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Biomedical subjects

P Hofmann

Publications and source records attributed to P Hofmann.

At least 37 records · Page 2Linked to original sources

Three spontaneous lymphomas in a colony of cotton-top tamarins (Saguinus oedipus).

Cotton-top tamarins are well known for their prevalence to idiopathic colitis and adenocarcinomas. At the same time, information on the incidence of spontaneous lymphomas in this highly endangered species is rare. Records, 212 in total, of cotton-top tamarins (Saguinus oedipus) necropsied at the German Primate Centre between 1979 and 1998 were viewed to establish the prevalence of lymphoid neoplasms. Neoplastic lymphoid cell growth was mentioned in three necropsy records. Immunohistology was performed in all three cases on the remaining formalin-fixed, paraffin-embedded tissue using antibodies against CD20, CD3, lysozyme, Ki-67, IgM, IgG, kappa, lambda and EBNA-2. Combining histological and immunohistological results, the lymphomas could be differentiated into two low-grade T-cell lymphomas and one high-grade multicentric polymorphic B-cell lymphoma. This corresponds to a 1.4% incidence of lymphomas in our cotton-top tamarin population over a period of 19 years. Although frozen material was not available and virological testing could not be carried out, clinical or histological evidence did not support an aetiological role of Herpes (H.) saimiri, H. ateles, simian T-cell leukaemia virus type 1 (STLV-1) or Epstein-Barr-related herpesvirus in any of these cases. The lymphomas were considered to be spontaneous.

Animals↗

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↗

Defense against influenza A virus infection: essential role of the chemokine system.

Monocytes/macrophages are highly susceptible to an infection with influenza A virus. After infection, de novo virus protein synthesis is detectable but rapidly interrupted before completion of the first viral replication cycle. Within 24-48 hours the infected monocytes die by apoptosis. Before cell death, infected monocytes initiate a cell-specific immune response. This includes the transcription and subsequent release of TNF-alpha (tumor necrosis factor alpha), IL-1beta (Interleukin 1beta), IL-6, type I inferferons and CC chemokines. Enhanced cytokine mRNA expression is due to a prolonged mRNA stability and an augmented gene transcription. Activation of transcription factors such as NF-kappaB (nuclear factor kappaB) and AP-1 are involved in activation of cytokine mRNA transcription. Infection of monocytes with influenza A virus induces the selective expression of mononuclear leukocyte attracting chemokines, such as MCP-1 (monocyte chemotactic protein 1), MIP-1alpha (macrophage inflammatory protein 1alpha) and RANTES (regulated upon activation, normal T cell expressed and secreted). In striking contrast, the release of the neutrophil-specific chemokines IL-8 (interleukin 8) and GRO-alpha (growth stimulatory activity alpha) is entirely suppressed. This differentially regulated chemokine expression may explain the mononuclear cell infiltrate characteristic for virus-infected tissue. Thus, infection of monocytes/macrophages with influenza A virus primes for a rapid proinflammatory reaction and induces an enhanced immigration of mononuclear cells into infected tissue. Taken together, these mechanisms may prepare the infected host for a fast and virus-specific immune response.

Animals↗

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↗

%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↗

A trigonal planar mu 3-fluorido coinage metal complex from a dicationic (diphosphinomethane)copper(I) dimer: syntheses, structures, and bonding.

The triflate and hexafluorophosphate salts of [Cu2(mu-dtbpm)2]2+ (1(2+)) [dtbpm = bis(di-tert-butylphosphino)methane, tBu2PCH2PtBu2] and of [Cu3(mu 3-F)(mu-dtbpm)3]2+ (2(2+)) were synthesized and characterized. Coordination of solvent or counterions to 1(2+) is observed neither in solution nor in the solid state. The two copper(I) centers in 1(2+) indicate weak d10-d10 closed-shell interactions. 1(2+) reacts slowly with PF6- anions in acetone or KF in CH2Cl2 to yield the mu 3-fluorido complex 2(2+) with idealized D3 symmetry, containing a trigonal planar Cu3F core, as shown by single-crystal X-ray diffraction. Distinct structural differences are observed compared to monocationic bicapped, trinuclear copper(I) dppm halide complexes [dppm = bis(diphenylphosphino)methane, Ph2PCH2PPh2]. The average Cu-Cu, Cu-F, and Cu-P distances and the P-Cu-P' angle in 2(2+) are 3.85, 2.22, and 2.28 A and 144.3 degrees, respectively. The P2Cu units are twisted out of the Cu3F plane by an average angle of 18.4 degrees. DFT calculations (BPW91/LANL2DZ) for the model [Cu3(mu 3-F)(mu-dhpm)3]2+ (dhpm = diphosphinomethane, H2PCH2PH2) are used to explain the formation, structure, and bonding pattern of 2(2+).

Journal Article↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗

[Hypophyseal-hypothalamo-thyroid axis in affective disorders].

For centuries there has been convincing evidence that diseases of the thyroid gland may produce psychiatric symptoms. Nowadays systematic data are available concerning a higher incidence of thyroid diseases in psychiatric patients and vice versa a higher incidence of psychiatric disorders in thyroid patients. A more subtle approach concerns challenge tests like the TRH test. It could be shown that depressive patients show a blunted TSH response to TRH in 30-40% of the cases. This might lead to a definition of a subgroup of depressives from a psychoneuroendocrinological point of view. But it also might have an impact on the prediction of treatment outcome in psychopharmacological treatment approaches.

Anxiety Disorders↗

Protective effects of fruits and vegetables against in vivo clastogenicity of cyclosphosphamide or benzo[a]pyrene in mice.

Seven fruits and 10 vegetables commonly consumed in Germany were investigated for their anticlastogenic potencies against cyclophosphamide (CP) and benzo[a]pyrene (BaP) in the in vivo mouse bone marrow micronucleus assay. We detected protective effects in 76.5% and 70.6% of the samples, respectively, and more or less distinct quantitative differences between the various plant materials and the two clastogens investigated. With respect to CP, moderate activities were exerted by sweet cherries, strawberries, cucumber, radish and tomatoes, average activities by bananas, oranges, peaches, asparagus and red beets and strong activities by yellow red peppers and especially spinach. Apples (cultivar Jona Gold), brussels sprouts, cauliflower and onions were inactive. With respect to BaP, we found moderate activities in strawberries, brussels sprouts and radish, average activities in sweet cherries, oranges, peaches, asparagus, red beets, cucumber and spinach and strong activities in bananas and kiwi. Apples, cauliflower, onions, tomatoes and yellow-red peppers were inactive. When oranges were fractionated according to previously described schemes (Edenharder et al., 1995), anticlastogenic activities against CP were exerted by materials extracted with n-hexane, acetone and 2-propanol and in the terminal residue, but not in the dichloromethane and water phases. With respect to BaP, materials extracted with acetone showed strong anticlastogenicity while the 2-propanol fraction, the aqueous phase and the terminal residue were less potent. The n-hexane and the dichloromethane fractions were inactive. In red beets, all fractions showed anticlastogenicity against CP and BaP as well. However, the n-hexane and dichloromethane fractions were most potent with respect to CP, while for BaP the aqueous phase and the terminal residue were most effective. These result suggest the presence of various (groups of) anticlastogenic compounds with different chemical structure.

Animals↗