A microtubule-organizing center directing intracellular transport in the early mouse embryo.

The centrosome is the primary microtubule-organizing center (MTOC) of most animal cells; however, this organelle is absent during early mammalian development. Therefore, the mechanism by which the mammalian embryo organizes its microtubules (MTs) is unclear. We visualize MT bridges connecting pairs of cells and show that the cytokinetic bridge does not undergo stereotypical abscission after cell division. Instead, it serves as scaffold for the accumulation of the MT minus-end-stabilizing protein CAMSAP3 throughout interphase, thereby transforming this structure into a noncentrosomal MTOC. Transport of the cell adhesion molecule E-cadherin to the membrane is coordinated by this MTOC and is required to form the pluripotent inner mass. Our study reveals a noncentrosomal form of MT organization that directs intracellular transport and is essential for mammalian development.

The aerodynamics of Argentavis, the world's largest flying bird from the Miocene of Argentina.

We calculate the flight performance of the gigantic volant bird Argentavis magnificens from the upper Miocene ( approximately 6 million years ago) of Argentina using a computer simulation model. Argentavis was probably too large (mass approximately 70 kg) to be capable of continuous flapping flight or standing takeoff under its own muscle power. Like extant condors and vultures, Argentavis would have extracted energy from the atmosphere for flight, relying on thermals present on the Argentinean pampas to provide power for soaring, and it probably used slope soaring over the windward slopes of the Andes. It was an excellent glider, with a gliding angle close to 3 degrees and a cruising speed of 67 kph. Argentavis could take off by running downhill, or by launching from a perch to pick up flight speed. Other means of takeoff remain problematic.

Biplane wing planform and flight performance of the feathered dinosaur Microraptor gui.

Microraptor gui, a four-winged dromaeosaur from the Early Cretaceous of China, provides strong evidence for an arboreal-gliding origin of avian flight. It possessed asymmetric flight feathers not only on the manus but also on the pes. A previously published reconstruction shows that the hindwing of Microraptor supported by a laterally extended leg would have formed a second pair of wings in tetrapteryx fashion. However, this wing design conflicts with known theropod limb joints that entail a parasagittal posture of the hindlimb. Here, we offer an alternative planform of the hindwing of Microraptor that is concordant with its feather orientation for producing lift and normal theropod hindlimb posture. In this reconstruction, the wings of Microraptor could have resembled a staggered biplane configuration during flight, where the forewing formed the dorsal wing and the metatarsal wing formed the ventral one. The contour feathers on the tibia were positioned posteriorly, oriented in a vertical plane for streamlining that would reduce the drag considerably. Leg feathers are present in many fossil dromaeosaurs, early birds, and living raptors, and they play an important role in flight during catching and carrying prey. A computer simulation of the flight performance of Microraptor suggests that its biplane wings were adapted for undulatory "phugoid" gliding between trees, where the horizontal feathered tail offered additional lift and stability and controlled pitch. Like the Wright 1903 Flyer, Microraptor, a gliding relative of early birds, took to the air with two sets of wings.

[Inpatient post-transplant services and intermittent rehabilitation in patients after kidney transplantation]. / Stationäre Anschlussheilbehandlung und intermittierende Rehabilitation bei Patienten nach Nierentransplantation. Sicherung des Transplantationslangzeiterfolgs.

Late graft outcome depends on an intensive post-transplant care program. Direct post-transplant inpatient rehabilitation in a specialized hospital as well as outpatient services, along with an inpatient check-up every 2-3 years are important for maintaining an excellent long-term graft function. In our experience recognizing and treating risk factors after organ transplantation such as arterial hypertension, vasculopathy, hyperlipidemia, metabolic syndrome including PTDM, osteoporosis, recurrent diseases and also the recipient's education (compliance) are most important landmarks in a post-transplant care program. This inpatient as well as outpatient post-transplant care program with the aim of long-term graft function for organ recipients, performed in a network, represents a modern health service including effective and economical aspects, which health insurance in Germany is obliged to pay for.

[Structure and process quality of inpatient urologic rehabilitation]. / Struktur- und Prozessqualität der stationären urologischen Rehabilitation.

Inpatient rehabilitation and "Anschlussheilbehandlung" (rehabilitation soon after operation or acute intervention) are effective and economic for long-term improvement of urologic patients. Only therapy guided by urologic specialists during rehabilitation and afterwards guarantees the possibility of excellent results. Especially QOL and functional deficits are improved markedly by urologic rehabilitation. Therefore, inpatient urologic rehabilitation should be initiated more often in the future.

The flight of Archaeopteryx.

The origin of avian flight is often equated with the phylogeny, ecology, and flying ability of the primitive Jurassic bird, Archaeopteryx. Debate persists about whether it was a terrestrial cursor or a tree dweller. Despite broad acceptance of its arboreal life style from anatomical, phylogenetic, and ecological evidence, a new version of the cursorial model was proposed recently asserting that a running Archaeopteryx could take off from the ground using thrust and sustain flight in the air. However, Archaeopteryx lacked both the powerful flight muscles and complex wing movements necessary for ground takeoff. Here we describe a flight simulation model, which suggests that for Archaeopteryx, takeoff from a perch would have been more efficient and cost-effective than from the ground. Archaeopteryx may have made short flights between trees, utilizing a novel method of phugoid gliding.

Protein A immunoadsorption (i.a.) in renal transplantation patients with vascular rejection.

Vascular rejection after renal transplantation is connected with a higher frequency of allograft dysfunction or graft loss. Plasmapheresis as an adjunctive therapy in the treatment of humoral mediated acute graft rejection was compared with protein A immunoadsorption. Eleven patients with acute graft rejection and high titers of cytotoxic HLA-Ab and/or signs of vascular rejection at graft biopsy (performed in 9 patients) have been treated. Six of them have a stable graft function, the longest graft survival until now is 41 months, four are back on haemodialysis and one patient died from CMV-pneumonia with a stable graft function 9 months after transplantation. We conclude that IA is a useful adjunctive therapy in the treatment of vascular rejection after renal transplantation. Further investigations are necessary to optimize criteria for inclusion.

Radiotherapy in stage IIA and IIB testicular seminoma with reduced portals: a prospective multicenter study.

PURPOSE: A prospective multicenter study was carried out to estimate the treatment outcome of radiotherapy in Stage II seminoma after the application of modern staging and radiotherapy techniques. The lower margin of the iliac field was positioned on the upper rim of the acetabulum to reduce the amount of scattered irradiation to the remaining testicle. METHODS AND MATERIALS: The study was carried out in 25 centers in Germany. Patients with pure seminoma, negative AFP-values, and retroperitoneal lymph node metastases of less than 5 cm in diameter were entered into the study. All patients received a ventrodorsal opposed field irradiation of the para-aortic and the ipsilateral iliac lymph nodes. The fields extended from the top of the 11th thoracic vertebra to the top of the acetabulum. Patients in Stage IIA (lymph nodes <2 cm ) received 30 Gy, and patients with Stage IIB (lymph nodes between 2 and 5 cm) 36 Gy total dose. RESULTS: 39 patients in Stage IIA and 19 patients in Stage IIB were evaluated. After a median observation time of 37 months all patients are alive and disease free. Recurrence free survival in stage IIA was 100%. Two patients in Stage IIB experienced a recurrence 10 and 17 months after the end of radiotherapy. The actuarial recurrence free survival estimate in Stage IIB was 94.1% for 1 year and 87.4% for 2 years. One recurrence in Stage IIB occurred in the mediastinum, one in the mediastinum, and one the lung. Both patients could be salvaged by chemotherapy. There were no pelvic recurrences. The treatment was well tolerated, with nausea being the most common side effect (56.9% Grade 1, 15.5% Grade 2, and 8.6% Grade 3). Diarrhea occurred in 15.5% (Grade 1), 15.5% (Grade 2), and 5.2% (Grade 3) of the patients. CONCLUSIONS: The outcome of para-aortic and ipsilateral iliac irradiation in Stage IIA/B testicular seminoma is excellent with the currently available staging methods and treatment facilities. The treatment is well tolerated. The lower margin of the iliacal field can be placed at the acetabulum.

Tandem bullet versus multiple gunshot wounds.

The differentiation of tandem bullets fired simultaneously versus multiple bullets fired separately entering through a single entrance wound may present difficulty in wound interpretation for the forensic pathologist. The authors present a case report of three separate projectiles entering through a single perforation. The differentiation of projectiles fired in tandem and multiple single projectiles is discussed.

Blood gas analyzers.

Laboratory-based blood gas analyzers have reliably produced pH, PCO2, and PO2 analyses for several decades. Over this time, their design changes reduced maintenance procedures, microprocessor-controlled functions simplified operation, and regulations governing their use have expanded. This article presents the electrochemical principles of the pH and blood gas electrodes and the operational procedures necessary to satisfy regulatory standards.

Effects of PUVA therapy on kidney allografts: results of a randomized prospective double-blind study.

After successful experimental organ transplant studies on the efficacy of PUVA therapy combining donor pretreatment with the photosensitizer 8-methoxypsoralen (P) and the ex vivo irradiation of organs with long-wave ultraviolet light (UVA) prior to transplantation, we started in 1989 the first randomized, prospective, double-blind study to clarify the efficacy of PUVA therapy in human kidney transplantation. This study included 50 kidney donors, 25 of whom were PUVA-treated. A total of 75 kidneys were transplanted in Berlin, Halle and Rostock. The complete data of these 75 recipients were available for the final evaluation. The PUVA group (n = 36) and the non-PUVA group (n = 39) were not statistically significantly different as to donor and recipient data. Regarding the results, no differences were seen in initial hospitalization time, early graft function, rejection rate, number and time of rejection episodes. After a follow-up of 24 months, both graft survival (PUVA vs. non-PUVA: 75% vs. 71.8%) and patient survival (97.2% vs. 97.4%, respectively) were comparably high. PUVA therapy did not influence the development of vascular rejection. Interestingly, the rate of late graft loss after the 6th posttransplant month was lower, but not statistically significantly so, in the PUVA than in the non-PUVA-group (2 vs. 6 graft losses). Thus, PUVA-pretreated kidneys may be associated with a reduced development of chronic rejection.

[The trend distribution quotient, a new tool for evaluating renal perfusion scintigraphy using 99mTc-DTPA following renal transplantation]. / Der Trendverteilungsquotient, ein neues Werkzeug zur Auswertung der Nierenperfusionsszintigraphie mit 99mTc-DTPA nach Nierentransplantation.

We developed a new quantitative concept in dynamic renal transplant imaging, the Trend Distribution Ratio, and tested its diagnostic usefulness in 137 examinations. This ratio is an expression of the distribution of blood flow velocity in different areas of the kidney. With regard to the differential diagnosis between acute tubular necrosis and the various forms of rejection we arrived at a sensitivity of 0.83 and a specificity of 0.54. A differentiation between the various histological types of rejection has not yet been possible.

[Factors influencing the result of kidney transplantation with special reference to the HLA system in conventional immunosuppression]. / Einflussfaktoren auf das Nierentransplantationsergebnis unter besonderer Berücksichtigung des HLA-Systems bei konventioneller Immunsuppression.

Among 331 recipients of cadaveric renal allografts, transplanted from 1976 to 1986 at the Rostock Transplant Center the graft survival rates have been analyzed. All patients have been treated by conventional immunosuppressive therapy using azathioprine and prednisolone. A relation between graft survival and immunological factors was found: the better the HLA match, the better the transplant results. The necessity of a restrictive transfusion regime was stressed. The higher the number of pretransplant transfusions, the higher is the panel reactivity with following lower graft survival. Cold ischemic time was without influence on graft survival. The introduction of cyclosporin may improve the graft survival rate as known of 10-20%.

[Clinical value of interleukin 1- and interleukin 2-determinations in patients after kidney transplantation]. / Klinische Wertigkeit von Interleukin 1- und Interleukin 2-Bestimmungen bei Patienten nach Nierentransplantation.

In a retrospective study of allograft rejections in renal transplant recipients we examined the value of cytokine production monitoring. Interleukin 1 (IL 1) and interleukin 2 (IL 2) activities were determined in supernatants of mitogen-stimulated peripheral blood lymphocytes in 8 renal transplant recipients serially for a period up to 60 days after transplantation. LPS-induced IL 1 as well as PHA-induced IL 2 production in patients after renal transplantation were significantly decreased in comparison to healthy controls. Seven episodes of cellular rejection were diagnosed in renal allograft recipients during this time, only 4 rejection episodes, however, were associated with a rise in the IL 1 and simultaneous IL 2 production occurred for 2 up to 3 days before the diagnosis of rejection. Moreover there were 12 instances in which an elevation of IL 1 and IL 2 production was found independently from the rejection. In 8 cases the augmentation of IL 1 and IL 2 production could be associated with clinical infections. We conclude from these results that a cytokine monitoring for the diagnosis of allograft rejection does not seem to be useful.

Frequency and therapy of end-stage renal disease due to diabetic nephropathy in the German Democratic Republic.

The prevalence of diabetic nephropathy among the German Democratic Republic (GDR) population is substantial, as is true of many other countries. An epidemiologic survey performed in the county of Neubrandenburg revealed increased creatinine values in 44.9% of diabetics with diabetes duration greater than 15 years, and in 24.9% of those with the disease less than 15 years. Given these data, the prevalence of renal insufficiency due to diabetic nephropathy is estimated as 27/100,000 in diabetics with greater than 15 years, and 9/100,000 in diabetics with less than 15 years of diabetes, including only patients up to the age of 49 years; this must be substantially greater when considering all age groups. Only 13% of all patients on chronic hemodialysis are diabetics. Although we offer each of our nephropathic diabetics such kidney replacement therapies as dialysis and transplantation, a substantial number of diabetics are not treated, presumably due to advanced macrovascular complications.

[Pathology of the transplanted kidney and basic renal disease of the recipient]. / Transplantatnierenpathologie und renale Grundleiden des Empfängers.

Among 359 kidney transplantations performed from 1976 to 1986 at Rostock the 4 most frequent original renal diseases were glomerulonephritis (280 x), pyelonephritis (74 x), diabetic nephropathy (22 x) and polycystic kidney disease (14 x). From 225 transplant kidneys in 284 cases pathomorphological examinations were performed (104 biopsies, 138 removed grafts, 42 postmortem transplant examinations). The most striking finding was the earlier occurrence of rejection in grafts from recipients with glomerulonephritis compared with pyelonephritis. Therefore, a more rapid and intense immune reaction could suggested in patients with glomerulonephritis as original renal disease.

Unreliability of oxygen tension-based indices in reflecting intrapulmonary shunting in critically ill patients.

Measurement of intrapulmonary shunting (Qsp/Qt), a widely used method for monitoring disturbances of pulmonary oxygen transfer in critically ill patients, involves calculation of arterial and mixed venous oxygen contents. In circumstances where mixed venous blood samples are not readily available, oxygen tension-based indices such as the alveolar to arterial oxygen tension differences (P[A-a]O2), arterial oxygen tension to alveolar oxygen tension ratio (PaO2/PAO2), PaO2 to FIO2 ratio (PaO2/FIO2) and respiratory index (RI) are widely utilized to reflect Qsp/Qt. Oxygen content-based indices such as the estimated shunt are not as widely utilized as the oxygen tension indices. In 75 critically ill patients in whom a pulmonary artery catheter was being utilized to augment clinical care, comparisons were made between Qsp/Qt and P(A-a)O2, PaO2/PAO2, PaO2/FIO2, RI, and estimated shunt to determine which index best reflected Qsp/Qt. Correlations between Qsp/Qt and estimated shunt were good (r = .94) and poor for the P(A-a)O2 (r = .62), PaO2/PAO2 (r = .72), PaO2/FIO2 (r = .71), and RI (r = .74). We conclude that there are no real substitutes for venous oxygen contents in critically ill patients. When pulmonary artery blood is not available for analysis, oxygen tension-based indices are unreliable reflectors of Qsp/Qt while the estimated shunt, an oxygen content-based index, provides a more reliable reflection of Qsp/Qt.

[Problems of metabolic control in type I diabetic patients with chronic renal failure]. / Probleme der Stoffwechselführung bei Typ-I-Diabetikern mit chronischer Niereninsuffizienz.

The aetiopathogenesis of the diabetic nephropathy today is still unknown. Uncontested is the contribution of chronic hyperglycemia in the pathogenesis of diabetic nephropathy. For this, there are convincing evidences from clinical and experimental experiences including transplantation surgery. The quality of the metabolic adjustment of the diabetics from the first time of diabetes manifestation is important to prevent the development of diabetic nephropathy. For this, an almost normoglycemic compensation of the glucose metabolism is mandatory. More problematically is the management of the diabetic metabolism during chronic renal insufficiency. Considerable fluctuations of the blood glucose concentration are predominately in the daily profile. The intensive conventional metabolic therapy by multiple insuline injections under self control of the blood glucose level are indicated absolutely in those patients. The therapeutic aim is a smoothing of the blood glucose fluctuation. With that it is possible--together with the elimination of hemodynamic risk factors--to delay effectively a progradient decline of the glomerulo-filtration rate and to improve the assumption to an invasive therapy.