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Biomedical subjects

M Moser

Publications and source records attributed to M Moser.

At least 163 records · Page 9Linked to original sources

Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo.

Dendritic cells (DC) are described as "nature's adjuvant," since they have the capacity to sensitize T cells in vivo upon first encounter with the antigen. The potent accessory properties of DC appear to develop sequentially. In particular, the ability to process antigens and to sensitize native T cells develops in sequence, a process termed "maturation" that is well described in vitro. Here, we obtain evidence for maturation in vivo in response to the bacterial product lipopolysaccharide (LPS). Before LPS treatment, many DC are found at the margin between the red and white pulp. These cells lack the M342 and DEC-205 markers, but process soluble proteins effectively. 6 h after LPS, DC with the M342 and DEC-205 markers are found in increased numbers in the T cell areas. These cells have a reduced capacity to process proteins, but show increases in the B7 costimulator and T cell stimulatory capacity. 48 h after LPS, the number of DC in the spleen is reduced markedly. We interpret these findings to mean that LPS can cause DC in the marginal zone to mature and to migrate into and then out of the T cell areas.

Animals↗

Long-term imprisonment leads to cognitive impairment.

The effects of long-term imprisonment on cognitive functions are investigated in a longitudinal study. Twenty-four serious offenders in an Austrian penitentiary underwent concentration and memory performance measurements via a questionnaire presented to them under controlled conditions in two sessions at a 42 month interval. The difference in the parameters indicated cognitive impairment after this period that was highly significant (P < 0.01); this can be interpreted as a direct consequence of imprisonment.

Adult↗

Identification and deletion of sequences required for feline leukemia virus RNA packaging and construction of a high-titer feline leukemia virus packaging cell line.

Sequences required for specific encapsidation of feline leukemia virus (FeLV) genomic RNA have not yet been defined. Deletion of 107 nucleotides between the splice donor (SD) and the gag coding region of a prototypic subgroup A FeLV, 61E, resulted in an approximately 200-fold reduction of packaged viral RNA. Virus particle production was not disrupted by the deletion, although viral infectivity was dramatically reduced. These data indicate that the 107-nucleotide sequence comprises a portion of the FeLV packaging signal. FeLV particles expressed from the deleted genome were able to efficiently package murine leukemia virus vectors, resulting in high-titer G418R virus production. This system can be easily adapted to produce FeLV particles that contain envelope proteins from other feline leukemia virus subgroups and will be broadly useful for studies of FeLV envelope/receptor interactions.

Animals↗

Management of hypertension, Part I.

Elevated systolic blood pressure increases the risk of a coronary heart disease event to as great or greater a degree as elevated diastolic blood pressure. The fifth Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure has incorporated systolic blood pressure into the new definitions of hypertension. Although the syndrome of white coat hypertension has been well defined, physicians should still rely on casual blood pressure readings taken in the office or clinic for treatment decisions. The levels of blood pressure used to determine risk or estimate prognosis have been based on office or clinic blood pressures. The JNC's suggestion that diuretics or beta blockers be the preferred initial therapy is based on evidence from long-term trials showing that these medications reduce morbidity and mortality not just for cerebrovascular, but also for cardiovascular diseases. The possibly adverse effects of diuretics or beta blockers on lipids and glucose metabolism have probably been overemphasized.

Adrenergic beta-Antagonists↗

Altered circadian activity rhythms and sleep in mice devoid of prion protein.

There is a wealth of data supporting a central role for the prion protein (PrP) in the neurodegenerative prion diseases of both humans and other species, yet the normal function of PrP, which is expressed at the cell surface of neurons and glial cells, is unknown. It has been speculated that neuropathology may be due to loss of normal function of PrP. Here we show that in mice devoid of PrP there is an alteration in both circadian activity rhythms and patterns. To our knowledge, this is the first null mutation that has been shown to affect sleep regulation and our results indicate that at least one of the inherited prion diseases, fatal familial insomnia, where there is a profound alteration in sleep and the daily rhythms of many hormones, may be related to the normal function of the prion protein.

Animals↗

Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie.

The 'protein only' hypothesis postulates that the prion, the agent causing transmissible spongiform encephalopathies, is PrP(Sc), an isoform of the host protein PrP(C). Protease treatment of prion preparations cleaves off approximately 60 N-terminal residues of PrP(Sc) but does not abrogate infectivity. Disruption of the PrP gene in the mouse abolishes susceptibility to scrapie and prion replication. We have introduced into PrP knockout mice transgenes encoding wild-type PrP or PrP lacking 26 or 49 amino-proximal amino acids which are protease susceptible in PrP(Sc). Inoculation with prions led to fatal disease, prion propagation and accumulation of PrP(Sc) in mice expressing both wild-type and truncated PrPs. Within the framework of the 'protein only' hypothesis, this means that the amino-proximal segment of PrP(C) is not required either for its susceptibility to conversion into the pathogenic, infectious form of PrP or for the generation of PrP(Sc).

Amino Acid Sequence↗

Crystallization and preliminary X-ray analysis of phosphoserine aminotransferase from Bacillus circulans subsp. alkalophilus.

Recombinant phosphoserine aminotransferase (EC 2.6.1.52) from Bacillus circulans subsp. alkalophilus was crystallized at room temperature from 0.1 M sodium acetate buffer, pH 4.6, and 2% PEG 20000, using macroseeding techniques. The crystals diffract X-rays to at least 2.0 A nominal resolution. They belong to space group C2 with unit cell dimensions a = 93.2 A, b = 93.1 A, c = 45.6 A, alpha = 90.0 degrees, beta = 106.8 degrees, gamma = 90.0 degrees. A native data set to 2.3 A has been collected. Assuming an average packing density of the crystals, there is one monomer in the asymmetric unit, resulting in a calculated solvent content of 48.2%.

Bacillus↗

Prevention of disease progression, left ventricular hypertrophy and congestive heart failure in hypertension treatment trials.

OBJECTIVES: This work was done to determine the role of hypertension treatment in the prevention of disease progression, left ventricular hypertrophy and congestive heart failure. BACKGROUND: Lowering of blood pressure in hypertensive patients has been reported to reduce morbidity and mortality from strokes and myocardial infarction. Data on primary prevention of disease progression, left ventricular hypertrophy and congestive heart failure have not previously been carefully quantified. METHODS: All the major long-term hypertension treatment trials over the past 20 years were reviewed. RESULTS: One thousand four hundred ninety-three of 13,342 subjects in the control groups compared with only 95 of 13,389 in the treated groups progressed from less severe to severe hypertension. The incidence of left ventricular hypertrophy in treated compared with control or placebo subjects was 140 of 6,150 and 216 of 6,098 subjects, respectively; congestive heart failure occurred in 240 of 6,923 subjects in the control group compared with only 112 of 6,914 treated subjects. CONCLUSIONS: The lowering of blood pressure over a 3- to 5-year period of time is effective in preventing severe disease, left ventricular hypertrophy and congestive heart failure in addition to strokes and myocardial infarction. In an era when expensive and often complicated methods are being used to prevent recurrence of congestive heart failure or myocardial infarction, it is important to highlight the role of antihypertensive therapy in primary prevention.

Antihypertensive Agents↗

Costimulation regulates the kinetics of interleukin-2 response to bacterial superantigens.

The aim of this study was to investigate the mechanisms by which B7-related costimulatory molecules (CD80, CD86) increase T-cell responsiveness to extracellular ligands. As a model study, the in vitro response of purified splenic CD4+ T cells to a bacterial superantigen, SEB, was characterized. Previous analysis of this experimental model led us to conclude that expression of B7-related molecules is strictly required in order to activate CD4+ T cells in the presence of bacterial superantigens. In the present report, we demonstrate that antigen-presenting cell-derived costimulatory signals regulate the kinetics of interleukin-2 (IL-2) production by SEB-activated splenic CD4+ T cells. Indeed, experiments performed with purified subpopulations of antigen-presenting cells and using B7-transfected cell lines indicated that increased levels of CD80 and/or CD86 cell surface expression is associated with a faster kinetics of IL-2 production in response to SEB. Accordingly, blocking of CD80 or CD86-derived signals by specific monoclonal antibodies led to a slower kinetics of IL-2 production in response to SEB. Thus these data demonstrate that similar strength of signal through the T-cell receptor can lead to immune responses displaying distinct kinetics depending on the level of costimulatory ligands on APC.

Animals↗

[Speech-specific cortical potentials--methodologic aspects and initial clinical results].

BACKGROUND: The purpose of this study was to find out whether specific cortical potentials can be evoked and identified after word stimulation. The clinical relevance was to be investigated in patients with aphasic syndromes. MATERIALS AND METHODS: In 20 young adults with no signs of hearing impairment and in patients with manifest aphasic syndromes, word-evoked cortical potentials were compared with those after an equivalent noise stimulus. The test words were selected from the Freiburger Speech Comprehension Test. The duration of the words was between 450 and 640 ms. The stimulus was presented monaurally. The peak level was 70 dB HL. The noise stimulus was produced by modifying a low-band noise. Potentials were measured between the ipsilateral mastoid and the contralateral forehead. Data were analysed offline. RESULTS: In healthy persons, the potentials after word and noise stimulation did not differ until 100 ms after the stimulus onset. After noise stimulation a negative maximum could be seen 100 ms after the stimulus onset, and a positive maximum 200 ms after the stimulus onset. After word stimulation, a positive maximum of higher amplitude than after noise stimulation was measured 150 ms after the stimulus onset, and a negative maximum was measured 270 ms after the stimulus onset. In all test persons the difference curve of word-and noise-evoked potentials revealed a speech-specific component 170 ms (N 170) after the stimulus onset. The single-word analysis showed that the potentials depend on the phonemes of the test word. The potentials do not alter when the stimulus side is changed. In patients with aphasia the potentials depend on the grade of the disturbance of speech perception: global and Wernicke's aphasia show no significant difference of speech-and noise-evoked potentials, whereas in Broca's aphasia a speech specific maximum is apparent. CONCLUSION: The speech-specific component may be regarded as a paradigm of cortical speech detection processes. Electrophysiological speech audiometry by means of word-evoked cortical potentials seems possible and may be used for clinical purposes.

Adult↗

Instrumentation for assessment of tremor, skin vibrations, and cardiovascular variables in MIR space missions.

A versatile and simple to use biomedical instrumentation for noninvasive examinations of cosmonauts at the Russian MIR space station was developed. It consists of a comfortable sensor jacket to assess signals from the body surface, a precision hand dynamometer to produce muscular and cardiovascular loads, and a small interactive microprocessor unit that controls the examination and stores measurement data. The sensor jacket includes highly sensitive piezo-resistive accelerometers, pulse sensors, an ECG system, and a skin-mountable mechanical vibrator. The functionality of this instrumentation was evaluated during long-term space flights and also proved very useful in laboratory and clinical studies.

Cardiovascular Physiological Phenomena↗

Serological and skin-test diagnosis of birch pollen allergy with recombinant Bet v I, the major birch pollen allergen.

BACKGROUND: Type I allergy represents a severe health problem in industrialized countries where up to 20% of the population suffer from allergic rhinitis, conjunctivitis and allergic asthma bronchiale and in severe cases from anaphylaxis, leading to death. OBJECTIVE: The aim of this study was to evaluate recombinant Bet v I, the major birch pollen allergen for in vivo and in vitro diagnosis of birch pollen allergy. METHODS: A group of 51 birch pollen allergic patients and eight non-allergic control individuals were tested for birch pollen allergy by skin-prick and intradermal testing, comparing commercial birch pollen extracts with recombinant Bet v I. Quantitative and qualitative serological testing was done with natural and recombinant allergens by radioallergosorbent test (RAST), enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Recombinant Bet v I allowed accurate in vivo and in vitro diagnosis of tree pollen allergy in 49/51 patients tested. No false positive results were obtained in any in vitro assay system (ELISA, Western blot) or by skin testing (skin-prick, intradermal test) with recombinant Bet v I. CONCLUSION: Our results document that recombinant Bet v I produced in bacterial expression systems allows accurate in vitro and in vivo diagnosis of birch pollen allergy in > 95% of birch pollen allergic patients.

Adult↗

Management of hypertension, Part II.

Although calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors are effective in lowering blood pressure, no long-term data show their effect on morbidity and mortality in hypertensive patients. They are suggested as alternative initial therapy in hypertensive patients. Short-acting calcium channel blockers are to be used with caution or not at all in the treatment of hypertension. Nonhydropyridine calcium channel blockers may reduce the incidence of second infarction but not congestive heart failure or mortality in patients with ischemic heart disease. The ACE inhibitors increase insulin sensitivity and decrease intraglomerular pressure. In combination with a diuretic, they are the preferred agents in the treatment of diabetic patients with hypertension, especially those with nephropathy. In both hypertensive and normotensive patients, ACE inhibitors reduce morbidity and mortality resulting from congestive heart failure in patients with poor left ventricular function who are also being treated with a diuretic and/or digitalis. They do not, however, reduce strokes or myocardial infarctions in hypertensive patients.

Antihypertensive Agents↗

Hypertension can be treated effectively without increasing the cost of care.

There is little reason to believe that patients with hypertension cannot be treated effectively without increasing the cost of care. Yet costs in the United States continue to increase. It is of interest to review some of the reasons for this and to emphasize that the management of hypertension has been successfully carried out over the past 20-30 years without the use of expensive technology or complicated treatment programs. This is an important message to non industrialized nations that are starting hypertension treatment programs. Hypertension costs can be controlled by: (1) limiting the complexities of the initial evaluation, avoiding the temptation to employ technologies which have not been shown to improve outcome, and (2) by selecting therapy based on data that have been collected over the past 20 years, and not on the latest promotional efforts. In addition, there is evidence that limiting physician visits to 2, 3 or at the most 4 per year is adequate to control the majority of hypertensive patients after initial blood pressure control is obtained--another important factor in the cost of care ($). There is no evidence that a more expensive approach to management will improve outcome compared to a less costly approach.

Antihypertensive Agents↗

Endocrine, metabolic and hematological changes associated with reduced growth performance during chronic pneumonia in calves: a case study.

A veal calf with chronic pneumonia was characterized by reduced weight gain, feed intake and increased feed/gain ratio. Concentrations of hemoglobin, packed cell volume, red blood cell number and blood plasma levels of iron, albumin, urea, glucose, insulin, insulin-like growth factor-I and triiodothyronine were decreased, while plasma levels of total protein, immunoglobulin G and nonesterified fatty acids were increased. White blood cell number, blood plasma concentrations of triglycerides, growth hormone, cortisol and tumor necrosis factor-alpha were not changed. Hematological, metabolic and endocrine changes were interpreted as expressions of reduced energy and protein intake and of nutrient partitioning which contributed to reduced growth performance.

Animals↗

Assessment of electrophysiological state of heart in astronauts in terms of decartographic and conventional electrocardiographic characteristics.

Long-term observation of the heart state during specialized professional activities plays an important part in preventive medicine. This study is aimed at assessment of electrophysiological state of heart in astronauts by common electrocardiography, vectorcardiography, and dipole electrocardiotopography (DECARTO technique). The subjects observed were two astronauts performing a long-term flight at the Mir orbital station. DECARTO technique was used to obtain an intelligible-pictorial representation of the data in the form of so-called decartograms for visual and quantitative analysis. The observations showed rather stable chronotopography of the heart depolarization process. However, there was an increase of the maximal magnitude of the electric heart vector and a decrease of the ventricular gradient vector in the middle part of the flight. Just upon landing, a pronounced decrease of the ventricular gradient magnitude, followed by a fast restoration of its value was observed in both subjects. The DECARTO technique used in combination with vectorcardiography facilitated the detailed visual analysis of the electrocardiographic data. (Fig. 3, Ref. 3.)

Astronauts↗

[Serologic and skin test diagnosis of birch pollen allergy with recombinant Bet v 1, the chief allergen of birch].

BACKGROUND: Type I allergy represents a severe health problem in industrialized countries where up to 20% of the population suffers from allergic rhinitis, conjunctivitis and allergic asthma bronchiale and in severe cases from anaphylaxis, leading to death. OBJECTIVE: The aim of this study was to evaluate recombinant Bet v 1, the major birch pollen allergen for in vivo and in vitro diagnosis of birch pollen allergy. METHODS: A group of 51 birch pollen allergic patients and eight non-allergic control individuals were tested for birch pollen allergy by skin-prick and intradermal testing, comparing commercial birch pollen extracts with recombinant Bet v 1. Quantitative and qualitative serological testing was done with natural and recombinant allergens by radioallergosorbent test (RAST), enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Recombinant Bet v 1 allowed accurate in vivo and in vitro diagnosis of tree pollen allergy in 49/51 patients tested. No false positive results were obtained in any in vitro assay system (ELISA, Westernblot) or by skin testing (skin-prick, intradermal test) with recombinant Bet v 1. CONCLUSION: Our results document that recombinant Bet v 1 produced in bacterial expression systems allows accurate in vitro and in vivo diagnosis of birch pollen allergy in > 95% of birch pollen allergic patients.

Adult↗