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Biomedical subjects

M Hertel

Publications and source records attributed to M Hertel.

13 recordsLinked to original sources

Dynamics and localization of activin A expression in rat gastric ulcers.

BACKGROUND: Activin A, the homodimer of the activin/inhibin betaA subunit, has been shown to participate in cutaneous wound healing. In this study we intended to determine its part in gastric ulceration. METHODS: Activin A expression was studied by immunohistochemistry and in situ hybridization in acetic-acid-induced chronic gastric ulcers in rat. The dynamics of this process were also assessed by quantitative real time RT-PCR and RNase protection assays (RPA). The effects of different doses of this cytokine on epithelial and mesenchymal cell proliferation were quantitated in vitro. RESULTS: Low amounts of activin A and its mRNA were expressed by epithelia, endothelia and fibroblasts in intact gastric tissue. Granulation tissue of gastric ulcers and gastric glands adjacent to the ulcer rim expressed markedly increased amounts of activin protein as well as activin/inhibin betaA mRNA. RPA and RT-PCR studies revealed a more than 3-fold increase in the relative abundance of this mRNA. Activin A did not affect the proliferation rate of fibroblasts and epithelial cells in vitro. CONCLUSIONS: Activin A participates in gastric ulcer healing in a similar fashion as in cutaneous wounding. Its expression on protein and mRNA level is markedly increased in ulcer base and rim.

Activins↗

The roles of activins in repair processes of the skin and the brain.

A recent study from our laboratory demonstrated a strong upregulation of activin expression during cutaneous wound healing. To further analyze the role of activin A in skin morphogenesis and wound repair, we generated transgenic mice that overexpress activin A under the control of the keratin 14 promoter. The latter targets expression of transgenes to the basal, proliferating layer of the epidermis. Hetero- as well as homozygous transgenic animals were viable and fertile. However, they were smaller than non-transgenic littermates and they had smaller ears and shorter tails. Histological analysis of their skin revealed dermal hyperthickening, mainly due to the replacement of fatty tissue by connective tissue, and an increase in suprabasal, partially differentiated epidermal layers. After cutaneous injury, a strong enhancement of granulation tissue formation was observed. Furthermore, the extent of re-epithelialization was increased in some of the wounds. These data demonstrate that activin A is a potent stimulator of the wound healing process. Using an in vivo model of local brain injury, we found that activin A also plays a significant role in the early cellular response to neuronal damage. Expression of activin mRNA and protein is markedly upregulated within a few hours of injury. If applied exogenously, recombinant activin A is capable of rescuing neurons from acute cell death. Studying the interaction between bFGF, a well-established neuroprotective agent, which is currently being tested in stroke patients, and activin A, we arrived at the unexpected conclusion that it is the strong induction of activin A by bFGF which endows the latter with its beneficial actions in patients. These findings suggest that the development of substances directly targeting activin expression or receptor binding should offer new possibilities in the acute treatment of stroke and brain trauma.

Activins↗

Induction of activin A is essential for the neuroprotective action of basic fibroblast growth factor in vivo.

Exogenous application of neurotrophic growth factors has emerged as a new and particularly promising approach not only to promote functional recovery after acute brain injury but also to protect neurons against the immediate effect of the injury. Among the various growth factors and cytokines studied so far, the neuroprotective and neurotrophic profile of basic fibroblast growth factor (bFGF) is the best documented. Using an animal model of acute excitotoxic brain injury, we report here that the neuroprotective action of bFGF, which is now being tested in stroke patients, depends on the induction of activin A, a member of the transforming growth factor-beta superfamily. Our evidence for this previously unknown mechanism of action of bFGF is that bFGF strongly enhanced lesion-associated induction of activin A; in the presence of the activin-neutralizing protein follistatin, bFGF was no longer capable of rescuing neurons from excitotoxic death; and recombinant activin A exerted a neuroprotective effect by itself. Our data indicate that the development of substances influencing activin expression or receptor binding should offer new ways to fight neuronal loss in ischemic and traumatic brain injury.

Activins↗

Connective tissue growth factor: a novel player in tissue reorganization after brain injury?

Recent studies have suggested a role of connective tissue growth factor (CTGF) in repair processes of the skin as well as in various types of fibrotic disease. However, a function of this molecule in central nervous system (CNS) repair has not been demonstrated yet. In this study we analysed the temporal and spatial expression pattern of CTGF after unilateral kainic acid lesions of the hippocampal CA3 region in mice. We found a strong induction of CTGF mRNA and protein expression in neurons and glial cells of the lesioned hippocampus. Interestingly, increased expression of this mitogen was accompanied by elevated levels of the extracellular matrix molecule fibronectin, which is a known target of CTGF action. Therefore, our data indicate a novel function of CTGF in postlesional restructuring of the hippocampus, where it possibly participates in glial scar formation.

Animals↗

Fibroblast growth factors-5 and -9 distinctly regulate expression and function of the gap junction protein connexin43 in cultured astroglial cells from different brain regions.

Astroglial cells contribute to neuronal maintenance and function in the normal and diseased brain. Gap junctions formed predominantly by connexin43 (cx43) provide important pathways to coordinate astroglial responses. We have previously shown that fibroblast growth factor (FGF)-2, which occurs ubiquitously in the CNS, downregulates gap junction communication in cortical and striatal, but not in mesencephalic astroglial cells in vitro (Reuss et al. Glia 22:19-30, 1998). Other members of the FGF family expressed in the CNS include FGF-5 and FGF-9. We show that both FGF-5 and FGF-9, like FGF-2, downregulate astroglial gap junctions and functional coupling. However, their effects are strikingly different from different brain regions, with regard to astroglial cells. FGF-5 specifically affects mesencephalic astroglial cells without changing coupling of cortical and striatal astroglia, while FGF-9 reduces gap junctional coupling in astroglia from all three brain regions. Both cx43 mRNA and protein levels as well as functional coupling assessed by dye spreading are affected. To clarify whether brain region-specific effects of FGFs on astroglial coupling are due to differential expression of FGF receptors (FGFR), we monitored expression of the four known FGFR mRNAs in astroglial cultures by RT-PCR. Irrespective of their regional origin, astroglial cells express mRNAs for FGFR-2 and FGFR-3. In summary, our results provide evidence for an important role of FGF-2, -5, and -9 in a distinct, CNS region-specific regulation mechanism of astroglial gap junction communication. The molecular basis underlying the regionally distinct responsiveness of astrocytes to different FGFs may be sought beyond distinct FGFR expression.

Animals↗

[Longterm ECG in the dog].

Holter monitoring was obtained from 44 clinically normal dogs and 68 dogs with heart disease or being suspicious for a cardiopathy. Several employments of the holter monitoring are shown by means of some examples. This method proved to be effective in the diagnosis of syncopes and the review of the therapy of arrhythmias. Limits and difficulties are discussed.

Animals↗

Differentiation of cytotoxicity using target cells labelled with europium and samarium by electroporation.

We report the simultaneous use of europium-DTPA (Eu-DTPA) and samarium-DTPA (Sm-DTPA) in cytotoxicity experiments to analyze simultaneously LAK and NK cell lysis and to differentiate between specific target lysis and bystander killing. The target cells were either labelled with Eu-DTPA or Sm-DTPA chelates by electroporation, which permits the use of target cell lines or primary leukemic B cells (B-CLL) that cannot be labelled by the conventional dextran-sulphate method. The release of europium and samarium reaches a maximum at comparable time intervals (2-3 h). Due to the shorter counting interval within the samarium window the labelling efficiency is about ten times less efficient compared to europium. Using europium as label for the LAK target Daudi and samarium as label for the NK sensitive cell line K562 the differentiation of LAK versus NK activity can be performed in a single culture assay. Also, the killing of B cells and bystander cells by cytotoxic T cells was analyzed in a system where T cells were redirected to B cells through CD3 x CD19 bispecific antibodies. In fact, no bystander killing was noted when bispecific antibodies were used to bridge cytotoxic T cells to the B cells. This approach provides a simple non-radioactive method for evaluating cytotoxicity against two different cells in a single culture well.

Cell Line↗

Fatty acid binding of myoglobin depends on its oxygenation.

In the present work we show with different binding assays chicken gizzard myoglobin is able to bind fatty acids and bromosulphophthalein (BSP) in vitro. The fatty acid binding depends on the oxygenation of the myoglobin. Freshly prepared chicken gizzard, chicken or bovine heart myoglobin have a high fatty acid binding capability. However, when oxy-myoglobin in converted to met-myoglobin by dialysis against acidic buffer at high ionic strength (or when commercially available myoglobins are used) a 60-70% lower fatty acid binding capacity is found. Like bovine serum albumin (BSA), gizzard myoglobin has the highest affinity for unsaturated fatty acids and a lower affinity for saturated fatty acids or dyes. Chicken gizzard smooth muscle myoglobin may function as an additional fatty acid binding protein in vivo.

Animals↗

Comparative analysis of glutaraldehyde-preserved porcine xenografts and fresh or glutaraldehyde-treated human aortic valves by holographic interferometry.

Although calcification and degeneration are recognized as the main causes of bioprosthetic heart valve failure, the reasons for such failure are not well understood. Hidden tissue anomalies in the valves may be the origin of later calcification. Application of hologram interferometry for non-destructive testing enables the detection of such tissue anomalies. A comparative study by holographic interferometry of ten porcine bioprosthetic valves (seven Carpentier-Edwards SAV, two BioImplant and one Valcor) with five human aortic valves before and after glutaraldehyde treatment is presented. Whereas irregularities were detected in the interferograms of eight out of ten bioprostheses, no similar distorted fringe pattern was found in the holographic interferograms of human specimens. The present results suggest that tissue abnormalities exist in standard bioprosthetic valves which are absent in human ones. These irregularities may be the origin of later calcification and valvular dysfunction.

Aged↗

Non-destructive evaluation of prosthetic heart valves by holographic interferometry.

Dysfunction of prosthetic heart valves is a common complication after heart valve replacement, affecting both biologic and mechanical prostheses. A preoperative, non-destructive test of each individual valve may help to prevent the implantation of a valve which has material weaknesses. To this end we developed a technique for testing heart valve prostheses by holographic interferometry. The advantage of this technique is that it provides a non-contact, non-destructive, highly sensitive three dimensional analysis of the valve under loading. Samples of several mechanical and biologic valve substitutes were investigated. Deformations of the valve, due to small pressure differences applied to the samples in a specially developed test chamber, were recorded by double exposure holography. A fringe pattern superimposed on the image of the valve reconstructed from the hologram clearly indicates the presence of even the slightest defect in the valve material. Our experimental results demonstrate the ability of non-destructive holographic screening testing to detect defects or weaknesses which may potentially lead to dysfunction in replacement valves.

Animals↗

Give-and-take in an ecumenical system. HealthEast St. Joseph's shared its traditions and gained a better balance.

When St. Joseph's Hospital in St. Paul, MN, owned and operated by the Sisters of St. Joseph of Carondelet, joined the ecumenical HealthEast healthcare system in 1987, many observers were skeptical of the venture's success. But an emphasis on their shared Judeo-Christian values has enabled the Catholic, Lutheran, and Baptist facilities to build a strong system. The beginnings of the merger were difficult, as facilities closed, others expanded their services, and staff shifted between them. An open communications policy between HealthEast leaders and staff members and dedication to the mission of healthcare that all the system facilities shared helped blend denominational identity and traditions at each member hospital and establish a corporate identity. The HealthEast system has adopted some of St. Joseph's policies and practices, particularly in the areas of mission, ethics, and spiritual care. HealthEast St. Joseph's has also benefited from being part of the HealthEast system, gaining a more diverse staff respectful of each others' beliefs, expanded spiritual care, and the means to continue serving its community. HealthEast plans to discontinue inpatient services at HealthEast St. Joseph's in downtown St. Paul and build a suburban facility, but the Sisters of St. Joseph of Carondelet are working with HealthEast to assess the downtown community's healthcare needs, especially among the homeless and immigrant populations, and ensure those needs will continue to be met.

Catholicism↗

[Long-term EKG in dogs: comparison between a computerized system and visual arrhythmia analysis].

Based on results of holter ecg recordings taken from 38 dogs the computerized analyses system turned out as method not exactly valuing the frequency and sensitivity of arrhythmias. Despite there was a significant correlation between the computerized and visual arrhythmia analysis for ventricular respectively supraventricular premature beats, in individual cases there was an important aberration between the particular values.

Animals↗