Showing papers by "Ludwig Maximilian University of Munich published in 1988"

Plant breeding: importance of plant secondary metabolites for protection against pathogens and herbivores

Abstract: Chemical protection plays a decisive role in the resistance of plants against pathogens and herbivores. The so-called secondary metabolites, which are a characteristic feature of plants, are especially important and can protect plants against a wide variety of microorganisms (viruses, bacteria, fungi) and herbivores (arthropods, vertebrates). As is the situation with all defense systems of plants and animals, a few specialized pathogens have evolved in plants and have overcome the chemical defense barrier. Furthermore, they are often attracted by a given plant toxin. During domestication of our crop and food plants secondary metabolites have sometimes been eliminated. Taking lupins as an example, it is illustrated that quinolizidine alkaloids are important as chemical defense compounds and that the alkaloid-free varieties (“sweet lupins”), which have been selected by plant breeders, are highly susceptible to a wide range of herbivores to which the alkaloid-rich wild types were resistant. The potential of secondary metabolites for plant breeding and agriculture is discussed.

Establishment of a human cell line (mono mac 6) with characteristics of mature monocytes

Abstract: A monocytic cell line, termed Mono Mac, was established from peripheral blood of a patient with monoblastic leukemia. Two clones, designated Mono Mac I and Mono Mac 6, were isolated and both were assigned to the monocyte lineage on the basis of morphological, cytochemical and immunological criteria. Most importantly, the clones express NaF-sensitive non-specific-esterase, produce reactive oxygen and stain with MAb My4. Mono Mac 6, in addition, constitutively exhibits phagocytosis of antibody-coated erythrocytes in 80% of the cells and reacts with a panel of MAbs that are specific for mature monocytes, i.e., M42, LeuM3, 63D3, Mo2 and UCHMI. By contrast, the monoblastic cell lines U937 and THP-I are negative for all these markers. Only expression of My4 could be detected after differentiation induced by interferon-gamma (IFN-gamma). Similar treatment of Mono Mac I, however, resulted in staining with all the monocyte-specific MAbs mentioned above, while IFN-gamma treatment of Mono Mac 6 enhanced antigen expression. In addition, the cells showed an increased frequency of multinucleated cells with a rise from 4.8% to 21.9%. Mono Mac 6 appears to be the only one of the cell lines studied to constitutively express phenotypic and functional features of mature monocytes.

SOCRATES: a highly efficient automatic test pattern generation system

Abstract: An automatic test pattern generation system, SOCRATES, is presented. SOCRATES includes several novel concepts and techniques that significantly improve and accelerate the automatic test pattern generation process for combinational and scan-based circuits. Based on the FAN algorithm, improved implication, sensitization, and multiple backtrace procedures are described. The application of these techniques leads to a considerable reduction of the number of backtrackings and an earlier recognition of conflicts and redundancies. Several experiments using a set of combinational benchmark circuits demonstrate the efficiency of SOCRATES and its cost-effectiveness, even in a workstation environment. >

Shock-wave lithotripsy of gallbladder stones. The first 175 patients.

Abstract: To substantiate the early results of extracorporeal shock-wave fragmentation of gallstones, we used this nonsurgical procedure to treat 175 patients with radiolucent gallbladder calculi. Chenodeoxycholic acid and ursodeoxycholic acid were administered as adjuvant litholytic therapy. The gallstones disintegrated in all patients except one and completely disappeared in 30 percent of all patients within 2 months after lithotripsy, in 48 percent at 2 to 4 months, in 63 percent at 4 to 8 months, in 78 percent at 8 to 12 months, and in 91 percent at 12 to 18 months. In patients with solitary stones up to 20 mm in diameter, the corresponding values were 45, 69, 78, 86, and 95 percent, respectively. Shock-wave therapy had no adverse effects except cutaneous petechiae (14 percent) and transient gross hematuria (3 percent). One third of the patients had one or more episodes of biliary colic before all the fragments disappeared. Two patients had mild pancreatitis, which necessitated endoscopic sphincterotomy in one. The patient with insufficient stone fragmentation underwent elective cholecystectomy; no additional operations were necessary. Extracorporeal shock-wave lithotripsy combined with medical therapy for stone dissolution is a safe and effective treatment in selected patients with radiolucent gallbladder calculi.

Gene for a novel tRNA species that accepts L-serine and cotranslationally inserts selenocysteine.

Abstract: The biological requirement of the trace element selenium was recognized 40 years ago. Selenium is incorporated into several enzymes and transfer RNA species of both prokaryotic and eukaryotic origin. In enzymes which contain a selenopolypeptide, selenium is present as covalently bound selenocysteine which participates in the catalytic reaction. Sequence analysis of the genes coding for two selenoproteins, formate dehydrogenase H from Escherichia coli and glutathione peroxidase from mouse and man, demonstrated that an in-frame UGA opal nonsense codon directs the incorporation of selenocysteine. In the case of formate dehydrogenase incorporation occurs cotranslationally. Recently, we identified four genes whose products are required for selenocysteine incorporation in E. coli. We report here that one of these genes codes for a tRNA species with unique properties. It possesses an anticodon complementary to UGA and deviates in several positions from sequences, until now, considered invariant in all tRNA species. This tRNA is aminoacylated with L-serine by the seryl-tRNA ligase which also charges cognate tRNASer. Selenocysteine, therefore, is synthesized from a serine residue bound to a natural suppressor tRNA which recognizes UGA.

Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion.

Abstract: To determine how arginine (Arg) stimulates GH secretion, we investigated its interaction with GHRH in vivo and in vitro. Six normal men were studied on four occasions: 1) Arg-TRH, 30 g arginine were administered in 500 mL saline in 30 min, followed by an injection of 200 micrograms TRH; 2) GHRH-Arg-TRH, 100 micrograms GHRH-(1-44) were given iv as a bolus immediately before the Arg infusion, followed by 200 micrograms TRH, iv; 3) GHRH test, 100 micrograms GHRH were given as an iv bolus; and 4) TRH test, 200 micrograms TRH were given iv as a bolus dose. Blood samples were collected at 15-min intervals for 30 min before and 120 min after the start of each infusion. Anterior pituitary cells from rats were coincubated with Arg (3, 6, 15, 30, and 60 mg/mL) and GHRH (0.05, 1, 5, and 10 nmol/L) for a period of 3 h. Rat GH was measured in the medium. After Arg-TRH the mean serum GH concentration increased significantly from 0.6 to 23.3 +/- 7.3 (+/- SE) micrograms/L at 60 min. TRH increased serum TSH and PRL significantly (maximum TSH, 11.1 +/- 1.8 mU/L; maximum PRL, 74.6 +/- 8.4 micrograms/L). After GHRH-Arg-TRH, the maximal serum GH level was significantly higher (72.7 +/- 13.4 micrograms/L) than that after Arg-TRH alone, whereas serum TSH and PRL increased to comparable levels (TSH, 10.2 +/- 3.0 mU/L; PRL, 64.4 +/- 13.6 micrograms/L). GHRH alone increased serum GH to 44.9 +/- 9.8 micrograms/L, significantly less than when GHRH, Arg, and TRH were given. TRH alone increased serum TSH to 6.6 +/- 0.6 mU/L, significantly less than the TSH response to Arg-TRH. The PRL increase after TRH only also was lower (47.2 +/- 6.8 micrograms/L) than the PRL response after Arg-TRH. In vitro Arg had no effect on basal and GHRH-stimulated GH secretion. Our results indicate that Arg administered with GHRH led to higher serum GH levels than did a maximally stimulatory dose of GHRH or Arg alone. The serum TSH response to Arg-TRH also was greater than that to TRH alone. We conclude that the stimulatory effects of Arg are mediated by suppression of endogenous somatostatin secretion.

Algae sequester heavy metals via synthesis of phytochelatin complexes

Abstract: A Cd-binding complex was isolated from Chlorella fusca and has been shown to be composed of phytochelating peptides, (γ-Glu-Cys) n -Gly, n=2–5. Members of six of the ten classes of Phycophyta revealed phytochelatin synthesis after exposure to cadmium ions. Phytochelatin was also induced by ions of lead, zinc, silver, copper and mercury. These experiments uneqiovocally demonstrated that algae sequester heavy metals by an identical mechanism as higher plants, namely via complexation to phytochelatins.

Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A.

Abstract: The protease encoded by the human immunodeficiency virus (HIV) processes the viral gag and gag-pol protein precursor by posttranslational cleavage. In this study we have demonstrated by site-specific mutagenesis (Asp----Thr) and by pepstatin A inhibition that the recombinant HIV protease is an aspartic-type protease. Furthermore, incubation of HIV-infected H9 cells with pepstatin A inhibited part of the intracellular processing of the HIV gag protein yet had no apparent toxicity on HIV-infected cells during 48 hr of incubation.

Antigenic Variability of Borrelia burgdorferi

Abstract: Borrelia burgdorferi strains (six isolates from North America and 28 isolates from Europe) were analyzed by physicochemical and immunological methods. By SDS-PAGE, all Borrelia burgdorferi strains tested had two major proteins with constant molecular weights of 60 and 41 kDa and one, two, or three variable low molecular weight proteins (OspA = 30-32 kDa, OspB = 34-36 kDa, pC = 21-22 kDa). All combinations--except OspB alone or OspB/pC--were observed. Borrelia burgdorferi strains were different from relapsing fever borreliae by strong reactivity with OspA- and/or pC-specific polyclonal antibodies, whereas relapsing fever borreliae were only weakly reactive. Among 25 Borrelia burgdorferi isolates, seven different serotypes of Borrelia burgdorferi were defined according to their reactivity in the Western blot with three monoclonal OspA-specific antibodies (H5332, H3TS, and LA5), four OspA- or OspB-specific polyclonal antibodies, and 12 polyclonal antibodies against whole borreliae. Antigenic differences between European CSF and skin isolates were observed, all skin isolates (n = 11) belonging to serotype 2 in contrast to only two out of seven CSF isolates. CSF isolates were antigenically heterogenous (serotypes 1, 2, 3, 4, and 5). Serotypes 6 and 7 were represented by two tick isolates, and the other European tick isolates are not yet fully characterized. Antigenic differences between European and North American strains may play a role in differences in the clinical picture of Lyme borreliosis.

Alteration of Monocyte Function Following Major Injury

Abstract: • The macrophage exerts its stimulatory and regulatory functions within the specific immune response via the interleukin 1 (IL-1) and prostaglandin E 2 (PGE 2 ), respectively. In a screening study of macrophage-related variables following injury, a total of 58 patients (mean age, 32 years; mean Injury Severity Score, 38), macrophagic phenotyping with the monoclonal antibody Leu M3 and serial measuring of the antagonistic monokines IL-1 and PGE 2 and of the macrophage-activating lymphokine interferon gamma were carried out on posttrauma days 0,1,3,5,7,10,14, and 21. The posttraumatic course was characterized by significant monocytosis, showing a peak value of 32% of Leu M3—positive cells compared with 15% of these cells in normal control subjects. During the posttrauma course, the macrophagic PGE 2 output was significantly elevated up to eightfold on days 5 and 7 compared with that of control subjects (0.441 ±0.14 ng/mL vs 0.052 ± 0.01 ng/mL). Conversely, macrophagic IL-1 synthesis was significantly suppressed until day 10. Levels of interferon gamma were suppressed to a significant degree during the two-day observation period, with a trend to slow recovery at the end of week 3. These data suggest that a negative regulatory macrophagic function may be the event initiating posttraumatic immunosuppression. To restore impaired macrophagic T-helper cell interaction, cyclo-oxygenase inhibition and substitution of interferon gamma may be useful to potentiate facilitatory macrophagic function and to block inhibitory macrophagic activity. ( Arch Surg 1988;123:287-292)

Biological effects of shock waves: kidney damage by shock waves in dogs--dose dependence.

Abstract: The effect of shock waves on normal canine kidneys was examined in three groups of dogs whose right kidneys were exposed to 500, 1500, or 3000 shock waves. Autopsy was performed 24–30 h later. The kidneys were enlarged with haemorrhages in the outer and inner renal capsule and intraparenchymally. Macroscopically intraparenchymal haemorrhages were restricted to the high pressure field of the shock wave and consisted of haematomas up to 18 mm diameter (most frequently 6 mm or less) and diffuse haemorrhages. Histologically, haemorrhages were shown to originate from interlobular and arcuate veins. Venous thrombosis, tubular dilatation, and diffuse interstitial haemorrhage occurred in the same area. The number of haematomas was larger, and diffuse haemorrhages were more extended after the application of 1500 and 3000 than after 500 shock waves. No difference was seen between 1500 and 3000 shock waves.

Complex RNA maturation in chloroplasts. The psbB operon from spinach.

Abstract: The psbB operon of the spinach plastid chromosome encodes the genes for the 51-kDa chlorophyll a apoprotein (psbB), the 10-kDa phosphoprotein (psbH), both associated with photosystem II, as well as cytochrome b6 (petB) and subunit IV (petD) of the cytochrome b/f complex in the order given. These genes are not expressed coordinately. The RNA pattern of this DNA region is complex and resolves into eighteen major RNA species. Using northern and S1 protection analysis we demonstrate (a) that all RNA species derive from one DNA strand and hybridize in an overlapping fashion; and (b) that they arise by processing rather than by multiple transcription initiation/termination. (c) The operon is bordered by a single prokaryote-like promotor in front of psbB, and by a putative factor-independent terminator with characteristic sequence elements following petD. The terminator appears to function bidirectionally. (d) At least four distinct modification activities operate on the putative primary transcript of 5650 nucleotides and on the processing intermediates, including a novel endonucleolytic activity cleaving within a characteristic hexanucleotide motif, 3'-exonucleolytic activity at discrete RNA ends, 5' shortage of mRNA (psbB), and excision of class II intervening sequences (petB and petD). (e) Kinetically, maturation of the primary transcript is largely a stochastic process. (f) Processing results ultimately in the formation of monocistronic mRNAs for each of the two photosystem II polypeptides and a bicistronic mRNA encoding both subunits of the cytochrome b/f complex. We postulate that these RNA species represent the translationally active components in the non-coordinate dark/light expression of these genes. (g) Light is without any noticeable effect on posttranscriptional modification. Under our conditions it appears to operate at a translational rather than a transcriptional or posttranscriptional level indicating that the biogenesis of thylakoid membranes is regulated at various levels.

Leichtlösliche, lichtechte Perylen‐Fluoreszenzfarbstoffe

Abstract: Die Synthese von Perylenfarbstoffen 2 mit terminalen Alkylgruppen wird beschrieben. Langkettige n-Alkylgruppen fuhren nicht zu einer Erhohung der Loslichkeit, sondern zu einer Erniedrigung. Cycloalkyl-Reste bewirken ein Minimum an Loslichkeit im Bereich der mittleren Ringe und ein Maximum beim Cyclotetradecyl-Rest (2p). Starke Loslichkeitserhohungen bewirken sekundare Alkylreste mit zwei langen Ketten. Von diesen ist der Farbstoff 2v mit zwei 1-Hexylheptyl-Resten mit einer Loslichkeit von uber 100 g/l in den meisten Losungsmitteln, einer Fluoreszenzquantenausbeute von ca. 100% und einer ausgesprochen hohen Lichtechtheit auch fur Spezialanwendungen geeignet.

Localization of collagen mRNA in normal and scleroderma skin by in-situ hybridization

Abstract: Scleroderma is a fibrotic disease occurring in a localized or systemic form. Disturbed regulation of connective tissue metabolism plays an important role in its pathogenesis. However, until now, most of the data available were obtained from studies of fibroblasts in culture and there is considerable doubt that fibroblasts in a monolayer reflect the in-vivo situation. Using in-situ hybridization with specific antisense RNAs on frozen sections of skin, cells were detected displaying enhanced messenger RNA levels for type I and type III collagen in patients with localized and systemic scleroderma. Activated fibroblastic cells were often located near blood vessels in the deep dermis of patients with early stages of the disease and were mostly surrounded by mononuclear cells. These findings are in agreement with the concept that the interaction of fibroblasts with 'immunocompetent cells' is crucial in the initial activation of connective tissue metabolism in fibrosis.

In vitro susceptibilities and biotypes of Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus.

Abstract: Candida albicans strains were isolated from the oral cavities of 62 human immunodeficiency virus (HIV)-infected patients at different stages of HIV infection. Only patients with persistent generalized lymphadenopathy-acquired immunodeficiency syndrome (AIDS)-related complex or full-blown AIDS showed typical clinical symptoms for oral candidiasis. In general, the microbiological recovery of Candida strains from the oral cavity increased with more advanced stages of HIV infection. The antifungal activity of ketoconazole, itraconazole, nystatin, amphotericin B, and flucytosine against all 62 strains was evaluated by means of a photometer-read broth microdilution method for determination of the 30% inhibitory concentrations of the drugs. The 95% ranges of 30% inhibitory concentrations were as follows: less than or equal to 0.063 to 32 micrograms/ml for ketoconazole, less than or equal to 0.063 to 8 micrograms/ml for itraconazole, 0.5 to 4 micrograms/ml for nystatin, less than or equal to 0.063 to 4 micrograms/ml for amphotericin B, and less than or equal to 0.063 to 8 micrograms/ml for flucytosine. Two strains were resistant to flucytosine, one was resistant to ketoconazole, and three were resistant to itraconazole. Isolates from patients with full-blown AIDS showed significantly less susceptibility to itraconazole, amphotericin B, and flucytosine. Strains were biotyped by using the API 20C carbohydrate assimilation system. The major biotype accounted for 63.9% of the isolates. At repeated evaluation, a change in biotype pattern was seen in 27.3%.

Raphe nucleus of the pons containing omnipause neurons of the oculomotor system in the monkey, and its homologue in man.

Abstract: Omnipause neurons take part in the generation of saccadic eye movements. They lie around the midline in the caudal pontine reticular formation, in an area usually ascribed to the nucleus raphe pontis (rp). In this study of the monkey (Macaca fascicularis and M. mulatta), we describe four series of experiments aimed at establishing that omnipause neurons lie within a distinctive cytoarchitectonic entity, which we call the nucleus raphe interpositus (rip): (1) cytoarchitectural study, (2) recording-lesion experiments to establish in which cell group omnipause neurons lie, (3) cytochrome oxidase distribution in the omnipause region and neighboring structures, and (4) neuroanatomical tracing experiments to demonstrate afferents to the omnipause region. In the detailed cytoarchitectural study of the midline structures in the caudal pons and rostral medulla, a distinctive group of neurons (rip) adjoining the ventrocaudal border of rp and dorsal to the nucleus raphe magnus (rm) is described. The striking features of rip are the uniformly arranged, narrow row of the cells either side of the midline, and the extensive horizontally oriented dendritic trees of its neurons. The abducens rootlets (NVI) pass through the reticular formation at the same rostrocaudal level as rip and form a reliable landmark for its location. Cytochrome-oxidase-stained sections demonstrated additional differences between rip and adjacent cell groups: in rip the neurons and their extensive dendrites stained strongly, but not the surrounding neuropile, whereas in rp both the neurons and the neuropile stained darkly, so that individual neurons were difficult to see. Unlike rp, rip coincides with the location of omnipause neurons, and lesions marking the sites of individual omnipause units lay within its boundaries. Tritiated leucine was injected into superior colliculus (sc), which is known to have monosynaptic connections with omnipause neurons. Labelled axons and patterns of silver grains taken to indicate the presence of terminal branching were found in and around rip, but no significant labelling was seen in rp or rm. It is concluded that the omnipause neurons lie within the rip in the monkey. These functional and morphological differences between rip and the adjacent raphe nuclei are used to justify its characterization as an independent cell group in the monkey. In order to relate these findings to man, cytochrome oxidase experiments were carried out on the human brainstem, and the pattern of staining at the level of the abducens rootlets was correlated with the cytoarchitecture.(ABSTRACT TRUNCATED AT 400 WORDS)

Inflammation of the hind limb as a model of unilateral, localized pain: influence on multiple opioid systems in the spinal cord of the rat

Abstract: Inoculation of the right hind paw with Mycobacterium butyricum rapidly led to swelling and inflammation. The afflicted limb showed an enhanced sensitivity to noxious pressure (hyperalgesia) and a reduced sensitivity to noxious heat 24 h following treatment. Both naloxone and MR 2266 (which has greater activity at κ-opioid receptors) further increased the sensitivity to pressure (that is, potentiated the hyperalgesia) but did not affect the response to heat. They did not affect the response of the uninflamed paw. At 1 week, only MR 2266 was effective. At both 24 h and 1 week, the inflamed paw showed pronounced supersensitivity to the antinociceptive action of morphine against noxious pressure. At both 24 h and (to a greater extent) 1 week, a rise in levels of immunoreactive (ir)-dynorphin (DYN) was seen in the ipsilateral dorsal horn of the lumbar spinal cord. There was no alteration in the contralateral dorsal horn or in either ventral horn. Furthermore, levels of ir-met-enkephalin (ME) and ir-leu-enkephalin (LE) were unaffected. There was no difference in the density of μ-, δ- or κ-binding sites in any part of the lumbar cord, at either 24 h or 1 week, between ipsilateral and contralateral tissue. By 3 and 5 weeks postinoculation, the symptoms had spread to the contralateral hind limb and ir-DYN was elevated in the contralateral dorsal horn and the ipsilateral ventral horn. At 5 weeks, levels of ir-ME and ir-LE also were increased in the ipsilateral and contralateral dorsal horns, but not in the contralateral ventral horn. Furthermore, levels of ir-DYN were increased in the cervico-thoracic spinal cord, and rats displayed adrenal hypertrophy and a rise in plasma levels of ir-β-endorphin (β-EP). These data indicate: 1. (1) Peripheral inflammation localized to a single limb selectively modifies levels of ir-DYN in ipsilateral dorsal horn. The effect is specific to DYN as compared to ME and LE. The density of μ-, δ-, or κ-receptors in the lumbar spinal cord is unmodified. 2. (2) The altered response to opioid agonists and antagonists shown by rats with an inflamed limb may be selective to the injured tissue. 3. (3) Alterations in opioid systems associated with unilateral hind limb inflammation may not be exclusively chronic in nature: they appear very rapidly (within 24 h) of the induction of pain. With time, the contralateral limb becomes affected and, eventually, the effects resemble those seen with generalized polyarthritis.

Reduction of beta-adrenoceptor density and evaluation of positive inotropic responses in isolated, diseased human myocardium

Abstract: Cardiac beta-adrenoceptors and the positive inotropic effects of adenylate cyclase-depentdent (dobutamine, histamine, forskolin) and adenylate cyclase-independent agents (isobutylmethylxanthine (IBMX), dibutyryl-cAMP (db-cAMP), digoxin, digitoxin and calcium were measured in papillary muscle strips from severely failing (NYHA IV), moderately failing (NYHA II–III) and non-failing (NYHA I) human hearts. The density of beta-adrenoceptors in three NYHA I patients were 40.0, 42.0 and 42.9 fmol mg−1protein. The density of cardiac beta-adrenoceptors was significantly reduced in NYHA II–III to 18.0 ±1.1 mg−1 protein (n =16) and further reduced in NYHA IV to 9.5±1.6 fmol mg−1 protein (n=7). The KD values did not differ between the groups. Correspondingly, the positive inotropic effect of dobutamine was significantly reduced in NYHA II–II and almost lost in NYHA IV. The positive inotropic effect of histamine was similar in non-failing and moderately failing myocardium but reduced in preparations from severely failing hearts (NYHA IV). The positive inotropic effect of IBMX was diminished in moderately and severely failing myocardium depending on the functional class of heart failure. In contrast, the effects of forskolin, db-cAMP, digoxin and digitoxin were not impaired in NYHA IV when compared with the maximal positive inotropic effect of calcium. It is concluded that in the failing human heart (a) the number of cardiac beta-adrenoceptors is reduced proportional to the severity of heart failure; (b) the receptor coupling of H2-receptors to adenylate cyclase may be impaired, but only in severe heart failure; (c) the basal cAMP formation may be diminished; and that (d) the catalytic subunit of the adenylate cyclase and the cAMP-dependent protein kinases may be promising targets for drugs to restore force of contraction in human heart failure.

Systemic scleroderma: clinical and pathophysiologic aspects

Abstract: Systemic scleroderma is a generalized disease of connective tissue involving mainly the skin, the gastrointestinal tract, the lungs, the heart, and the kidneys. It can be present in different forms, of which acroscleroderma, with limited cutaneous and extracutaneous involvement, and diffuse scleroderma within a more rapid progression are most characteristic. Circulating antibodies against antinucleolar antigens are present in most patients with systemic scleroderma. They are helpful for establishing a classification and for determining the prognosis of the disease; their involvement in the pathogenesis, however, is still unclear. Alterations of the blood vessels and induction of fibroblasts by potent mediators are thought to play an important role in the early phase of scleroderma. Therefore early diagnosis is required, which then can initiate vasoactive therapy. In patients with systemic scleroderma, who also suffer from additional myositis, interstitial lung diseases, or arthritis, anti-inflammatory treatment with prednisolone and azathioprine is suggested. Development and progression of fibrosis cannot yet be influenced sufficiently. Only d-penicillamine affecting cross-linking of collagen has been widely used in scleroderma and has some beneficial effect.