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Biomedical subjects

G Lindner

Publications and source records attributed to G Lindner.

At least 19 recordsLinked to original sources
PubMed2004

Characterization of pathogenic Escherichia coli isolated from humans in Austria: phenotypes, toxin gene types and epidemiology.

One hundred and ten clinical Escherichia coli isolates of serovar O157 (n = 102) and O26 (n = 8) were characterized for the presence of putative virulence genes by PCR. All but one of these isolates contained the eae gene. The EHEC-hly gene could be detected in all E. coli O157 and in 50% of E. coli O26 isolates. Forty-five (40.9%) of the 110 E. coli were positive for both stx(1) and stx(2) genes, 2 (1.8%) isolates were positive for stx(1) and 57 isolates (51.8%) were positive for stx(2) only. Among the 102 stx(2) positive isolates, 14 (13.7%) E. coli O157 contained also the stx(2c) variant gene. No other stx(2) variant was identified. Six clinical isolates (five E. coli O157:H7 and one E. coli O26) did not contain stx genes. Ten non-pathogenic E. coli isolates which were amplified as controls didn't contain any stx and eae gene but two of the ten strains contained the EHEC-hly gene. By their growth on chromogenic media, all but two of 50 E. coli O157 could be differentiated from eight E. coli O26 and 10 non-pathogenic E. coli. Sixty-one of the O157:H7 isolates were further subjected to pulsed-field gel electrophoresis (PFGE) which identified 49 distinguishable patterns. In five cases where contact infection among family members was suspected, indistinguishable PFGE patterns confirmed the epidemiological relatedness of the isolates. Moreover, two PFGE clusters were identified which comprised five and three strains, respectively. These findings indicate the occurrence of both family and diffuse outbreaks of E. coli O157 infections in Austria during recent years and demonstrate the need for molecular subtyping of these pathogens.

Adhesins, Bacterial↗
PubMed2001

Patterns of proliferation and apoptosis during murine hair follicle morphogenesis.

In this study, we have correlated cutaneous apoptosis and proliferation in neonatal mice during hair follicle morphogenesis. We have applied a novel triple- staining technique that uses Ki67 immunoreactivity as a marker of proliferation as well as TUNEL and Hoechst 33342 staining as apoptosis markers. We have also assessed the immunoreactivity of interleukin-1 beta-converting enzyme, caspase 1, a key enzyme in the execution of apoptosis, and of P-cadherin, which has been suggested as a key adhesion receptor in segregating proliferating keratinocytes. The TUNEL data were systematically compared with high resolution light microscopy and transmission electron microscopy data. Virtually all keratinocytes of the developing hair bud were strongly Ki67(+), suggesting that the hair bud is not an epidermal invagination but primarily the product of localized keratinocyte proliferation. As hair follicle development advanced, three distinct foci of proliferation became apparent: the distal outer root sheath around the hair canal, the mid outer root sheath, and the proximal hair matrix. Of these proliferating hair follicle keratinocytes only defined subsets expressed P-cadherin. TUNEL(+) cells in the hair follicle were not found before stage 5 of murine hair follicle morphogenesis. During the early stages of hair follicle development, interleukin-1 beta-converting enzyme immunoreactivity was present on all keratinocytes, but virtually disappeared from the proximal hair follicle epithelium later on. High resolution light microscopy/transmission electron microscopy revealed scattered and clustered apoptotic keratinocytes in all epithelial hair follicle compartments throughout hair follicle development, including its earliest stages. This highlights striking differences in the demarcation of apoptotic hair follicle keratinocytes between the TUNEL technique and high resolution light microscopy/transmission electron microscopy and suggests a role for apoptosis in sculpting the hair follicle even during early hair follicle development.

Animals↗
PubMed2000

High-dose proinflammatory cytokines induce apoptosis of hair bulb keratinocytes in vivo.

BACKGROUND: Hair loss following skin inflammation may in part be mediated by keratinocyte (KC) apoptosis. While the effects of different cytokines or other apoptosis stimulating agents such as interferon (IFN)-gamma or tumour necrosis factor (TNF)-alpha on KC apoptosis in vitro have been addressed in several studies, little is known about the effects of proinflammatory cytokines on KC apoptosis in vivo. OBJECTIVES: To study the effects of intradermally injected TNF-alpha, interleukin (IL)-1beta and IFN-gamma on KC apoptosis in the back skin of C57BL/6 mice. METHODS: Apoptosis in epidermal and hair bulb KCs was analysed by immunohistology using TUNEL staining. RESULTS: Injection of TNF-alpha induced a significantly higher number of apoptotic cells within the epidermis than vehicle; all three proinflammatory cytokines together further increased their number. Intrafollicular hair bulb KCs were much more susceptible to apoptosis induction by TNF-alpha or IL-1beta; their injection significantly upregulated apoptosis after 6 h, which was further increased after 24 h. The combination of all cytokines together accelerated intrafollicular apoptosis after 6 h by doubling the number of apoptotic cells per hair bulb, compared with the effects of TNF-alpha or IL-1beta alone. CONCLUSIONS: These data suggest that programmed cell death of proliferating KCs in vivo can be induced by proinflammatory cytokines.

Animals↗
PubMed2000

Involvement of hepatocyte growth factor/scatter factor and met receptor signaling in hair follicle morphogenesis and cycling.

HGF/SF and its receptor (Met) are principal mediators of mesenchymal-epithelial interactions in several different systems and have recently been implicated in the control of hair follicle (HF) growth. We have studied their expression patterns during HF morphogenesis and cycling in C57BL/6 mice, whereas functional hair growth effects of HGF/SF were assessed in vivo by analysis of transgenic mice and in skin organ culture. In normal mouse skin, follicular expression of HGF/SF and Met was strikingly localized: HGF/SF was found only in the HF mesenchyme (dermal papilla fibroblasts) and Met in the neighboring hair bulb keratinocytes. Both HGF/SF and Met expression peaked during the initial phases of HF morphogenesis, the stage of active hair growth (early and mid anagen), and during the apoptosis-driven HF regression (catagen). Met+ cells in the regressing epithelial strand appeared to be protected from undergoing apoptosis. Compared to wild-type controls, transgenic mice overexpressing HGF/SF under the control of the MT-1 promoter had twice as many developing HF and displayed accelerated HF development on postnatal day 3. They also showed significant catagen retardation on P17. In organ culture and in vivo, HGF/SF i.c. resulted in a significant catagen retardation. These results demonstrate an important role of HGF/SF and Met in murine hair growth control and suggest that Met-mediated signaling might be exploited for therapeutic manipulation of human hair growth disorders.-Lindner, G., Menrad, A., Gherardi, E., Merlino, G., Welker, P., Handjiski, B., Roloff, B., Paus, R. Involvement of hepatocyte growth factor/scatter factor and Met receptor signaling in hair follicle morphogenesis and cycling.

Animals↗
PubMed2000

Control of murine hair follicle regression (catagen) by TGF-beta1 in vivo.

The regression phase of the hair cycle (catagen) is an apoptosis-driven process accompanied by terminal differentiation, proteolysis, and matrix remodeling. As an inhibitor of keratinocyte proliferation and inductor of keratinocyte apoptosis, transforming growth factor beta1 (TGF-beta1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF-beta1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the potential involvement of TGF-beta1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF-beta1 null mice and age-matched wild-type littermates, and assessed the effects of TGF-beta1 injection on murine anagen hair follicles in vivo. At day 18 p.p., hair follicles in TGF-beta1 -/- mice were still in early catagen, whereas hair follicles of +/+ littermates had already entered the subsequent resting phase (telogen). TGF-beta1-/- mice displayed more Ki-67-positive cells and fewer apoptotic cells than comparable catagen follicles from +/+ mice. In contrast, injection of TGF-beta1 into the back skin of mice induced premature catagen development. In addition, the number of proliferating follicle keratinocytes was reduced and the number of TUNEL + cells was increased in the TGF-beta1-treated mice compared to controls. Double visualization of TGF-beta type II receptor (TGFRII) and TUNEL reactivity revealed colocalization of apoptotic nuclei and TGFRII in catagen follicles. These data strongly support that TGF-beta1 ranks among the elusive endogenous regulators of catagen induction in vivo, possibly via the inhibition of keratinocyte proliferation and induction of apoptosis. Thus, TGF-betaRII agonists and antagonists may provide useful therapeutic tools for human hair growth disorders based on premature or retarded catagen development (effluvium, alopecia, hirsutism).

Animals↗
PubMed1999

A role for p75 neurotrophin receptor in the control of hair follicle morphogenesis.

During hair follicle (HF) morphogenesis, p75 neurotrophin receptor (p75NTR) reportedly is the first growth factor receptor found to be expressed by those fibroblasts that later develop into the dermal papilla (DP) of the HF. However, the functional role of p75NTR in HF morphogenesis is still unknown. Studying HF development in fetal and neonatal C57BL/6 murine back skin, we show that p75NTR-immunoreactivity (IR) is prominently expressed by DP fibroblasts as well as by skin nerves during the early steps of HF development. In contrast, p75NTR-IR disappears from the DP in the fully developed HF and it is expressed only in the epithelial outer root sheath of the HF. Compared to age-matched wild-type animals, p75NTR knockout (-/-) mice show significant acceleration of HF morphogenesis, and DP fibroblasts of p75NTR knockout mice show reduced proliferative activity in situ, indicating alterations in their transition from proliferation to differentiation. Although no significant differences in the expression of adhesion molecules (NCAM), selected morphogens (TGFbeta-2, HGF/SF, FGF-2, KGF), or their receptors (TGFbetaR-II, m-met, FGFR-1) were seen between DP of p75NTR knockout and wild-type mice, p75NTR mutants showed a prominent upregulation of FGFR-2, a high-affinity receptor for KGF, in both follicular DP and epithelium. Furthermore, the administration of anti-KGF neutralizing antibody significantly inhibited acceleration of HF morphogenesis in p75NTR knockout mice in vivo. These observations suggest that p75NTR plays an important role during HF morphogenesis, functioning as a receptor that negatively controls HF development, most likely via alterations in DP fibroblast proliferation/differentiation and via downregulation of KGF/FGFR-2 signaling in the HF.

Animals↗
PubMed1999

Noggin is a mesenchymally derived stimulator of hair-follicle induction.

The induction of developmental structures derived from the ectoderm, such as the neural tube or tooth, occurs through neutralization of the inhibitory activity of members of the bone-morphogenetic protein (BMP) family by BMP antagonists. Here we show that, during hair-follicle development, the neural inducer and BMP-neutralizing protein Noggin is expressed in the follicular mesenchyme, that noggin-knockout mice show significant retardation of hair-follicle induction, and that Noggin neutralizes the inhibitory action of BMP-4 and stimulates hair-follicle induction in embryonic skin organ culture. As a crucial mesenchymal signal that stimulates hair-follicle induction, Noggin operates through antagonistic interactions with BMP-4, which result in upregulation of the transcription factor Lef-1 and the cell-adhesion molecule NCAM, as well as through BMP4-independent downregulation of the 75 kD neurotrophin receptor in the developing hair follicle.

Animals↗
PubMed1999

Hair follicle apoptosis and Bcl-2.

Hair follicle (HF) morphogenesis and cycling are characterized by a tightly controlled balance of proliferation, differentiation and apoptosis. The members of the bcl-2 family of proto-oncogenes are important key players in the apoptosis control machinery of most cell types. Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter, show tightly regulated, hair cycle-dependent expression patterns: during catagen, the distal ORS of the HF remains strongly positive for Bcl-2 and Bax; in contrast, the proximal epithelial part of the HF loses most Bcl-2 expression while it remains strongly positive for Bax. In Bcl-2 null mice, skin becomes markedly hypopigmented during the first postnatal anagen probably due to increased melanocyte apoptosis. Reportedly, these mice also show a retardation of the first anagen development after birth. Transgenic mice overexpressing Bcl-2 under the control of the keratin-1 promoter display multifocal epidermal hyperplasia and aberrant expression of keratin-6, while alterations of HF cycling have not been investigated. Surprisingly, Bcl-2 overexpression under the control of the keratin-14 promoter leads to accelerated catagen progression and increased chemotherapy-induced apoptosis, HF dystrophy and alopecia. Transgenic mice overexpressing Bcl-X(L), another anti-apoptotic bcl-2 family member, under the control of the K14 promoter, reportedly also display accelerated catagen development. These and other Bcl-2 transgenic and null mice are now available to further dissect the as yet unclear, and likely complex, role of Bcl-2 in HF growth and pigmentation.

Animals↗
PubMed1998

A new role for neurotrophin-3: involvement in the regulation of hair follicle regression (catagen).

Nervous system and hair follicle epithelium share a common ectodermal origin, and some neurotrophins (NTs) can modulate keratinocyte proliferation and apoptosis. Therefore, it is reasonable to ask whether NTs are also involved in hair growth control. Here, we show that the expression of NT-3 and its high-affinity receptor, tyrosine kinase C, in the skin of C57BL/6 mice is strikingly hair cycle-dependent, with maximal transcript and protein expression seen during spontaneous hair follicle regression (catagen). During catagen, NT-3 and tyrosine kinase C are co-expressed by terminal deoxynucleotidyl transferase-mediated in situ nick end labeling-positive keratinocytes in the club hair and secondary germ. NT-3-overexpressing transgenic mice show precocious catagen development during the postnatal initiation of hair follicle cycling, whereas heterozygous NT-3 knockout (+/-) mice display a significant catagen retardation. Finally, NT-3 stimulates catagen development in organ culture of normal C57BL/6 mouse skin. These observations suggest that the hair follicle is both a source and target of NT-3 and that NT-3/tyrosine kinase C signaling is functionally important in the control of hair follicle regression. Therefore, tyrosine kinase C agonists and antagonists deserve systematic exploration for the management of hair growth disorders that are related to premature (alopecia/effluvium) or retarded catagen (hirsutism/hypertrichosis).

Animals↗
PubMed1997

Interleukin-15 protects from lethal apoptosis in vivo.

Interleukin-15 shares many biological activities with IL-2 and signals through the IL-2 receptor beta and gamma chains. However, IL-15 and IL-2 differ in their controls of expression and secretion, their range of target cells and their functional activities. These dissimilarities may include differential effects on apoptosis. For example, IL-2 induces or inhibits T-cell apoptosis in vitro, depending on T-cell activation, whereas IL-15 inhibits cytokine deprivation-induced apoptosis in activated T cells. Studying whether and how IL-15 modulates distinct apoptosis pathways, we show here that apoptosis induced by anti-Fas, anti-CD3, dexamethasone, and/or anti-IgM in activated human T and B cells in vitro is inhibited by IL-15 in a manner dependent on RNA synthesis. In vivo, anti-Fas-induced lethal multisystem apoptosis in mice is suppressed by a novel IL-15-IgG2b fusion protein. Only IL-15, but not IL-2, completely protected from lethal hepatic failure. Thus, IL-15 is a potent, general inhibitor of apoptosis in vitro and in vivo with intriguing therapeutic potential.

Animals↗
PubMed1997

Analysis of apoptosis during hair follicle regression (catagen)

Keratinocyte apoptosis is a central element in the regulation of hair follicle regression (catagen), yet the exact location and the control of follicular keratinocyte apoptosis remain obscure. To generate an "apoptomap" of the hair follicle, we have studied selected apoptosis-associated parameters in the C57BL/6 mouse model for hair research during normal and pharmacologically manipulated, pathological catagen development. As assessed by terminal deoxynucleotide transferase dUTP fluorescein nick end-labeling (TUNEL) stain, apoptotic cells not only appeared in the regressing proximal follicle epithelium but, surprisingly, were also seen in the central inner root sheath, in the bulge/isthmus region, and in the secondary germ, but never in the dermal papilla. These apoptosis hot spots during catagen development correlated largely with a down-regulation of the Bcl-2/Bax ratio but only poorly with the expression patterns of interleukin-1beta converting enzyme, p55TNFR, and Fas/Apo-1 immunoreactivity. Instead, a higher correlation was found with p75NTR expression. During cyclophosphamide-induced follicle dystrophy and alopecia, massive keratinocyte apoptosis occurred in the entire proximal hair bulb, except in the dermal papilla, despite a strong up-regulation of Bax and p75NTR immunoreactivity. Selected receptors of the tumor necrosis factor/nerve growth factor family and members of the Bcl-2 family may also play a key role in the control of follicular keratinocyte apoptosis in situ.

Administration, Topical↗
PubMed1996

Factors affecting the transfer of radiocaesium from soil to roe deer in forest ecosystems of southern Germany.

Since 1987, in Southern Germany, as a consequence of the Chernobyl accident, the 137Cs activity concentration in roe deer (Capreolus capreolus) has been intensively monitored. A large data set is now available with approximately 5000 samples, with information about the location of the animal, the time of slaughtering, soil characteristics and distance to intensively managed agricultural land. Both the roe deer 137Cs activity concentrations and aggregated transfer coefficients soil-roe deer (T(ag,r)) show a considerable variability with geometric mean and geometric standard deviation in meat of 270.3.5 +/- 1 Bq.kg-1 and 0.01.3.5 +/- 1 m2.kg-1, respectively. From 1987 to 1991, T(ag,r) values exhibited a decline with an ecological half-life of about 3 years. Since 1991, no further decrease of the roe deer contamination level was observed. This general trend is superimposed by an increase in T(ag,r) in autumn that has occurred in almost every year, which is probably due to consumption of mushrooms. This hypothesis is supported by a significant positive correlation between the precipitation during July and August, stimulating the fungi's growth and the height of the maximum in T(ag,r) in autumn. Animals are less contaminated when living in parts of the forest from where they have access to intensively managed agricultural land. A small, but significant correlation is observed between the T(ag,r) and soil parameters; the total potassium content of the soil and the pH of the organic soil layer. The highest transfer coefficients soil-roe deer were found on a peat bog, where most values ranged from 0.01-0.1 m2.kg-1, and neither a pronounced seasonal variation, nor a long-term decrease was observed. On sites with coniferous forests, most T(ag,r) values range from 0.005 to 0.05 m2.kg-1, on sites with a mixture of coniferous and deciduous trees, the transfer coefficients range mostly from 0.002 to 0.02 m2.kg-1. This is a further indication of the importance of the uppermost soil layers and the biological processes therein with respect to the bioavailability of caesium. On the two sites, the values at the lower boundary are more typical for animals that have access to agricultural areas, whereas the higher values were observed in autumn and for animals grazing distant from agricultural areas.

Animals↗
PubMed1996

Ethylene-oxide and steam-sterilised polysulfone membrane in dialysis patients with eosinophilia.

Eosinophilia and some acute dialysis side-effects, such as itching, flushing and bronchospasm, are often associated with the presence of ethylene oxide (ETO) as dialyzer sterilizing agent. This study evaluated the effects of two different polysulfone (PS) hollow-fiber dialysers sterilized with ETO and steam in 31 chronic dialysis patients with eosinophilia. Clinical symptoms, metabolic and biochemical parameters, complement (C3a and C5a) activation and production were evaluated in each patient dialysed for two months at a time with Cuprophan dialyser, ETO-PS dialyser and steam-PS dialyser. The steam-sterilizer agent does not alter the purifying capacity of the PS membrane which maintains its superiority over Cuprophan in terms of biocompatibility. Using steam-PS, intradialytic eosinophil kinetics seems to improve. In some patients with high serum levels of ETO-specific IgE these levels tend to diminish. Generic intradialytic symptoms do not differ between the two sterilization methods, although some hypersensitivity symptoms during the first dialysis hour are considerably lower in some patients when steam-sterilized PS is used.

Adult↗
PubMed1995

Dialysis-related amyloidosis in a large CAPD population.

We studied 212 patients from 13 Italian dialysis centers to evaluate the clinical aspects of dialysis-related amyloidosis in continuous ambulatory peritoneal dialysis (CAPD). The mean age was 64.2 +/- 12.3 years and mean time on dialysis was 36.9 +/- 25.1 months. Residual diuresis was 615.7 +/- 554.0 mL/day and plasma beta 2-microglobulin (beta 2M) level was 27.0 +/- 12.8 mg/L. Radiological skeletal examination, neurological problems related to beta 2M, and urinary and dialytic balance of beta 2M were evaluated. Correlations between age, time on dialysis, residual diuresis, beta 2M plasma levels, beta 2M peritoneal and renal removal, carpal tunnel syndrome, and bone disease were studied. Only the number of bone lesions had a significant positive correlation with patient age and negative correlation with residual diuresis. The latter had an inverse relation with beta 2M plasma levels. Dialytic age did not correlate with any of the parameters. No other correlation was observed. Hand lesions were found in 85% of patients with bone dialysis-related amyloidosis. In conclusion, residual diuresis in our patients played a positive role in the number of bone localizations. Only age, but not time on dialysis, had a positive impact on the bone lesions. The high percentage of hand lesions suggests that the observation of this skeletal segment is a simple, safe, and effective modality of bone follow-up for dialysis-related amyloidosis.

Adult↗