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Biomedical subjects

M Gruber

Publications and source records attributed to M Gruber.

At least 19 recordsLinked to original sources
PubMed1996

A polyoma-based episomal vector efficiently expresses exogenous genes in mouse embryonic stem cells.

We describe the ability of novel episomally maintained vectors to efficiently promote gene expression in embryonic stem (ES) cells as well as in established mouse cell lines. Extrachromosomal maintenance of our vectors is based on the presence of polyoma virus DNA sequences, including the origin of replication harboring a mutant enhancer (PyF101), and a modified version of the polyoma early region (LT20) encoding the large T antigen only. Reporter gene expression from such extrachromosomally replicating vectors was approximately 10-fold higher than expression from replication-incompetent control plasmids. After transfection of different ES cell lines, the polyoma virus-derived plasmid variant pMGD20neo (7.2 kb) was maintained episomally in 16% of the G418-resistant clones. No chromosomal integration of pMGD20neo vector DNA was detected in ES cells that contained episomal vector DNA even after long term passage. The vector's replication ability was not altered after insertion of up to 10 kb hprt gene fragments. Besides undifferentiated ES cells, the polyoma-based vectors were also maintained extrachromosomally in differentiating ES cells and embryoid bodies as well as in established mouse cell lines.

Animals↗
PubMed1996

Transition rate kinetics from ethanol oxidation to glucose utilisation within a structured model of baker's yeast.

The transition rate kinetics from ethanol oxidation to glucose utilisation, within a structured model of baker's yeast, described previously, were experimentally identified. The shift in metabolism has been assessed through glucose pulses during batch growth on ethanol. The influence of glucose concentration (between 0.25 g l-1 and 0.90 g l-1) and initial biomass concentration (between 0.61 g l-1 and 1.44 g l-1) on the transition rate was determined. The transition rate can not be described by a first-order saturation-type kinetics with respect to glucose only. A corrective term, which takes into account biomass concentration should be included.

Culture Media↗
PubMed1996

Impact of fluorodeoxyglucose positron emission tomography on the clinical management of patients with glioma.

The past decade has seen the identification of many clinical settings in the treatment of primary brain tumors in which information from fluorodeoxyglucose positron emission tomography (FDG-PET) might be useful, if not essential, to therapeutic formulation. FDG-PET is currently used at referral centers in the management of primary brain tumors. The clinical pattern of FDG-PET use was assessed and its value compared to other information sources in clinical decision making. The clinical records of 75 glioma patients who were evaluated by FDG-PET were reviewed. The range of circumstances in which FDG-PET was employed included: pretherapeutic baseline studies for monitoring the effect of a therapy (1% of all cases), mapping of hypermetabolic regions before surgery or biopsy (2%), mapping of hypermetabolic regions before radiotherapy (2%), postsurgical evaluation for residual tumor (2%), assessment of the malignancy of a mass as a substitute for biopsy (11%), and distinguishing between radiation necrosis and recurrent tumor (87%). Other sources of information that contributed to the therapeutic management of patients included: gadolinium-enhanced MRI, contrast-CT, and clinical findings.

Brain↗
PubMed1996

Detection of cancer cells in peripheral blood stem cells of women with breast cancer by RT-PCR and cell culture.

The benefit of high-dose therapy and blood stem cell reinfusion for women with high-risk breast cancer is currently under investigation. Contaminations of autologous blood stem cells with cancer cells have been described. Cancer micrometastases may be detected by immunocytochemistry, culture techniques and cytokeratin-19 mRNA reverse transcriptase PCR. Women with breast cancer received adjuvant HD-CTM with peripheral blood stem cell (PBSC) support after surgical therapy and 4 cycles conventional chemotherapy. Peripheral blood stem cells were mobilised by G-CsF and harvested after the third or fourth cycle of standard therapy. Aliquots of PBSC-collections (10(7)-2*10(7) cells) were subjected to CK19-mRNA reverse transcriptase PCR. RNA was extracted by standard methods and reverse transcription was performed with MMV-RT. Integrity of RNA was checked by coamplification of housekeeping sequences. Aliquots of the RT-mix were subjected to PCR-amplification with outer and inner primer pairs, subsequently. A second aliquot of 2*10(7) cells was cultured over 42 days in liquid culture. Cytospins were prepared weekly from cultured cells and evaluated by light microscopy with or without prior immunocytochemistry. Ten leukaphereses from 6 women were available for PCR-analysis and cell culture. Six leukaphereses were negative for CK19-mRNA and for detection of cancer cells by culture technique, two samples were positive for CK19-mRNA and culturally enriched cells and two samples were positive for CK19-mRNA and negative for cultured cancer cells. No sample was positive for cultured cells and negative for CK19-mRNA. Overall, the results corresponded in 80%. Two sensitive techniques for the detection of cancer micrometastases were applied to aliquots from 10 leukaphereses of six breast cancer patients with corresponding results in 80%. PCR-mediated detection of cancer cells was confirmed by culture technique and light microscopy, however, further comparison of CK19-PCR with standard techniques like cell culture and immunocytochemistry is still necessary.

Breast Neoplasms↗
PubMed1995

Personality self-representations of patients with hand injury, and its relationship with work injury.

This study compared the personality self-representations of 288 hand injured patients with those of 959 young people (15-25 years old) randomly selected from the general population (noted GP), and with those of 336 unemployed people of all ages in professional training (U) in Lorraine (north-eastern France). The relationship between patients' personality self-representations and injury was also investigated. Personality self-representations included 14 questions: in your own opinion are you sociable?, at ease with others?, serious?, careful?, dynamic?, optimistic?, worried?, irritable?, clumsy?, solitary?, organised?, ambitious?, do you have a sense of responsibility?, and many plans? The patients had similar self-representations to GP except for the items non clumsy (odds ratio adjusted on age and sex OR = 2.40, p < 0.05) and optimistic (OR = 1.70, but 0.05 < p < 0.10). The frequencies of non irritable, non clumsy and non solitary people were higher in patients than in the U group (OR about 2.40, p < 0.01). By contrast, the other items were more favourable for the U group except for the items sociable, organised and having many plans. Self-representation items were significantly related to some socio-demographic data. The work injured workmen having one or more previous work injuries during the last five years were more at ease with others than the other subjects. Among the work injured workmen who had had no previous work injury during this time, the people aged 29 or less (the highest risk age class) were more optimistic than the others (71% vs 49%, p < 0.05); a difference was also found for the items at ease with others, careful, dynamic, and non worried, but it was not significant possibly due to the small number of subjects. The sum of these five items differed between the two age groups (3.29 +/- 1.49 vs 2.55 +/- 1.68, p < 0.05). These simple items would provide an interesting approach in terms of personality which could explain in part the excess of work injuries in young people, though the work requirement still seemed to be the highest risk factor.

Accidents, Occupational↗
PubMed1995

Properties of bispecific single chain antibodies expressed in Escherichia coli.

Single chain bispecific antibodies, in which the genes that encode the VH and VL regions are linked in tandem, may offer some advantages over other methods of bispecific antibody preparation. To begin to evaluate the potential of this system, a single chain bispecific antibody (scFv2) that binds to the T cell receptor of a cytotoxic T cell clone and to the hapten fluorescein was constructed. The individual scFv regions were joined by a 25 amino acid linker, and the scFv2 protein was obtained from insoluble inclusion bodies after guanidine solubilization and refolding. Fluorescein-purified scFv2 is active at concentrations of approximately 10 nM (approximately 1 microgram/ml) and above in mediating lysis of fluorescein-coupled tumor cells by the cytotoxic T lymphocytes (CTL). This system has now been used to evaluate various features of the scFv2 approach: (a) affinities of the scFv2 for the TCR and fluorescein, (b) yields of the scFv2 from several different purification schemes, (c) relationship of antigen density (i.e., fluorescein density on tumor cells) to the ability to redirect lysis of the tumor cell, and (d) relationship of scFv2 affinity for the tumor antigen to the ability to redirect lysis. This study was performed by using several analogs of fluorescein for which the scFv2 had different affinities. Results showed that it should be possible to select antibodies with appropriate affinities such that tumor cells with typical antigen densities of 10(4)-10(5) molecules per cell will be lysed and normal cells that have lower levels of the antigen will be spared.

Animals↗
PubMed1994

Efficient tumor cell lysis mediated by a bispecific single chain antibody expressed in Escherichia coli.

Recent advances in the expression of Abs in Escherichia coli have raised the possibility that virtually any specificity can be obtained by either cloning Ab genes from characterized hybridomas or by de novo selection using Ab gene libraries. Bispecific Abs have been more difficult to engineer because of problems inherent in the proper folding and association of VH and VL domains. In this report, a model system for expressing and testing the activity of a single chain bispecific Ab was used. The Ab contained the VH and VL genes from the anti-TCR Ab 1B2 joined by a 25 amino acid residue linker to the VH and VL genes from the anti-fluorescein Ab 4420. The 57-kDa single chain bispecific Ab (scFv2) was purified in a single step by affinity chromatography through a fluorescein column at a yield of 1 mg/L of bacterial culture. Despite the presence of 1B2 V regions at the NH2-terminus and a 10-residue c-myc peptide at the COOH-terminus, the refolded protein had an affinity for fluorescein that was nearly identical with the monospecific single chain Ab. The scFv2 also bound the TCR of the mouse CTL clone 2C and redirected the lysis of human tumor cells that had fluorescein covalently linked to their surface. Lysis was mediated at scFv2 concentrations that were 100-fold lower than the concentrations of Ab that inhibited normal recognition by CTL 2C. These results show that single chain bispecific Abs can mediate CTL lysis of target cells without the immunosuppressive side effects associated with the use of anti-TCR Abs.

Amino Acid Sequence↗
PubMed1994

Chemo-somatosensory event-related potentials in response to repetitive painful chemical stimulation of the nasal mucosa.

The aim of the study was to investigate how chemo-somatosensory event-related potentials (CSSERPs) and pain ratings are modified by repetitive painful stimulation of the nasal mucosa (58% v/v CO2, 200 msec duration). Twenty-two subjects performed 3 experiments during which trains of stimuli were applied. The interstimulus interval (ISI) between stimuli was constant for each experiment, but varied between experiments (8, 4, and 2 sec). CSSERPs were obtained from 5 positions (Fz, C3, Cz, C4, and Pz). The subjects not only rated the overall perceived intensities but also reported the quality of the stimuli. At an ISI of 8 sec estimates decreased and only stinging sensations were reported. In contrast, at an interval of 2 sec estimates increased being accompanied by the buildup of burning pain. This phenomenon was interpreted in terms of the superposition of first (sharp and stinging pain: A delta fibers) and second pain (dull and burning pain: C fibers), respectively. However, given the special circumstances of short ISIs CSSERP amplitudes decreased the more the shorter the ISI was. In line with previous investigations it is hypothesised that CSSERPs predominantly reflect nociceptive information transmitted via A delta fibers.

Adult↗
PubMed1994

Dose-related effects of ibuprofen on pain-related potentials.

1. The aim of this study was to investigate the dose-related effects of ibuprofen (placebo, 400 and 800 mg rac-ibuprofen [Aktren], administered orally) on experimentally-induced tonic and phasic pain. 2. Eighteen volunteers participated in this randomized, double-blind, three-fold cross-over study. Measurements were obtained before and 90 min after administration of the drugs. Phasic pain was produced by CO2 pulses of two concentrations applied to the right nostril. The left nostril was stimulated with a constant stream of dry air which produced a tonic painful sensation described as dull and burning. Subjects rated the intensity of the painful stimuli by means of visual analogue scales. In addition, chemo-somatosensory event-related potentials (CSSERP) were also recorded in response to phasic painful CO2 stimuli. 3. While mean intensity estimates of both tonic and phasic painful stimuli showed a non-significant dose-related decrease, a statistically significant dose-related decrease was observed for CSSERP amplitudes. 4. In conclusion, in order to investigate analgesic drug effects, CSSERP appear to be a more sensitive measure compared with psychophysically obtained responses.

Adult↗
PubMed1993

Pilot study of natural human interleukin-2 in patients with chronic hepatitis B. Immunomodulatory and antiviral effects.

Ten patients with chronic hepatitis B received increasing doses of nIL-2 (30,000 U, 100,000 U, 300,000 U, 1.0 million U) subcutaneously in a phase I trial. Each dose was applied once per week over 3 weeks. Serum samples were taken before and 2, 12, 24, 48 and 72 h after the first application of each dose level. Serum concentrations of interleukin-1 (IL-1), IL-2, IL-6, interferon-alfa (IFN-alpha), IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and GM-CSF as well as the cytokine-dependent serum components neopterin, beta-2-microglobulin (B2M), C-reactive protein (CPR), soluble IL-2-receptor (sIL-2R) and 2'-5'-oligoadenylate synthetase (2-5 OA) were assayed using ELISAs and RIAs. None of the samples tested contained measurable cytokine levels other than IL-2. A low and non-toxic dose of 300,000 U nIL-2 was already biologically active with induction of neopterin, B2M and sIL-2R. Dose-dependent changes peaked 24-48 h after application. The same patients were then enrolled in a phase II trial. Treatment in five of the patients was continued twice per week for 3 months with a biologically active dose of 300,000 U nIL-2 subcutaneously. Two of these patients as well as another five patients from the original group were treated with 1.0 million U nIL-2 subcutaneously, twice weekly for 3 months. Neither a biologically active but non-toxic dose of 300,000 U nIL-2, nor a toxic dose of 1.0 million U resulted in permanent clearance of hepatitis B early antigen (HBeAg).(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1993

Post-traumatic stress disorder and GI endoscopy: a case study.

Post-traumatic stress disorder (PTSD) can be caused by experiencing or witnessing a variety of harsh traumatic events. Rape, burglary, war, torture, violence, and other catastrophic events have been known to precipitate flashbacks, nightmares, and inability to cope with the demands of daily life. The symptoms associated with PTSD can interfere with work, sleep, appetite, relationships, and health. In a Veterans Administration hospital population, PTSD is not an uncommon patient problem: it usually results from witnessing and/or participating in war or military service-related circumstances. This case study describes a 42-year-old man who was a prisoner of war in Vietnam. The form of torture his Vietnamese captors subjected him to presented a challenging situation when he required an endoscopic examination of the upper gastrointestinal tract. The purpose of this case study is to offer suggestions to the GI and endoscopy nursing staff who care for these patients, and to make GI health care providers aware of the special needs of this patient population.

Adult↗
PubMed1993

The development of a position statement using the Delphi technique.

The need to develop practice-related documents in an accurate, efficient, and economical manner is the responsibility of the Board of Directors of the Society of Gastroenterology Nurses and Associates (SGNA). When the results of large, randomized, controlled, clinical trials are available, documents can be based on the information published in scientific literature. GI nursing, however, is in a novice phase regarding controlled research trials; thus, other methods of obtaining reliable information are required. The Delphi technique was selected to obtain the consensus of experts. The Delphi technique enables a free and open exchange of ideas while respecting the economics of a deficit budget. This article describes the Delphi process and the manner in which it was used to prepare the SGNA position statement, "Responsibilities of the Gastroenterology Registered Nurse related to Conscious Sedation."

Delphi Technique↗
PubMed1993

The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage.

Cerebral amyloid angiopathy is a common cause of spontaneous lobar hemorrhage in elderly patients. We discuss seven patients with amyloid angiopathy presenting without major lobar hemorrhage. The patients' presentations fell into two groups: recurrent transient neurologic symptoms and rapidly progressive dementia. The cases with transient episodes had a spread of symptoms to contiguous body areas during episodes. Each had evidence of small hemorrhage or subsequent large hemorrhage in the cortical location corresponding to the symptoms, suggesting petechial hemorrhage with focal seizure as the cause of the transient spells. Three cases of dementia developed with relatively rapid time courses, progressing from intact baseline to profound dementia in spans of a few days to 2 years. Pathologic abnormalities, in addition to amyloid angiopathy, included patchy white matter demyelination and tissue loss, petechial cortical hemorrhages, cortical infarctions, and a variable degree of neuritic plaques and neurofibrillary tangles. The clinical spectrum of cerebral amyloid angiopathy includes these two neurologic syndromes.

Aged↗
PubMed1992

Continuous in vivo treatment with catecholamines suppresses in vitro reactivity of rat peripheral blood T-lymphocytes via alpha-mediated mechanisms.

A 20 h continuous treatment of rats with catecholamines, using subcutaneously implantable retard tablets, had either no (adrenaline, isoproterenol, midodrine) or a slight (noradrenaline) suppressive effect on the in vitro responsiveness of peripheral blood T-lymphocytes. A marked suppression of the mitogen response ensued when adrenaline, noradrenaline or midodrine, but not isoproterenol, was applied together with the beta-receptor blocker propranolol, whereas the combination with the alpha-receptor blocker phentolamine had no effect. The mitogen response of splenic lymphocytes was not affected by any of these treatments. This alpha-mediated adrenergic suppression of peripheral blood T-cells was not correlated with general metabolic alterations, shifts in white blood cell counts or CD4+/CD8+ subsets, or with elevated glucocorticoid levels. The data suggest that to consistently influence the reactivity of rat peripheral blood lymphocytes by chronic adrenergic stimuli in vivo requires both high catecholamine levels and a bias towards alpha-adrenergic receptivity.

Animals↗
PubMed1992

Seroprevalence of antibodies to the human immunodeficiency virus in dialysis workers: results of a multi-center study.

The Center for Devices and Radiological Health, in collaboration with the Department of Veterans Affairs Medical Center, Brooklyn, N.Y., conducted a multi-center, multi-institutional study of the seroprevalence of antibodies to the human immunodeficiency virus (HIV) among dialysis workers. Seven dialysis units and 112 dialysis workers participated in the study over a period of 2 years. Participation was limited to dialysis workers who, by questionnaire, denied non-occupational risk factors for HIV infection. The vast majority of the study participants were drawn from areas where the prevalence of HIV infection and AIDS cases are substantially greater than the national average. Study participants received the ELISA test for HIV antibodies. All 112 of the participants tested negative for HIV antibodies. These results are encouraging, as they failed to reveal unrecognized occupational transmission of HIV infection among dialysis workers.

HIV↗
PubMed1991

Regulatory elements and DNA-binding proteins mediating transcription from the chicken very-low-density apolipoprotein II gene.

The chicken Very-Low-Density Apolipoprotein II (apoVLDL II) gene is specifically expressed in liver in response to estrogen. In this study, we performed a functional analysis of the 300-base pair region immediately 5' to the gene by gene transfer of chloramphenicol acetyl transferase (CAT) constructs into chicken embryonic hepatocytes (CEH). Two estrogen response elements (EREs) could be distinguished which together form a potent estrogen response unit. Stimulation of transient expression by co-transfection with a plasmid expressing rat C/EBP confirmed that a similar protein in chicken liver may be involved in apoVLDL II transcription. In vitro DNaseI footprinting and band-shift analysis with liver, oviduct and spleen nuclear extract revealed the tissue distribution of the proteins binding to the promoter region. A liver-specific protein bound to multiple sites of which some resembled the recognition sequence of the CCAAT/Enhancer binding protein, C/EBP. Of the other proteins binding to the apoVLDL II promoter, one was identified as the liver-specific LF-A1 by mobility shift analysis, using purified bovine LF-A1, and another as the general COUP-transcription factor, using an antiserum against the human COUP-TF.

Animals↗
PubMed1991

Susceptibility contrast imaging of cerebral blood volume: human experience.

Magnetic resonance (MR) can offer a unique window on the structure/function relationships in the brain, by utilizing the established link between tissue function, metabolism, and hemodynamics. This report focuses on recent applications of MR-based cerebral blood volume (CBV) imaging in humans. Our methodology uses high-speed "single-shot" or echo planar imaging techniques, which provide the necessary temporal resolution for mapping the rapid cerebral transit of contrast agents. These MR CBV mapping techniques have been used to study normal human brain task activation and in the clinical study of patients with brain tumors. In the latter, positron emission tomography imaging was used for functional metabolic and CBV correlation. Susceptibility contrast CBV imaging should allow us to improve our understanding of the relationship between the detailed physiology and morphology of the microvascular bed and functional attributes of the brain. These techniques can be applied to understanding fundamental questions of cognitive neuroscience and can aid in improving diagnostic sensitivity and specificity in various neuropathologies.

Brain↗