Functional domains of the Drosophila melanogaster muscle myosin heavy-chain gene are encoded by alternatively spliced exons.

The single-copy Drosophila muscle myosin heavy-chain (MHC) gene, located at 36B(2L), has a complex exon structure that produces a diversity of larval and adult muscle MHC isoforms through regulated alternative RNA splicing. Genomic and cDNA sequence analyses revealed that this 21-kilobase MHC gene encodes these MHC isoforms in 19 exons. However, five sets of these exons, encoding portions of the S1 head and the hinge domains of the MHC protein, are tandemly repeated as two, three, four, or five divergent copies, which are individually spliced into RNA transcripts. RNA hybridization studies with exon-specific probes showed that at least 10 of the 480 possible MHC isoforms that could arise by alternative RNA splicing of these exons are expressed as MHC transcripts and that the expression of specific members of alternative exon sets is regulated, both in stage and in muscle-type specificity. This regulated expression of specific exons is of particular interest because the alternatively spliced exon sets encode discrete domains of the MHC protein that likely contribute to the specialized contractile activities of different Drosophila muscle types. The alternative exon structure of the Drosophila MHC gene and the single-copy nature of this gene in the Drosophila genome make possible transgenic experiments to test the physiological functions of specific MHC protein domains and genetic and molecular experiments to investigate the mechanisms that regulate alternative exon splicing of MHC and other muscle gene transcripts.

[Case numbers and revenues of main and affiliated ophthalmological departments: Developments since 2005]. / Fallzahlen und Erlöse in ophthalmologischen Haupt- und Belegabteilungen : Entwicklungen seit 2005.

BACKGROUND: Currently, very little data exist on the development of healthcare-related and financial parameters of both types of inpatient treatment: clinical units run by affiliated physicians and those run by hospital physicians. AIM: This study used a methodology based on published secondary data to estimate the annual number of cases and revenues for in inpatient ophthalmological treatment differentiated into clinical units run by affiliated physicians and those run by hospital physicians. MATERIAL AND METHODS: The case-based flat-rate catalogs and accompanying research data published annually by the Institute for the Hospital Remuneration System (Institut für Entgeltsysteme im Krankenhaus, InEK) served as a data source. The numbers of annual cases according to major diagnostic categories (MDC) and diagnosis-related groups (DRG), stratified by the unit type are reported for the period 2005-2012. The cumulative total revenues were calculated based on the number of ophthalmological cases, the effective DRG cost weighting, the length of stay and the national basic case values. RESULTS: Between 2005 and 2012 the units run by affiliated physicians showed a contrasting trend to those run by hospital physicians: the number of cases in units run by hospital physicians increased by 14 %, while those in units run by affiliated physicians decreased by 6 %. Up to 2012 the effective cost weighting for cases in units run by hospital physicians decreased to 0.60 (- 3 %) and increased to 0.43 (+ 5 %) for units run by affiliated physicians. In 2012 the corresponding effective case revenue accounted for 1767 euros and 1271 euros, respectively. Total revenue estimates for all inpatient ophthalmological treatment increased from 549 million euros in 2005 to 630 million euros in 2012, while the share of units run by affiliated physicians amounted to 10.6 % and 9.7 %, respectively. CONCLUSION: According to the indicators "number of cases" and "total revenue", the affiliated ophthalmologists lost ground compared with inpatient units run by hospital physicians over the period from 2005-2012.

Regional differences in the fine structure of the ciliary epithelium related to accommodation.

The ciliary bodies of five monkey eyes and one human eye were subdivided into five zones. The ciliary epithelium with its bordering stroma was investigated electron microscopically. The number of cell organelles of the nonpigmented (NPE) and pigmented (PE) epithelium (mitochondria, rough endoplasmic reticulum, Golgi complexes); intercellular junctions between NPE and NPE, PE and PE, and NPE and PE (desmosomes, puncta adhaerentia, gap junctions, tight junctions); and fenestrations of the capillary endothelium were quantitatively evaluated. All these types of cell organelles, fenestrations of the capillary endothelium, and gap junctions in the NPE were found in greater numbers at the crests of the ciliary processes than in the valleys between processes. On the other hand, the number of puncta adhaerentia is significantly higher in the valleys than at the crests. In the valleys, the internal limiting membrane performs an elaborate network of electron-dense strands in which many fine zonular fibers terminate. These fibers are believed to belong to the "tension fiber system." Their firm attachment to the ciliary epithelium and the great number of intercellular junctions known as mechanical structures lend further support to our concept that these structures function as a fulcrum in the process of accommodation.

Attenuation of oxidant-mediated endothelial cell injury with docosahexaenoic acid: the role of intracellular iron.

Previous studies have demonstrated that altering the fatty acid composition of porcine pulmonary artery endothelial cells (PAEC) significantly modulates their susceptibility to oxidative stimuli, e.g. H2O2. Based on observations that fatty acids also function to transport iron, an important catalyst for H2O2-mediated hydroxyl radical generation, we hypothesized that fatty acid-induced alterations in PAEC iron metabolism contribute to modulation of PAEC oxidant susceptibility. To test this hypothesis, PAEC were treated with culture medium supplemented with 0.1 mM oleic (18:1), linolenic (18:3) or docosahexaenoic (22:6) acids or with an equivalent volume of ethanol vehicle for 3 h. After thorough washing and incubation in unsupplemented culture medium for 24 h, PAEC monolayers were subjected to additional studies. Supplementation with 22:6 attenuated lactate dehydrogenase (LDH) release from PAEC 2 h following treatment with 100 microM H2O2 for 30 min (% LDH release: ETOH-control = 7.9 +/- 1.6, 22:6-control = 5.9 +/- 0.9, ETOH-H2O2 = 26.4 +/- 4.2, 22:6-H2O2* = 16.2 +/- 2.9; *P < 0.05 vs ETOH-H2O2). In a non-cellular system, 18:1 and 18:3 were more effective than their methyl ester derivatives or 22:6 at translocating iron from aqueous to hydrophobic environments. In contrast, only supplementation with 22:6 significantly increased PAEC uptake of 57Fe and human umbilical vein endothelial cell (HUVEC) ferritin content, whereas none of the supplementation conditions altered PAEC catalytic iron measured with bleomycin. These novel observations indicate that specific fatty acids are capable of altering PAEC iron uptake and ferritin content thereby contributing to the understanding of the mechanisms by which fatty acids modulate the oxidant susceptibility of vascular endothelial cells.

A clinical evaluation of the effects of topically applied levobunolol and timolol on increased intraocular pressure.

Data from two short-term double-masked studies using 24 and 16 subjects suggest that topically applied levobunolol safely and effectively treats open-angle glaucoma and ocular hypertension. The onset of effect of a single drop of 0.5% levobunolol occurred within the first hour, producing a maximal hypotensive effect of more than 8 mm Hg after two hours. An intraocular pressure deceased of greater than or equal to 2 mm Hg was still observed after 24 hours for both concentrations of levobunolol tested (0.5% and 1%). Intraocular pressure decreases of more than 9 mm Hg persisted during a one-month trial in which patients were treated twice daily, confirming the results obtained in the 24-hour study. Systemic effects of both timolol (0.5%) and levobunolol (0.5% and 1%) included a consensual intraocular pressure-decreasing effect in the untreated eye and clinically significant reductions in heart rate. Diastolic blood pressure was decreased at two and four hours after administration of 0.5% levobunolol.

Long-term ocular hypotensive effect of levobunolol: results of a one-year study.

Data for the first 12 months are reported for an ongoing, multicentre, clinical study comparing the long-term, ocular hypotensive efficacy and safety of topical levobunolol (0.5% and 1%) and timolol (0.5%). This study was a double-masked trial testing 88 patients with chronic open angle glaucoma or ocular hypertension. During the 12-month period drops were instilled twice daily into both eyes after a washout of prestudy ocular hypotensive medication. The effect of the three treatments in reducing intraocular pressure (IOP) was similar. Mean IOP reductions over the 12 months averaged 7.2 mmHg for the 0.5% levobunolol group, 6.2 mmHg for the 1% levobunolol group, and 6.0 mmHg for the timolol group. Decreases in mean heart rate of up to 5 beats per minute were observed in the 0.5% levobunolol group, up to 8 beats per minute in the 1% levobunolol group, and up to 4 beats per minute in the timolol group. Several patients were removed from the study owing to side effects possibly related to levobunolol treatment.

Anticipatory postural adjustments before load pickup in a bi-manual whole body lifting task.

Balance regulation and movement control were examined in the context of bi-manual lifting. Subjects picked up a load (20% body mass) after several unloaded cycles using the leg-lift technique. The addition of the load to the body caused the system center of mass to shift forward and thus presented the subject with an expected perturbation of balance. To examine whether the disturbances to balance were counteracted by anticipatory postural adjustments, the last cycle, in which the barbell was grasped and lifted, was compared with the preceding unloaded cycle. Using a global mechanical analysis of the movement, we found that anticipatory postural adjustments were present before load pickup in bi-manual lifting. These anticipatory postural adjustments were characterized by a backward directed horizontal momentum, a backward directed horizontal component of the ground reaction force accompanied with a forward shift of the center of pressure, and a backward shift of the center of mass (CoM). These characteristics could all be understood from the mechanical consideration that adding a load in front of the body induces a forward shift of the CoM. However, major compensations of the position of the CoM were also observed after bar grasp. It is therefore proposed that commands giving rise to postural adjustments are closely tied to commands controlling the ongoing movement. On the basis of this insight the strict dichotomy in the control of posture and movement is being questioned.

Optimizing the determination of the body center of mass.

The position or trajectory of the body center of mass (COM) is often a parameter of interest when studying posture or movement. For instance, in balance control studies the body COM can be related to the ground reaction force or to the base of support. Since small displacements of the body COM are important in balance control studies, it is essential to obtain valid estimates of the body COM. The main source of error in the determination of the body COM is the estimation of the masses and centers of mass of the body segments. Especially the determination of the trunk COM is prone to error. In the current study five subjects maintained three postures, differing in trunk angle, during a few seconds. The relation between the center of pressure of the ground reaction force and the vertical projection of the body COM during the postures was used to optimize the trunk COM position. Additionally the subjects performed two lifting movements. The validity of the body COM trajectory estimation during the lifting movements, both with and without optimized trunk COM, was checked by relating the external moment of the ground reaction force with respect to the body COM to the rate of change of the angular momentum of the whole body. It was shown that the correspondence between the external moment and the rate of change of the angular momentum improved after optimization of the trunk COM. This suggests that the body COM trajectory estimation can be improved by the proposed optimization procedure.

The rehabilitation/school matrix: a model for accommodating the noncompliant child with severe burns.

Some children with severe burns may have difficulty following therapeutic recommendations after discharge from a burn center. Noncompliance may result in complications that affect function, surgical management, community reintegration, and successful reentry into school. We present a case study in which a child with significant compliance issues was managed in a coordinated interdisciplinary model. This model extended from acute recovery through reintegration into the classroom. A behavior-modification program was implemented across different levels of care. Educational reentry was facilitated by including a transitional period in a special-needs classroom in a freestanding special-needs school. Requirements for using educational resources to which some children are legally entitled are reviewed. Rehabilitation services that interface with the educational system for children with burns may improve outcomes as these children reintegrate into the community.

Treatment of elevated intraocular pressure with concurrent levobunolol and pilocarpine.

Between July 1983 and January 1986, 54 patients with open-angle glaucoma or ocular hypertension were treated for 3 months with 2% pilocarpine hydrochloride (given four times daily) and one of two beta-adrenoceptor blocking drugs, levobunolol hydrochloride (0.5% [17 patients] or 1% [19 patients]) or 0.5% timolol maleate (18 patients), given twice daily. Before entry into the study all patients had had stable intraocular pressure (IOP) with treatment with 0.5% timolol and 2% pilocarpine. Stable IOP was successfully maintained in up to 88% of the patients in the two levobunolol-pilocarpine groups and in 83% of those in the timolol-pilocarpine group. Two patients experienced adverse reactions: one, who received timolol and pilocarpine, suffered blepharoconjunctivitis, and the other, who received 1% levobunolol and pilocarpine, experienced bradycardia. The results indicate that the levobunolol-pilocarpine regimens were as safe and effective as the timolol-pilocarpine regimen in stabilizing IOP.

[Respiratory symptoms and function of coal miners presenting radiological pulmonary abnormalities]. / Symptômes et fonction respiratoires des mineurs de charbon présentant des anomalies radiologiques pulmonaires.

Respiratory symptoms and lung function of 80 coal workers suspected of pneumoconiosis (pulmonary X-rays classified 0/1 or 1/0 according to International Labour Organisation classification) who worked for at least 10 years at face work (Ts) were studied in comparison with two control groups matched by age (+/- 2 years), height (+/- 5 cm), weight (+/- 10 kg) and smoking habits: the Tn group constituted by 80 coal workers who worked for at least 10 years at face work with normal pulmonary X-rays, and the HTn group constituted by 80 underground miners who worked mainly out of face work with normal pulmonary X-rays. The frequencies of cough, expectoration, chronic bronchitis or dyspnoea were significantly higher in Ts group than in the two others. The one-second forced expiratory volume to vital capacity ratio (FEV1/VC) was lower, closing volume to vital capacity (CV/VC) or to total lung capacity ratios (CV/TLC) were higher in Ts group than in the control groups. Unexpectedly, vital capacity (VC), one-second forced expiratory volume (FEV1), total lung capacity (TLC), compliance, diffusing capacity (DLCO) referred to alveolar volume (VA) were higher. In Ts group, the small rounded opacities were noted in the top part of the lung (56.9%), the irregular ones were distributed on the entire lung (65.5%). There were no relation between the category of small opacities and respiratory symptoms or lung function.

[LP-X in newborns: increased incidence of positive tests without cholestasis (author's transl)]. / Lipoprotein-X bei Neugeborenen: Gehäuftes Auftreten ohne nachweisbare Cholestase

The investigation of 194 newborns has shown that during the first weeks of life the abnormal lipoprotein-X (LP-X) was present in the serum of nearly 50% of the infants, with no clinical chemical evidence of cholestasis. The percentage of LP-X positive tests was even higher in the group of immature newborns (65%). There was no correlation between the bilirubin concentration and the detection of LP-X. The activities of leucine arylamidase (EC 3.4.1.1) and gamma-glutamyltransferase (EC 2.3.2.2) as well as the concentrations of total and free cholesterol did not differ in the LP-X positive and negative infants. Except in one case, LP-X was never detectable on the first day of life. The earliest date of appearance was the second day. In the serum of some infants, who were LP-X positive shortly after birth, the lipoprotein could still be found at the age of 2--3 months. The incidence of LP-X was not higher in newborns with blood group incompatibility than in newborns with unspecific hyperbilirubinaemia. After exchange transfusions LP-X disappeared in most cases, but it could later often be detected again. In some newborns, who were LP-X negative a few days after birth LP-X was first detected at the age of 2-3 months. The LP-X test is of no use for th diagnosis of cholestasis in newborn infants. The test is specific for cholestasis only after the first year of life. The increased incidence of positive LP-X tests in newborns is discussed as a consequence of immature liver function.

[Beta-blocking treatment (author's transl)]. / Kardiovaskuläre und pulmonale Wirkungen bei lokaler Beta-Blockergabe.

Twenty-six patients with open-angle glaucoma were investigated to see if and to what extent topical treatment with timolol 0.5% produced systemic effects. All of the patient had contraindications to the systemic use of beta-blockers such as bradycardia, cardiac insufficiency and chronic obstructive pulmonary disease. In some patients the treatment had marked cardiovascular or pulmonary effects, especially in the group with chronic obstructive pulmonary disease.

[The effect of timolol and dipivalyl-epinephrine in the treatment of the elevated intraocular pressure (author's transl)]. / Timolol und Adrenalindipivalat bei der Behandlung des erhöhten intraocularen Druckes.

Twenty-seven patients with ocular hypertension or open angle glaucoma were tested to see if, and to what extent, timolol and dipivalyl-epinephrine produced a supplementary reduction of intraocular pressure. In a shortterm study, 14 patients were tested with timolol (0.1%) and dipivalyl-epinephrine (0.25%). Simultaneous application of both substances produced a statistically more significant reduction of intraocular pressure than either timolol (0.1%) or dipivalyl-epinephrine (0.25%) alone. In 13 patients a comparison was made between patients who received both timolol (0.25%) and dipivalyl-epinephrine (0.1%) bis x and patients who received only timolol (0.25%) bis x over a period of 6, 9 and 12 weeks. Both substances used in combination produced a statistically more significant reduction in intraocular pressure than timolol (0.25%) bis x alone. The simultaneous application of an alpha and beta-adrenergic agonist and beta-adrenergic antagonist is not contradictory. The results are discussed on the basis of the mode of action of the applied substances.

[Metipranolol 0.1% and pilocarpine 2% as a fixed combination compared to each substance alone in the treatment of glaucoma. A controlled, randomized clinical study comparing the intraindividual effects and tolerance]. / Metipranolol 0,1% und Pilokarpin 2% als fixe Kombination im Vergleich zu den Monosubstanzen in der Behandlung des Glaukoms. Eine kontrollierte, randomisierte klinische Studie zum intraindividuellen Wirkungs- und Verträglichkeitsvergleich.

A fixed combination of pilocarpine 2% and metipranolol 0.1% was found to have a better pressure-lowering effect than pilocarpine 2% alone or metipranolol 0.1% alone, as well as being tolerated well, both subjectively and objectively. In many cases only the fixed combination was successful in lowering intraocular pressure to tolerable values.

Essential contribution of thrombocytes to the occurrence of catecholamine-induced cardiac necroses.

The role of thrombocytes in the production of isoproterenol-induced cardiac necrosis was investigated in rats rendered thrombocytopenic (A) as well as in rats treated with a prostacyclin analogue (B). According to quantitative morphometric evaluation the area of necrotic tissue amounted to about 1% 9 h following administration of isoproterenol (40 mg/kg). In both groups of treated animals the number and area of necroses were strongly reduced (to 23% group A, to 34% group B, P less than or equal to 0.1 for both groups). In contrast, the reduction of myocardial adenine nucleotide levels induced by isoproterenol was the same (5.06 to 3.57 and 3.60 microM/g wet wt, respectively) in thrombocytopenic and non-thrombocytopenic rats. Quantitative comparison of the fraction of necrotic tissue and of the fraction of lost nucleotides suggests that non-necrotic rather than necrotic tissue predominantly contributes to the reduction of nucleotides. The dependence of cardiac necrosis production on the presence or normal aggregability of platelets points out at platelet-dependent microvascular alterations as a main cause of isoproterenol-induced cardiac necroses.

[Timolol and acetazolamide in the treatment of increased intraocular pressure (author's transl)]. / Timolol und Acetazolamid bei der Behandlung des erhöhten intraocularen Druckes.

Twenty-four patients with open-angle glaucoma were tested to see if, and to what extent, timolol and acetazolamide produced a supplementary reduction of intraocular pressure. Twelve patients were treated with timolol eye drops, 0.5% b.d over a period of one week and then received one dose i.v. acetazolamide 250 mg which produced a statistically significant drop in intraocular pressure. Twelve patients with open-angle glaucoma who had been treated with acetazolamide 500 mg t.d.s. orally over a period of one week, received one drop of timolol 0.25% which produced a statistically significant additional effect. These results are discussed on the basis of the mode of action of the applied medications.

[The effect of timolol and parasympathicomimetica in the treatment of the elevated intraocular pressure (author's transl)]. / Timolol und Parasympathicomimetica bei der Behandlung des erhöhten intraocularen Druckes.

45 patients with ocular hypertension or open-angle glaucoma were tested to see if, and to what extent timolol and three other different parasympathicomimetics (pilocarpine 2%, carbachol 1.5%, aceclydine 2%) produced an supplementary reduction of the intraocular pressure. An equally marked, additional drop in eye pressure was achieved when patients who had been given timolol over an extended period of time, were additionally treated with one dose of pilocarpine 2% or carbachol 1.5%. Aceclydine 2% produced no statistically significant additional effect. Patients who had only been treated with pilocarpine 2% over an extended period of time and then were given one dose of timolol 0.25% produced a drop in eye presure more than double that of those patients who had been primarily treated with timolol and then received pilocarpine or carbachol. These results will be discussed on the basis of the mode of action of the applied medications.