted GCMa in mice. Genetic ablation of murine GCMa (mGCMa) is embryonic lethal, with mice dying between 9.5 and 10 days postcoitum. At the time of death, no abnormalities were apparent in the embryo proper. Nervous system development, in particular, was not impaired, as might have been expected in analogy to Drosophila GCM. Instead, placental failure was the cause of death. In agreement with the selective expression of mGCMa in labyrinthine trophoblasts, mutant placentas did not develop a functional labyrinth layer, which is necessary for nutrient and gas exchange between maternal and fetal blood. Only a few fetal blood vessels entered the placenta, and these failed to thrive and branch normally. Labyrinthine trophoblasts did not differentiate. All other layers of the placenta, including spongiotrophoblast and giant cell layer, formed normally. Our results indicate that mGCMa plays a critical role in trophoblast differentiation and the signal transduction processes required for normal vascularization of the placenta.

Animals↗

Influence of oxygen concentration on argon plasma coagulation-induced tissue damage in isolated pig tracheas.

BACKGROUND: Argon plasma coagulation (APC) is used during bronchoscopy to restore passage of central airways. Concern has been raised about the possibility that elevated oxygen concentration may increase the tissue damage by APC. OBJECTIVE: to examine the extent of tissue damage at different concentrations of oxygen in isolated pig tracheas. METHODS: The APC-induced tissue damage was investigated macroscopically and microscopically in isolated and artificially ventilated pig tracheas at oxygen concentrations of 21, 50, 75 and 100%. RESULTS: There was deep coagulation of all tissue layers reaching the adventitia independent of the oxygen concentration up to 75% O(2). With 100% O(2), only tissue damage increased and combustion occurred. CONCLUSIONS: APC-induced tissue damage in ex vivo pig tracheas was independent of the oxygen concentration relevant for clinical practice.

Animals↗

Use of the blue MACS: acceptance by clinical instructors and self-reports of adherence.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate clinical instructors' (CIs') acceptance of and self-reported adherence to instructions for use of The Blue MACS (5th edition) for evaluating the clinical performance of physical therapist students. SUBJECTS AND METHODS: One hundred twenty-four usable survey instruments were returned by CIs. RESULTS: Twenty-two items from The Blue MACS were collapsed into a score representing acceptance, and 10 items were collapsed into a score representing reported adherence to instructions. Ninety-six percent of the CIs surveyed expressed a positive opinion of the instrument. Ninety-eight percent of the CIs reported at least moderately consistent adherence to instructions. CONCLUSION AND DISCUSSION: The instrument was regarded as a useful tool, and most CIs reported using the instrument according to the instructions. A positive opinion of the clinical performance assessment instrument is desirable to facilitate its use by CIs. Consistent use by different CIs is desirable to promote accurate communication among students, CIs, and the educational institution.

Adult↗

Lymphocyte transformation test for the evaluation of adverse effects of antituberculous drugs.

The usefulness of the lymphocyte transformation test (LTT) for the analysis of adverse reactions to antituberculous drugs was evaluated. - The LTT was performed with isoniazid and rifampicin in 15 tuberculosis and 2 MOTT (Mycobacteria other than tuberculosis)-infection patients who suffered drug reactions, in 23 patients without any adverse reactions, in 7 controls previously exposed to antituberculous drugs, and in 14 controls who had never been exposed. 4/15 of the hepatotoxic reactions only showed a positive LTT with rifampicin, 3/15 only with isoniazid, and in 8/15 the LTT was negative. In an anaphylactoid shock reaction the LTT was extremely exaggerated for both rifampicin and isoniazid. In patients without any side effects only one slightly increased LTT due to isoniazid was observed. Two healthy controls with previous contact to these drugs showed a positive LTT for isoniazid, one of those with both rifampicin and isoniazid. The LTT was negative in all control persons without any former contact to antituberculous medications. In most cases hepatotoxicity seems to be a pure toxic reaction without the participation of cellular immune mechanisms. LTT can be useful for identifying the drug responsible for immunological side effects.

Adult↗

mGCMa is a murine transcription factor that overrides cell fate decisions in Drosophila.

During neural development of Drosophila melanogaster, Glial Cells Missing (GCM), functions as a binary switch that promotes glial cell fate while simultaneously inhibiting the neuronal fate. Sequence similarities between GCM and the recently identified mouse protein mGCMa are strictly limited to the aminoterminal DNA-binding domain. Here we show that mGCMa efficiently activates transcription in Drosophila cells just as Drosophila GCM activates transcription in mammalian cells. Transactivation potential was present in two separate regions of mGCMa outside the DNA-binding domain. One of them mapped to the carboxyterminal 88 amino acids, a location corresponding exactly to the transactivation domain of GCM. Similarities between GCM and mGCMa were also observed in vivo. Overexpression of mGCMa in the developing nervous system of Drosophila embryos led to an increase in glial-like cells at the expense of neurons. Outside the neurogenic region, mGCMa interfered with epidermal development, as evident from changes in cell morphology and marker expression. Thus, mGCMa function is at least partially independent of a cell's predisposition to a neural fate. The potent activity of mGCMa in Drosophila and its extensive functional similarities to GCM make mGCMa a candidate for a regulator of mouse glial development.

Animals↗

Alterations of the extracellular matrix of venous walls in varicous veins.

BACKGROUND: Investigation of changes in normal veins which result in the formation of varicosis led to examination of the histological organisation of the vessel wall and to histomorphological alterations in the region of the extracellular matrix. PATIENTS AND METHODS: The expression pattern of the matrix proteins collagen IV, fibronectin, laminin, tenascin, and undulin as well as the structure and orientation of elastic fibres were determined by means of immunohistochemical staining. RESULTS: All varices exhibited an increased expression pattern in comparison to healthy veins. The venous vessel wall was often non-homogeneously enlarged. The intima was always more involved than the media and showed enhanced accumulation, whereas, the adventitia was not influenced by the pathological process. Collagen IV exhibited an early accumulation, especially in the subendothelial region. The other matrix proteins demonstrated an increase in fibre propagation parallel to the enlargement of the vessel wall. Essentially, an augmented de novo synthesis of fibres with an irregular arrangement and the formation of local plaques was found. Elastic fibres were enhanced by slight involvement of the vessel wall and were reduced and fragmented during increased involvement of the venous wall which explained the rigidity of varices in contrast to normal veins.

Elastic Tissue↗

Continuous infusion of FVIII and FIX concentrates: in vitro analysis of clinically relevant parameters.

A high purity factor VIII/von Willebrand Factor (FVIII/vWF) concentrate (IMMUNATE [STIM plus]) (n = 6 batches), and a high purity factor IX (FIX) concentrate (IMMUNINE [STIM plus]) (n = 7 batches), were assessed in vitro for their applicability to continuous infusion. Parameters pertinent to continuous infusion were investigated and included stability, sterility and, in the case of FIX, the generation of potentially thrombogenic components. Four stationary or transportable mini infusion pumps, equipped with polyethylene, polypropylene or polyvinylchloride plastic components were used. The concentrates were reconstituted without extra filling volume and perfused at 12.5 mL h-1 and 1 mL h-1; sampling was carried out at the start of the experiment and for up to 48 h. The FVIII procoagulant activity (FVIII:C) was assayed by amidolytic, 1-stage and 2-stage assays; vWF was examined for ristocetin cofactor activity, antigen and multimers. The FIX coagulation activity (FIX:C) was determined by a 1-stage coagulation assay; thrombogenicity potential was assessed in vivo (Wessler stasis model in rabbits) and in vitro (FIXa and nonactivated thromboplastin time). Reconstituted concentrate incubated under the same conditions served as a control. Both concentrates remained sterile throughout the testing period. The perfused and control samples remained stable, retaining over 95% of activity for FVIII:C and over 90% for FIX:C for up to 48 h. Intermittent decrease of FVIII:C or FIX:C was not observed, suggesting no adsorption of FVIII or FIX onto plastic surfaces during either short or long-term exposure. No thrombogenic components were detected in the high purity FIX concentrate. Thus, under the in vitro conditions used, FVIII/vWF and FIX were found to be suitable for administration by continuous infusion.

Blood Coagulation Tests↗