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T Harder

Publications and source records attributed to T Harder.

At least 55 records · Page 3Linked to original sources

Caveolae, DIGs, and the dynamics of sphingolipid-cholesterol microdomains.

There is accumulating evidence that lateral assemblies (rafts) of sphingolipids and cholesterol form platforms that serve to support numerous cellular events in membrane traffic and signal transduction. Raft membrane microdomains are thought to function by preferentially associating with specific proteins while excluding others. The basic forces driving raft formation are lipid interactions which are, per se, weak and transient. Sphingolipid rafts should therefore be considered to be dynamic structures in which cholesterol plays an important role as a linker. Caveolins influence these dynamics by forming stabilized raft domains in intracellular membranes as well as at the plasma membrane. Recent data suggest that clustering of raft components could regulate raft dynamics and therefore represents an important feature in the function of these membrane microdomains.

Animals↗

Overweight and obesity in infants of mothers with long-term insulin-dependent diabetes or gestational diabetes.

OBJECTIVES: To analyse the development of body weight and frequencies of overweight and obesity in infants of long-term insulin-dependent diabetic mothers as compared to those of gestational diabetic mothers. DESIGN: Retrospective study. SUBJECTS: Two hundred infants of mothers with pregestational insulin-dependent diabetes mellitus (IDM) and 117 infants of gestational diabetic mothers (IGDM) born between 1980 and 1990 at the Clinic of Obstetrics and Gynaecology, Berlin-Kaulsdorf, Germany. MEASUREMENTS: Birth weight, birth length, plasma insulin, interscapular skinfold, symmetry index (SI) and body mass index (BMI) at birth; SI and BMI in childhood (1-9y of age). RESULTS: Neonatally, mean relative weight (SI) was found to be increased in both groups of infants. It was positively correlated to interscapular skinfold (P < 0.001) and insulin (P < 0.005). However, IDM had higher insulin levels (P < 0.001) and a higher frequency of obesity (P < 0.05) than IGDM at birth. Throughout childhood frequencies of overweight (SI > 1.1) were elevated in both IDM as well as IGDM. In IDM the percentage of obesity (SI > 1.2) displayed a significant increase from 11.2% in children 1-4y old up to 25.8% at 5-9y (P < 0.05). Similar frequencies and a highly significant increase of overweight during childhood of IDM (P < 0.005) were observed when BMI > or = 95th percentile was used to determine overweight. Relative weight in childhood was positively correlated to relative weight at birth (P < 0.05). Large-for-gestational-age infants displayed a significantly higher percentage of overweight (SI > 1.1) in childhood than appropriate-for-gestational-age infants (P < 0.05). CONCLUSIONS: Infants of mothers with diabetes during pregnancy are predisposed to develop overweight and obesity during childhood. These alterations seem to be related to insulin and relative body weight at birth. Pathophysiological mechanisms which might be involved into the development of these changes are discussed. Prophylactic measures are recommended to reduce morbidity in infants of diabetic mothers.

Birth Weight↗

Specific release of membrane-bound annexin II and cortical cytoskeletal elements by sequestration of membrane cholesterol.

Annexin II is an abundant protein which is present in the cytosol and on the cytoplasmic face of plasma membrane and early endosomes. It is generally believed that this association occurs via Ca(2+)-dependent binding to lipids, a mechanism typical for the annexin protein family. Although previous studies have shown that annexin II is involved in early endosome dynamics and organization, the precise biological role of the protein is unknown. In this study, we found that approximately 50% of the total cellular annexin was associated with membranes in a Ca(2+)-independent manner. This binding was extremely tight, since it resisted high salt and, to some extent, high pH treatments. We found, however, that membrane-associated annexin II could be quantitatively released by low concentrations of the cholesterol-sequestering agents filipin and digitonin. Both treatments released an identical and limited set of proteins but had no effects on other membrane-associated proteins. Among the released proteins, we identified, in addition to annexin II itself, the cortical cytoskeletal proteins alpha-actinin, ezrin and moesin, and membrane-associated actin. Our biochemical and immunological observations indicate that these proteins are part of a complex containing annexin II and that stability of the complex is sensitive to cholesterol sequestering agents. Since annexin II is tightly membrane-associated in a cholesterol-dependent manner, and since it seems to interact physically with elements of the cortical actin cytoskeleton, we propose that the protein serves as interface between membranes containing high amounts of cholesterol and the actin cytoskeleton.

Animals↗

Canine distemper virus in Lake Baikal seals (Phoca sibirica).

The virus epizootic which resulted in significant mortality in Siberian seals (Phoca sibirica) in Lake Baikal during 1987/88 was caused by canine distemper virus. Sequence analysis of the virus glycoprotein genes revealed that it was most closely related to recent European field isolates of canine distemper virus. This paper presents evidence that the same virus continued to circulate in seals in Lake Baikal after the initial epizootic. Three out of 45 brain tissue samples collected from seals culled in the spring of 1992 were positive for canine distemper virus-specific nucleic acid by the reverse transcription/polymerase chain reaction and the sequences were closely related to that of the original virus isolated in 1988.

Animals↗

Comparative analysis of the attachment protein gene (H) of dolphin morbillivirus.

DMV, dolphin morbillivirus, a paramyxovirus of uncertain origin recently emerged in Mediterranean dolphins. This study presents the complete nucleotide sequence of the hemagglutinin (H) gene including the gene boundaries. The single open reading frame of the DMV H gene encodes a protein of 604 residues which exhibits overall sequence characteristics similar to the H genes of other morbilliviruses. When compared to its closest homologues, measles virus (MV) and rinderpest virus (RPV), DMV has, respectively, 44 and 46% of amino acid residues in identical positions. The primary sequence of the DMV H protein is markedly less conserved than that of the fusion protein. The comparative data at the genomic level correspond with cross-neutralization studies with different morbilliviruses. Retrospective serogical studies dating back to 1983 indicate DMV-like infections in whales of the eastern Atlantic. The presented data support and extend previous studies suggesting that this novel morbillivirus is one of the phylogenetically oldest morbilliviruses known to circulate today. The relationship of DMV and established morbilliviruses to the newly emerged candidate morbillivirus infecting horse and man is discussed.

Amino Acid Sequence↗

Influence of low dose alcohol on fixation suppression.

The decrease of fixation suppression after small doses of alcohol was studied in 40 healthy volunteers (20 male, 20 female) using rotatory stimulation. 0.5 g alcohol per kg body weight were given within 20 min. The maximum fixation suppression and blood alcohol concentrations (BAC) were measured before and at 15, 30, 45, 60, 120, 180 and 240 min after ingestion. We determined the maximum angular acceleration during which total suppression of the vestibulo-ocular-reflex (VOR) was still possible. Fixation suppression was successful up to mean values of 43.6 degrees/S2 before ingestion of alcohol (reference level). A first significant deterioration of fixation suppression was observed at BAC of 20 mg/100 ml decreasing constantly with increasing BAC. At the median maximum BAC of 65 mg/100 ml, fixation suppression was possible up to acceleration values of 20% compared with reference levels. Measuring of the maximum fixation suppression in rotational tests is a reproducible easy method to describe the central nervous system control of vestibular functions. This method shows impressingly the enormous effects of low doses of alcohol on equilibrium. It is concluded that at BAC of more than 50 mg/100 ml a remaining vestibular nystagmus might be observed when driving a bend.

Adult↗

[Results of catheter embolization of renal cell carcinoma].

PURPOSE: We pointed out the value of catheter embolisation of kidney tumours. METHODS AND PATIENTS: We treated 42 patients with kidney tumours. For peripheral embolisation we placed Histoacryl or Ethibloc into the kidney artery via a transfemoral catheter. 33 patients had haematuria. 8 patients were lost for follow up. 26 patients were treated by embolisation alone and 8 patients were treated before nephrectomy. RESULTS: Haematuria was stopped in 98% and never reoccurred. The intraoperative blood-loss was 600 ml on average. 55% of patients treated by embolisation alone died within the first year. 51% of patients suffered from a slight postinfarction syndrome. One patient died of sepsis and one had pulmonary insufficiency due to AV shunt and pulmonary embolism. CONCLUSIONS: Peripheral embolisation of kidney tumours can be used successfully and is minimal invasive, in case of haematuria and pain. The perioperative risk is reduced due to limited blood loss.

Adult↗

The annexin II2p11(2) complex is the major protein component of the triton X-100-insoluble low-density fraction prepared from MDCK cells in the presence of Ca2+.

Annexin II2p11(2) is present in the submembranous region of cells expressing both subunits of the complex. Most probably, this subcellular distribution is maintained through the interaction of annexin II2p11(2) with membrane phospholipids and/or elements of the cortical cytoskeleton known to occur in vitro in a Ca(2+)-dependent manner. To determine whether membrane or cytoskeleton interactions are primarily responsible for anchoring annexin II2p11(2) in the cell cortex, we subjected Madin-Darby canine kidney (MDCK) cells to serial extractions using different detergents and identified annexin II and p11 in the different fractions employing specific antibodies. The complex but not monomeric annexin II remains insoluble when the cells are extracted with Triton X-100 in the presence of Ca2+. However, treatment of the Triton X-100-insoluble cell remnants with a series of other detergents known to solubilize GPI-anchored proteins leads to a partial extraction of annexin II2p11(2) even in the presence of Ca2+. Using sucrose density gradient analysis in the presence of Ca2+ as a different means of fractionating the Triton X-100-insoluble cell remnants we show that the majority of annexin II2p11(2) copurifies with a low-density fraction which has been reported to contain GPI-anchored proteins, certain glycolipids, and VIP21/caveolin. Annexin II2p11(2) is by far the most abundant protein component in this fraction indicating that its association with the low-density material occurs via lipid binding and is not due to the interaction with a certain protein.

Animals↗

[Computed tomography in malignant primary soft tissue tumors].

The results of CT examinations in 36 patients suffering from histologically confirmed malignant primary tumours of the soft tissues are presented (6 rhabdomyosarcomas, 4 leiomyosarcomas, 6 liposarcomas, 4 malignant schwannomas, 5 malignant fibrous histiocytomas, 4 malignant haemangiopericytomas, 3 angiosarcomas, 1 fibrosarcoma, 1 renal sarcoma, 2 malignant mesenchymal tumours without histologically clear classification). The CT image alone will not yield information on the type of tumour or on the tumour status. However, CT continues to rank in the diagnosis of tumours of the soft tissues and is even superior to MR especially in the identification of gas accumulations due to infection in a tumour of the soft tissues that is otherwise unclear. Comparing the literature conclude that MR is now the imaging method of choice in the diagnosis of soft tissue tumours.

Adolescent↗

[Pseudoaneurysm of the internal carotid artery following a peritonsillar abscess].

A pseudoaneurysm of the internal carotid artery is a rare major complication of peritonsillar abscess. We present a 95-year-old women, who had a persistent bleeding from peritonsillar fossa after a routine tonsillectomy and ligation of the external carotid artery. Postoperative performed intraarterial angiography verify the diagnosis of a pseudoaneurysm of the internal carotid artery. Subsequent ligation of the internal carotid artery superior the bifurcation stops the hemorrhage. Review of literature demonstrate the importance of angiography in such cases.

Aged↗

[Giant mucocele of the paranasal sinuses with extension to the contralateral posterior cranial fossa and reversible retrocochlear deafness].

Report on a huge mucocele of the right maxillary sinus extending into the ethmoid and sphenoid sinuses, and protruding into the contralateral left posterior cranial fossa. The patient, a 45-year old male, had no history of paranasal sinus energy, nasal or paranasal symptoms. He went to his physician because of a slowly developing deafness in his left ear and because of episodes of loss of consciousness when blowing his nose. A reversible episode of vertigo and reversible paresis of the left abducent nerve 17 years previously, were later assumed to have been the first symptoms of endocranial extension of the mucocele. The diagnosis of a mucocele was made by MRI. MRI in T2 weighted spin-echo sequences is the best imaging technique for diagnosing a mucocele. The mucocele was treated primarily with endonasal surgery of the paranasal sinuses, using telescopes and an operating microscope. After opening the right maxillary sinus via the middle meatus liquid contents of the mucocele poured into the nasal cavity. The sack of the mucocele was removed partially. Three months later the patient was reoperated with a combined transfacial and endonasal approach, because of progression from partial hearing loss to total deafness. Postoperatively hearing improved nearly completely and compression of the pons and the posterior fossa had disappeared on MRI. It is concluded that in mucoceles no longer the extirpation of the sack, but endonasal marsupialization, using the operating microscope and telescopes, is the therapy of choice.

Audiometry, Evoked Response↗

The subcellular distribution of early endosomes is affected by the annexin II2p11(2) complex.

The tyrosine kinase substrate annexin II is a member of a multigene family of Ca2+ and lipid-binding proteins which have been implicated in a number of membrane-related events. We have analyzed the subcellular distribution of annexin II in relation to other cellular components in normal and specifically manipulated MDCK cells. In a polarized monolayer of MDCK cells annexin II and its cellular ligand p11 are restricted almost exclusively to the cortical regions of the cells which also contain peripheral early endosomes. Treatment of the polarized cells with low Ca2+ medium leads to a disintegration of the cortical cytoskeleton and a translocation of both, the annexin II2p11(2) complex and early endosomes, to the cytoplasm. A similar translocation which is however specific for the annexin II2p11(2) complex and early endosomes and does not affect other elements of the cell cortex is observed in cells expressing a trans-dominant annexin II-p11 mutant. This chimeric mutant protein causes the aggregation of endogenous annexin II and p11 and the simultaneous detachment of early endosomes from the cell periphery resulting in the binding of the early endosomes but no other components of the endocytotic or biosynthetic pathways to the annexin II/p11 aggregates. The specificity of this effect argues for the association of the annexin II2p11(2) complex with early endosomes and suggests that this association contributes to establish the peripheral localization of early endosomal structures.

Actins↗

Formation of the annexin II2p112 complex upon differentiation of F9 teratocarcinoma cells.

Murine teratocarcinoma F9 cells, which remain undifferentiated under standard cell culture conditions, can form cellular layers resembling early embryonic tissues upon induction of differentiation by retinoic acid and cyclic AMP. We have employed a combination of Northern and Western blot analyses to elucidate the regulation of expression of the tyrosine kinase substrate annexin II and its cellular ligand p11 during this differentiation process. Interestingly, the synthesis of the two subunits of the annexin II2p112 complex is not coregulated during F9 differentiation. Annexin II, which is only very weakly expressed in undifferentiated F9 cells, shows a strong increase in the amount of transcript and protein once the differentiated phenotype is established. The level of this induction does not depend on the type of F9 differentiation. In contrast to the regulated synthesis of annexin II, a significant amount of p11 mRNA and protein is already present in the undifferentiated cells and remains constant during the differentiation of F9 cells. Immunofluorescence analysis reveals that annexin II and p11 are concentrated in the submembranous region of the differentiated F9 cells. In contrast, p11 is uniformly distributed throughout the cytoplasm of undifferentiated cells. p11 is translocated to the submembranous region of the undifferentiated F9 cells upon coexpression of an exogenous annexin II introduced by transient transfection. Thus the localization of annexin II and p11 to the submembranous cytoskeleton depends on the formation of the tight annexin II2p112 complex.

Animals↗