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Biomedical subjects

A Prokop

Publications and source records attributed to A Prokop.

At least 19 recordsLinked to original sources

Absence of PS integrins or laminin A affects extracellular adhesion, but not intracellular assembly, of hemiadherens and neuromuscular junctions in Drosophila embryos.

We have examined the role of integrins in the formation of the cell junctions that connect muscles to epidermis (muscle attachments) and muscles to neurons (neuromuscular junctions). To this end we have analyzed muscle attachments and neuromuscular junctions ultrastructurally in single or double mutant Drosophila embryos lacking PS1 integrin (alphaPS1betaPS), PS2 integrin (alphaPS2betaPS), and/or their potential extracellular ligand laminin A. At the muscle attachments PS integrins are essential for the adhesion of hemiadherens junctions (HAJs) to extracellular matrix, but not for their intracellular link to the cytoskeleton. The PS2 integrin is only expressed in the muscles, but it is essential for the adhesion of muscle and epidermal HAJs to electron dense extracellular matrix. It is also required for adhesion of muscle HAJs to a less electron dense form of extracellular matrix, the basement membrane. The PS1 integrin is expressed in epidermal cells and can mediate adhesion of the epidermal HAJs to the basement membrane. The ligands involved in adhesion mediated by both PS integrins seem distinct because adhesion mediated by PS1 appears to require the extracellular matrix component laminin A, while adhesion mediated by PS2 integrin does not. At neuromuscular junctions the formation of functional synapses occurs normally in embryos lacking PS integrins and/or laminin A, but the extent of contact between neuronal and muscle surfaces is altered significantly. We suggest that neuromuscular contact in part requires basement membrane adhesion to the general muscle surface, and this form of adhesion is completely abolished in the absence of laminin A.

Animals

The muscleblind gene participates in the organization of Z-bands and epidermal attachments of Drosophila muscles and is regulated by Dmef2.

We report the embryonic phenotype of muscleblind (mbl), a recently described Drosophila gene involved in terminal differentiation of adult ommatidia. mbl is a nuclear protein expressed late in the embryo in pharyngeal, visceral, and somatic muscles, the ventral nerve cord, and the larval photoreceptor system. All three mbl alleles studied exhibit a lethal phenotype and die as stage 17 embryos or first instar larvae. These larvae are partially paralyzed, show a characteristically contracted abdomen, and lack striation of muscles. Our analysis of the somatic musculature shows that the pattern of muscles is established correctly, and they form morphologically normal synapses. Ultrastructural analysis, however, reveals two defects in the terminal differentiation of the muscles: inability to differentiate Z-bands in the sarcomeric apparatus and reduction of extracellular tendon matrix at attachment sites to the epidermis. Failure to differentiate both structures could explain the partial paralysis and contracted abdomen phenotype. Analysis of mbl expression in embryos that are either mutant for Dmef2 or ectopically express Dmef2 places mbl downstream of Dmef2 function in the myogenic differentiation program. mbl, therefore, may act as a critical element in the execution of two Dmef2-dependent processes in the terminal differentiation of muscles.

Animals

ROP, the Drosophila Sec1 homolog, interacts with syntaxin and regulates neurotransmitter release in a dosage-dependent manner.

The Sec1 family of proteins is thought to function in both non-neuronal and neuronal secretion, although the precise role of this protein family has not been defined. Here, we study the function of ROP, the Drosophila Sec1 homolog, in neurotransmitter release. Electrophysiological analyses of transgenic lines overexpressing ROP and syntaxin, a presynaptic membrane protein, indicate that ROP interacts with syntaxin in vivo. Characterization of four point mutations in ROP shows that they fall into two phenotypic classes. Two mutations cause a dramatic reduction in both evoked and spontaneous neurotransmitter release. In contrast, the other two mutations reveal an increase in evoked neurotransmission. Our data further show that neurotransmission is highly sensitive to the levels of ROP function. Studies on heterozygote animals indicate that half the amount of wild-type ROP results in a dramatic decrease in evoked and spontaneous exocytosis. Taken together, these results suggest that ROP interacts with syntaxin in vivo and is a rate-limiting regulator of exocytosis that performs both positive and inhibitory functions in neurotransmission.

Animals

An encapsulation system for the immunoisolation of pancreatic islets.

Over a thousand combinations of polyanions and polycations were tested to search for new polymer candidates that would be suitable for encapsulation of living cells. The combination of sodium alginate, cellulose sulfate, poly (methylene-co-guanidine) hydrochloride, calcium chloride, and sodium chloride was most promising. In parallel, a novel multiloop chamber reactor was developed to control the time of complex formation and to negate gravitational effects such as pancreatic islet sedimentation and droplet deformation during the encapsulation process. Encapsulated rat islets demonstrated glucose-stimulated insulin secretion in vitro, and reversed diabetes in mice. This new capsule formulation and encapsulation system allows independent adjustments of capsule size, wall thickness, mechanical strength, and permeability, which may offer distinct advantages for immunoisolating cells.

Animals

[Treatment strategies in bite injuries].

Animal and human bites are a extremely common problem. Despite the prevalence of this problem, few systematic studies have been done. There is astounding sparsity of factual information in the literature to aid the therapeutic decision. Crucial questions regarding suturing, antibiotics, and other matters have been left unanswered. Therefore the literature was reviewed and therapeutic guidelines extracted.

Animals

Hip fracture.

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Femur Head Necrosis

A Drosophila neurexin is required for septate junction and blood-nerve barrier formation and function.

Septate and tight junctions are thought to seal neighboring cells together and to function as barriers between epithelial cells. We have characterized a novel member of the neurexin family, Neurexin IV (NRX), which is localized to septate junctions (SJs) of epithelial and glial cells. NRX is a transmembrane protein with a cytoplasmic domain homologous to glycophorin C, a protein required for anchoring protein 4.1 in the red blood cell. Absence of NRX results in mislocalization of Coracle, a Drosophila protein 4.1 homolog, at SJs and causes dorsal closure defects similar to those observed in coracle mutants. nrx mutant embryos are paralyzed, and electrophysiological studies indicate that the lack of NRX in glial-glial SJs causes a breakdown of the blood-brain barrier. Electron microscopy demonstrates that nrx mutants lack the ladder-like intercellular septa characteristic of pleated SJs (pSJs). These studies identify NRX as the first transmembrane protein of SJ and demonstrate a requirement for NRX in the formation of septate-junction septa and intercellular barriers.

Amino Acid Sequence

[Segmental displacement by callus distraction in extended tibial defects].

In open tibial fractures with defects over 4 cm, spongiosaplasty is considered to be insufficient. Since 1988 we have tried to apply Ilisarov's ideas of callus distraction in combination with modern external fixation devices and AO/ASIF implants. By August 1995, 15 patients with severe tibial fractures had been treated. The bone defect averaged 7 cm. Thus, more than 1 m of tubular bone was produced. Eleven male and 4 female patients, averaging 21.3 years in age, were given this treatment. The defect was caused by resection of a malignancy in 3 cases and a second- or third-degree open fracture in 12 cases, accompanied by osteomyelitis in 6 cases. Reconstruction required an average of 5.3 operations. The complication rate was 53%, and the median duration of treatment was about 1 year. The final results were excellent or good. Amputation could be avoided in all instances. This treatment is contra indicated if the patient exhibits a lack of compliance. There is a realistic chance of salvaging the limb in cases of severe soft tissue and bone defects. In terms of economical considerations, this treatment is cost effective. Physical integrity and mobility without aid is the important motivation for these patients.

Adolescent

[Partial median sternotomy in resection of metastases of the upper thoracic spine].

A modified method of access to the upper thoracic spine is presented based on a case report. The third and fourth thoracic vertebral bodies can be reached by partial upper sternotomy. This approach takes the local anatomic situation into account, thus avoiding the typical complications of complete sternotomy and reducing the postoperative pain. Closure was done using biodegradable sutures, achieving satisfactory stabilisation and a low rate of complications. In only 4 of 130 cases (3%) did a superficial wound infection occur. There was no case of deep infection, osteomyelitis or dehiscence of the sternum.

Aged

[Roentgen image presentation in the patient's room. Simple equipment for demonstration and storage of roentgen images].

Immediate presentation of the more significant X-ray pictures facilitates planning and supervision of therapy in trauma surgery and orthopedics. If a wire rope is stretched in front of the window X-ray pictures can be clipped onto it, which avoids time-consuming searches. Suspended filing boxes placed in each sickroom make appropriate storage of each patient's X-ray pictures possible. The expenditure for all this amounted to 100 DM for each two-bedded room. Wire ropes and boxes were technically easy to install with a minimum investment of time. The presentation of X-ray pictures considerably increased the patients' understanding of their illness. It was also very rare for X-ray pictures to get mixed up once this system had been instituted.

Equipment Design

Value of bronchoscopic pneumonia diagnosis: prospective study.

In a prospective clinical study we examined whether bronchoscopically controlled suctioning is preferable to the blind suctioning of mucus aspirates for bacterial identification of intensive care unit patients with pneumonia. Forty patients with clinical and radiologic signs of pneumonia underwent both bronchoscopically controlled and blind endotracheal lavage. Bronchoscopically controlled suctioning did not demonstrate greater sensitivity for identifying organisms than the results obtained from blind suctioning (58 organism were bronchoscopically identified, compared to 57 organisms identified by blind suctioning; p = 0.32, NS). Arterial and mixed venous partial oxygen pressure and shunt also showed no significant differences 15 minutes before and after examination, nor did the blood pressure or pulse. The use of four of the bronchoscopes resulted in preinterventional contamination with Pseudomonas. Bronchoscopically controlled lavage shows no advantages over blind endotracheal lavage for diagnosing pneumonia. Blind suctioning with single-use sterile catheters can be done more quickly and inexpensively with fewer personnel and a lower complication rate.

Adult

Presynaptic development at the Drosophila neuromuscular junction: assembly and localization of presynaptic active zones.

We describe the extent to which presynaptic structures at the embryonic neuromuscular junction of Drosophila can form in mutants where development of postsynaptic somatic muscles is affected. Although twist mutant embryos lack mesoderm, motor axons still grow out of the CNS and form morphologically normal presynaptic active zones, independent of their target cells. In myoblast city mutant embryos, myoblasts do not fuse but form fully differentiated mononucleate muscles, which make functional neuromuscular synapses with correctly localized presynaptic active zones. Myoblasts also fail to fuse but still attract appropriate innervation in mef2 mutant embryos. However, these myoblasts fail to differentiate into muscles and presynaptic active zones fail to localize at neuromuscular contacts. Thus, the process of synapse formation can be genetically separated from the process of target recognition, revealing that localization of presynaptic active zones requires mef2-dependent muscle differentiation.

Animals

Validity of SEP monitoring in carotid surgery. Review and own results.

OBJECTIVE: The sensitivity of intraoperative monitoring by means of somatosensory evoked potentials (SEP) in carotid surgery is to be examined. EXPERIMENTAL DESIGN: Prospective clinical investigation. In addition, the influence of circulatory parameters on SEP curves will also be tested. SETTING: Department of Surgery of a university clinic. MATERIALS AND METHODS: A total of 200 patients underwent intraoperative monitoring by means of somatosensory evoked potentials (SEP) during carotid endarterectomy between March 1, 1991 and August 1, 1994. MEASURES: In order to exclude blood pressure variations as a cause for amplitude changes the blood pressure and pulse were documented during the entire phase of preparation and clamping. RESULTS: A significant correlation could not be established between parameters of circulation and amplitude changes (r = 0.0026; p = 0.62). In seven cases of intraoperative amplitude reduction of more than 50% a stroke has been avoided by inserting a shunt. Despite the lack of an amplitude reduction, a watershed stroke of A.cerebri media and A.cerebri posterior occurred in two instances. Taking this into consideration the sensitivity of monitoring is 99.0% at a specificity of 100%. CONCLUSIONS: SEP-monitoring in carotid endarterectomy is simple to execute and is superior in sensitivity to EEG analysis. To avoid artefaction by anesthesia, a standard injection anesthesia is recommended. Farfield potentials should also be derived to avoid watershed infarctions.

Blood Pressure

[Trauma in the last trimester of pregnancy].

Although accidents during pregnancy are fairly rare, besides endangering the mother, they nearly always mean a vital threat to the fetus: lethality rates are up to 8% for the mother and up to 34% for the fetus. Besides depression of the circulatory system in the mother, coupled with fetal hypoxy, injury to the placenta and uterus is also possible. Moreover, the unborn child may be injured by direct trauma. If the fetus sustains a direct injury, the head of the child is affected in the majority of instances. In addition, the risk of an intrauterine death is very high. If the injured baby survives after a section, permanent damage must be taken into account. Pregnant women who are injured in an accident should quickly be checked by sonography and cardiotocography. If no danger is expected for the child, the usual therapeutic rules that apply for traumatology should be followed. If the mother and child are endangered, a cesarean section must be undertaken along with simultaneous accident-related surgery on the mother. Case reports are presented on three cases in our clinic last year, and the current literature is discussed. All three mothers and newborns survived because of the cooperation between surgeons, gynecologists and pediatricians.

Adult

[Treatment methods for geriatric patients at the Traumatology Clinic at the University of Cologne --retrospective studies].

From 1st January 1988 until 31st December 1994, a total of 123 patients, aged over 80 years (2% of all patients) were treated in our clinic. Forty of the admitted patients showed degenerative alterations whereas 93 patients had had an accident. 77% of the falls at home constituted the most frequent cause resulting in a total of 81 fractures in 64 patients. Most of the fractures were located in the distal radius, the subcapital humerus by femoral shaft and the neck of the femur. Thirty-three patients received conservative treatment whereas ninety patients had to undergo surgery. 40% of the patients were operated on the first day of admittance. Median preoperative time amounted to one day. The perioperative mortality rate was 0.8%. Average time spent in the clinic amounted to 21 days. 74% of the patients could be discharged to their customary habitat. After discharge from the hospital, 25 cases required additional help and care. After more than 3 months following discharge 58% of all patients felt that reintegration into their former social environment had been achieved. In particular, the fractures of the lower extremities ought to be operated early for rapid mobilization. Long time of immobilization due to conservative methods of treatment increases the rate of complications. Reintegration into the normal environment at home and securing the necessary support for the patient after release are significant aspects of treatment in order to make the dusk their life as active, enjoyable and social as possible.

Aged

Syntaxin and synaptobrevin function downstream of vesicle docking in Drosophila.

In synaptic transmission, vesicles are proposed to dock at presynaptic active zones by the association of synaptobrevin (v-SNARE) with syntaxin (t-SNARE). We test this hypothesis in Drosophila strains lacking neural synaptobrevin (n-synaptobrevin) or syntaxin. We showed previously that loss of either protein completely blocks synaptic transmission. Here, we attempt to establish the level of this blockade. Ultrastructurally, vesicles are still targeted to the presynaptic membrane and dock normally at specialized release sites. These vesicles are mature and functional since spontaneous vesicle fusion persists in the absence of n-synaptobrevin and since vesicle fusion is triggered by hyperosmotic saline in the absence of syntaxin. We conclude that the SNARE hypothesis cannot fully explain the role of these proteins in synaptic transmission. Instead, both proteins play distinct roles downstream of docking.

Animals