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Biomedical subjects

P Hofmann

Publications and source records attributed to P Hofmann.

At least 19 recordsLinked to original sources
PubMed2001

Catalyst screening by electrospray ionization tandem mass spectrometry: Hofmann carbenes for olefin metathesis.

A new screening methodology, which combines in situ synthesis of complexes with an assay by electrospray ionization tandem mass spectrometry (ESI-MS), is introduced in order to investigate highly active, cationic ruthenium-carbene catalysts in ring-opening metathesis polymerization (ROMP). The parameter space, whic is defined by systematic variation of four structural features of the catalyst [[R2P(CH2),PR2-kappa2-P]XRu=CHR']+ (the halogen ligand, the diphosphane bite-angle, the steric bulk of the phosphane, and the carbene ligand) and the variation of the metathesis substrate, is mapped out. Chloride as the anionic ligand X, a small chelating angle (n = 1), and reduced steric demand of the substituents R (Cy versus tBu) lead to the most reactive complex in acyclic olefin metathesis, whereas variation of the carbene moiety CHR' has only a modest influence. The overall rate in the gas phase depends on the pi-complex preequilibrium and metallacyclobutane formation, which was found to be the rate-determining step. In ROMP reactions backbiting has a profound influence on the overall rate. Moreover, we were able to establish that the reactivity trends determined in the gas phase parallel solution-phase reactivity. The overall rate in solution is also determined by a favorable dimer/ monomer preequilibrium providing the active catalyst by facile dissociation of dicationic, dinuclear catalyst precursors.

Journal Article↗
PubMed2001

First outbreak of callitrichid hepatitis in Germany: genetic characterization of the causative lymphocytic choriomeningitis virus strains.

Callitrichid hepatitis (CH) is a highly fatal, rodent-borne zoonosis of New World primates (family Callitrichidae) caused by lymphocytic choriomeningitis virus (LCMV). It is unclear whether virulence in Callitrichidae is associated with specific genetic or phylogenetic markers of the virus as only a partial S RNA sequence of a single CH-associated isolate is known. In a period of 10 months, three pygmy marmosets (Cebuella pygmaea) and one Goeldi's monkey (Callimico goeldii) died from CH in a German zoo. LCMV was most likely transmitted by wild mice. Infection was associated with characteristic histopathological lesions in liver, brain, and lymphoid tissue. Virus sequences from all callitrichids and a captured mouse were > or =99.2% identical. LCMV strains from a pygmy marmoset and the Goeldi's monkey were isolated in cell culture and the 3.4-kb S RNA was completely sequenced. Both strains differed considerably in their genetic and phylogenetic characteristics from known LCMV strains, including the previously described CH-associated strain. These data show that CH is widespread and can be caused by distantly related LCMV strains.

Amino Acid Sequence↗
PubMed2001

Sound attenuation of polymerizing actin reflects supramolecular structures: viscoelastic properties of actin gels modified by cytochalasin D, profilin and alpha-actinin.

Polymerization and depolymerization of cytoskeletal elements maintaining cytoplasmic stiffness are key factors in the control of cell crawling. Rheometry is a significant tool in determining the mechanical properties of the single elements in vitro. Viscoelasticity of gels formed by these polymers strongly depends on both the length and the associations of the filaments (e.g. entanglements, annealings and side-by-side associations). Ultrasound attenuation is related to viscosity, sound velocity and supramolecular structures in the sample. In combination with a small glass fibre (2 mm x 50 microm), serving as a viscosity sensor, an acoustic microscope was used to measure the elasticity and acoustic attenuation of actin solutions. Changes in acoustic attenuation of polymerizing actin by far exceed the values expected from calculations based on changes in viscosity and sound velocity. During the lag-phase of actin polymerization, attenuation slightly decreases, depending on actin concentration. After the half-maximum viscosity is accomplished and elasticity turns into steady state, attenuation distinctly rises. Changes in ultrasound attenuation depend on actin concentration, and they are modulated by the addition of alpha-actinin, cytochalasin D and profilin. Thus absorption and scattering of sound on the polymerization of actin is related to the packing density of the actin net, entanglements and the length of the actin filaments. Shortening of actin filaments by cytochalasin D was also confirmed by electron micrographs and falling-ball viscosimetry. In addition to viscosity and elasticity, the attenuation of sound proved to be a valuable parameter in characterizing actin polymerization and the supramolecular associations of F-actin.

Acoustics↗
PubMed2001

Suppression of proinflammatory cytokines and induction of IL-10 in human monocytes after coxsackievirus B3 infection.

Coxsackievirus B3 (CVB3) causes acute and chronic myocarditis, which is accompanied by an intense mononuclear leukocyte infiltration. Because myocardial tissue damage may either result from viral infections or from a dysregulated immune response, the susceptibility of human monocytes and macrophages to CVB3 was examined in this study with regard to virus replication, virus persistence, and release of cytokines. Monocytes were infected by CVB3 as shown by the intracellular appearance of plus- and minus-strand viral RNA, which was also capable of persisting for more than 10 days. Fresh monocytes were not permissive for full virus replication whereas monocyte-derived macrophages yielded a low amount of new viruses, which led to cell death. Although CVB3 infection induced the mRNA for the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, and IL-6, only little cytokine production occurred. When infected monocytes were stimulated in addition by lipopolysaccharides (LPS), cytokine production was partially suppressed. In striking contrast, IL-10 expression was strongly and persistently induced by CVB3 on the mRNA and the protein level. These data show a dysregulated cytokine response in CVB3-exposed human monocytes and macrophages, which is characterized by a suppression of proinflammatory cytokines and a dominance of IL-10. This viral strategy may aid CVB3, causing chronic myocardiopathy.

Cell Death↗
PubMed2001

[understanding and radiation hygiene assessment of solar UV exposure in Germany].

In order to monitor the natural ultraviolet (UV) radiation and to assess it from the point of view of radiation hygiene, the Federal Office for Radiation Protection (BfS) and the Federal Environmental Agency (UBA) have built up a common network for UV monitoring. Since 1993, the ground-level solar UV radiation has been measured at four sites in Germany every 6 minutes, with spectroradiometers in the wavelength range between 290 and 400 nm. Because erythema (sunborn) is of special interest in terms of radiation hygiene, the erythemal weighted irradiance was used as a measure for the biological effect of UV exposure. For this purpose, the measured spectral irradiance was multiplied by the relative erythemal weighting function, and the resulting function integrated from 290 to 400 nm. In the summer months of June and July 1999, the erythemal irradiance exceeded regularly the value of 175 mW/m2 in the south of Germany. In the north, values of not less than 160 mW/m2 were measured during this period. These values correspond to an UV index of more than 7 or 6, respectively--a high exposure regarding to the classification of the German Radiation Protection Commission (SSK), for which (absolute) sun protection is recommend. Between 1995 and 1999, the four sites were characterized by a small increase of the ground-level UV exposure of approx. 10%. Nevertheless, in consideration of the manifold factors affecting the acquired data, the measuring period of 5 years is still insufficient to demonstrate an ozone-dependent effect.

Erythema↗
PubMed2001

Immunohistochemical detection of simian immunodeficiency virus (SIV) in rectal mucosa of experimentally infected rhesus macaques (Macaca mulatta).

Experimental simian immunodeficiency virus (SIV) infection is the most appropriate animal model for human HIV infection. Eight male rhesus monkeys (Macaca mulatta) were intravenously or intrarectally infected with SIVmac251/MPBMC to comparatively investigate the distribution and spread of the virus within the rectum during the course of the disease. SIV-positive cells were immunohistochemically detected in rectal biopsies obtained at days 3 and 7 and week 2, 4 and 12 postinfection. SIV-expressing cells were detected for the first time at one week after experimental infection and were present in the lamina propria and lymph follicles. Numbers of positive cells per individual animal varied strongly in time, with a more rapid rise in animals with rapid progression of the disease. Differences were not observed between intravenous and intrarectal infection. Our observations support the significance of the intestinal tract as target organ in initial pathogenesis of SIV infection.

Animals↗
PubMed2001

A physiological profile of tennis match play.

PURPOSE: The aim of this investigation was to examine physiological demands of single match play in tennis. METHODS: 20 players performed 10 matches of 50 min. Respiratory gas exchange measures (RGEM) and heart rates (HR) were measured using two portable systems. Lactate concentration was determined after each game. The average oxygen uptake (VO2) of 270 games was 29.1 +/- 5.6 mL.kg-1.min-1 (51.1 +/- 10.9% of VO2max). Average VO2 for a game ranged from 10.4 to 47.8 mL.kg-1.min-1 (20.4 and 86.8% of VO2max). Average lactate concentration (LA) was 2.07 +/- 0.9 mmol.L-1 (ranging from 0.7 to 5.2 mmol.L-1). Furthermore, we monitored the duration of rallies (DR), the effective playing time (EPT), and the stroke frequency (SF). The average values of 270 games were DR: 6.4 +/- 4.1 s, EPT: 29.3 +/- 12.1%, SF: 42.6 +/- 9.6 shots.min-1. RESULTS: Multiple regression revealed that the DR was the most promising variable for the determination of VO2 in match play (r = 0.54). The body surface area (BSA) and EPT were also entered into the calculation model. In games of two defensive players, VO2 was significantly higher than in games with at least one offensive player. CONCLUSION: Our results suggest that energy demands of tennis matches are significantly influenced by DR. The highest average VO2 of a game of 47.8 mL.kg-1.min-1 may be regarded as a guide to assess endurance capacity required to sustain high-intensity periods of tennis matches compared with average VO2 of 29.1 mL.kg-1.min-1 for the 270 games. Our results suggest that proper conditioning is advisable especially for players who prefer to play from the baseline.

Adult↗
PubMed2001

%HRmax target heart rate is dependent on heart rate performance curve deflection.

UNLABELLED: The percent of maximal heart rate (%HRmax) model is widely used to determine training intensities in healthy subjects and patients when prescribing training intensities in these groups of subjects. PURPOSE: The aim of the study was to investigate the influence of the time course of the heart rate performance curve (HRPC) on the accuracy of target training heart rate. METHODS: Sixty-two young healthy male subjects performed an incremental cycle ergometer exercise test until voluntary exhaustion. Subjects were then divided into four groups according to the time course of the HRPC. Groups were classified in regular HR response (kHR2 > 0.2), indifferent HR response (0 < kHR2 < 0.2), linear HR response (kHR2 = 0), and inverted HR response (kHR2 < 0). The first and the second lactate turn point (LTP1, LTP2) as well as the heart rate turn point (HRTP) were determined as submaximal markers of performance. Linear regression lines were calculated for HR in the three regions of energy supply defined by LTP1 and LTP2. RESULTS: HR at LTP1 and HRmax was not significantly different between all four groups. HR at LTP2 was dependent on the time course of the HRPC and was significantly lower (P < 0.05) as kHR2 decreased. Power output and blood lactate concentration at LTP1, LTP2 and maximal workload (Pmax) were not significantly different between the groups. CONCLUSION: From our data, we conclude that target training HR detected by means of the %HRmax method may be overestimated in cases where the HR response is not regular, as it was found in many of our subjects.

Adult↗
PubMed2000

Phenotype, intestinal morphology, and survival of homozygous and heterozygous endothelin B receptor--deficient (spotting lethal) rats.

BACKGROUND/PURPOSE: Spotting lethal (sl) rats, a model for Hirschsprung's disease, recently have been found to carry a deletion in the endothelin B (ET(B)) gene, causing functional lack of ET(B) receptors. The ET(B) receptor mediates, together with and in counterbalance to the ET(A) receptor, endothelin actions on vessels, cell proliferation, and migration. The authors investigated the effect of homozygosity (sI/sI) or heterozygosity (+/sl) on phenotype, intestinal morphology, and survival. METHODS: Weight, circumference, and serum albumin were measured. Histological tests of major organs and immunoperoxidase reaction for Peripherin, glial fibrillary acid protein (GFAP), and S-100 in small and large intestine were performed. Peripherin-immunostained sections of colon and jejunum were analyzed morphometrically. Screening for sepsis included search for enterocolitis, bacterial infection, endotoxin, and iNOS mRNA. RESULTS: Sl/sl rats died within 4 weeks of life, showing an early and a later death group. Serum albumin levels were decreased in sl/sl rats, whereas signs of sepsis were rare. Immunostaining uncovered alterations in nerve and glial cells in the whole gut of sl/sl rats, and to a subtle degree also in +/sl rats, which appear clinically normal. Morphometric quantification yielded statistically significant alterations in sl/sl rats only. No obvious abnormalities were found in other organs. CONCLUSIONS: Sl/sl rats die from malnutrition rather than sepsis, too early for ischemic complications to occur. Rats of the later death group are a suitable model for studying the ET8 receptor in vivo. Subtle abnormalities in the enteric nervous system of heterozygous rats underline the critical role of the "gene dose" for functional compensation.

Animals↗
PubMed2000

Prolactin and beta-endorphin serum elevations after ECT in manic patients.

OBJECTIVE: Alterations in prolactin and beta-endorphin serum levels after ECT are well-established findings in depression. The present study focuses on electroconvulsive therapy (ECT) response patterns of the mentioned parameters in patients suffering from acute mania. METHOD: Following the first three ECTs of a treatment series in 19 patients diagnosed according to DSM-III-R criteria as suffering from mania, blood samples were drawn before, and 20, 30 and 40 minutes after ECT. Serum prolactin and beta-endorphin levels were established in order to gain information about the effects of ECT on different neurotransmitter systems. RESULTS: A significant transient increase in serum prolactin after ECT was found. Furthermore, in females but not males, delta(max)prolactin diminished over the course of treatment as prolactin baseline levels increased. beta-endorphin levels showed a stable transient increase after ECT stimulus regardless from sex or treatment. CONCLUSION: The reported findings reflect those established in depression. This suggests that they are epiphenomenal to ECT.

Acute Disease↗
PubMed2000

Total numbers of lymphocyte subsets in different lymph node regions of uninfected and SIV-infected macaques.

Human immunodeficiency virus (HIV) infection leads to a decline of CD4+ T-cells in blood. Because blood represents only a small proportion of the total lymphocyte pool, it is important to investigate other lymphoid organs. So far, only relative proportions of lymphocyte subsets in single peripheral lymph node (LN) regions of HIV-infected patients and simian immunodeficiency virus (SIV)-infected macaques have been documented. We have therefore quantified the absolute numbers of lymphocyte subsets in blood and six different LN regions of 10 uninfected and 26 SIV-infected macaques. In addition, we have determined the expression of markers of activation and differentiation. Already, in uninfected monkeys, there were significant differences in the cellular composition of different LN regions. Infection with SIV resulted in drastic changes in the proportion as well as absolute numbers of different lymphocyte subsets. Moreover, the relative contribution of the single LN regions to the total lymphocyte pool was also altered.

Animals↗
PubMed2000

Selective induction of the monocyte-attracting chemokines MCP-1 and IP-10 in vesicular stomatitis virus-infected human monocytes.

It is characteristic of viral infections that monocytes/macrophages and lymphocytes infiltrate infected tissue, and neutrophils are absent. CC and non-ELR CXC chemokines predominantly attract mononuclear leukocytes, whereas the ELR motif-expressing CXC chemokines primarily act on neutrophils. To investigate the general role of chemokines in viral diseases, we determined their release and expression patterns after infection of human monocytes with vesicular stomatitis virus (VSV). Human monocytes were productively infected by VSV. Surprisingly, VSV did not induce the release of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6. In contrast, we found a strong induction of the CC chemokine monocyte chemotactic protein-1 (MCP-1) and the non-ELR CXC chemokine interferon-gamma (IFN-gamma) inducible protein-10 (IP-10) by VSV on the gene and protein level. The expression and release of the neutrophil chemoattractants IL-8 and growth-related oncogene-alpha (GRO-alpha) remained unaffected after VSV infection. Our results indicate that the typical monocyte and lymphocyte-dominated leukocyte infiltration of virus-infected tissue is based on a selective induction of mononuclear leukocyte-attracting chemokines.

Cells, Cultured↗
PubMed2000

Change in left atrial and ventricular dimensions during and immediately after exercise.

PURPOSE: The aim of this study was to evaluate differences in the left atrial (LAD), total ventricular end-diastolic (TEDD), end-systolic diameters (TESD), and left ventricular shortening fraction (SF) compared with heart rate (HR) and systolic blood pressure (SBP) during exercise and recovery. METHODS: Healthy young male (N = 15) and female (N = 16) subjects performed an incremental cycle ergometer test in upright position, and three phases of energy supply were defined by means of blood lactate concentration (LA) and respiratory gas exchange variables (I: aerobic; II: aerobic-anaerobic transition; III: anaerobic). Subjects were required to rest their arms on a steering bar and to lean their upper body forward; two dimensional (2-D) echocardiograms were obtained over the left parasternal area at rest (R), at the end of each phase, immediately within 15 s post, and 6 min after exercise (6 min). By using VINGMED's "Anatomical M-Mode," it was possible to extract M-Mode Sweeps from stored 2-D-Loops and perform the M-Mode measurement. RESULTS: In contrast to the significant decrease in TEDD and TESD from III to 15 s up to resting values and the significant increase in SF from III to 15 s, the moderate decrease in HR immediately post exercise (15 s) was not significant. The SBP showed a significantly decrease from III to 15 s; in contrast to TEDD, TESD, and SF, the values at 15 s were comparable with the values at II. For LAD, significant increase during exercise and a decrease during recovery were observed. Sex-specific differences of changes in measured variables could not be found. CONCLUSION: We concluded that post exercise measurement of left ventricular and atrial dimensions or SF were not valid to describe heart function at maximal exercise although immediately post exercise HR was near maximal level.

Adult↗
PubMed2000

Cytokine profiles in heart, spleen, and thymus during the acute stage of experimental coxsackievirus B3-induced chronic myocarditis.

Since cytokines play an important role in the pathogenesis of virus-induced chronic heart diseases, cytokine mRNA expression was studied in coxsackievirus B3-infected NMRI mice during the acute phase of myocarditis until the onset of chronic cardiac disease. Virus replication, cytokine induction, inflammatory cell infiltration and myocardial damage were studied by titer determination, reverse transcription-polymerase chain reaction (RT-PCR), and histopathology. To investigate whether the coxsackievirus B3-induced cytokine mRNA accumulation was only limited to the heart or generalized, spleen and thymus specimens were also included. Surprisingly, interleukin (IL)-10 as a deactivator of T cell and macrophage functions was transcribed in the myocardium nearly in parallel with virus replication from Day 1 through Day 14. At Day 3 p.i., the mRNA of IL-1alpha, tumor necrosis factor (TNF)-alpha, IL-6, and interferon (IFN)-beta accumulated. At Days 4, 7, and 14, IL-12-specific mRNA was produced. Furthermore, increasing amounts of IFN-gamma mRNA were found, whereas IL-2 and IL-4 mRNA remained undetectable. TNF-alpha, IL-1alpha, IL-10, IL-12, and IFN-gamma mRNA persisted into the late stage of myocarditis. In the spleen a closely correlated expression of virus and IL-10-specific mRNAs was also found, and in addition, IFN-beta, TNF-alpha, and IL-6 were detected. In striking contrast to heart and spleen tissue, the distinct expression of viral RNA in the thymus was not accompanied by an increased cytokine mRNA production. These data provide evidence for a unique coxsackievirus B3-induced cytokine pattern in the myocardium and spleen and suggest that persistently expressed IL-10 may play a leading role in acute and chronic myocarditis by subverting the immune response.

Acute Disease↗
PubMed2000

[Performance enhancement through training at medium altitude-- from the perspective of sports medicine].

In the last 20 years, maximal oxygen uptake (VO2max) of athletes in different sport disciplines has increased, and the world records in endurance sports have improved markedly. One of the factors that has influenced the increase in endurance performance has been perceived to be altitude training. In this paper we describe the advantages and disadvantages of a "regular" altitude training (live high/train high) aiming to improve sea level performance and compare it with a new method, the so called "live high/train low" method. This method uses the advantages and avoids the side effects of altitude exposure. Several papers have shown that altitude training is able to improve VO2max but the individual response may be substantially different. In most cases it is not possible to prove statistical significance and therefore we have no data about differences between both altitude training methods. However, it is suspected that the risk of overtraining is reduced in the high/low method. Although not statistically significant it is suggested that the "high/low" method can more efficiently improve endurance performance at sea level. A monitoring of submaximal variables of exercise performance is recommended to avoid overtraining and to control the development of performance. From the current knowledge the "live high/train low" method is suggested to be the more effective altitude training method for athletes.

Acclimatization↗
PubMed1999

The heart rate turn point reliability and methodological aspects.

PURPOSE: The aim of the study was to test protocol variations on the heart rate performance curve (HRPC) and the heart rate turn point (HRTP) according to Conconi et al. (1996). Respiratory gas exchange variables were used to define three phases of energy supply (I, II, III). METHODS: Eighteen healthy young male subjects performed 4 tests (T1-T4). T1: initial speed of 6 km x h(-1) followed by increments of 0.6 km x h(-1) every 60 s. Subjects were than randomized for the next three tests. T2: initial speed 5.6 km x h(-1) followed by increments of 0.2 km x h(-1) every 20 s; T3: similar to T2, in the second half of phase III acceleration (S) was increased. T4: like T2, at the beginning of phase III, S was increased. No differences were found in the degree of the deflection of the HRPC expressed as factor kHR between T1 (0.228 +/- 0.225) and T2 (0.248 +/- 0.231) but a significant increase was found in T3 (0.533 +/- 0.248) and T4 (0.770 +/- 0.258). RESULTS: The modifications of the protocol (T3 and T4) systematically influenced the deflection of the HRPC, but kHR was highly reproducible in all tests. Eleven subjects showed degrees of deflection in the HRPC in all tests. There were no significant differences for S, HR, and VO2 at the HRTP. An HRTP was not found in seven subjects in neither T1 or T2; however, in T3 and T4, these seven subjects showed a deflection of HRPC resulting from the protocol. The HRTP was found to be dependent on the start of the acceleration in phase III. In cases with a linear time course in the HRPC in T1 and T2, in T3 an HRTP was found at 15.6 km x h(-1) and in T4 at 13.6 km x h(-1) , respectively. CONCLUSION: The Conconi test protocol with an accelerated increase in S in the final phase of the test has a major influence on the occurrence of the HRTP in cases of near linear HRPC.

Adolescent↗
PubMed1999

CD2-mediated CD59 stimulation in keratinocytes results in secretion of IL-1alpha, IL-6, and GM-CSF: implications for the interaction of keratinocytes with intraepidermal T lymphocytes.

Normal epidermal keratinocytes are here shown to express membrane-associated complement inhibitory protein CD59 in vitro that protects keratinocytes from damage by complement because preincubation with blocking antibodies to CD59 renders the cells susceptible to complement mediated lysis. CD59 expression in keratinocytes is constitutive and not modulated by inflammatory cytokines, phorbol myristate acetate (PMA), and a number of other agents tested. Antibody mediated cross-linking of CD59, however, revealed an additional function of CD59: keratinocytes in vitro are activated to secrete the cytokines IL-1alpha, IL-6, and GM-CSF. CD59 mediated induction of these cytokines is regulated at the transcriptional level. Binding of keratinocytes to HL60 cells that express CD59 ligand CD2 induced the same pattern of secreted cytokines whereas binding to CD2-negative HL60 cells did not. Induction of cytokine secretion was completely blocked by preincubation of keratinocytes with both anti-CD58 and anti-CD59 antibodies together. The results demonstrate that CD2-mediated CD59 stimulation in human keratinocytes leads to synthesis of a particular set of cytokines implying a potential activation pathway in the interaction of keratinocytes with intraepithelial CD2+ T cells.

Antibodies, Blocking↗