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Biomedical subjects

J Fuchs

Publications and source records attributed to J Fuchs.

At least 73 records · Page 4Linked to original sources

Modification of spatial and temporal gains of stimulated brillouin and raman scattering by polarization smoothing

Significant reductions of stimulated Brillouin (SBS) and Raman (SRS) scattering are measured by adding polarization smoothing (PS) to a random phase plate smoothed beam. The associated plasma waves, as measured by Thomson scattering, are spatially and temporally modified and reveal that the interplay between SBS and SRS has to be taken into account to understand the effect of the smoothing. The results also support the numerical simulations [S. Huller et al., Phys. Plasmas 5, 2706 (1998); R. Berger et al., Phys. Plasmas 6, 1043 (1999)] predicting a reduction of self-focusing with PS, resulting in a decrease of the maximum laser intensity and consequently of SBS and SRS gains.

Journal Article↗

First observation of ion acoustic waves produced by the langmuir decay instability

Thomson scattering measurements are presented which demonstrate conclusively the occurrence of the Langmuir decay instability (LDI) in a laser-produced plasma experiment. Both products of the instability, the ion acoustic wave and the electron plasma wave, were simultaneously observed and identified with their spectral characteristics. The secondary decay of the LDI-generated electron plasma wave, into another Langmuir wave and an ion acoustic wave, has been observed for the first time. The connection with growth and saturation of the stimulated Raman instability is discussed.

Journal Article↗

Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation.

Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, a dominantly inherited disorder of connective tissue that primarily involves the cardiovascular, ocular, and skeletal systems. There is a remarkable degree of variability both within and between families with Marfan syndrome, and FBN1 mutations have also been found in a range of other related connective tissue disorders collectively termed type-1 fibrillinopathies. FBN1 mutations have been found in almost all of the 65 exons of the FBN1 gene and for the most part have been unique to one affected patient or family. Aside from the "hot spots" for the neonatal Marfan syndrome in exons 24-27 and 31-32, genotype-phenotype correlations have been slow to emerge. Here we present the results of temperature-gradient gel electrophoresis analysis of FBN1 exons 59-65. Six mutations were identified, only one of which had been previously reported. Two of the six mutations were found in patients with mild phenotypes. Taken together with other published reports, our results suggest that a sizable subset (ca. 40%) of mutations in this region is associated with mild phenotypes characterized by the lack of significant aortic pathology, compared with about 7% in the rest of the gene. In two cases, mutations affecting analogous positions within one of the 43 cbEGF modules of FBN1 are associated with mild phenotypes when found in one of the 6 C-terminal modules (encoded by exons 59-63), but are associated with classic or severe phenotypes when found in cbEGF modules elsewhere in the gene.

Adolescent↗

Conformal boundary conditions and three-dimensional topological field theory

We present a general construction of all correlation functions of a two-dimensional rational conformal field theory, for an arbitrary number of bulk and boundary fields and arbitrary topologies. The correlators are expressed in terms of Wilson graphs in a certain three-manifold, the connecting manifold. The amplitudes constructed this way can be shown to be modular invariant and to obey the correct factorization rules.

Journal Article↗

Genotoxic potential of porphyrin type photosensitizers with particular emphasis on 5-aminolevulinic acid: implications for clinical photodynamic therapy.

Photodynamic therapy (PDT) uses exogenously administered photosensitizers activated by light to induce cell death or modulation of immunological cascades, presumably via formation of reactive oxygen species (ROS). 5-Aminolevulinic acid (ALA) mediated photosensitization is increasingly used for the treatment of nonmelanoma skin cancer and other indications including benign skin disorders. Long-term side effects of this investigational modality are presently unknown. Just as tumor treatments such as ionizing radiation and chemotherapy can cause secondary tumor induction, PDT may potentially have a carcinogenic risk. Evaluation of the biological effects of ALA in absence of activating light and analysis of the mechanism of ALA-PDT and porphyrin-type photosensitizers mediated photosensitization indicate that this therapy has a pro-oxidant and genotoxic potential. However, porphyrin type molecules also possess antioxidant and antimutagenic properties. ALA-PDT delays photocarcinogenesis in mice, and topical ALA alone does not increase skin cancer incidence in these animals. Patients with increased tissue levels of ALA have an increased incidence of internal carcinoma, however, it is not clear whether this relationship is casual or causal. There is no evidence indicating higher rates of skin cancer in patients with photosensitivity diseases due to presence of high protoporphyrin IX (PP) levels in skin. Overall, the presently available data indicate that the risk for secondary skin carcinoma after topical ALA-PDT seems to be low, but further studies must be carried out to evaluate the carcinogenic risk of ALA-PDT in conditions predisposed to skin cancer.

Aminolevulinic Acid↗

Hepatocyte growth-factor-scatter factor can stimulate post-operative tumor-cell proliferation in childhood hepatoblastoma.

Rapid growth of residual tumor after partial hepatectomy has been observed during the period of liver regeneration in children with malignant embryonal hepatoblastoma. The aim of this study was to elucidate the role of hepatocyte growth-factor-scatter factor (HGF-SF) in this phenomenon. Markedly increased serum levels of HGF-SF up to 15 ng/ml were found in 13/18 patients after liver resection and in 6/16 patients with regressive tumors after chemotherapy, in comparison with 15 patients with non-pre-treated hepatoblastoma and 20 healthy children of the same age group. In the tumors, epithelial tumor cells highly expressed the HGF-SF receptor c-met, as shown by immunohistochemistry and m-RNA RT-PCR. The hepatoblastoma cell lines HepT1, HepT3 and HUH6 reacted with significantly increased proliferation to rhHGF-SF in these concentrations (1-15 ng/ml). In the tumors, HGF-SF was found to be expressed in the stromal fibroblasts. In culture, hepatoblastoma cells (HepT3, HUH6) stimulated secretion of the factor by human fibroblasts, indicating the paracrine fashion of intratumoral HGF-SF production. Cultured hepatoblastoma cells ceased to proliferate at 20-50 ng/ml HGF-SF, and they underwent cell death at >/=100 ng/ml. In contrast, the hepatocellular-carcinoma cell line HepG2 decreased growth under HGF-SF in a dose-dependent manner. We conclude that post-operatively secreted and intratumorally produced HGF-SF can function as a growth factor for hepatoblastoma, while the same agent has a cytostatic effect in unphysiologically high concentrations.

Cell Division↗

[Surgical specialty department in the world wide web. Tribute to contemporary life style or information network?].

An increasing number of surgical departments is creating its own home-page in the World Wide Web (WWW). We investigated 184 presentations concerning their quality in content and technical realization. Our research revealed that most presentations regard patients as their main target group in order to meet the patients' demand for information and transparency. However, universities are especially concentrating on scientific development and neglecting the patients. Only a few presentations contain means for web-based training. In general, technical realization seems to be much better than the content itself. As patients tend to appear as customers who will choose the hospital they feel comfortable with, every clinical department that is a competitor should create a communication and information base for their customers. Thus, they will be able to keep in touch, present their treatment types and to enable patients to compare a multitude of surgical departments. The usefulness for colleagues or cooperating institutions must be improved. The WWW has become an important center of information in surgery.

Germany↗

[Extended liver resection in small children under circulatory arrest and "low-flow" cardiopulmonary bypass].

In order to perform resections of tumors at critical sites in the liver in young children, liver resections in cardiac arrest and deep hypothermia under cardiopulmonary bypass have been developed. We report our experience with liver resection under cardiopulmonary bypass in three children with hepatoblastoma. In the first child the operation was performed under cardiac arrest and, the other two children were operated on under "low flow" conditions. The periods under cardiopulmonary bypass circulation were well tolerated. Extended right liver resections with vascular reconstructions were performed. The postoperative increase of liver enzymes was moderate. The increase in GOT was between 100 and 200 U/l. In spite of the extended tumor growth, reasonable long-term results were achieved by resection in combination with chemotherapy. One child has been living 8 years and another 10 months without tumor recurrence. The third child died due to sepsis during adjuvant chemotherapy, after she had recovered well from liver resection.

Age Factors↗

Congenital adrenal hyperplasia associated with maternal pregnancy luteoma and the Antley-Bixler syndrome.

The authors report on a child with indifferent external genitalia consisting of severe micropenis with penile urethra leading to the tip of the glans and bilateral cryptorchidism. Diagnostic workup findings showed a female karyotype, homozygous 21-hydroxylase deficiency, and excessive testosterone exposure prenatally as a consequence of maternal pregnancy luteoma, altogether causing this unusual phenotype. In addition, the girl suffered from skeletal anomalies consistent with the diagnosis of Antley-Bixler syndrome. Our case shows that, although the association of congenital adrenal hyperplasia with other syndromes is rare, and even if other possible reasons for in utero virilization are present, complete diagnostic workup including karyotyping and hormonal status should be done in all patients with ambiguous genitalia, especially in cases of an unusual phenotype. The authors report on the diagnostic procedures and discuss the surgical approach in this particular case, never described before in the literature.

Abnormalities, Multiple↗

Post-transplant epididymitis and orchitis following Listeria monocytogenes septicaemia.

We report the occurrence of epididymitis and orchitis 1 week after the onset of Listeriosis in an 11-month-old boy receiving an orthotopic liver transplantation for biliary atresia. Immunologic implications of Listeria monocytogenes-induced testicular inflammation are discussed, and the potential role of immunosuppression with tacrolimus is also discussed.

Biliary Atresia↗

Cohesin ensures bipolar attachment of microtubules to sister centromeres and resists their precocious separation.

The multisubunit protein complex cohesin is required to establish cohesion between sister chromatids during S phase and to maintain it during G2 and M phases. Cohesin is essential for mitosis, and even partial defects cause very high rates of chromosome loss. In budding yeast, cohesin associates with specific sites which are distributed along the entire length of a chromosome but are more dense in the vicinity of the centromere. Real-time imaging of individual centromeres tagged with green fluorescent protein suggests that cohesin bound to centromeres is important for bipolar attachment to microtubules. This cohesin is, however, incapable of resisting the consequent force, which leads to sister centromere splitting and chromosome stretching. Meanwhile, cohesin bound to sequences flanking the centromeres prevents sister chromatids from completely unzipping and is required to pull back together sister centromeres that have already split. Cohesin therefore has a central role in generating a dynamic tension between microtubules and sister chromatid cohesion at centromeres, which lasts until chromosome segregation is finally promoted by separin-dependent cleavage of the cohesin subunit Scc1p.

Anaphase↗

Electron paramagnetic resonance spectroscopy for the investigation of the fluidity of human spermatozoa plasma membranes: a feasibility study.

Spermatozoal membrane perturbations may play a role in abnormal sperm functions. The objective of this investigation was to study the feasibility of measuring membrane fluidity of isolated human sperm by electron paramagnetic resonance (EPR) spectroscopy and to compare the order parameter of spectra obtained from the sperm plasma membranes of living sperm of fertile men with that of infertile men. Ejaculates of infertile and fertile men were washed and the spermatozoa labelled with 5-doxylstearic acid (5-DSA) and 16-doxylstearic-acid (16-DSA) (10 nmol per 4 x 10(7) sperm). The reporter group of 5-DSA partitions into the outer, hydrophilic part of the sperm plasma membrane, whereas that of 16-DSA is distributed in the inner hydrophobic part. The following results were obtained: (i) the lowest measurable cell count was 3.6 to 7 x 10(6) sperm and the interassay variance of the order-parameter s was < 1%; (ii) swim-up experiments revealed a higher fluidity of sperm with a higher percentage of motility; (iii) sperm membranes of infertile patients exhibited a decreased fluidity of their plasma membranes in the polar interface region of 5-DSA compared with volunteer semen donors and fertile men (P=0.002). No difference of membrane fluidity was found between the different groups using 16-DSA. It is concluded that EPR spectroscopy can be used to study the fluidity of sperm plasma membranes in fertile and infertile men.

Adult↗

Effective treatment of infantile choriocarcinoma in the liver with chemotherapy and surgical resection: a case report.

Infantile choriocarcinoma of the liver is an extremely rare entity, and outcome has been fatal in almost all published cases. To the authors' knowledge, this is the first report on successful treatment with preoperative chemotherapy. A 10-week-old girl presented with a large liver tumor, ovarian cysts, cardiac insufficiency, progressive hemolytic anemia, and thrombocytopenia. Ultrasound scan and magnetic resonance tomography (MRT) showed the typical pattern of infantile hemangioendothelioma. An emergency laparotomy was performed because of increasing cardiac insufficiency with ligation of the right hepatic artery, tumor biopsy, and subtotal resection of the ovarian cysts. Histology findings showed a choriocarcinoma of the liver and corpus luteum cysts of the ovaries. Serum beta-human chorionic gonadotropin (beta-HCG) was elevated to 1.600.00 U/L. Chemotherapy was initiated with etoposide and cisplatin. When x-ray examination showed development of lung metastases, chemotherapy was intensified with etoposide, cisplatin, and ifosfamid according to the German Study Group of Extracranial Nontesticular Malignant Germ Cell Tumors in Childhood and Adolescence (MAKEI-96). Serum beta-HCG levels decreased further, ultrasound examination showed significant tumor reduction, and pulmonal metastasis could no longer be found in chest x-rays. After the fourth course, a complete tumor resection was achieved by an extended right hemihepatectomy with adjuvant chemotherapy being administered after the operation. The child has been in complete remission for 22 months. The authors' experience shows that chemotherapy is effective for preoperative tumor reduction.

Choriocarcinoma↗

Assessing the prevalence of hand osteoarthritis in epidemiological studies. The reliability of a radiological hand scale.

OBJECTIVE: The hands are often involved in the osteoarthritic disease process. A radiological grading scale is presented, derived from a published atlas, to assess the prevalence of hand osteoarthritis (OA) involvement in clinical and epidemiological studies and its reproducibility is studied. METHODS: This hand scale is based on the radiological feature "joint space narrowing", which represents the macromorphological process of cartilage loss. Osteophytes and sclerosis are less important unless seen in conjuction with joint space narrowing. Nine individual joints per hand (four proximal interphalangeal joints (PIP), four distal interphalangeal joints (DIP), first carpometacarpal joint (CMC-1)) are scored dichotomously for the presence of OA. To save time and to increase reliability a severity grading of radiological features is not performed. To determine inter-rater and intra-rater reliability of the individual joints and the presence of OA in two separate joint groups (>/= 2 PIP or DIP and at least one CMC-1, used to define "generalised OA" in the ongoing Ulm Osteoarthritis Study) 50 pairs of anteroposterior hand radiographs were read by two investigators twice within one month. The kappa coefficient was calculated to quantify the strength of associations. RESULTS: On average five minutes were needed to score one hand radiograph. Both raters were able to reproduce their own readings in all individual joints and for the presence of OA in two separate joint groups after one month. Reliability was highest for the PIP joints (kappa: 0.56-1. 00) it was slightly lower for the DIP joints (0.38-0.87), for the CMC-1 joints (0.58-0.69) and for OA in two separate joint groups (0. 54). The values for inter-rater agreement were good as well, kappa coefficients ranged from 0.52 to 0.92. CONCLUSION: This grading scale was shown to be reliable within and between readers for all the individual joints as well as for the presence of OA in two separate joint groups. Scoring a limited number of joints dichotomously makes this scale efficient and therefore useful for clinical and epidemiological trials, when dealing with large patient samples.

Aged↗

Centromere clustering is a major determinant of yeast interphase nuclear organization.

During interphase in the budding yeast, Saccharomyces cerevisiae, centromeres are clustered near one pole of the nucleus as a rosette with the spindle pole body at its hub. Opposite to the centromeric pole is the nucleolus. Chromosome arms extend outwards from the centromeric pole and are preferentially directed towards the opposite pole. Centromere clustering is reduced by the ndc10 mutation, which affects a kinetochore protein, and by the microtubule poison nocodazole. This suggests that clustering is actively maintained or enforced by the association of centromeres with microtubules throughout interphase. Unlike the Rabl-orientation known from many higher eukaryotes, centromere clustering in yeast is not only a relic of anaphase chromosome polarization, because it can be reconstituted without the passage of cells through anaphase. Within the rosette, homologous centromeres are not arranged in a particular order that would suggest somatic pairing or genome separation.

Anaphase↗

Induction of DNA single-strand breaks by 131I and 99mTc in human mononuclear blood cells in vitro and extrapolation to the in vivo situation.

The radionuclides (131)I and (99m)Tc are frequently used for therapy of benign and malignant thyroid disease ((131)I) and for diagnosis of thyroid and other diseases ((99m)Tc). However, the levels of DNA single-strand breaks (SSBs) induced in cells of patients after administration of (131)I and (99m)Tc are not known. In this study, we measured the number of SSBs per cell induced by (131)I and (99m)Tc in vitro, extrapolated the results to the clinical situation, and assessed their biological relevance by comparing levels of SSBs induced after therapeutic administration of (131)I and (99m)Tc to those induced by endogenous processes or by occupational exposure to genotoxic substances. A linear dose-response relationship between the radioactivity concentrations of (131)I and (99m)Tc and SSBs in human mononuclear blood cells (determined by alkaline elution) was obtained after incubation at 4 and 37 degrees C. At 4 degrees C, where almost no repair of SSBs takes place, (131)I and (99m)Tc induced 81 and 7 SSBs per cell per hour/(MBq/ml), respectively. At 37 degrees C, only 20 and 1.6 SSBs per cell per hour/(MBq/ml) were observed after incubation with (131)I and (99m)Tc. To estimate the induction of SSBs in vivo in cells of patients after administration of 3700 MBq (131)I (oral) or 60 MBq (99m)Tc (i.v.), the rates of induction of SSBs obtained in vitro were extrapolated to the concentrations of (131)I and (99m)Tc measured in blood of patients. The total number of SSBs (mean +/- standard deviation) accumulated after oral administration of 3700 MBq (131)I up to 70 h after administration was calculated as 200 +/- 59 SSBs/cell. After administration of 60 MBq (99m)Tc (i.v.), 0.032 +/- 0.009 SSBs per cell (total SSBs up to 2 h after administration) were cumulated. The induction of SSBs by endogenous processes (estimated 2,000 SSBs per cell per hour) and by occupational exposure to genotoxic substances (125-430 SSBs per cell) has been estimated in earlier studies. In conclusion, the frequency of SSBs induced by thyroid diagnosis with 60 MBq (99m)Tc is approximately 5 orders of magnitude smaller than the frequency of spontaneous SSBs and thus is most probably without biological relevance. Since the frequency of induction of SSBs by therapy with (131)I (3700 MBq) is about 6000-fold higher compared to thyroid diagnosis by (99m)Tc, its biological relevance is more difficult to assess. Nevertheless, the number of SSBs induced by therapy with (131)I is substantially lower than that induced by endogenous processes.

DNA Damage↗

Using ICD-10 for case groups.

The definition of German case groups now uses an adaptation of the ICD-10: ICD-10-SGBV. For the transformation of the existing ICD-9-based definition into the ICD-10-SGBV an ICD-9/ICD-10 conversion table was used. The derived raw definitions were manually refined in detail. Due to the transformation of the classification system, the number of definitions increased immensely, as the ICD-10 SGBV is by far more detailed than the formerly used ICD-9. In our opinion, ICD-10 SGBV is not ideal for the definition of case groups, because this classification system is designed to support statistics on morbidity and mortality, but definitions of case groups are oriented to cost factors. Therefore the definition of case groups should be based on a specially designed classification system or one should reassess the necessity of a parallel definition by codes of classifications as well as by text. In both alternatives the introduction of a detailed and systematic medical documentation with expressive terminology systems will offer the advantage of classifying patients into medical oriented classifications as well as case groups.

Diagnosis-Related Groups↗