Search PubMed⌕ Search

Biomedical subjects

J Fischer

Publications and source records attributed to J Fischer.

At least 109 records · Page 6Linked to original sources
PubMed2000

Large Proper-Motion Infrared

We report the detection of proper motions in [Fe ii] 1.644 µm emission among the southeasternmost features in the Herbig-Haro object complex GGD 37. Imaging observations were made over a period of 5 yr, at epochs 1993.67, 1996.71, and 1998.68, that reveal proper-motion velocities of 400+/-200 km s-1 at GGD 37:W2 and 850+/-200 km s-1 at a newly identified object, designated GGD 37:RWPF 1. We believe the proper-motion velocity of GGD 37:RWPF 1 is the highest found to date for a Herbig-Haro object. The direction of GGD 37:RWPF 1's proper motion is almost due west, away from the nearby young stellar object complex in Cep A East. GGD 37:W2's direction of proper motion is north/northwest, which does not lead back to any of the compact objects in Cep A East.

Journal Article↗
PubMed2000

Clinical and genetic studies of 3 large, consanguineous, Algerian families with Mal de Meleda.

BACKGROUND: Mal de Meleda (MIM 248300), also referred to as keratosis palmoplantaris transgrediens of Siemens, is a rare autosomal recessive skin disorder with a prevalence in the general population of 1 in 100,000. The main clinical characteristics are transgressive palmoplantar keratoderma, hyperhidrosis, and perioral erythema, but there are also associated features such as brachydactyly, nail abnormalities, and lichenoid plaques. OBSERVATIONS: We studied the clinical and genetic characteristics of 3 large, consanguineous, Algerian families, including 14 affected individuals. Homozygosity mapping of the third family confirmed localization of the responsible gene to 8qter in all 3 families. CONCLUSIONS: Although some differences in phenotypic expression among subjects were noted, genetic analysis of the 3 families who shared a common ethnic background indicated that a single gene is responsible for mal de Meleda in this population.

Acitretin↗
PubMed2000

Differential regulation of microglial keratan sulfate immunoreactivity by proinflammatory cytokines and colony-stimulating factors.

Resident microglia of the rat CNS express a unique type of keratan sulfate immunoreactivity (KS-IR) that is lacking on peripheral monocytes/macrophages and associated with a so far unknown proteoglycan core protein. Microglial KS-IR is downregulated during T-cell-mediated autoimmune inflammation but largely preserved in degenerative lesion paradigms. This study addresses the role of cytokines and colony-stimulating factors in the regulation of microglial KS-IR. In vitro, ramified microglia in coculture with astrocytes, but not isolated microglia, constitutively expressed KS-IR under control conditions. In both culture paradigms, KS-IR was increased significantly by macrophage- (M-CSF) and granulocyte/macrophage colony-stimulating factors (GM-CSF), as well as tumor necrosis factor-alpha (TNF-alpha). By contrast, the Th1 cytokine interferon-gamma (IFN-gamma) downregulated KS-IR, both when applied alone or in combination with either GM-CSF, M-CSF, or TNF-alpha. In vivo, the intracerebroventricular administration of IFN-gamma, but not TNF-alpha, to healthy rats led to an almost complete disappearance of KS-IR from ramified brain microglia. Our data suggest that the expression of microglial KS-IR is under dominant negative control by the Th1 cell cytokine IFN-gamma and represent the first evidence of cytokine-dependent proteoglycan regulation in the CNS.

Animals↗
PubMed2000

Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two-dimensional electrophoresis.

A model system for studying chemoresistance in human melanoma cells (MeWo) has been established utilizing the four commonly used cytotoxic drugs vindesine, cisplatin, fotemustine and etoposide to yield stable drug-resistant sublines. We analyzed phenotypical differences between MeWo cells and their chemoresistant counterparts using two-dimensional electrophoresis. Proteins that were overexpressed in chemoresistant cell lines were purified and identified using matrix assisted laser desorption/ionization-time of flight - mass spectrometry (MALDI-TOF-MS) and microsequencing. Here we show that four proteins, namely the translationally controlled tumor protein, the human elongation factor 1-delta, tetratricopeptide repeat protein and the isoform 14-3-3-gamma of the 14-3-3-family are overexpressed in chemoresistant melanoma cell lines. The significance of these findings is now being verified using transfection experiments with the aim of developing more effective chemotherapy protocols.

Drug Resistance, Neoplasm↗
PubMed2000

Syringe size and flow rate affect drug delivery from syringe pumps.

PURPOSE: To evaluate the effect of syringe size and infusion rate on drug delivery after vertical displacement of syringe pumps. METHODS: Four syringes (10 ml, 20 ml, 30 ml, 50 ml) were studied at three infusion speeds (2 ml x hr(-1), 1 ml x hr(-1) and 0.5 ml x hr(-1)). Fluid delivery was measured gravimetrically using an electronic balance. Aspiration volume (amount of fluid retracted into the syringe-infusion line assembly) and zero-drug delivery time (time between the lowering of the syringe pump and reattainment of the initial weight) were determined after lowering the syringe pump 130 cm or 50 cm. Then, infusion bolus was measured after elevating the pump to its initial position. Syringe compliance was calculated from the occlusion release bolus at an occlusion pressure of 300 mmHg. RESULTS: Zero-drug delivery time, aspiration volume and infusion bolus increased with syringe size (P < 0.0001). At 0.5 ml x hr(-1), a zero-drug delivery time of 29.7 +/- 0.6 min was recorded for the 50 ml syringe and 5.5 +/- 0.15 min for the 10 ml syringe. As infusion rates increased, zero-drug delivery times decreased following a 1/x ratio. Zero-drug delivery time highly correlated with calculated syringe compliance (Pearson's r = 0.97, P < 0.001), which was closely related to syringe plunger area (R2 = 0.93, P < 0.001). CONCLUSIONS: Vertical displacement of syringe pumps causes flow irregularities which correlate directly with syringe size and indirectly with infusion rate. Extreme vertical maneuvering of syringe pumps should be avoided. Infusion rates > or = 1 ml x hr(-1) and low-compliant, small syringes are recommended when highly concentrated drugs are administered.

Humans↗
PubMed2000

[The effect of air within the infusion syringe on drug delivery of syringe pump infusion systems] .

Application of highly concentrated short-acting vasoactive drugs in the critically ill patient requires precisely working syringe pump systems for continuous intravenous drug delivery. We performed a bench study to investigate the consequences of small amounts of air entrapped within a 50-ml infusion syringe. In particular we studied the effect of entrapped air on drug delivery after moderate vertical displacement of the pump by 50 cm (e.g. in preparation for transport) and the effect on the time required to trigger the pressure alarm after occlusion of the infusion line. At a flow rate of 1 ml/h, lowering the syringe pump prolonged the zero-drug delivery time from (mean +/- SD) 4.1 +/- 0.8 min (without air) to 6.2 +/- 0.9 (with 1 ml air) and to 13.1 +/- 0.9 min (with 2 ml of air, p < 0.001 for all comparisons). Entrapping of 2 ml of air within the syringe resulted in a 2.6-fold prolongation of the occlusion alarm time after accidental occlusion of the infusion line and a 3-fold increase of the resulting infusion bolus after occlusion. Enclosed air within infusion syringes considerably affects the syringe compliance. It increases the susceptibility of constant drug delivery to vertical displacement of syringe pumps and impairs the occlusion alarm function. Therefore, any air in syringe of infusion pump systems should be carefully removed. To avoid infusion boluses of short-acting vasoactive drugs after accidental occlusions, the occluded infusion line should be released to ambient pressure first.

Air↗
PubMed2000

Improving the processing of high-gold metal-ceramic frameworks by a pre-firing heat treatment.

OBJECTIVES: High-gold metal-ceramic alloys are difficult to elaborate due to their soft surface. Overlappings after grinding cause porosities at the metal-ceramic interface. Poor mechanical strength at high temperatures leads to thermal distortion of the framework. During firing hardness and high temperature strength of the alloy improve, thus improving processing. Therefore the question arises if by a pre-firing heat treatment hardening can be anticipated without affecting the mechanical strength after firing. METHODS: Four commercially available alloys were investigated with regard to hardness, thermal distortion, proof stress, and grain growth in the as-cast state, after a pre-firing heat treatment at 950 degrees C for 10 min, after a complete firing cycle and after a combination of both heat treatments. Hardness was measured as HV5/30, thermal distortion by means of a three point bending test and proof stress according to ISO 9693: 1991. The results were compared by means of Student's t-test (p < 0.05). RESULTS: For all alloys hardness, resistance to thermal distortion, and proof stress significantly increased after the pre-firing heat treatment compared to the as-cast state. When a pre-firing heat treatment was performed before the complete firing cycle, hardness may slightly drop, but proof stress and resistance to thermal distortion remained at least constant or even improved, compared to the results obtained after a complete firing cycle. Grain growth due to the pre-firing heat treatment was not observed. SIGNIFICANCE: The results showed, that a heat treatment of high-gold frameworks performed directly after casting improves processing without affecting mechanical strength.

Ceramics↗
PubMed2000

Refined deletion mapping in sporadic breast cancer at chromosomal region 8p12-p21 and association with clinicopathological parameters.

We have further refined the loss of heterozygosity (LOH) pattern on the human chromosomal region 8p12-p21 using 15 well characterised microsatellite markers in a panel of 50 breast carcinomas. The allelic loss pattern of these tumours suggests the presence of five commonly deleted regions on 8p12-p21. The most commonly deleted region was located between markers D8S1734 and D81989, spanning a distance of approximately 3 cM and reaching 56% LOH at locus NEFL. LOH at 8p12-p21 was significantly correlated with large tumour size (T>5 cm). Patients with the age at diagnosis of breast cancer between 45 and 55 years showed significantly more LOH than patients older than 55 years or younger than 45 years. No correlation was observed between 8p12-p21 alterations and histological tumour type, grade and the presence of lymph node metastases.

Adult↗
PubMed2000

The families of papain- and legumain-like cysteine proteinases from embryonic axes and cotyledons of Vicia seeds: developmental patterns, intracellular localization and functions in globulin proteolysis.

Families of papain- and legumain-like cysteine proteinases (CPR) were found in Vicia seeds. cDNAs and antibodies were used to follow organ specificity and the developmental course of CPR-specific mRNAs and polypeptides. Four papain-like cysteine proteinases (CPR1, CPR2, proteinase A and CPR4) from vetch seeds (Vicia sativa L.) were analysed. CPR2 and its mRNA were already found in dry embryonic axes. CPR1 was only detected there during early germination. Both CPR1 and CPR2 strongly increased later during germination. In cotyledons, both CPR1 and CPR2 were only observed one to two days later than in the axis. Proteinase A was not found in axes. In cotyledons it could only be detected several days after seeds had germinated. CPR4 mRNA and polypeptide were already present in embryonic axes and cotyledons during seed maturation and decreased in both organs during germination. Purified CPR1, CPR2 and proteinase A exhibited partially different patterns of globulin degradation products in vitro. Although the cDNA-deduced amino acid sequence of the precursor of proteinase A has an N-terminal signal peptide, the enzyme was not found in vacuoles whereas the other papain-like CPRs showed vacuolar localization. Four different legumain-like cysteine proteinases (VsPB2, proteinase B, VnPB1 and VnPB2) of Vicia species were analysed. Proteinase B and VnPB1 mRNAs were detected in cotyledons and seedling organs after seeds had germinated. Proteinase B degraded globulins isolated from mature vetch seeds in vitro. VsPB2 and proteinase B are localized to protein bodies of maturing seeds and seedlings, respectively, of V. sativa. Like VsPB2 from V sativa, also VnPB2 of V. narbonensis corresponds to vacuolar processing enzymes (betaVPE). Based on these results different functions in molecular maturation and mobilization of storage proteins could be attributed to the various members of the CPR families.

Chemical Fractionation↗
PubMed2000

Successful treatment of relapsed CML after cord blood transplantation with donor leukocyte infusion IL-2 and IFNalpha.

A 3-year-old girl with BCR/ABL-positive CML relapsed after related HLA-identical cord blood transplantation. She was treated with three cycles of donor lymphocyte (DLI) infusion from her 15-month-old brother. Interferon alpha was added after the second DLI, whereas a trial of IL-2 had to be discontinued because of increasing immature myeloid cells in the blood smear. No signs of GVHD were observed, but she developed myelosuppression and needed one platelet and one red blood cell transfusion. She achieved a molecular remission after 6 months with transient molecular relapse followed by sustained remission for 15 months. Thus, DLI with or without interferon alpha might prove to be a promising treatment option with tolerable side-effects in relapsed CML after cord blood transplantation. Bone Marrow Transplantation (2000) 25, 219-222.

Blood Component Transfusion↗
PubMed2000

The effects of syringe plunger design on drug delivery during vertical displacement of syringe pumps.

Fluid delivery from four types of commercially available 50-ml syringes was measured using an electronic balance at an infusion rate of 1 ml.h(-1). Retrograde aspiration volume and zero-drug delivery time were recorded after lowering the syringe pump by 50 cm. Syringe compliance was calculated from the volume of bolus released after occlusion at 100 mmHg. Zero-drug delivery times differed significantly between syringes, ranging from [mean (SD)] 3.26 (0.40) min to 6.38 (0.56) min (F = 55.5, d.f. = 3/20, p < 0.0001). Syringe compliance correlated well with aspiration volume (Pearson r(2) = 0.92, p < 0.001) and zero-drug delivery time (r(2) = 0.90, p < 0.001). Syringe design affected the internal syringe compliance. All syringes were associated with potentially relevant zero-drug delivery times after moderate vertical displacement. To minimise this risk, vertical displacement of syringe pumps delivering highly vasoactive drugs should be avoided.

Compliance↗
PubMed2000

Deletions in the spinal muscular atrophy gene region in a newborn with neuropathy and extreme generalized muscular weakness.

A newborn presented with respiratory insufficiency requiring artificial ventilation, inability to swallow, lack of spontaneous movements including the facial muscles, and areflexia. Nerve conduction velocities were not recordable. Molecular analysis showed a homozygous deletion in the spinal muscular atrophy (SMN) gene region on chromosome 5q. Pathological and neuropathological examination revealed a normal number of anterior horn cells, hypomyelinated axons in peripheral nerves and some atrophy of skeletal muscle fibres in combination with sarcoplasmic glycogen accumulation. This observation illustrates that severe congenital neuropathy can result from deletions in the SMN gene.

Axons↗
PubMed2000

[Goal-oriented measurement of short-, medium- and long-term effects in pneumological rehabilitation].

UNLABELLED: Assessment of goal-oriented short-, mean-, and long-term effects in pneumological rehabilitation: Despite of increasing quality in rehabilitation, the amount of treatment in pneumological rehabilitation has decreased by 40% in the last few years. A typical mark of quality is determination of individual objectives to reach a goal of therapy. METHODS: In 566 patients (381 male, 185 female, mean age 47.0 year, body mass index 27.5 kg/m2) goals have been assessed by a questionnaire given at the beginning, the end, 6, and 12 months after rehabilitation. The effect size (ES) of single symptoms, defined as difference between initial and following score values, divided by their standard deviation was used as mild (ES < 0.4), mean (ES < 0.8), or strong (ES > = 0.8) effect. Only those patients were considered, who initially rated for "often" and "very often" in a single symptom. RESULTS: At the end of rehabilitation the effect size was strong in 22 of 24 symptoms, mainly nocturnal symptoms. After 12 months 9 symptoms still revealed strong, and 12 mean effect sizes. These mainly again concerned nocturnal symptoms as palpation of the heart, breathlessness, cough, sweating, and headache, but even diurnal tiredness, spontaneously falling asleep, and lack of concentration revealed ES > 0.8. Additionally in 46 patients, who were incapable for work in more than 6 weeks the year before rehabilitation, a reduction of 81 days off job was measured in the year after rehabilitation. DISCUSSION: The definition of aims of therapy is a mark of quality, and ES proves as a sensitive instrument of assessment, giving remarkable effects even one year after medical rehabilitation.

Female↗
PubMed2000

Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity.

Autosomal recessive ichthyosis (ARI) includes a heterogeneous group of disorders of keratinization characterized by desquamation over the whole body. Two forms largely limited to the skin have been defined: lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). A first gene for LI, transglutaminase TGM1, has been identified on chromosome 14, and a second one has been localized on chromosome 2. In a genomewide scan of nine large consanguineous families, using homozygosity mapping, two new loci for ARI were found, one for a lamellar form in a 6-cM interval on chromosome 19 and a second for an erythrodermic form in a 7.7-cM interval on chromosome 3. Linkage to one of the four loci could be demonstrated in more than half of 51 consanguineous families, most of them from the Mediterranean basin. All four loci could be excluded in the others, implying further genetic heterogeneity in this disorder. Multipoint linkage analysis gave maximal LOD scores of 11.25 at locus D19S566 and 8.53 at locus D3S3564.

Chromosome Mapping↗
PubMed2000

Elucidation of the genetic basis of the common 'intermediate metabolizer' phenotype for drug oxidation by CYP2D6.

A subgroup of 10-15% of Caucasians are termed phenotypical 'intermediate metabolizers' of drug substrates of CYP2D6 because they have severely impaired yet residual in-vivo function of this cytochrome P450. Genotyping based on the currently known CYP2D6 alleles does not predict this phenotype satisfactorily. A systematic sequencing strategy through 1.6 kb of the CYP2D6 5'-flanking sequence revealed six mutations of which three were exclusively associated with the functional CYP2D6*2 allele (-1496 C to G; -652 C to T; and -590 G to A), two were associated with the nonfunctional *4 and with the functional *10-alleles (-1338 C to T and -912 G to A) and one (-1147 A to G) was seen in all *2, *4 and *10-alleles investigated. The -1496 C to G mutation was found to be polymorphic within CYP2D6*2 alleles. In a family study, the wild-type CYP2D6 *2[-1496 C] and the novel variant [-1496 G] allele co-segregated with lower and higher CYP2D6 in-vivo function, respectively, as shown by phenotyping using sparteine as probe drug. In a representative population sample selected for genotypes comprising one CYP2D6*2 and one non-functional allele, the median urinary metabolic ratio (MRs) for sparteine oxidation was 4.4-fold reduced in individuals with the variant allele (*2[-1496 G], MRs = 0.53, n = 27) compared with individuals lacking the mutation (*2[-1496 C], MRs = 2.33, n = 12; P < 0.0001). The mutation -1496 C to G has an estimated frequency of approximately 20% in the general population and allows establishment of a genotype for the identification of over 60% of intermediate metabolizers in Caucasian populations.

Base Sequence↗
PubMed2000

Impact of infusion line compliance on syringe pump performance.

To determine the impact of infusion line compliance on the time to occlusion alarm (occlusion time) and the size of the subsequent occlusion release bolus, we studied three different infusion lines in combination with a 50-ml and 10-ml syringe. The mean occlusion time of the 50-ml syringe amounted to 20.3 +/- 0.28 min and increased to 26.2 +/- 0.19 min with the infusion with the infusion line yeielding the largest compliance (P<0.0001). The mean occlusion time of the 10-ml syringe was 2.5 +/- 0.75 min and showed a 2.7-fold variation with the three infusion lines (2.6+/-0.08, 5.6 +/- 0.28 and 6.9 +/- 0.35 min, respectively; P<0.0001). Occlusion times correlated strongly to be calculated estimated compliance of the syringe-infusion line assembly (Pearson's r=0.998, P<0.0001). Infusion line compliance has an important impact on time to occlusion, particularly when using small, low compliant infusion pump syringes.

Compliance↗
PubMed2000

Factors affecting late fixture loss and marginal bone loss around teeth and dental implants.

BACKGROUND: The predictability and high success rate of implant treatment have averted attention from factors affecting fixture loss and bone loss around implants. PURPOSE: The goal of this study was to retrospectively evaluate late fixture loss and marginal bone loss around implants that have been in function for 5 years and to relate these findings to bone loss in the natural dentition. MATERIALS AND METHODS: One hundred and forty-three consecutively treated patients who had received an implant-anchored fixed prosthesis and completed a 5-year follow-up were selected. Intraoral and panoramic radiographs were used to assess bone loss. RESULTS: The bone loss was greater around remaining implants in patients who had lost implants after loading. No correlation was found between bone loss around implants and that around teeth. Only 2% of the fixtures were lost during 5 years of functional load. Most fixtures losses occurred in the edentulous maxilla. Seven of the nine patients who lost fixtures were smokers. CONCLUSION: These findings show that patients who lost implants also lost more bone around the remaining implants. There was no correlation between bone loss around implants and that around teeth, indicating that different interacting mechanisms are involved.

Aged↗