Biomedical subjects
Publications and source records attributed to C Müller.
The article presents views and recommendations of the World Marrow Donor Association regarding the need for donor and liability insurance for hematopoietic stem cell donor registries, and donor and collection centers.
The turnip sawfly, Athalia rosae Linnaeus, is a pest on cruciferous crops. Larvae sequester secondary plant compounds, namely glucosinolates, in their haemolymph. When attacked, their integument is easily disrupted and a droplet of haemolymph is exuded ('easy bleeding'). This has been shown to be an effective, chemical-based, defence against invertebrate predators. The efficiency of this proposed defence was tested against a vertebrate predator, using groups of the iguanid lizard Anolis carolinensis Voigt as a model predator. Caterpillars of Pieris rapae Linnaeus and Pieris brassicae Linnaeus served as control prey species that do not sequester glucosinolates. Lizards attacked far fewer sawfly larvae than pierid caterpillars. Several of the sawfly larvae were rejected after an initial attack, demonstrating unpalatability to the lizards, while the Pieris larvae were not rejected. However, P. rapae larvae topically treated with extracts of haemolymph of A. rosae had no deterrent effect on the lizards and no avoidance learning occurred over a period of two weeks. Adult sawflies do not easy bleed but have glucosinolates carried over from the larval stage. Lizards attacked them at a higher rate than larvae and they were never rejected. The results suggest that for the defensive effectiveness of the pest sawfly species against vertebrates the chemical cue is not necessarily sufficient. Movement and colour may be important additional factors triggering the behaviour of vertebrate predators.
BACKGROUND: Amplification of 20q13 is a frequent chromosomal alteration in solid tumors and harbors a number of putative oncogenes (CAS/CSE1-L, NABC1, or Aurora2). Amplifications on 20q13 have been identified as an independent prognostic marker indicating worse survival in breast and ovarian cancer. However, little is known about the prognostic significance of 20q13 gains in sporadic colorectal cancers. The aim of this study was to correlate 20q13 gains in sporadic colorectal cancers with other known prognostic factors, tumor progression, and overall survival. METHODS: Nuclei were extracted from 146 paraffin-embedded colorectal cancers of different UICC stages and used for fluorescence in situ hybridization (FISH) with a directly labeled probe for 20q13.2 (VYSIS). Signals were counted in 120 nuclei per sample. 20q13 was considered gained when > or =40% of the nuclei showed 3 or more FISH signals. Statistical correlations were tested with log-rank tests and Kaplan-Meier survival curves. RESULTS: Signal numbers for 20q13.2 were gained in 78 cases (53%). Cases with gains on 20q13.2 showed worse outcome than cases without: the gain of 20q13.2 was an independent prognostic marker for overall survival (P=0.006) as well as tumor progression (P=0.012) in univariate and multivariate analyses. Gains on 20q13.2 did not correlate with tumor stage. However, there was a significant association between 20q13.2 gains and tumor location in the left-sided colon and an inverse correlation between histologic grade and 20q13.2 gains. CONCLUSION: These data indicate that gains on 20q13.2 correlate with faster tumor progression and worse patient survival independent from tumor size and lymph node involvement. Therefore, alterations on 20q13 are an important biological event in colorectal tumor progression with independent prognostic relevance.
The Tower of London (ToL) test is widely used for measuring planning and aspects of problem solving. The primary focus of this study was to asses the relationship among different measures on the ToL. A secondary purpose was to examine the putative relationship between intelligence and working memory with that of ToL performance. Analyses of the interrelation of several ToL parameters indicated that better ToL performance was associated with longer preplanning time and shorter movement execution time. Good performers showed a stronger increase in preplanning duration with task difficulty then intermediate or poor planners. Stepwise multiple regression analysis yield fluid intelligence as the only significant predictor of ToL performance. These result suggest that the Tower of London assesses predominantly planning and problem solving and could not be explained by other cognitive domains.
We study e(-)e(+) pair creation in the collision of a heavy nucleus with an intense x-ray laser, where the produced e(-) is simultaneously captured into the K shell of the projectile nucleus. The parameters of the colliding system are chosen such that the absorption of at least two photons from the laser wave is required in order to surmount the energy threshold of the reaction. Considering this fundamental nonlinear strong-field process for the first time, we estimate the total production rate as well as the angular and energetic distributions of the emitted positrons. According to our results, the process of nonlinear bound-free pair creation could become observable by the aid of the upcoming x-ray laser facilities.
Twofold stacked InGaAs/GaAs quantum dot (QD) layers are grown on GaAs(001) substrates patterned with square arrays of shallow holes. We study the surface morphology of the second InGaAs QD layer as a function of pattern periodicity. Comparing our experimental results with a realistic simulation of the strain energy density E(str) distribution, we find that the second InGaAs QD layer sensitively responds to the lateral strain-field interferences generated by the buried periodic QD array. This response includes the well-known formation of vertically aligned QDs but also the occurrence of QDs on satellite strain energy density minima. Our calculations show that base size and shape as well as lateral orientation of both QD types are predefined by the E(str) distribution on the underlying surface.
From 1990 to 1997, 113 eligible patients with classical osteosarcoma received neo-adjuvant chemotherapy consisting of high-dose methotrexate, cisplatin and doxorubicin. Good histological responders continued to receive the same therapy postoperatively, while poor responders received salvage therapy with an etoposide/ifosfamide combination. With a median follow-up of 83 months, the projected metastasis-free and overall survival rates at 5 years are 63 and 74%, respectively. Independent favourable prognostic factors for outcome were tumour volume < 190 ml, 24-h serum methotrexate > 4.5 microM and female gender. The etoposide/ifosfamide replacement combination did not improve outcome in the poor histological responders. In conclusion, this intensive multi-agent chemotherapy results in > 70% of patients with classical osteosarcoma surviving for 5 years. The data obtained from this non-randomised study do not support discontinuation and exchange of all drugs used preoperatively in histological poor responders. As observed in previous Scandinavian osteosarcoma studies, female gender appears to be a strong predictor of a favourable outcome.
Larvae of several tenthredinid sawfly species readily release droplets of haemolymph through their integument when attacked by predators. This defence mechanism via 'bleeding' is characterised by a low integument resistance and a high haemolymph deterrence. Both traits are variable, and negatively correlated among species. We sought to determine if such differences in the propensity to bleed also occur intraspecifically by studying the heritability of traits potentially associated with the bleeding phenomenon in the turnip sawfly Athalia rosae ruficornis Jakovlev (Hymenoptera: Tenthredinidae, Allantinae). For three European populations, heritabilities were estimated in the laboratory in a parent-offspring and a full-sib design for haemolymph deterrence (measured as concentration of sequestered glucosinolate), integument resistance, body mass of eonymph and adult, and developmental time. Within A. rosae, no significant negative phenotypic correlation was found between the two traits directly related to the defence mechanism: integument resistance and haemolymph deterrence. However, the significant heritabilities found for these traits in the full-sib analysis (0.39 and 0.35, respectively, for males in the Swiss population) show that the variation has a genetic component. While full-sib analysis revealed highly significant heritabilities for most traits in all the three populations, parent-offspring regression revealed little or no evidence of heritable variation. Effects of common environment for siblings and variation in the host-plant quality between insect generations are likely to be the main factors explaining these differences. A consequence of such host-plant variation in the wild might be that genetic variation of such chemical defensive traits is largely invisible to natural selection.
We report the cloning and characterization of the spermatogenesis associated 6 gene (Spata6) encoding a predicted protein of 488 amino acids. It exhibits similarity with the motor domain of kinesin related proteins and with the Caenorhabditis elegans neural calcium sensor protein (NCS-2). The gene encodes three mRNAs of approximately 2.6, approximately 1.8 and approximately 1.2 kb. The expression of the 2.6 kb mRNA is detected at low levels in testis, ovary, thymus and placenta, while the 1.8 and 1.2 kb transcripts are exclusively expressed in testis. The 1.8 and 1.2 kb transcripts are specifically expressed in haploid germ cells. Data from in situ hybridization experiments suggested that mRNA expression of Spata6 in spermatids is higher than in spermatocytes and spermatogonia. RT-PCR analysis and whole mount in situ hybridization demonstrate that the Spata6 transcript is expressed during embryonic development and is localized in neural tube, somites and limb buds of mouse embryo. The Spata6 gene consists of 15 exons ranging in size between 40 and 596 bp. The 2.6 and 1.8 kb transcripts have different 5' untranslated sequences but have the same translational initiation site and therefore may encode the same protein with a predicted molecular weight of 49.7 kDa. The 1.2 kb transcript is derived from a proximal promoter between exons 7 and 8, and contains a translation initiation codon AUG, which is in frame with initiator AUG codon of the 2.6 and 1.8 kb transcripts. Therefore, the 1.2 kb transcript may code for a truncated protein of 32 kDa. Western blot analysis with the antiserum raised against a synthetic peptide from the C-terminal of the deduced Spata6 protein detects only a single protein of 53 kDa in all tissues studied. The Spata6 gene was localized to chromosome 5, region q34-35 in the rat and to chromosome 1, region p32-35 in the human. In an effort to determine the function of Spata6, we inactivated the mouse gene in embryonic stem cells through homologous recombination. Although the heterozygous mutant cells were able to generate low coat colour chimeric mice, all chimeras did not transmit the targeted allele to their progeny suggesting that a high contribution of Spata6(+/-) cells lead to the lethality of the chimeric embryos.
Over 200 genes have been shown to be associated with infertility in mouse models. However, knockout mice reveal unexpected functional redundancy of some germ cell expressed genes. Single null mutations in mouse genes encoding four male germ cell proteins, transition protein 2 (Tnp2), proacrosin (Acr), histone H1.1 (H1.1), histone H1t (H1t) and sperm mitochondria-associated cysteine-rich protein (Smcp) have been generated and analysed. Tnp2 is believed to participate in the removal of the nuclear histones and initial condensation of the spermatid nucleus. Proacrosin is an acrosomal protease synthesized as a proenzyme and activated into acrosin during the acrosome reaction. The linker histone subtype H1.1 belongs to the group of main-type histones and is synthesized in somatic tissues as well as in germ cells during the S-phase of the cell cycle. The histone gene Hist1h1t is expressed exclusively in spermatocytes and may have a function in establishing an open chromatin structure for the replacement of histones by transition proteins and protamines. Sperm mitochondria-associated cysteine-rich protein (Smcp) is a major structural element of the mitochondria in the midpiece of the sperm tail. Male mutant mice lacking any of these proteins show no apparent defects in spermatogenesis or fertility. To examine the synergistic effects of these proteins in spermatogenesis and during fertilization four lines of double knockout mice Hist1h1a/Mcsp, Hist1h1t/Mcsp, Tnp2/Mcsp and Acr/Mcsp were established. It was found that even when knockout mice are heterozygous for one allele (-/+) and homozygous for the other allele (-/-), mice were subfertile. Homozygous double knockout mice of all four lines are nearly infertile. However, in the four homozygous double knockout mouse lines, different characteristic abnormalities are prominently manifested: In Hist1h1a-/-/Mcsp-/- the migration of spermatozoa is disturbed in female genital tract, in Hist1h1t-/-/Mcsp-/- spermatozoa show morphological head abnormalities, in Tnp2-/-/Mcsp-/- the motility of sperm is affected, and in Acr-/-/Mcsp-/- the sperm-oocyte interaction is impaired. These findings indicate strongly that male germ cell expressed genes have synergistic effects on male fertility.
The involvement of ceramide signaling in tumor necrosis factor alpha (TNFalpha) mediated nuclear transcription factor kappa B (NF-kappaB) activation was studied. The cell response modifier ceramide has been shown to modulate apoptosis, cell differentiation and cell proliferation in different cell populations. Sphingomyelin hydrolysis is one pathway generating intracellular ceramide increase. Previously, we could show that TNFalpha induces a ceramide increase in primary human keratinocytes and HaCaT keratinocytes and consequently apoptosis was initiated. It is well known that TNFalpha activates the transcription factor NF-kappaB, but there have been controversial reports on the role of ceramide in TNFalpha-mediated NF-kappaB activation. Here we show by different lines of experimental evidence that TNFalpha is a strong inducer of NF-kappaB in both cell types, whereas C2-ceramide failed to activate NF-kappaB in HaCaT keratinocytes in contrast to primary keratinocytes.
This study was designed to evaluate the impact of circulatory arrest on renal function in open-heart surgery on infants. Renal function was described by diuresis, urine/plasma creatinine ratio, creatinine clearance, urinary albumin, and N-acetyl-beta-D-glucosaminidase measurements. Seven patients who underwent circulatory arrest (group 1) were compared with 37 patients operated on with cardiopulmonary bypass without circulatory arrest (group 2). In group 1, bypass time was 164 minutes and the lowest body temperature was 25.6 degrees C (median), compared with 106 minutes and 31.3 degrees C in group 2 (p < 0.05). Although diuresis and creatinine clearance revealed no differences between the groups, urine measurements, which had normal values before cardiopulmonary bypass, increased during reperfusion to 58.6 (range 16.2-75.5) mg gCrea(-1) albumin and to 14.8 (range 1.6-21.8) U gCrea(-1) N-acetyl-beta-D-glucosaminidase in group 1, compared with 8.1 (range 0-127.7) mg gCrea(-1) and 1.9 (range 0-47.8) U gCrea(-1) in group 2 (p < 0.05). Thus, deep hypothermic circulatory arrest (DHCA) subjected the kidney to ischemia reperfusion injury. Although the findings are mild and do not indicate severe ischemic renal damage, potential renal damage by DHCA should be taken into account when planning surgical procedures for congenital heart disease patients with additional risks of acute renal failure.
AIMS: A prospective analysis to differentiate the angiographic appearance of pigment epithelial detachments (PED) in age-related macular degeneration (AMD) was performed. The aim was to verify if characteristics of polypoidal choroidal vasculopathy (PCV) can be observed in elderly patients with Central European background. PATIENTS AND METHODS: Fluorescein and indocyanine green angiography was performed in 101 consecutive patients (53-87 years, 63 females, 38 males) with clinical signs of PED and drusen. RESULTS: Different types of PED could be differentiated: PCV-associated PED in 14 patients (13.9%), vascularized PED in 72 patients (71.2%), and nonvascularized PED in 15 patients (14.9%). CONCLUSIONS: The clinical diagnosis of PED in AMD can be differentiated by angiography into PCV-associated PED, vascularized PED, and nonvascularized PED. This differentiation is important because PCV-associated PED may have a pathogenetic and genetic background other than age-related changes in Bruch's membrane. These patients also may share a natural course and treatment options different from PED in AMD.
After a snakebite by the Costa Rican bushmaster Lachesis stenophrys, a 64-year-old patient developed cardiovascular shock and coagulopathy. After intensive care and antivenom treatment, he was discharged after 4 days but had to be hospitalised again 3 days later because of abdominal pain and bowel obstruction. An emergency laparotomy revealed a necrotic ileum and caecum, and an obstruction of the superior mesenteric artery. Until now, this type of intestinal ischemic complication after a snakebite has not been reported in the literature. The effects of bushmaster venom are discussed.
Central core disease is a congenital myopathy with muscle weakness defined pathologically by the presence of extensive areas in muscle fibres that are devoid of oxidative enzyme activity. The gene responsible has been shown to be the ryanodine receptor 1 on chromosome 19q13 and mutations have now been identified in several patients. Some cases with the morphological defect remain molecularly undefined, particularly those studied before molecular studies were available. We have studied three families with congenital onset, each with a dominantly inherited mutation in a C-terminal exon of the ryanodine receptor 1. They illustrate the spectrum of pathology that can be observed in patients with the myopathic features of central core disease. We show that extensive fibrosis and fat may be present, type 1 fibre uniformity may occur in the absence of cores; cores may be central or peripheral, single or multiple; and that an appearance of multiple focal minicores might cause a diagnostic pathological dilemma. In addition, we show the value of immunocytochemistry in identifying cores, in particular the use of antibodies to desmin and gamma-filamin.
Various factors are influencing the Swiss health care system, and therefore, surgeons' actual and future profession. Initiated by the current president of the Swiss Society of Surgery, a group of eight young Swiss surgeons constituted the ad hoc committee "Chirurgie 2020". The goal was to develop several scenarios of the surgeon's professional situation in 20 years. The future direction of surgery will be markedly influenced by medical innovation, political and economic relationships between Switzerland and Europe. However, the development of health care costs represents the most powerful factor predicting all further changes. The current situation of today's surgeons is best characterised as "hamsters in the treadmill" who try to fulfill a multitude of diverging tasks causing major demotivation. In order to retain a leading role in the health care system, surgeons must take part in social and political activities. To provide an excellent curriculum, university and county hospitals must join together to form clinical and educational networks. A clearly defined and structured curriculum must be introduced by the Swiss Society of Surgery. From our current point of view, only everyone's strong personal commitment will help to find solutions and to improve the current and future situation. In particular, today's surgical residents must actively take part in the development of tomorrow's surgery.
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BACKGROUND: To evaluate the efficacy, safety and limitation of a new 6F-compatible nitinol stent (Dynalink(TM). MATERIAL AND METHODS: We treated 50 patients (17 women, 33 men, mean age 72 +/- 8 years) by implanting 80 Dynalink(TM)-stents into 75 vessels during a 6-month period. Target lesions were: iliac artery: 25, femoral artery: 31, popliteal artery: 16, femoro-popliteal bypass: 5, subclavian vein: 3. Preinterventional Rutherford classifications: Class 1 : 3 legs (5 %), class 2 : 27 legs (51 %), class 3 : 16 legs (31 %), class 4 : 2 legs (4 %), class 5 : 5 legs (9 %). 40 % stents each were implanted ipsilateral, 60 % cross-over. RESULTS: All interventions were successful regardless of a sometimes anatomically difficult access to the lesion. The device was characterised by a high flexibility and radial force and the stent did not shorten. COMPLICATIONS: One distal stent dislocation during placement occurred, no puncture site complication. The mean diameter stenosis was reduced from 91 +/- 10 % (75 - 100 %) to 4 +/- 8 % (0 - 30 %). The ankle-brachial index was improved from 0.46 +/- 0.22 to 0.75 +/- 0.23 (p < 0.001). Post-interventional Rutherford classifications: Class 0 : 43 legs (81 %), class 1 : 5 legs (4,5 %), class 5 : 5 legs (4,5 %). CONCLUSIONS: The new 6F-sheath compatible nitinol stent is characterised by a good flexibility, radial force, and a lack of shortening. By the reduction of the diameter of the device to 6F, the potential risk of a local bleeding complication may be reduced and 6F sealing devices will be usable. Disadvantages are the 0.018 inch guide-wire lumen and the limited stent sizes.