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Biomedical subjects

M Bacher

Publications and source records attributed to M Bacher.

At least 55 records · Page 3Linked to original sources
PubMed1997

TNF-alpha up-regulates renal MIF expression in rat crescentic glomerulonephritis.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a potent proinflammatory mediator that participates in the pathogenesis of endotoxemia and experimental crescentic glomerulonephritis. However, very little is known about how MIF production is regulated in disease. We therefore examined whether tumor necrosis factor alpha (TNF-alpha), a known inducer of MIF expression by macrophages in vitro, up-regulates local and systemic MIF expression in a macrophage-mediated rat model of crescentic glomerulonephritis. MATERIALS AND METHODS: Anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of six primed rats. Animals were treated with 1 mg/kg soluble TNF-alpha receptor (TNFbp) or saline from the time of disease induction until they were killed on Days 1, 7, or 14. Renal MIF expression was assessed by in situ hybridization, immunohistochemistry, and ELISA, and compared with macrophage accumulation and indices of renal damage. RESULTS: Although TNFbp treatment on Day 1 of the disease had only a partial effect upon the up-regulation of glomerular MIF expression, on Days 7 to 14 it almost completely abrogated the increase in glomerular and interstitial MIF mRNA and protein expression. In addition, TNFbp treatment significantly inhibited MIF secretion by cultured glomeruli and reduced serum MIF levels. The inhibition of renal MIF expression was paralleled by a significant inhibition of glomerular and interstitial macrophage infiltration (p < 0.001 versus saline treated), a significant suppression of renal injury (proteinuria and serum creatinine), and a marked reduction in histologic damage (glomerular hypercellularity, crescent formation, and interstitial fibrosis; all p < 0.01 versus saline treated). CONCLUSIONS: This study demonstrates for the first time that TNF-alpha up-regulates local MIF expression by both infiltrating macrophages and resident kidney cells in rat crescentic glomerulonephritis. In addition, TNF-alpha regulates systemic MIF production. Thus, TNF-alpha, together with MIF, may play a pathological role in immunologically induced renal disease.

Animals↗
PubMed1996

An essential regulatory role for macrophage migration inhibitory factor in T-cell activation.

The protein known as macrophage migration inhibitory factor (MIF) was one of the first cytokines to be discovered and was described 30 years ago to be a T-cell-derived factor that inhibited the random migration of macrophages in vitro. A much broader role for MIF has emerged recently as a result of studies that have demonstrated it to be released from the anterior pituitary gland in vivo. MIF also is the first protein that has been identified to be secreted from monocytes/macrophages upon glucocorticoid stimulation. Once released, MIF acts to "override" or counter-regulate the suppressive effects of glucocorticoids on macrophage cytokine production. We report herein that MIF plays an important regulatory role in the activation of T cells induced by mitogenic or antigenic stimuli. Activated T cells produce MIF and neutralizing anti-MIF antibodies inhibit T-cell proliferation and interleukin 2 production in vitro, and suppress antigen-driven T-cell activation and antibody production in vivo. T cells also release MIF in response to glucocorticoid stimulation and MIF acts to override glucocorticoid inhibition of T-cell proliferation and interleukin 2 and interferon gamma production. These studies indicate that MIF acts in concert with glucocorticoids to control T-cell activation and assign a previously unsuspected but critical role for MIF in antigen-specific immune responses.

Animals↗
PubMed1996

An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction.

30 years ago, investigations into the molecular basis of the delayed-type hypersensitivity reaction (DTH) provided evidence for the first lymphokine activity: a lymphocyte-derived mediator called macrophage migration inhibitory factor (MIF), which inhibited the random migration of peritoneal macrophages. Despite the long-standing association of MIF with the DTH reaction and the cloning of a human protein with macrophage migration inhibitory activity, the precise role of MIF in this classic cell-mediated immune response has remained undefined. This situation has been further complicated by the fact that two other cytokines, interferon gamma and IL-4, similarly inhibit macrophage migration and by the identification of mitogenic contaminants in some preparations of cloned human MIF. Using recently developed molecular probes for mouse MIF, we have examined the role of this protein in a classical model of DTH, the tuberculin reaction in mice. Both MIF messenger RNA and protein were expressed prominently in DTH lesions, as assessed by reverse transcription polymerase chain reaction, in situ hybridization, and immunostaining with anti-MIF antibody. The predominant cellular origin of MIF appeared to be the monocyte/macrophage, a cell type identified recently to be a major source of MIF release in vivo. The administration of neutralizing anti-MIF antibodies to mice inhibited significantly the development of DTH, thus affirming the central role of MIF in this classic immunological response.

Animals↗
PubMed1996

New clinical applications for the Jasper Jumper.

This article describes the use of the Jasper Jumper in the treatment of class III anomalies, both theoretically and with a case report. Contrary to its use in class II anomalies, the Jasper Jumper is fixed to the 6-year-molars in the lower jaw and in the canine area in the upper jaw. This results in a continuously working mechanism--independent of co-operation on the part of the patient.

Activator Appliances↗
PubMed1996

Macrophage migration inhibitory factor production by Leydig cells: evidence for a role in the regulation of testicular function.

Macrophage migration inhibitory factor (MIF), described originally as a product of activated T lymphocytes, recently has been found to be released by monocytes/macrophages and the anterior pituitary gland. Immunohistochemical studies of the adult rat testis using an affinity-purified polyclonal antimurine MIF antibody demonstrated strong staining for MIF in Leydig cells and their putative precursors. Peritubular myoid cells and the seminiferous epithelium were negative for MIF staining; however, a weak reaction around the heads of elongated spermatids also was observed. The expression of MIF messenger RNA and protein in whole rat testis was demonstrated by Northern blot and Western blot analyses, respectively. Both MIF messenger RNA and protein immunoreactivity in Leydig cells was observed in testes obtained from long term hypophysectomized rats. Significant concentrations of intracellular MIF were detected in lysates of the TM3 Leydig cell line (7.23 +/- 2.6 pg/microgram protein), and testicular interstitial fluid contained 14.7 +/- 1.6 ng/ml MIF protein, as measured by MIF-specific enzyme-linked immunosorbent assay. To gain insight into the possible biological role of MIF in the testis, cultures of adult rat seminiferous tubules and purified Leydig cells were incubated together with recombinant murine MIF (rMIF). Neither rMIF (50 ng/ml) nor a neutralizing anti-MIF antiserum was found to affect basal or LH-stimulated Leydig cell steroidogenesis in vitro. However, a dose-dependent decrease in the secretion of inhibin by the seminiferous tubules was observed at rMIF concentrations ranging from 10-100 ng/ml. Taken together, these data indicate that Leydig cells produce MIF in vivo and suggest an important regulatory role for this newly discovered mediator of testicular function.

Animals↗
PubMed1996

Congenital palatal ulcers in newborn infants with cleft lip and palate: diagnosis, frequency, and significance.

Congenital decubital ulcers were found in 94% of newborn infants with unilateral cleft lip and palate in the course of a systematic study of a large cohort study (N = 52). The procedures for diagnosis, documentation, and follow-up are described. The ulceration area at birth varied over a wide range. The ulcerations were usually located in the posterior part of the vomer. Sonographic evidence supports the hypothesis that the ulcerations are caused mechanically by the motor activity of the tongue during the fetal and newborn period. The decubital ulcer disappeared in each case within 5 days following the implementation of a palatal plate.

Cleft Lip↗
PubMed1996

De Novo renal expression of macrophage migration inhibitory factor during the development of rat crescentic glomerulonephritis.

Macrophage migration inhibitory factor (MIF), a key mediator of the delayed-type hypersensitivity response, was originally thought to be produced by activated T cells. However, recent studies have found that MIF is produced in many cell types including monocytes/macrophages and anterior pituitary cells. The current study has examined MIF expression in normal and diseased kidney using in situ hybridization, immunohistochemistry, and Northern blotting. MIF mRNA and protein are constitutively expressed in normal kidney, being largely restricted to tubular epithelial cells and some glomerular visceral and parietal epithelial cells. During the development of rat anti-glomerular basement membrane glomerulonephritis, a model of macrophage-mediated renal injury, there was marked de novo expression of MIF by intrinsic kidney cells including endothelium and glomerular and tubular epithelial cells. Up-regulation of MIF expression correlated with macrophage accumulation within the glomerulus (P < 0.001) and tubulointerstitium (P < 0.001). Of significance, the accumulation of macrophages was exclusively localized to areas of strong MIF expression, contributing to focal glomerular and tubulointerstitial lesion formation. In addition, up-regulation of MIF expression by parietal epithelial cells was associated with macrophage accumulation within Bowman's space and crescent formation. Combined in situ hybridization and immunostaining also demonstrated MIF expression by macrophages, T cells, and fibroblast-like cells within renal lesions. In conclusion, these data provide the first demonstration that renal epithelial cells are a major source of MIF in both normal and diseased kidney. Furthermore, the up-regulation of MIF expression may play an important role in macrophage accumulation and progressive renal injury in rat crescentic glomerulonephritis.

Animals↗
PubMed1995

MIF as a glucocorticoid-induced modulator of cytokine production.

Glucocorticoid hormones are important for vital functions and act to modulate inflammatory and immune responses. Yet, in contrast to other hormonal systems, no endogenous mediators have been identified that can directly counter-regulate their potent anti-inflammatory and immunosuppressive properties. Recent investigations of the protein macrophage migration inhibitory factor (MIF), which was discovered originally to be a T-lymphocyte-derived factor, have established it to be a pro-inflammatory pituitary and macrophage cytokine and a critical mediator of septic shock. Here we report the unexpected finding that low concentrations of glucocorticoids induce rather than inhibit MIF production from macrophages. MIF then acts to override glucocorticoid-mediated inhibition of cytokine secretion by lipopolysaccharide (LPS)-stimulated monocytes and to overcome glucocorticoid protection against lethal endotoxaemia. These observations identify a unique counter-regulatory system that functions to control inflammatory and immune responses.

Animals↗
PubMed1995

Cloning and characterization of the gene for mouse macrophage migration inhibitory factor (MIF).

An emerging body of data indicates that the protein mediator described originally as macrophage migration inhibitory factor (MIF) exerts a central and wide ranging role in host inflammatory responses. MIF is a major constituent of corticotrophic cells within the anterior pituitary gland and is secreted into the circulation in a hormone-like fashion. MIF also exists performed in monocytes/macrophages and is a pivotal mediator in the host response to endotoxic shock. To gain further insight into the biologic expression of this protein that encompasses components of both the immune and the endocrine systems, we have cloned the mouse MIF gene and identified potential regulatory sequences present within the 5'-proximal promoter region. The gene for mouse MIF is located on chromosome 10, spans approximately 1 kb, and shares a high degree of structural homology with its human counterpart. Of note, the consensus enhancer/promoter motifs identified include both inflammatory/growth factor-related elements and sites associated with the genes for certain peptide hormones. We also report the structures of two MIF pseudogenes that account for early observations suggesting that mouse MIF is encoded by a highly homologous multigene family.

Amino Acid Sequence↗
PubMed1995

[Maximal force measurements of lip and tongue pressures and their significance for the diagnosis of orofacial dyskinesias].

The functioning of the orofacial muscular system essentially determines the shape of the jaw and of the dental arch as well as the position of the axis of the anterior teeth. Disturbances of the normal functioning can cause anomalies of the position of teeth or malformations of the bone structure. With the help of the newly developed device "Myometer 160" we now have the possibility to measure the intra- and extraoral forces. We examined 107 persons aged 8 to 37 years. The maximal force was measured by ventral tongue pressure, when the lips were pressed against each other and when a brass button was pulled. In addition clinical results as well as a functional status were ascertained in order to record orofacial dyskinesias. A significant connection between the age respectively the sex of the persons and the determined force was found. However, no clear relationship between the occlusal position respectively the functional anomaly and the results of maximal force was determined. Thus it does not seem sensible to use maximal force measurement within the framework of the determined. Thus it does not seem sensible to use maximal force measurement within the framework of the diagnosis of orofacial dyskinesias.

Adolescent↗
PubMed1995

Expression of mitochondrial heat shock protein 60 in distinct cell types and defined stages of rat seminiferous epithelium.

Changes in the level of the gene transcript of heat shock protein (hsp)60, a mitochondrial chaperonin, during the cycle of rat seminiferous epithelium and its cellular localization were studied. The seminiferous epithelium showed a cell type-specific expression of hsp60. Immunostaining of adult rat testis revealed localization in Sertoli and Leydig cells. In germ cells, mitochondria of spermatogonia and early primary spermatocytes were immunoreactive for hsp60. Mitochondria of all other germ cell types were completely negative for hsp60. Stage-specific expression of hsp60 was determined from pooled segments of stage-specific microdissected tubules by a combination of Western blotting and polymerase chain reaction (PCR). High concentrations of hsp60 were found in stages I-V and IX-XIV, and low levels were detected in the other stages, i.e., VI-VIII. In stages with high hsp60 expression, spermatogonia divide mitotically, whereas in stages lacking mitosis, the hsp60 level was much weaker. In seminiferous epithelium, two different types of mitochondria are present. Therefore, immunoelectron microscopy was used to differentiate these two morphologically distinct types of mitochondria. The crista type of mitochondria (e.g., in Sertoli cells and spermatogonia) reacted with the antibody against hsp60, whereas hsp60 was negative in so-called "condensed"-type mitochondria found in midpachytene spermatocytes and more advanced germ cells. It could be shown for the first time that expression of the hsp60 gene is regulated during the cycle of the seminiferous epithelium. The results indicate that the gene product is primarily needed during the initial steps of spermatogenesis in which most of the cell divisions occur, while its expression during the differentiation of spermatids and sperm is obviously not necessary. The presence of hsp60 in stages with mitotic activity suggests a very active mitochondrial protein import and protein assembly machinery that generates further mitochondria for the dividing cells.

Animals↗
PubMed1994

Characterization of a high molecular weight tumor necrosis factor-alpha mRNA in influenza A virus-infected macrophages.

Infection by influenza A virus has previously been shown to prime macrophages for a high TNF-alpha production. Influenza A virus induced a TNF-alpha mRNA accumulation that consisted of two types: a regular 1.7 kb and an additional high m.w. 2.4 kb species in murine macrophages, and a high m.w. 3.6 kb species in human monocytes. In this study, we further characterized this virus-induced, novel high m.w. TNF-alpha mRNA. The additional high m.w. TNF-alpha mRNA represented a true polyadenylated mRNA and its induction required exposure to infectious viruses. The regular and the high m.w. TNF-alpha mRNA were both found in the nuclear fraction and the cytoplasm. We excluded that the novel high m.w. TNF-alpha mRNA was an intron-containing precursor TNF-alpha mRNA that could have persisted in virus-infected macrophages. When TNF-alpha exons 1 to 4 and TNF-alpha exons 2 to 4 were amplified by polymerase chain reaction, only regular and no high m.w. bands were detected. By use of specific TNF-alpha intron I and intron III cDNA we could definitely demonstrate the absence of introns in the high m.w. TNF-alpha mRNA. The high m.w. TNF-alpha mRNA was free of TNF-beta and TNF intergenic region elements but contained the 5' and 3' untranslated region of TNF-alpha. Influenza A virus infection also induced a double band of IL-1 beta and IL-6 mRNA. Whether this novel high m.w. TNF-alpha mRNA represents a virus-induced abnormality or a superinduction of an otherwise normal but minor TNF-alpha transcript, and whether this high m.w. TNF-alpha mRNA species codes for a biologically active product, remains to be examined.

Animals↗
PubMed1994

[Orthodontics and implantology. Their course and results after joint planning].

The therapeutical repertoire for treating patients with missing teeth was significantly expanded by the development of modern implant methods. We have performed a retrospective analysis covering all children who between 1977 and 1993 had been considered for implants as a method for gap management. All patients were pretreated up to early adolescence using standard orthodontic procedures. Unfortunately, it turned out that an originally planned implant was not suitable in approximately 2/3 of the patients because of inadequate alveolar conditions. These patients were subsequently treated by conventional orthodontic gap closure or adhesive prosthetics.

Adolescent↗
PubMed1994

Programmed cell death (apoptosis) in human monocytes infected by influenza A virus.

Although infection of monocytes by influenza A virus primes for a high cytokine release, it also leads to cell death within 20-30 hours. In this brief report, we demonstrate that influenza A virus-induced monocyte killing was due to programmed cell death (apoptosis) and not to necrosis. Morphologically, chromatin condensation and margination occurred and biochemically, an apoptosis-specific internucleosomal DNA fragmentation into multimers of 180 bp ("DNA ladder") was found. Induction of apoptosis and not necrosis in influenza A virus-infected monocytes may serve three purposes: 1. Virus replication is limited, 2. a priming for a high cytokine response is initiated and 3. damaging and inflammation-inducing lysosomal enzymes are held back from monocytes undergoing controlled cell death.

Apoptosis↗
PubMed1994

Relationship of calcitonin mRNA expression to the differentiation state of HL 60 cells.

Raised plasma levels of immunoreactive human calcitonin (ihCT) can be found in patients with myeloid leukemia and seem to indicate a poor prognosis. High levels were found in acute undifferentiated and acute myeloblastic leukemia. To test whether CT expression could be a marker of myeloid differentiation, we used the promyelocytic leukemia cell line HL 60 which also expresses ihCT as a model system for myeloid differentiation. Exponentially growing HL 60 cells as well as differentiation induced HL 60 cells expressed a single 1.0 Kb CT transcript. The induction of HL 60 cell differentiation along the granulocytic lineage by DMSO or HMBA had no effect on the level of CT transcripts. Induction of monocytic/macrophagic differentiation by TPA resulted in a transient, about 10-fold elevated expression of CT steady state mRNA after 24 h. In contrast to TPA, induction of HL 60 cell differentiation along the monocytic pathway by Vit D3 had no detectable effect on the level of the CT in RNA expression at corresponding time points. These findings suggest that the transient induction of CT steady state mRNA expression by TPA is rather a direct effect of the phorbol ester than commitment along the monocytic line of differentiation.

Acetamides↗
PubMed1993

The coordination of posture and voluntary movement in patients with hemiparesis.

Postural adjustments associated with the task of raising oneself on tiptoes were investigated in a reaction time paradigm in six normal subjects and six patients with hemiparesis due to stroke. Body and ankle position in space were measured by means of a movement analysis system (ELITE). The findings indicate that the task of going up on tiptoes is performed in two steps. First, the centre of gravity is shifted forward to a position perpendicular to the forefoot. This movement is initiated by a phasic burst of EMG activity in the tibialis anterior (TA). The activity of the quadriceps femoris (QUA) aids the forward shift and together with the biceps femoris (BF) stabilizes the knee. Following these postural adjustments, the action of going up on tip-toes is performed mainly by the gastrocnemius medialis (MG). The basic pattern of preparatory (TA, QUA, BF) and focal (MG) activity was disturbed in its temporal sequence in patients with hemiparesis. The analysis of the biomechanical data showed smaller movement velocities for leaning forward and going up on tiptoes in patients, with increased movement amplitude on the paretic side. In addition, the correlation between the start of horizontal (leaning forward) and vertical (going up on tiptoes) hip movement was lost in patients. The preserved correlation between the latency of MG activity and the onset of the vertical hip movement on the paretic side in patients and the loss of correlation on the non-paretic side indicates that the EMG activity on the healthy side is adapted to the functional requirements of the affected side.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗