[Bilateral subconjunctival foreign bodies. Loiasis with bilateral Loa ophthalmia].
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
M Klüppel
Publications and source records attributed to M Klüppel.
[Operation of the floppy eyelid. Symptomatic cases require surgical eyelid stabilization].
BACKGROUND: Floppy Eyelid is a rare condition causing chronic papillary conjunctivitis and chronic corneal disorders (superficial punctate keratitis, epithelial and stromal ulcers). It is characterized by an extremely enlarged and "floppy" upper eyelid which can be easily everted by slight elevation. Usually obese men are affected who use to sleep face down either on the right or on the left side. Pushing the eyelid against the pillow, the lid is intermittently everted at sleep. This lagophthalmus with rubbing of the exposed eye and lid structures causes all pathologic disorders. Shielding the eye at night may help temporarily. PATIENTS: We performed surgery on 7 men with symptomatic floppy eyelid in the age of 42 to 61 years. The patients had been symptomatic between 1 month and 4 years prior to the definite diagnosis. Follow-up time has been 7 months to 4.5 years. RESULTS: In all cases surgery achieved improvement. CONCLUSIONS: Cases of unclear conjunctival or corneal damage and inflammation should led consider Floppy Eyelid as a possible cause. The typical clinical findings make diagnosis easy. As complete stopping of eyelid-rubbing by changing the patient's sleeping habits is mostly not easily possible, for acute therapy of threatening damages to cornea and conjunctiva a surgical shortening of the lid is necessary which stabilizes the lid in order to avoid nightly spontaneous eversion for a long time.
Adult↗
Lacrimal gland choristoma of the iris.
Intraocular lacrimal gland tissue is an extremely rare choristoma. A newborn girl was seen with a fleshy, vascular tumor arising from the peripheral iris and the anterior chamber angle. The tumor was treated with topical steroids on suspicion of a juvenile xanthogranuloma; later, it grew slightly and a secondary glaucoma developed. Histopathological examination of the resected tumor showed lacrimal gland tissue in the iris. Twelve cases of intraocular lacrimal gland tissue have been reported in the literature.
Anterior Chamber↗
Developmental origin and Kit-dependent development of the interstitial cells of cajal in the mammalian small intestine.
Interstitial cells of Cajal (ICCs) form a network of cells between the external longitudinal and circular muscle layers at the level of the Auerbach's plexus in the mammalian small intestine. These cells express the Kit receptor tyrosine kinase and are essential for intestinal pacemaker activity. W mutant mice carrying structural mutations in the Kit gene lack both the network of ICCs and intestinal pacemaker activity. We were interested in the developmental origin of the cells that make up the network of ICCs. In addition, the specific stages of ICC development that require a functional Kit receptor have not been characterized. We show that ICCs originate from mesenchymal progenitor cells that coexpress both Kit and smooth muscle myosin heavy chain, a marker specific for smooth muscle, during embryogenesis. ICC and longitudinal smooth muscle lineages begin to diverge late in gestation. Embryos homozygous for the regulatory Wbanded (Wbd) mutation do not express Kit in these mesenchymal progenitor cells. Nevertheless, Wbd/Wbd mice display a normal network of ICCs and normal smooth muscle layers at postnatal day 5 (p5). Adult Wbd/Wbd mice lack a functional ICC network and intestinal pacemaker activity due to a failure of the ICCs to increase in numbers after p5. These data suggest a common developmental origin of the ICCs and the longitudinal smooth muscle layers in the mammalian small intestine and show that Kit expression is necessary for the postnatal development and proliferation of ICCs but not for the initial cell lineage decision toward an ICC fate during embryogenesis or for smooth muscle development.
Animals↗
Aquarius, a novel gene isolated by gene trapping with an RNA-dependent RNA polymerase motif.
In a retinoic acid (RA) gene trap screen of mouse embryonic stem (ES) cells, a novel gene, named Aquarius (Aqr), was identified and characterized. The promoterless lacZ marker was used to trap the genomic locus and to determine the expression pattern of the gene. Aqr transcripts are strongly induced in response to RA in vitro. During embryogenesis, Aqr is expressed in mesoderm, in the neural crest and its target tissues, and in neuroepithelium. Expression was first detected at 8.5 days postcoitum, when neural crest cells are visible at the lateral ridges of the neural plate. The gene-trapped Aqr locus was transmitted through the mouse germ line in three genetic backgrounds. In the F2 generation, the expected mendelian ratio of 1:2:1 was observed in all backgrounds, indicating that homozygous mice are viable. Homozygotes are normal in size and weight and breed normally. The gene trap insertion, however, does not seem to generate a null mutation, because Aqr transcripts are still present in the homozygous mutant animals. The Aqr open reading frame has weak homology to RNA-dependent RNA polymerases (RRPs) of the murine hepatitis viruses and contains an RRP motif. Aqr was mapped to mouse chromosome 2 between regions E5 through F2 by using fluorescence in situ hybridization analysis.
Amino Acid Sequence↗
recessive spotting: a linked locus that interacts with W/Kit but is not allelic.
BACKGROUND: The murine coat-colour mutation recessive spotting (rs) maps very closely to the W/Kit locus, encoding the proto-oncoprotein Kit, the protein tyrosine kinase receptor for stem cell factor. Kit is important in the development of melanocytes, germ cells, interstitial cells of Cajal (ICC) and haemopoietic lineages, including mast cells. rs has never been genetically separated from Kit, and interacts with Kit mutations, suggesting that it is a recessive allele of Kit. Here we have tested this possibility. We have shown previously that diploid rs/rs melanocytes proliferated more slowly than did +/+ melanocytes, as did an immortal line of rs/rs melanocytes, melan-rs. RESULTS: The Kit mRNA level in rs/rs melanocytes was indistinguishable from that of other melanocyte lines. The Kit cDNA sequence from rs/rs melanocytes and the kinase activity of Kit in rs/rs mast cells appeared to be normal. No deficiency of mast cells or ICC was observed in rs/rs mice. Moreover, following the overexpression of a normal Kit cDNA, proliferation of rs/rs melanocytes was retarded further, but that of +/+ melanocytes was increased, indicating an intracellular interaction between rs and Kit. Of other closely linked tyrosine kinase genes, melanocytes and melanoblasts did not express mRNA for Pdgfra, Flk-1 or Txk, but both expressed Tec, encoding a nonreceptor kinase that interacts with Kit. CONCLUSIONS: rs is not a mutation in Kit, although we have confirmed that rs interacts with Kit. It seems unlikely that rs affects Pdgfra, Flk-1 or Txk, but Tec remains a candidate for rs.
Alleles↗
[Therapy of advanced amoeba keratitis with keratoplasty à chaud and adjuvant cryotherapy].
BACKGROUND: Since the mid-1980s acanthamoeba keratitis has been diagnosed with increasing frequency, especially in contact lens wearers. The assignment to specialized centers is often delayed many months and there is hardly any chance of controlling the disease by conservative treatment alone. In these cases, penetrating keratoplasty offers the only chance for rehabilitation. The therapeutic role of penetrating keratoplasty and supportive intraoperative cryotherapy is demonstrated by the courses of six patients with unilateral acanthamoeba keratitis. PATIENTS AND METHODS: The data of six patients aged 41.2 (22-63) years with medically uncontrollable acanthamoeba keratitis were evaluated retrospectively. The diagnosis was confirmed histologically in all cases. All patients were contact lens wearers. They underwent a total of ten keratoplasties between November 1986 and January 1995. The donors were 44.8 (23-58) years of age. The transplant diameters varied between 7.7 and 9.5 mm. The margins of the host cornea were intraoperatively frozen by a cryoprobe in three patients with a far advanced stage of corneolimbal parasitic infiltration. RESULTS: During a follow-up period of +/-10.2 (1-22) months, five of six eyes were rehabilitated with visual acuities between 0.4 and 1.0. One eye went blind after the fourth keratoplasty because of uncontrollable secondary glaucoma. After three keratoplasties with simultaneous application of cryocoagulation because of an especially high risk of persisting acanthamoeba infection, all corneae remained clear and free of recurrences. CONCLUSIONS: In advanced acanthamoeba keratitis which has not responded to conservative treatment, penetrating keratoplasty not only provides elimination of the pathogen, but also good functional results. In far advanced stages, the intraoperative application of cryocoagulation for parasite elimination in the host cornea seems to be a very effective measure against local recurrences of the infection.
Acanthamoeba Keratitis↗
[Surgical management of Marfan-associated and idiopathic lens dislocations].
BACKGROUND: The ideal and safe surgical method for Marfan-associated or idiopathic lens subluxations is still a matter of debate. PATIENTS AND METHODS: Between 1990 and 1995, 23 eyes were operated for lens subluxations, mainly because of decreased visual acuity, but also because of conservatively uncontrolled secondary glaucoma. Marfan patients were 27.0 (5-62) years old at surgery; patients with idiopathic lens subluxations were 38.5 (11-63) years old. Surgical procedure depended on patient age and anatomical conditions. RESULTS: All patients achieved an increase in visual acuity. Amblyopia existed in six patients. All problems due to glaucoma were controlled postoperatively. Our greatest concern was rhegmatogenous retinal detachment. It occurred in only one eye of a non-Marfan patient. CONCLUSION: The prognosis for lens surgery in Martan-associated and idiopathic lens subluxations is good. The implantation of a posterior chamber lens provides a good and secure means of optical rehabilitation. Our preferred primary transscleral suture technique guarantees high security and stability of position. Previously feared surgical risks have been reduced by modern surgical procedures.
Adolescent↗
Long-range genomic rearrangements upstream of Kit dysregulate the developmental pattern of Kit expression in W57 and Wbanded mice and interfere with distinct steps in melanocyte development.
Mutations in the murine dominant white spotting (W) locus cause pleiotropic developmental defects that affect hematopoietic cells, melanocytes, germ cells and the interstitial cells of Cajal in the gut. W mutations either alter the coding sequence of the Kit receptor tyrosine kinase, resulting in a receptor with impaired kinase activity, or affect Kit expression. Here we describe the molecular and cell-type-specific developmental defects of two of the latter class of regulatory W alleles, W57 and Wbanded(bd). In both mutants, the temporal and spatial patterns of Kit expression are dysregulated during embryogenesis and in adult animals. In Wbd mice, ectopic expression of Kit in the dermatome of the somites at days 10.8 and 11.8 of development seemed to interfere with melanoblast development. In contrast, the W57 allele leads to an intrinsic pigmentation defect by downregulating developmental Kit expression in trunk melanoblasts, but not melanoblasts around the otic vesicle. Both mutations affect transcriptional initiation of the Kit gene. The W57 allele is associated with a 80 kb deletion 5' of the Kit-coding region while Wbd is associated with a 2.8 Mb genomic inversion of chromosome 5 with the distal breakpoint between Kit and the platelet-derived growth factor receptor alpha (Pdgfra) gene, and the proximal breakpoint between the genes for the GABA receptor beta 1 (Gabrb1) and the Tec tyrosine kinase, juxtaposing the Kit and Tec tyrosine kinase genes. Neither W57 nor Wbd affect genomic sequences previously suggested in in vitro experiments to control cell-type-specific expression of Kit. These results link specific mechanisms of cellular and developmental defects to long-range genomic rearrangements that positively and negatively affect Kit transcription in different cell lineages as well as in different subpopulations of the same lineage.
Alleles↗
Embryonic and adult expression patterns of the Tec tyrosine kinase gene suggest a role in megakaryocytopoiesis, blood vessel development, and melanogenesis.
The Tec cytoplasmic tyrosine kinase is a member of a family of src-like proteins that are thought to play important roles in hematopoiesis. Here we describe the temporal and spatial expression of the Tec gene during embryogenesis and in the adult. Our data demonstrate that embryonic Tec expression is restricted to distinct hematopoietic cells as well as structures and cell types that share a common feature of containing fluid in an enclosed cavity, e.g., endothelial cells. In addition, Tec is expressed in melanocytes late in gestation. The observed developmental expression pattern of Tec suggests a role for this gene in several aspects of hematopoiesis and/or blood vessel development as well as in late stages of melanogenesis.
Animals↗
W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity.
The pacemaker activity in the mammalian gut is responsible for generating anally propagating phasic contractions. The cellular basis for this intrinsic activity is unknown. The smooth muscle cells of the external muscle layers and the innervated cellular network of interstitial cells of Cajal, which is closely associated with the external muscle layers of the mammalian gut, have both been proposed to stimulate pacemaker activity. The interstitial cells of Cajal were identified in the last century but their developmental origin and function have remained unclear. Here we show that the interstitial cells of Cajal express the Kit receptor tyrosine kinase. Furthermore, mice with mutations in the dominant white spotting (W) locus, which have cellular defects in haematopoiesis, melanogenesis and gametogenesis as a result of mutations in the Kit gene, also lack the network of interstitial cells of Cajal associated with Auerbach's nerve plexus and intestinal pacemaker activity.
Action Potentials↗
[5-fluorouracil injection treatment after fistulating glaucoma operations].
BACKGROUND: Since 1984 subconjunctival 5-Fluorouracil injections have been applied with success after filtering surgery. It was the purpose of this retrospective study to find out whether the results justify this treatment in view of all side effects. MATERIALS AND METHODS: Between 2/1991 and 1/1993 twenty-nine eyes of 11 female and 16 male patients with high-risk glaucoma (unsuccessful previous filtering surgery and a high risk of scarring) were treated with subconjunctival injections of 5-Fluorouracil after filtering surgery in the University Eye Hospital Düsseldorf. The mean age of the patients was 58 (11-84) years and the mean follow-up period was 16 (4-24) months. The mean amount of injected 5-Fluorouracil was 43 (5-85) mg. Glaucoma was regarded as controlled when intraocular pressure levels were reduced by more than 20% of the preoperative level and stayed consistently below 21 mm Hg. RESULTS: 26 (89.6%) of the eyes had controlled intraocular pressure during the follow-up period. Two eyes were controlled only after additional cyclocrycoagulation, and 1 glaucoma has remained uncontrolled. Postoperatively we observed fistulas of the conjunctiva in 24% of the eyes and 69% of the eyes had corneal epithelial breakdown problems. It is unlikely that subconjunctival injections of 5-Fluorouracil work only by inhibiting scarring of the filtration bleb. Long-lasting e-vacuo-symptoms in single cases with no functioning bleb at all as well as scarred blebs in 9 of 26 eyes with controlled glaucoma must be interpreted as a probable sign of 5-Fluorouracil toxicity on the ciliary epithelium. CONCLUSIONS: Subconjunctival injections of 5-Fluorouracil after filtering surgery are helpful to control high-risk glaucoma, but there are several disadvantages of this treatment as fistulas of the conjunctiva, corneal surface problems, discomfort for the patient, difficult follow-up and a potential toxicity on the ciliary epithelium that may be pronounced in some cases. Therefore, subconjunctival injections of 5-Fluorouracil after filtering surgery are a useful means for eyes with a high risk of scarring. However, 5-Fluorouracil should not be applied for primary normal glaucoma surgery.
Adolescent↗
Reporter constructs with low background activity utilizing the cat gene.
Reporter plasmids utilizing the cat gene for the analysis of promoter and enhancer sequences in vertebrate cells, were constructed. These plasmids minimize the background of transcription derived from cryptic promoters or cryptic regulatory elements within the vector.
Animals↗
The mouse tyrosinase promoter is sufficient for expression in melanocytes and in the pigmented epithelium of the retina.
The mouse c locus encodes tyrosinase (monophenol monooxygenase; monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1), the key enzyme in melanin synthesis, which is expressed in the pigment epithelium of the retina and in melanocytes derived from the neural crest. To define regulatory regions of the gene that are important for cell type-specific expression, a deletion series of the tyrosinase 5' region was fused to a chloramphenicol acetyltransferase (CAT) reporter gene and electroporated into tyrosinase-expressing and -nonexpressing cell lines. We show that 270 base pairs 5' of the transcriptional start site is sufficient for CAT expression in a human and a mouse melanoma cell line. This 5' flanking fragment, when cloned in the context of a tyrosinase minigene construct and injected into fertilized eggs of an albino mouse strain, is sufficient for cell type-specific expression in mice. The transgenic mice were pigmented in both skin and eyes. In situ hybridization analysis shows that the 270-base-pair regulatory region contains elements sufficient for specific expression of the transgene both in the pigmented epithelial cells of the retina, which are derived from the optic cup, and in neural crest-derived melanocytes.
Animals↗
Does treatment with beta-adrenoceptor antagonists in vivo alter human adenylate cyclase responsiveness in vitro?
1. Treatment with beta-adrenoceptor antagonists in vivo can alter adenylate cyclase responsiveness in the human heart. We have determined the effects of treatment with four different beta-adrenoceptor antagonists in vivo on the responsiveness of lymphocyte and platelet adenylate cyclase in vitro in healthy volunteers. 2. Propranolol (non-selective, 4 x 40 mg day), bisoprolol (beta 1-selective, 1 x 10 mg day), and ICI 118.551 (beta 2-selective, 3 x 25 mg day) were tested as drugs without and pindolol (non-selective, 2 x 5 mg day) as a drug with intrinsic sympathomimetic activity. Adenylate cyclase stimulation by GTP, prostaglandin E1 and forskolin was determined before, after a 7 day treatment period and 7 days after drug withdrawal. 3. Neither treatment with or withdrawal of any of the beta-adrenoceptor antagonists altered adenylate cyclase responsiveness. 4. We conclude that adenylate cyclase responsiveness in circulating blood cells underlies different regulatory mechanisms than that in solid tissues such as the human heart. Our data suggest that circulating blood cells do not always reflect alterations in solid tissues.
Adenylyl Cyclases↗