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P Zabel

Publications and source records attributed to P Zabel.

At least 37 records · Page 2Linked to original sources

The role of tumor necrosis factor in the development of multiple organ failure in a murine model.

OBJECTIVE: To elucidate the role of tumor necrosis factor (TNF) in the development of multiple organ dysfunction syndrome (MODS) after zymosan-induced peritonitis in mice. DESIGN: Prospective controlled laboratory study on zymosan-induced generalized inflammation in mice. Over < or =28 days, a single intraperitoneal administration of zymosan induced a three-phase illness in C57BL mice, rendering them very ill with MODS-like symptoms from day 7 onward. Additionally, the same experiment was performed on C57BL/6 TNF-Rc-p55 knockout mice to elucidate the role of TNF and its receptor p55. SETTING: Animal research laboratory. SUBJECTS: Inbred C57BL mice and C57BL p55-/- mice received a single sterile intraperitoneal injection of zymosan suspended in paraffin oil (0.75 mg/g of body weight). MEASUREMENTS AND MAIN RESULTS: The animals were monitored for survival, condition, and body weight for < or =28 days. At 3, 7, 14, and 28 days after zymosan administration, bronchoalveolar lavage was performed and lungs and livers were extracted for isolation of RNA and histopathologic evaluation. Reverse-transcriptase-polymerase chain reaction was performed to quantify TNF-alpha messenger RNA (mRNA) in the respective organs. Both animal strains went through initial shock with a high mortality rate during the first 3 days. The C57BL mice developed MODS with typical symptoms and histopathologic results correlating with excessive TNF-alpha mRNA expression from day 7 onward. In contrast, no disease, histopathologic changes, nor TNF-alpha mRNA expression in liver or lung was found within the TNF-Rc-p55-/- mice. CONCLUSION: Organ-derived TNF-alpha plays a crucial role in the development of MODS in this murine model.

Animals↗

Procalcitonin as a marker of severity in septic shock.

BACKGROUND/AIMS: Procalcitonin (PCT) was shown to be related to the severity of bacterial infection and is recommended as a new parameter of inflammation and infection. To evaluate the prognostic value in septic shock, PCT levels were repeatedly determined and compared with tumour necrosis factor-alpha (TNF-alpha)- and interleukin (IL)-6 bioactivity as well as with C-reactive protein (CRP) serum levels. PATIENTS: Twenty-four surgical patients with septic shock were included. Eight patients died within the study period of 14 days. METHODS: Serum levels of TNF-(WEHI 164) and IL-6 (B13-29 subclone 9) bioactivity, CRP and PCT were determined on days 1, 3, 5, 7, 10 and 14 following diagnosis of septic shock. RESULTS: Survivors and non-survivors were comparable in terms of age and severity of sepsis characterized by the APACHE II score and multiple-organ-failure score. Predominant causes of sepsis were peritonitis and necrotiszing pancreatitis. TNF levels increased in non-survivors with no significant difference to survivors. IL-6 bioactivity was increased on day 1 (P = 0.06) and remained elevated in non-survivors, in whom it was significant on day 7 (P<0.05). CRP was constantly elevated with no difference between the groups. In nonsurvivors PCT remained increased, while the course of survivors was characterized by decreased values which were significantly lower (P<0.05) at every time point compared with those patients who died. A significant correlation could be found on day 1 (P<0.05) and at the end of the observation period (P<0.01) when comparing PCT levels with the multiple-organ-failure score. CONCLUSIONS: PCT seems to be a more reliable prognostic parameter in septic shock than IL-6, while TNF and CRP did not show any difference between survivors and non-survivors. These data indicate that PCT may represent a valuable parameter not only in the diagnosis of sepsis but also in the clinical course of the disease.

APACHE↗

High resolution FISH in plants - techniques and applications.

Fluorescence in situ hybridization (FISH) is an effective and accurate cytogenetic tool for mapping single copy and repetitive DNA sequences on chromosomes. Attempts to increase the detection sensitivity of very small chromosomal targets, and to improve the spatial resolution of signals derived from flanking sequences, have led to the development of a variety of novel techniques: it is now possible to perform in situ hybridizations on interphase nuclei, meiotic pachytene chromosomes and isolated chromatin (DNA fibres). The recent application of these techniques has indicated that a spatial resolution of 1 kb between adjacent targets and a sensitivity of targets smaller than 1 kb is now feasible. Here, we describe the benefits of these novel chromosome analysis techniques and discuss their relevance for the study of plant genomes.

Journal Article↗

Effect of pentoxifylline in severe sepsis: results of a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the effect of pentoxifylline on organ dysfunction, survival, and mediator response in patients with severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Surgical intensive care units at 2 university hospitals. PATIENTS: Fifty-one surgical patients with severe sepsis were randomized to receive pentoxifylline continuously (27 patients) or saline infusion as placebo (24 patients). INTERVENTIONS: PATIENTS received pentoxifylline (1 mg/kg of body weight per hour; maximum, 1800 mg/d) during 28 days or until they were discharged from the intensive care unit or died. MEASUREMENTS AND MAIN RESULTS: Vital signs and organ function were determined at diagnosis; daily from day 1 to 7; on days 10, 14, 17, 21, and 24; and 28 days after diagnosis of sepsis. There were no differences in characteristics of patients at diagnosis in the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (mean+/-SEM, 17+/-4 points for the pentoxifylline group and 18+/-5 points for the placebo group), the multiple organ dysfunction score (mean+/-SEM, 11.0+/-0.8 vs 11.8+/-1.0 points), tumor necrosis factor alpha and interleukin 6 bioactivity, serum endotoxin levels, or organ dysfunction. At study entrance, 23 of 27 patients in the pentoxifylline group and 21 of 24 patients in the placebo group experienced septic shock. No adverse effects of pentoxifylline treatment were observed. The 28-day mortality rate was 30% (8/27) in pentoxifylline-treated patients and 33% (8/24) in the placebo group. Hospital mortality was 41% (11/27) in the pentoxifylline group and 54% (13/24) in the placebo group. The multiple organ dysfunction score decreased in patients receiving pentoxifylline 4 days after diagnosis of sepsis compared with placebo-treated patients; a significant difference was reached on day 14 (P<.05; Student t test, Bonferoni correction). The PaO2/FIO2 (fraction of inspired oxygen) ratio was significantly improved in pentoxifylline-treated patients on days 14 and 17 (P<.05), and the pressure-adjusted heart rate was significantly improved on day 6 (P<.05) compared with the placebo group. Serum endotoxin levels, tumor necrosis factor alpha and interleukin 6 bioactivity were not different between the groups during the study. CONCLUSIONS: Continuous intravenous administration of pentoxifylline beneficially influenced cardiopulmonary dysfunction in patients with sepsis without adverse effects. Larger trials are needed to evaluate the efficacy in improving organ function in relation to the outcome for patients with severe sepsis.

APACHE↗

Gender differences in human sepsis.

BACKGROUND: In animal studies, gender differences were related to hormonal and immunologic changes that were associated with an increased susceptibility to sepsis in males. OBJECTIVE: In a prospective study, gender differences in patients with surgical sepsis were evaluated in terms of survival, sex hormones, and proinflammatory as well as anti-inflammatory mediators. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Fifty-two patients (19 women and 33 men) with surgical sepsis. MEASUREMENTS AND MAIN RESULTS: In a prospective study, tumor necrosis factor alpha and interleukin 6 bioactivity and plasma levels of interleukin 10 (using enzyme-linked immunosorbent assay), total testosterone, and 17-beta estradiol (using radioimmunoassay) were determined on days 1, 3, 5, 7, 10, and 14 after diagnosis of sepsis. There were no differences in characteristics of patients in age (mean age, 55.4 years for women and 53.1 years for men) or cause and severity of sepsis (Acute Physiology and Chronic Health Evaluation II score, 17.3 for women and 18.5 for men; multiple organ dysfunction score, 9.9 vs 10.8, respectively). Although no difference could be found in the multiple organ dysfunction score from day 1 to day 28, the prognosis of sepsis was significantly different in women compared with men. Hospital-mortality rate was 70% (23 of 33 patients) in male and 26% (5 of 19) in female patients (P<.008, log-rank test). Bioactivity of tumor necrosis factor continuously increased in men after diagnosis of sepsis, with significantly elevated levels on day 10 (P<.05, Mann-Whitney U test with Bonferroni correction), whereas no difference was found for interleukin 6 bioactivity. Women displayed enhanced interleukin 10 levels compared with men from day 1 to day 10 that reached a significant difference on days 3 and 5 (P<.05). Total testosterone levels were below the normal range for men, and estradiol levels were initially increased in both men and postmenopausal women, with higher levels for women. CONCLUSIONS: In this prospective study, gender differences were confirmed in human sepsis, with a significantly better prognosis for women, which may be related to increased levels of anti-inflammatory mediators. The hypothetical different ratio of proinflammatory and anti-inflammatory mediators may be important for further therapeutic interventions in sepsis.

APACHE↗

Genetic and physical localization of the root-knot nematode resistance locus mi in tomato.

As part of a map-based cloning strategy designed to isolate the root-knot nematode resistance gene Mi, tomato F2 populations were analyzed in order to identify recombination points close to this economically important gene. A total of 21,089 F2 progeny plants were screened using morphological markers. An additional 1887 F2 were screened using PCR-based flanking markers. Fine-structure mapping of recombinants with newly developed AFLP markers, and RFLP markers derived from physically mapped cosmid subclones, localized Mi to a genomic region of about 550 kb. The low frequency of recombinants indicated that recombination was generally suppressed in these crosses and that crossovers were restricted to particular regions. To circumvent this problem, a population of Lycopersicon peruvianum, the species from which Mi was originally introgressed, that was segregating for resistance was developed. Screening of this population with PCR, RFLP and AFLP markers identified several plants with crossovers near Mi. Recombination frequency was approximately eight-fold higher in the Mi region of the L. peruvianum cross. However, even within the wild species cross, recombination sites were not uniformly distributed in the region. By combining data from the L. esculentum and L. peruvianum recombinant analyses, it was possible to localize Mi to a region of the genome spanning less than 65 kb.

Animals↗

Paracentromeric sequences on tomato chromosome 6 show homology to human satellite III and to the mammalian CENP-B binding box.

In order to isolate centromeric sequences from tomato (Lycopersicon esculentum) chromosome 6, a large-scale RAPD screen was performed. Among 1500 polymorphic RAPD markers tested, 100 were identified as chromosome 6-specific, using a L. esculentum substitution line carrying chromosome 6 from L. pennellii. Fifty-seven of these markers proved to originate from L. pennellii, and of these, 13 were genetically mapped between the morphological markers yellow virescent (yv) and thiaminless (tl), which flank the centromere. These markers could be assigned to three genetic loci, with 11 of the markers mapping to a single locus. Further resolution of this cluster was achieved using radiation-induced deletions that removed yv or tl but not the centromere. Seven markers were shown to be located outside all of the deletions. These seven markers and three of the other markers of the cluster were cloned and sequenced. Five of the clones are present as single-copy or low-copy-number sequences and five represent middle repetitive sequences. Three sequences show homology to the mammalian CENP-B binding box; clone AG12 contains two of these boxes and also shows homology to human satellite III.

Autoantigens↗

Comparative study on effects of pentoxifylline, prednisolone and colchicine in experimental alveolitis.

Neutrophil alveolitis is a hallmark of cryptogenic fibrosing alveolitis (CFA), known for its poor prognosis. Corticosteroids, as the remedy of choice, are ineffective in a majority of patients. More and more evidence indicates that pentoxifylline (POF) could be an effective therapeutic alternative. Furthermore, colchicine has been proposed for therapy of CFA for many years now. We conducted an experimental study comparing the efficacy of these drugs in preventing neutrophil alveolitis in vivo. Alveolitis was induced in male rats by intratracheal instillation of bleomycin. Treatment consisted of daily injections of POF i.p., colchicine i.p., or prednisolone i.m. After 8 days the animals were sacrificed and body weights, cell differentials in BAL, amount of proliferating interstitial cells as determined by KI-67 staining of lung tissue, and collagen concentrations in lungs were determined. Bleomycin instillation was followed by a significant weight loss in the animals, a neutrophil alveolitis in BAL and an increased amount of proliferating cells in lung interstitium. POF significantly inhibited any of the parameters named, whereas prednisolone and colchicine had little effect. Data cannot be applied directly in human disease. There are however many similarities between CFA and bleomycin-induced lung injury and alveolitis. We conclude that POF is an effective inhibitor of neutrophil alveolitis, whereas neither colchicine nor prednisolone exerted significant influence in our model. We suggest POF effects should be further investigated regarding anti-inflammatory and anti-fibrotic properties.

Animals↗

FISH studies reveal the molecular and chromosomal organization of individual telomere domains in tomato.

The molecular and cytological organization of the telomeric repeat (TR) and the subtelomeric repeat (TGR1) of tomato were investigated by fluorescence in situ hybridization (FISH) techniques. Hybridization signals on extended DNA fibres, visualized as linear fluorescent arrays representing individual telomeres, unequivocally demonstrated the molecular co-linear arrangement of both repeats. The majority of the telomeres consisted of a TR and a TGR1 region separated by a spacer. Microscopic measurements of the TR and TGR1 signals revealed high variation in length of both repeats, with maximum sizes of 223 and 1330 kb, respectively. A total of 27 different combinations of TR and TGR1 was detected, suggesting that all chromosome ends have their own unique telomere organization. The fluorescent tracks on the extended DNA fibres were subdivided into four classes: (i) TR-spacer-TGR1; (ii) TR-TGR1; (iii) only TR; (iv) only TGR1. FISH to pachytene chromosomes enabled some of the TR/TGR1 groups to be assigned to specific chromosome ends and to interstitial regions. These signals also provided evidence for a reversed order of the TR and TGR1 sites at the native chromosome ends, suggesting a backfolding telomere structure with the TGR1 repeats occupying the most terminal position of the chromosomes. The FISH signals on diakinesis chromosomes revealed that distal euchromatin areas and flanking telomeric heterochromatin remained highly decondensed around the chiasmata in the euchromatic chromosome areas. The rationale for the occurrence and distribution of the TR and TGR1 repeats on the tomato chromosomes are discussed.

Base Sequence↗

Tumor necrosis factor-alpha hyporesponsiveness of rat intestinal mononuclear cells and whole portal venous blood after hemorrhagic shock.

OBJECTIVE: To determine the effect of hemorrhagic shock on spontaneous and endotoxin-induced cytokine release from intestinal mononuclear cells compared with whole portal venous blood and splenic macrophages. DESIGN: Random assignment to either unmanipulated control group, sham operation group, or hemorrhagic shock group. SETTING: University animal laboratory. SUBJECTS: Male Wistar rats, weighing between 300 and 350 g. INTERVENTIONS: Rats were bled to 30 mm Hg for 30 mins by withdrawal/reinfusion of shed blood and Ringer's lactate equivalent to the shed blood volume. MEASUREMENTS: Rats were killed immediately, 4 hrs, or 24 hrs after reperfusion. Portal venous blood, splenic macrophages, and small bowel mononuclear cells were obtained and spontaneous (unstimulated) and endotoxin-induced supernatant tumor necrosis factor (TNF)-alpha (WEHI 164 subclone 13) and interleukin (IL)-6 (B 13-29 clone 9) release was measured by bioassay. MAIN RESULTS: Increased endotoxin-induced TNF release from gut mononuclear cells and portal venous blood was suppressed 4 and 24 hrs after reperfusion compared with sham operated animals (p < .05). TNF release from splenic macrophages could be significantly increased (p < .05) by addition of endotoxin in all groups with no difference between control, sham, and shock animals. In shock animals, endotoxin-stimulated IL-6 release was significantly greater (p < .05) than control and sham operated rats 4 hrs after reperfusion in portal blood and from splenic macrophages. In contrast to splenic macrophages, gut mononuclear cells and portal venous blood demonstrated high spontaneous IL-6 concentrations without further stimulation by endotoxin. CONCLUSIONS: Hemorrhagic shock induced a hyporesponsiveness from gut mononuclear cells and whole portal venous blood 4 and 24 hrs after reperfusion. Spontaneous and endotoxin-induced stimulation of IL-6 indicates a different modulation of cytokines in gut, portal vein and spleen. The differences of gut mononuclear cells and portal blood compared with the splenic macrophages indicate a compartmentalized cytokine response.

Animals↗

Glutamine dipeptides-supplemented parenteral nutrition reverses gut mucosal structure and interleukin-6 release of rat intestinal mononuclear cells after hemorrhagic shock.

Glutamine is an essential substrate for gut mucosal structure, but the role for gut immune function is not fully known. To determine the effect on gut cytokine release in relation to bacterial translocation and gut morphology, a nonlethal hemorrhagic shock (30 min, 30 mmHg) was performed in male Wistar rats followed by 4 days of different way of feeding. A conventional total parenteral nutrition (TPN) solution was compared with an isocaloric and isonitrogenous TPN solution supplemented with alanin-L-glutamine and glycyl-L-glutamine. An enteral chow-fed control group was included. Gut mononuclear cells and splenic macrophages were obtained and endotoxin-induced supernatant tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) bioactivity was measured. Histological specimen of the small bowel were taken and mesenteric lymph nodes (MLN) were separated. Enteral feeding following hemorrhagic shock was accompanied by a normal mucosal structure and no bacterial translocation could be detected. TPN was characterized by suppression of cytokine release in gut mononuclear cells and splenic macrophages compared with the enteral-fed control (p < .05). Decreased TNF and IL-6 release was associated with a significantly increased mucosal injury score (p < .05) and a high incidence of bacterial translocation to MLN (66%, p < .05 vs. control). Supplementation of glutamine-dipeptides did not prevent TPN-induced bacterial translocation to MLN (p < .05 vs. control) but significantly improved mucosal injury (p < .05 vs. TPN). Down-regulation of TNF release in TPN-fed rats could not be reversed by glutamine dipeptides while IL-6 release was significantly increased compared with TPN-fed animals (p < .05), and no difference to enteral-fed controls could be found. Enteral nutrition following hemorrhagic shock is superior to parenteral nutrition with regard to mucosal structure, cytokine release, and bacterial translocation. Supplementation of TPN with glutamine dipeptides could reverse TPN-induced suppression of IL-6 release and improved mucosal structure, which may be beneficial in various disease conditions in which TPN is an integrated part of patients management.

Animals↗

The root knot nematode resistance gene Mi from tomato is a member of the leucine zipper, nucleotide binding, leucine-rich repeat family of plant genes.

The Mi locus of tomato confers resistance to root knot nematodes. Tomato DNA spanning the locus was isolated as bacterial artificial chromosome clones, and 52 kb of contiguous DNA was sequenced. Three open reading frames were identified with similarity to cloned plant disease resistance genes. Two of them, Mi-1.1 and Mi-1.2, appear to be intact genes; the third is a pseudogene. A 4-kb mRNA hybridizing with these genes is present in tomato roots. Complementation studies using cloned copies of Mi-1.1 and Mi-1.2 indicated that Mi-1.2, but not Mi-1.1, is sufficient to confer resistance to a susceptible tomato line with the progeny of transformants segregating for resistance. The cloned gene most similar to Mi-1.2 is Prf, a tomato gene required for resistance to Pseudomonas syringae. Prf and Mi-1.2 share several structural motifs, including a nucleotide binding site and a leucine-rich repeat region, that are characteristic of a family of plant proteins, including several that are required for resistance against viruses, bacteria, fungi, and now, nematodes.

Amino Acid Sequence↗

Differences in the anti-inflammatory effects of theophylline and pentoxifylline: important for the development of asthma therapy?

Antiasthma drugs are now being re-evaluated for their anti-inflammatory effects. Theophylline is an immunomodulator; however, weak effects and the narrow therapeutic window make it a controversial drug. We compared the immunomodulatory potencies of theophylline with those of the xanthines pentoxifylline (POF) and A802715. Using a whole-blood, cell-culture system, we studied the effects on the release of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6) in six healthy subjects, and, in granulocyte suspensions, the effects on the release of reactive oxygen species (ROS). We also studied the influence of a 14-day treatment with theophylline or POF on the release of the cytokines named above in 14 asthmatics. We found that equimolar concentrations of A802715 most effectively inhibit ROS generation, followed by POF; the effects of theophylline were weakest. A802715-inhibited release of TNF-alpha was four times as potent as that of theophylline, and POF two times as potent. Inhibition of IFN-gamma by A802715 was three times as potent, and by POF two times. Neither drug influenced IL-6 release. After a 14-day treatment of asthmatics, POF proved to inhibit TNF-alpha release more effectively (by 44.3%) than theophylline (7.5%). It is concluded that study of xanthine derivatives in asthmatics might help the development of asthma therapy. POF seems to be an especially promising candidate.

Adult↗

Serum level of interleukin 8 is elevated in idiopathic pulmonary fibrosis and indicates disease activity.

It has been shown that interleukin 8 (IL-8) is increased in bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF) and there is increasing evidence that it is involved in the pathogenesis of this disease. To date, no data are available as to whether IL-8 is elevated in sera of IPF patients. We obtained sera from 42 patients with IPF and 20 healthy controls at time of BAL. From 20 of 42 patients with IPF and 12 of 20 controls BALF was available, enabling us to measure IL-8 in serum and BALF of the same time point. IL-8 was significantly elevated in serum (54.7 +/- 7.5 pg/ml, p < 0.0001) and BALF (715.7 +/- 112.4 pg/ml, p < 0.0001) of patients with IPF compared with controls (IL-8 in serum, 5.2 +/- 0.8 pg/ml; IL-8 in BALF, 67.3 +/- 9.7 pg/ml). We observed a significant positive correlation between IL-8 levels in BALF and percentage of BALF neutrophils (p < 0.001) and between serum IL-8 and BALF IL-8 levels (p < 0.005) in patients with IPF. Consequently, the serum IL-8 level correlated positively with the percentage of BAL neutrophils (p < 0.01), indicating that it may reflect the degree of neutrophilic alveolitis in IPF. Furthermore, the serum IL-8 level showed a negative correlation with important indicators of impairment of lung function (DL(CO), TLC, VC) and PaO2. In conclusion, we were able to demonstrate that the degree of neutrophilic alveolitis in IPF is reflected by increased serum levels of IL-8 and we suggest that the serological assessment of IL-8 may provide a useful parameter for clinicians in monitoring patients with IPF.

Anti-Inflammatory Agents↗

[Limits of beryllium detection with laser microprobe mass spectrometry (LAMMS)].

Search for beryllium (Be) in tissues or urine in suspected beryllium disease is often disappointing due to inferior sensitivity of the methods employed. We evaluated the clinical use of laser microprobe mass spectrometry (LAMMS) for measurement of Be and detected the metal to a minimum concentration of 1 microM. We then investigated the biological relevance of this concentration. We looked at the alveolar macrophages in 7 patients subsequent to an incubation period of 24 h as well as peripheral blood mononuclear cells (PBMNC) and various cell lines with and without addition of beryllium sulfate (BeSO4). We also investigated skin biopsies of two patients 28 days after intracutaneous injections of BeSO4 (beryllium skin testing) and alveolar macrophages of A/J mice at various time intervals after a beryllium sensitisation protocol and a single intratracheal injection of BeSO4 (maximum interval: 15 weeks). Be was not defectable in native patient alveolar macrophages (AM), but in 6 of 7 cases after coincubation with BeSO4. There was no significant Be signal in any analysed PBMNC sample or cell line--even after coincubation with Be--or in the skin probes. Murine AM, however, had incorporated significant amounts of Be, which were detectable until the end of the experiments 15 weeks later. We conclude that concentrations of Be in acute disease (here, inoculation of Be in mice) exceed 1 microM and are thus detectable by LAMMS. On the other hand, concentrations in chronic processes (in this cosar, skin testing) are below the detection limits of LAMMS. Further results suggest compartmentalisation of the immune processes induced by Be because the alveolar macrophages were able to incorporate Be while PBMNC were not and because AM--at least in the animal experiments--seem to store Be intracellularly.

Adult↗

[Pentoxifylline as adjuvant therapy of multiple organ failure].

To evaluate the therapeutic effect of pentoxifylline (POF) on cardiopulmonary, renal and hepatic dysfunction, 51 patients with sepsis were randomized to receive POF or saline solution as placebo. Continuous intravenous administration of POF beneficially influenced cardiopulmonary organ function without adverse effects. PO2/FiO2-ratio as parameter of pulmonary dysfunction was significantly improved in the second week after diagnosis while parameter of cardial function were significantly different in the initial phase of sepsis. The clinical efficacy of POF in terms of organ dysfunction, however, did not result in improved survival.

Combined Modality Therapy↗

[Spinach powder-induced exogenous allergic alveolitis].

A 51-year old woman developed hypersensitivity pneumonitis to spinach powder, which is used as a food dye. The diagnosis was confirmed by demonstration of IgG2-antibodies in the patient's serum to distinct bands of spinach extract by Western blotting. Furthermore an exposure test with the natural allergen was positive. Severe disease with fever, chills and dyspnoea developed after inhalation of native spinach powder. Arterial pO2 dropped significantly and pulmonary function tests showed severe restrictive impairment and reduction of diffusion capacity. Leucocyte count and the serum concentrations of the cytokines TNF alpha and IL6 and of the soluble IL2-receptor rose significantly in peripheral blood, whereas the concentration of neopterine did not change. 24 hours after exposure bronchoalveolar lavage showed an increase of neutrophils. In lung parenchyma mononuclear interstitial infiltrates and an epitheloid cell granuloma were seen.

Alveolitis, Extrinsic Allergic↗

Tomato chromosome 1: high resolution genetic and physical mapping of the short arm in an interspecific Lycopersicon esculentum x L. peruvianum cross.

A detailed map of part of the short arm of chromosome 1 proximal to the Cf-4/Cf-9 gene cluster was generated by using an F2 population of 314 plants obtained from the cross between the remotely related species Lycopersicon esculentum and L. peruvianum. Six markers that cosegregate in an L. esculentum x L. pennellii F2 population showed high recombination frequencies in the present interspecific population, spanning an interval of approximately 13 cM. Physical distances between RFLP markers were estimated by pulsed field gel electrophoresis of high-molecular-weight DNA and by identifying YACs that recognized more than one RFLP marker. In this region 1 cM corresponded to 55-110 kb. In comparsion with the value of 730 kb per cM averaged over the entire genome, this reflects the remarkably high recombination frequencies in this region in the hybrid L. esculentum x L. peruvianum progeny population. The present data underline the fact that recombination is not a process that occurs randomly over the entire genome, but can vary dramatically in intensity between chromosomal regions and among populations.

Chromosome Mapping↗