Search PubMed⌕ Search

Biomedical subjects

G Gruber

Publications and source records attributed to G Gruber.

At least 73 records · Page 4Linked to original sources
PubMed1996

Inadequate production of hematopoietic growth factors in hairy cell leukemia: up-regulation of interleukin 6 by recombinant IFN-alpha in vitro.

The course of hairy cell leukemia (HCL) is characterized by progressive pancytopenia. The pathogenesis of this phenomenon is still not fully understood. To study if the decrease in hematopoiesis in HCL is accompanied by abnormal concentrations of growth factors, we investigated the production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 3 (IL-3), interleukin 6 (IL-6), and tumor necrosis factor alpha by peripheral blood mononuclear cells (PBMCs) of eight patients with HCL. The results point to a severe deficiency of production of all cytokines tested as compared to healthy donors. However, enrichment of autologous monocytes by counterflow centrifugation resulted in a marked increase of the levels of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IL-6, and tumor necrosis factor alpha. The most pronounced effects were seen with IL-6. Reverse transcription-PCR analysis indicated that pokeweed mitogen, IFN-alpha, and poly(I:C) are capable of inducing the expression of IL-6-specific mRNA in HCL cells. These findings are substantiated on the protein level by immunofluorescence analysis. Incubation of PBMCs with IFN-alpha resulted in a significant increase of intracellular IL-6 in HCL but not in healthy donors. This increase was also seen in hairy cells positive for CD19 and CDllc. Furthermore, IFN-alpha induced the secretion of IL-6 from PBMCs of HCL patients but not healthy donors. In conclusion, our studies with PBMCs from patients with HCL revealed an inadequate supply of hematopoietic growth factors that might, in part, be due to the monocytopenia characteristic for this disease. The findings also indicate that IFN-alpha is capable of inducing the production of IL-6 in the patients' PBMCs as well as in their hairy cells. These data from our in vitro studies support the clinical observation that treatment with IFN-alpha leads to reconstitution of hematopoiesis.

Adult↗
PubMed1996

[Sonography of the knee extensor system].

In standardised ultrasound examination of the knee joint, ventral, medial, lateral and dorsal sectional planes are used. Sonographic examination of the knee joint can supply important information on many pathological alterations of the periarticular soft-tissues. Since complete diagnostic examination of the bony structures of the joint by ultrasound is not possible, radiological examination in two sectional planes cannot be replaced by this modality.

Humans↗
PubMed1996

Restricted antigenic variability of the epitope recognized by the neutralizing gp41 antibody 2F5.

OBJECTIVE: To investigate whether variations of the conserved gp41 amino-acid sequence ELDKWA affect its binding or neutralization by monoclonal antibody (MAb) 2F5. DESIGN AND METHODS: Neutralization assays were performed with primary isolates from different HIV-1 subtypes and the sequences corresponding to the 2F5 epitope region were analysed. Studies of MAb 2F5 peptide reactivity were performed by spot analysis, using peptides immobilized on cellulose. The frequency of emergence of neutralization-resistant virus variants was determined by immune selection experiments in the presence of MAb 2F5. RESULTS: Primary isolates from clades A, B and E were neutralized by MAb 2F5. Neutralization sensitivity correlated with the presence of the LDKW motif. A K-to-N change in the core sequence was identified in a neutralization-resistant patient isolate. Neutralization resistant virus variants that were selected in the presence of MAb 2F5 were found to contain D-to-N, D-to-E, or K-to-N changes within the LDKW sequence. Neither in natural isolates nor in variants obtained under immune selection conditions in the laboratory were changes in the L and W positions observed. Studies of MAb 2F5 binding to variations of the ELDKWA peptide confirmed that the changes at the first and last positions did not significantly reduce binding capacity, whereas amino-acid changes from D to N, D to E, and K to N almost completely abrogated binding of MAb 2F5. CONCLUSION: Sequence analysis of a variety of primary isolates suggests that the major determinant of MAb 2F5 binding corresponds to the amino-acid sequence LDKW. Naturally occurring and in vitro selected neutralization-resistant viruses contained changes in the D and K positions of the ELDKWA motif.

Antibodies, Monoclonal↗
PubMed1996

First-night-effects on generalized anxiety disorder (GAD)-based insomnia: laboratory versus home sleep recordings.

First-night effects (FNE) were comparatively investigated in patients with disorders in initiating and maintaining sleep (DIMS) associated with generalized anxiety disorder (GAD) in laboratory (n = 22) and home sleep polysomnography (n = 21). Patients had to be drug-free for at least 2 weeks prior to the first recording. Evaluation measures included 1) objective data on sleep initiation and maintenance; 2) sleep architecture based on polysomnographic recordings, analyzed visually according to the criteria of Rechtschaffen and Kales; 3) subjectively estimated sleep and awakening quality, assessed by a self-rating scale and visual analogue scales; 4) objective awakening quality as measured by a psychometric test battery; and 5) psychophysiological data, including critical flicker frequency, muscle strength, pulse, and blood pressure. Statistical analysis using multivariate analysis of variance (MANOVA) demonstrated multiple FNE in both groups regarding sleep efficiency, total sleep time, percentage of time in stage 2 sleep, percentage of time in stage 3/4 sleep, minutes of rapid eye movement (REM) sleep, and REM sleep latency. There was a group-by-night effect in the number of awakenings. There were no significant FNE regarding subjective sleep and awakening quality in either group. Differential adaptation effects were observed in attention and fine motor activity, with improvement in laboratory-recorded patients and deterioration in home-recorded patients. Differential findings also occurred in regard to evening blood pressure, with laboratory-recorded patients showing more adaptation.

Adult↗
PubMed1995

[Possibilities of ultrasound diagnosis in Tossy type III acromioclavicular joint injuries in comparison with loaded roentgen images].

We inform about 20 patients (19 men, 1 woman) with acute acromioclavicular striking, type Tossy III, which were operated. By usual preoperative diagnostic and physical examination, x-ray standard pictures of the shoulder in two planes and x-ray panoramic picture (loaded with 10 kp and unloaded) in ap-axis we made an additional sonographic examination of the hurt shoulder. This is practiced in the commendable standardised pattern of DEGUM (German Society of Ultrasound in Medicine). After the standardised sonographic examination we focussed the acromioclavicular joint sonographically in a modified lateral vertical axis. All of the 20 examined shoulder joints belong to the stage Tossy III. In the preoperative diagnosis the difference in elevation between the lateral portion of the clavicula and the medial portion of the acromion amounts in comparison to the two shoulders (loaded versus unloaded shoulder joints) sonographically 6.2 +/- 2.6 mm (max. difference of the sides 10 mm), by the radiological examination 6.5 +/- 3.7 mm (max. difference of the sides 14 mm). The sonographical examination of the shoulder joint makes it possible to get more information about the acromioclavicular lesion, especially by an AC examination according to Tossy degree III. At present there is no possibility of substituting the standardised x-ray pictures in two axes to diagnose or exclude fractures.

Acromioclavicular Joint↗
PubMed1995

Kringle 4 of human apolipoprotein[a] shares a linear antigenic site with human catalase.

Monoclonal antibody (mab) 1A2, directed against human apolipoprotein[a] (apo[a]), revealed a strong reaction with peroxisomes as shown by immuno-gold labeled cryosections of human liver biopsies. This reactivity was not due to the presence of apo[a] in peroxisomes but to a cross-reactivity of mab 1A2. Immunoblot analysis of peroxisomal fractions and purified human catalase demonstrated that mab 1A2 reacts with catalase. Conversely, an anti-catalase antibody also recognized apo[a]. By sequence comparison we identified a 4-amino acid motif (Y-Y-P-N) that is shared between the highly repetitive kringle 4 motif of apo[a] and the carboxy-terminal third of the peroxisomal marker enzyme catalase. No other identical sequences were identified in these proteins. Results from the following experiments indicated that 1A2 recognizes this short linear epitope. i) Mab 1A2 reacted only with the 4 amino acid peptide sequence in a pin-ELISA using immobilized overlapping peptides. ii) A synthetic peptide including this sequence completely inhibited the 1A2 immunoreactivity to apo[a] and catalase. iii) A recombinant fusion protein tagged with the putative epitope was recognized by mab 1A2. Our findings demonstrate that unknown linear epitopes in native proteins can be identified by sequence comparison between known proteins. The practical implication is that antibodies against apo[a] must be controlled for this cross-reactivity before using them for immunohistochemical studies of intracellular apo[a] in tissues or cells.

Amino Acid Sequence↗
PubMed1995

[Possible applications of ultrasound in corticotomy-callus distraction].

Sonographic examination can yield additional information in the course of corticotomy-callus distraction. Hence, we focus on individual slices--which are different from the standardised ultrasound examination of the skeleton system--in the area of the corticotomy-callus distraction. In ultrasound examination the structure of corticalis in the field of corticotomy is scanned circularly. Depending on the point of time of the corticotomy between the structure of corticalis, the callus can be visualised sonographically. The callus distraction can be divided into three stages: I. echo-poor structure between the two ends of the corticalis, II. echo-rich structure between the two ends of the corticalis, III. area of corticalis in the area of distraction with (III a), visualised without (III b) break. The described method is an additional low-cost imaging procedure in diagnosis, for the patient free of radiation and stress, which can yield additional information during and after completed callus distraction (question of permissible emotional stress). The examination is reproducible. The x-ray-controls in the course of time are mandatory, because the sonographic examination cannot judge reliably the deviation of the axis in the area of callus distraction.

Adolescent↗
PubMed1995

[Clinical diagnosis in sleep laboratory patients based on ICD-10, DSM-III-R and ICSD classification criteria].

For the diagnosis of sleep disorders, 3 different standardized classification systems are available: the International Statistical Classification of Diseases and Related Health Problems (ICD-10), the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R/DSM-IV) and the International Classification of Sleep Disorders (ICSD). These 3 classification schemata were comparatively evaluated in 50 sleep-disturbed patients who were admitted within 1 year to a non-specialized sleep laboratory for diagnostic evaluation and treatment. 17 female and 33 male sleep-disturbed patients, aged 54 +/- 12 years, were recorded polysomnographically in 3 subsequent nights (adaptation night, baseline/diagnosis night, treatment night) for measuring objective sleep quality. The subjective sleep quality as well as the subjective and objective awakening quality was assessed by means of rating scales, as well as psychometric and psychophysiological test battery. During the day, EEG, EEG-mapping, psychodiagnostic tests as well as, in many cases, pulmonary function, otolaryngological, CT, MRT and pharyngometric investigations were carried out. Psychic disorders were the leading cause for sleep problems in all 3 classification systems. Based on the ICD-10, the most frequent diagnosis was non-organic insomnia (46%), followed by sleep apnea (18%) and other organic sleep disorders (14%). Based on the DSM-III-R, 46% of the patients were diagnosed as insomnias based on another mental disorder, 38% as organic hypersomnias and 14% as parasomnias. Based on the ICSD Classification, sleep disorders associated with anxiety disorders were leading (30%), followed by sleep disorders based on affective disorders (16%), obstructive snoring (14%), primary snoring (8%) and sleep disorders based on neurological disorders (6%). While the broader ICD-10 and DSM-III-R diagnoses are syndrome-etiologically oriented and may be easily utilized by the practicing physician, the more narrowly defined, extensive, pathogenetically oriented polysomnographic features including ICSD diagnoses are suited better for the specialist.

Adult↗
PubMed1994

Stability of cardiovascular responses across subjects and situations: a systematic approach.

This study describes the reproducibility of behaviorally elicited cardiovascular response patterns, 111 subjects were studied over a 1-year interval. Physiological variables recorded were heart rate, systolic and diastolic blood pressure, and respiratory rate. Test-retest stability coefficients were calculated and compared with the results of a study with a 3-day interval between test sessions. The physiological data are depicted in a four-dimensional data box (subjects, situations, replications, variables), and the variance components of the factors and their interactions are estimated. Some of the interaction components are associated with specificity principles and with temporal stability. To comprehensively describe special aspects of stability, measures for stability were generated (concerning subjects, situations, or both), adopting basic ideas from the covariance partitioning approach. The stability measures were compared with simple test-retest reliability coefficients and with generalizability coefficients, and systematic relationships between the stability measures are discussed.

Adolescent↗
PubMed1994

Laser welding--suitable for vascular anastomosis?

Carotid arteries of 21 piglets were transsected and reanastomosed either by laser welding (Neodym:YAG laser) or by conventional suture anastomosis. Histological specimens of the anastomoses obtained 2 to 32 days after the operation showed less foreign body reaction and intimal hyperplasia after laser welding than after suturing. There was, however, no significant difference when comparing occurrence of thrombosis, patency rate, or growth of the anastomosis in growing animals. Neither our study nor a review of the literature of laser-assisted vascular anastomosis in microvessels and large arteries up to 5 mm diameter could establish a definite clinical application for laser welding in vascular anastomosis.

Anastomosis, Surgical↗
PubMed1994

A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1.

We have established a hybridoma clone, designated 2F5, secreting a neutralizing human monoclonal antibody (MAb) specific for gp41 of human immunodeficiency virus type 1 (HIV-1). The epitope of MAb 2F5 was mapped to amino acid sequence Glu-Leu-Asp-Lys-Trp-Ala on the ectodomain of gp41. In this study different in vitro test systems were used to characterize the neutralizing properties of MAb 2F5. In syncytium inhibition assays, fusion inhibition experiments, and neutralization assays on different HIV-susceptible cells (H9, U937, and peripheral blood mononuclear cells) MAb 2F5 showed broad-spectrum neutralizing capacity against HIV-1 laboratory isolates IIIB, MN, RF, and SF2. In addition, primary isolates from AIDS patients were also neutralized.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Generation of human monoclonal antibodies against HIV-1 proteins; electrofusion and Epstein-Barr virus transformation for peripheral blood lymphocyte immortalization.

Electrofusion and EBV transformation were studied by immortalizing human PBLs from blood of HIV-1-positive volunteers. A panel of 33 cell lines producing human monoclonal antibodies (Hu-MAbs) against HIV-1 was established by cell fusion or EBV transformation. For the first fusion experiments the source of B lymphocytes was peripheral blood of HIV-1-infected donors in CDC stages II or III with CD4 cell counts higher than 500/mm3. Later on, from these patients only, those with high anti-HIV titers were chosen as blood donors. By that means the yield of stable specific hybridomas was increased twofold. In our experiments electrofusion turned out to be a more efficient immortalization method than EBV transformation, due to a high and constant immortalization rate. The hybridomas were stable after intensive subcloning and could be cultivated over a period of 8 months without loss in monoclonal antibody production. Immunoglobulin class, subtype, reactivity against HIV-1 proteins, Western blot patterns, immunofluorescence, and epitopes were characterized. The subtype of all antibodies was IgG1 or IgG3. The light chain was predominantly kappa. All antibodies showed reactivity against HIV-1 envelope or core protein. All hybridomas were stable and suited for mass production. Several Hu-MAbs are becoming an important tool in the field of diagnosis, research, and immunotherapy.

Antibodies, Monoclonal↗
PubMed1993

[Prospective study of determining the value of D-dimer in diagnosing pulmonary embolism].

Pulmonary embolism (PE) is still misdiagnosed in a high proportion of cases. 107 patients admitted for suspected pulmonary embolism were studied prospectively to shed light on the value of ELISA-D-dimer and Latex-D-dimer. Pulmonary embolism was ruled out by negative perfusion scans in 66 patients (61.7%) and by angiography in 24 patients. 58% of the scans suggesting a high probability of PE were confirmed by angiography, but only 18% of the scans suggesting a low or intermediate probability of PE. Sensitivity and specificity were 88% and 79%, respectively for the D-dimer ELISA, versus 94% and 90% for the Latex agglutination test. The Latex test increased the positive predictive value of lung scanning suggesting low to intermediate probability of PE (group B) from 18% to 75% and that of lung scanning suggesting high probability of PE (group C) from 58% to 93%. The positive predictive value was improved by ELISA-D-dimer in both groups to 75%. In order to augment the diagnostic efficacy in clinical practice the determination of Latex-D-dimer simultaneously with lung scanning is recommended.

Adult↗
PubMed1992

[Ultrasound image of the Lachman test in lesions of the anterior cruciate ligament].

The sonographic examination of the knee-joint can, in many pathological alterations of the knee-joint, supply additional informations. In the standardized ultrasound examination of the knee-joint ventral and dorsal sectional planes will be adjusted (4, 7, 14, 17). For the examination of the lesions of the anterior cruciate ligament direct adjustment techniques in the aere of origin of the anterior cruciate ligament (15, 16) and indirect examination methods are known (7, 8, 9, 20). While Hien chose a direct medial parapatellaric horizontal sagittal sectional plane in the course of the lig. patellae (8), we carry out our examination in a ventral infrapatellaric sagittal plane. The examinations were conducted with an ultrasound unit of the type Siemens Sonoline SL 2 with a linear transducer with a frequency of 5 MHz without a stand off pad. In the course of a prospective clinical examination an anteromedial test of stability of both knee-joints was conducted on 360 patients with the help of a sonographic Lachman-test. Two examination groups were formed: in group 1 60 patients with a arthroscopically secured lesion of the anterior cruciate ligament were registered and set against 300 probationers with "empty" anamnesis of the knee-joint of group 2. In the group of patients with a cruciate ligament injury a tibia translation of 5.3 mm in the Lachman-test was found; the side difference between the leg injured and the one uninjured amounted to 3.0 mm. In the control group the tibia translation amounted to 2.9 mm with a side difference of 0.9 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[A basic psychodiagnostic program for internists].

The increasing frequency of disturbances of the health, in which psychic and/or social influential factors are significant, reflects also in the number of patients of the specialist of internal medicine who is working in the outpatient department, the hospital and in a subspeciality. This requires from the specialists of internal medicine, if he will satisfy the claims of his patients for a comprehensive diagnostics and effective therapy, from the very beginning and in all phases of the care the involvement of a basic psychodiagnostics. Hereby the problem in question is an enhanced internal establishment of the anamnesis under psychodiagnostic aspect, which serves for the clarification of psychic and/or social influences on signs and symptoms, the experience of the and the course of the disease. An orientating systematization and a way to the positive diagnostics of neuroses, psychosomatic diseases or disturbances and further functional syndromes in the field of internal medicine are presented which demand the graduated psychotherapeutic measure.

Humans↗
PubMed1990

[Psychophysiologic particularities in patients with functional syndromes].

Patients with gastroenterological or cardiovascular functional syndromes (n = 109) were examined by means of an extensive psychological standardized diagnostic programme and psychological strain analysis was carried out under psychogenic stress in laboratory. The results were compared with healthy probands (n = 51) likewise examined. Patients with functional syndromes significantly discriminated of healthy probands by more psychosocial risk constellation under strain caused by more distress and in parameters of performance and in psychophysiological field in some strain variables (heart rate, blood pressure, acral vasomotricity) and their dynamics.

Adult↗
PubMed1989

Isolation of human monoclonal antibody isoproteins by preparative isoelectric focusing in immobilized pH gradients.

A method for preparative isolation of human monoclonal antibody isoproteins is described in the present paper. A human monoclonal antibody directed against the transmembrane protein gp 41 from the human immunodeficiency virus (HIV-1) was used in this study. The antibody belongs to the IgG1 subtype and exhibits antibody dependent cellular cytotoxicity. The resolving power of conventional preparative protein separation techniques such as ion-exchange chromatography, chromatofocusing and lectin affinity chromatography is too poor for a complete separation of isoproteins. The more sophisticated technique of chromatofocusing on FPLC-based material (Mono P, Pharmacia) did not satisfy our expectation. With semipreparative IEF in immobilized pH gradients we were able to prepare the different isoproteins of a human monoclonal antibody in milligram amounts. No significant difference between the single isoproteins with respect to specificity and avidity to the recombinant antigen (rec gp 160) was detected. Therefore, we assume that the separation conditions did not influence the immunochemical nature of the antibody and significant denaturation and/or precipitation of the IgG did not occur. Furthermore the method affords preparative separation with resolution equivalent to analytical runs. Experiments for scale up and further characterization of isoproteins (carbohydrate composition, amino acid analysis, half life times etc.) are in progress.

Animals↗