Search PubMed⌕ Search

Biomedical subjects

P Fischer

Publications and source records attributed to P Fischer.

At least 73 records · Page 4Linked to original sources
PubMed2000

Multiplex FISH and three-dimensional DNA imaging with near infrared femtosecond laser pulses.

We report on a novel technology for multicolor gene and chromosome detection as well as for three-dimensional (3D) DNA imaging by multiphoton excitation of multiple FISH fluorophores and DNA stains. Near infrared femtosecond laser pulses at 770 nm were used to simultaneously excite the visible fluorescence of a wide range of FISH fluorophores, such as FITC, DAC, Cy3, Cy5, Cy5.5, rhodamine, spectrum aqua, spectrum green, spectrum orange, Jenfluor, and Texas red as well as of DNA/chromosome stains, for example Hoechst 33342, DAPI, SYBR green, propidium iodide, ethidium homodimer, and Giemsa. In addition to the advantage of using only one excitation wavelength for a variety of fluorophores, multiphoton excitation provided the intrinsic possibility of 3D fluorescence imaging. The technology has been used in human genetics for the diagnosis of numerical chromosome aberrations and microdeletions. In particular, multicolor 3D images of the intranuclear localization of FISH-labeled chromosome territories in interphase nuclei of amniotic fluid cells have been obtained. Using the high light penetration depth at 770 nm, optical sectioning of Hoechst 33342-labeled DNA within living culture cells and within tissue of living tumor-bearing mice was performed.

Adult↗
PubMed2000

Identification of a stress-responsive Onchocerca volvulus glutathione S-transferase (Ov-GST-3) by RT-PCR differential display.

The effects of oxidative insult on gene transcript levels in the filarial nematode Onchocerca volvulus were investigated using differential display RT-PCR. Oxidative stress was applied with the reagents paraquat, plumbagin and xanthine-xanthine oxidase. In all three cases, a cDNA fragment encoding a novel glutathione S-transferase (GST) resembling members of the theta-class was identified as upregulated (PQ29, PG112, XOD26). The subsequently isolated full-length cDNA harbors a 753-bp open reading frame encoding a GST with 268 amino acid residues and a predicted molecular mass of 31 kDa. This stress-responsive GST (Ov-GST-3) possesses only 14 and 21% sequence identity with the other O. volvulus GSTs (Ov-GST-1 and Ov-GST-2, respectively). Interestingly, Ov-GST-3 shares higher sequence identity with GSTs that are upregulated due to environmental stress. In order to confirm the specific upregulation of the Ov-GST-3 transcripts identified by differential display and to analyze the mRNA levels of the other Ov-GSTs (Ov-GST-1 and Ov-GST-2) under elevated stress conditions, a semi-quantitative polymerase chain reaction-enzyme-linked immunosorbent assay was performed. The Ov-GST-3 gene transcript level increased dramatically in response to xanthine-xanthine oxidase and to a lesser extent with paraquat and plumbagin. In contrast, Ov-GST-1 and Ov-GST-2 did not show any significant alterations in their steady-state mRNA levels in response to oxidative stress when examining the same mRNA samples. The present study clearly demonstrates that Ov-GST-3 is a critical enzyme in the defense against oxidative stress.

Amino Acid Sequence↗
PubMed2000

IVIG-bound IgG and IgM cloned by phage display from a healthy individual reveal the same restricted germ-line gene origin as in autoimmune thrombocytopenia.

Intravenous immunoglobulin preparations (IVIG) have shown positive effects in the treatment of immune defects and autoimmune diseases. It is not clear how IVIG interacts with the components of the immune system. To investigate this, we cloned previously a large number of phage displayed IgG Fab fragments derived from three patients with autoimmune thrombocytopenia (AITP) that were specifically bound by IVIG molecules. Many of these Fabs reacted with platelets. Sequencing revealed that the most frequently used germ-line gene segments of all IVIG-bound Fabs were identical to those observed for many other autoantibodies. Particularly, the loci 3-30 or 3-30/3-30. 5, 3-23 and 3r, 3l, and 2a2 represented the most abundant genes used for the heavy (VH) and light chain V region (VL), respectively. This suggested a specific interaction of IVIG molecules with B cells that present B cell receptors derived from these germ-line genes. In the current study we determined the genetic origin of IVIG-reactive IgG and IgM cloned from a healthy person. A favoured selection of antibodies derived from the same germ-line origins as in AITP was observed. Because 3-30 and 3-23 are the most frequently rearranged VH germ-line gene segments among human B cells, our results suggest that this favoured anti-idiotypic interaction may have an important role for the development and control of the normal B cell repertoire.

Adult↗
PubMed2000

[Para-limbic relaxing incisions for reduction of astigmatism within the scope of catarct surgery].

PURPOSE: Limbal relaxing incision (LRI) is an easy and safe procedure to reduce astigmatism. It should be clarified, whether the effect is discussed controversely, because the varying corneal diameter and consequently the varying LRI position was not considered. PATIENTS AND METHODS: 56 patients aged 76 +/- 9 years with preoperative astigmatism of 1.6 D (0.6 to 7.0 D) underwent an almost astigmatically neutral cataract procedure (3.2 mm temporal clear corneal phacoemulsification with foldable lens implantation) and received independently from the given corneal diameter limbus related relaxing incisions of 80 degrees length and 0.6 mm depth. We performed the paired LRI in 4.5 mm, 5 mm and 5.5 mm distance from the corneal center on the steeper meridian. RESULTS: 4.3 months postoperatively we observed an astigmatic reduction of -1.0 D (-0.1 to -3.2 D) following LRI with a 9 mm optical zone, LRI with 10 mm diameter led to an astigmatic reduction of -0.4 D (-0.1 to -2.9 D) and LRI with 11 mm diameter were followed by an astigmatic reduction of -0.3 D (+0.5 to -1.1 D). Undercorrections were more frequently observed in younger patients, overcorrections more in elderly people. CONCLUSION: The application of three different kinds of limbus related relaxing incisions, with 4.5, 5 and 5.5 mm distance from the corneal center or 9, 10 and 11 mm optical zone respectively, corresponds to the variable anatomic situation of the limbus, therefore leading to nearly predictable data and explaining the divergent results of previous reports. The nearer the LRI is applied to the corneal center, the stronger is the relaxing effect.

Aged↗
PubMed2000

[Peripapillary melanoma; 10-year follow-up].

In early stages choroidal peripapillary choroidal melanoma may be confused with a choroidal nevus or melanocytoma. CASE REPORT: A 41-year old female was diagnosed having a choroidal nevus in close proximity to the optic nerve head. Unfortunately the patient did not show up for annual review of this lesion. Ten years after the patient was examined for the second time. A massive increase in tumor size and prominence was noted including serous retinal detachment. Medical work up excluded any metastatic growth, and the globe was enucleated. Three years later, the patient is still healthy and there are no signs of metastatic spreading. HISTOLOGICAL WORK UP: Heavily pigmented peripapillary choroidal melanoma with fascicularly vasocentric proliferative structure, but no infiltration of the sclera or the lamina cribrosa of the optic nerve. The tumor cells were of midgrade size and some of the nucleoli were slightly enlarged. Mitosis and a syncytial structure were present. Immunohistochemically S-100 proteins, HMB 45 and NSE were found. The TNM classification was: ICD-O C 69.3; pT2, G1, S0, V0, pNx, pMx, microscopically RO. CONCLUSION: Pigmented juxtapapillary tumors resembling choroidal nevi require annual surveillance.

Adult↗
PubMed2000

Daily mortality and air pollution in The Netherlands.

We studied the association of daily mortality with short-term variations in the ambient concentrations of major gaseous pollutants and PM in the Netherlands. The magnitude of the association in the four major urban areas was compared with that in the remainder of the country. Daily cause-specific mortality counts, air quality, temperature, relative humidity, and influenza data were obtained from 1986 to 1994. The relationship between daily mortality and air pollution was modeled using Poisson regression analysis. We adjusted for potential confounding due to long-term and seasonal trends, influenza epidemics, ambient temperature and relative humidity, day of the week, and holidays, using generalized additive models. Influenza episodes were associated with increased mortality up to 3 weeks later. Daily mortality was significantly associated with the concentration of all air pollutants. An increase in the PM10 concentration by 100 micrograms/m3 was associated with a relative risk (RR) of 1.02 for total mortality. The largest RRs were found for pneumonia deaths. Ozone had the most consistent, independent association with mortality. Particulate air pollution (e.g., PM10, black smoke [BS]) was not more consistently associated with mortality than were the gaseous pollutants SO2 and NO2. Aerosol SO4(-2), NO3-, and BS were more consistently associated with total mortality than was PM10. The RRs for all pollutants were substantially larger in the summer months than in the winter months. The RR of total mortality for PM10 was 1.10 for the summer and 1.03 for the winter. There was no consistent difference between RRs in the four major urban areas and the more rural areas.

Adolescent↗
PubMed2000

Low birth weight and preterm delivery as risk factors for asthma and atopic dermatitis in young adult males.

Gestational factors have been hypothesized to play a role in the susceptibility to asthma and atopic dermatitis. We examined whether fetal growth was associated with asthma and atopic dermatitis separately in a population of 4,795 male conscripts born between 1973 and 1975 in Denmark. The prevalence of asthma was 4.7%. The prevalence odds ratio of asthma in conscripts with a birth weight below 2,501 g was 1.5 (95% confidence interval = 0.7-3.1) compared with conscripts with a birth weight of 3,001-3,500 g, adjusted for gestational age and potential confounders. The adjusted prevalence odds ratio among conscripts born before 34 gestational weeks was 0.8 (95% confidence interval = 0.3-2.0) compared with conscripts born at term. The prevalence of atopic dermatitis was 1.0%. The prevalence odds ratio of atopic dermatitis among those with a birth weight below 2,501 g was 3.0 (95% confidence interval = 0.8-11.9) compared with those whose birth weight was between 3,001 and 3,500 g. Men whose gestational age had been below 34 weeks had an adjusted prevalence odds ratio of 0.3 (95% confidence interval = 0.0-3.1). These findings indicate that fetal growth retardation rather than preterm delivery of male infants is the main gestational factor underlying the associations but does not explain the apparent increase over time of asthma or atopic diseases.

Adult↗
PubMed2000

Effect of home and hospital delivery on long-term cognitive function.

We examined the relation between place of birth and cognitive function in young adult life in a historical cohort study based upon birth data from the computerized Danish Medical Birth Registry and cognitive function as measured at time of drafting for military service in two Danish counties. The cohort included 4,296 Danish conscripts born between 1973 and 1976, 123 born at home and 4,173 born in hospital or at a birth clinic. Cognitive function was measured by the Boerge Prien test in men, 18 to 20 years of age. The highest possible score is 78. The mean Boerge Prien test score was 43.1 for conscripts born in specialized hospital departments, 2.4 higher for conscripts born in a birth clinic (95% confidence interval = 0.9-4.0), and 2.1 lower for conscripts born at home (95% confidence limits = -3.8 to -0.4) after adjusting for birth weight, length at birth, birth order, gestational age, maternal age, and marital and occupational status. Our findings raise the possibility that home birth can lead to lower cognitive function in adulthood; however, from our data we could not distinguish between planned and unplanned births at home.

Adult↗
PubMed2000

Occurrence of mirtazapine-induced delirium in organic brain disorder.

Mirtazapine is the first of a new class of antidepressants, the noradrenergic and specific serotonergic antidepressants. Its antidepressant effect appears to be related to its dual enhancement of both noradrenergic neurotransmission and serotonin 5-HT1 receptor-mediated serotonergic neurotransmission. Mirtazapine has demonstrated superior tolerability to the tricyclic antidepressants, primarily on account of its relative absence of anticholinergic, adrenergic and serotonin-related adverse effects. We observed mirtazapine-induced delirium in one organically depressed and two major depressed patients with subclinical brain disease. The appearance of hallucinations, psychomotoric agitation and cognitive changes after initiation of mirtazapine, and their prompt improvement after drug discontinuation, led to the impression that these were drug-induced phenomena. One possible hypothesis for the observed deliria is a central increase of norepinephrine after acute administration of mirtazapine. Subclinical brain disease might have favoured the occurrence of delirium in the three cases.

Aged↗
PubMed2000

Detection of DNA of nocturnally periodic Brugia malayi in night and day blood samples by a polymerase chain reaction-ELISA-based method using an internal control DNA.

An internal control was used in a polymerase chain reaction (PCR)-ELISA-based technique to detect the Hha I repeat of the filarial parasite Brugia malayi. A single microfilaria added to 200 microl of blood was reliably detected. The assay was evaluated on field samples from persons living in an area endemic for Anopheles-transmitted, nocturnally periodic B. malayi in central Sulawesi, Indonesia. Examination of night blood of 138 individuals for the presence of microfilariae by filtration revealed 44 microfilaria carriers. All microfilaria carriers were also positive in the PCR-ELISA and, in addition, 14 more samples were proven to contain parasite DNA. The sensitivity of both methods was compared on night and on day blood samples collected from 113 persons. Whereas 37 microfilaria carriers were identified by filtration of night blood, no microfilariae were observed in the corresponding day blood samples. The PCR-ELISA result was positive in all 37 night blood samples of microfilaria carriers and in an additional 13 night blood samples without microfilariae. Parasite DNA was detected in 31 day blood samples of microfilaria carriers and in 3 day blood samples of amicrofilaremic persons. Assuming a sensitivity of the PCR-ELISA on night blood of 100%, the sensitivity of night blood filtration is 74% and that of the PCR-ELISA on day blood is 68%. These data suggest that the described PCR-ELISA method is capable of detecting infections with nocturnally periodic B. malayi in day blood samples. Therefore, this method may facilitate both the identification of endemic areas and the monitoring of control programs.

Adult↗
PubMed2000

Application of a polymerase chain reaction-ELISA to detect Wuchereria bancrofti in pools of wild-caught Anopheles punctulatus in a filariasis control area in Papua New Guinea.

Chemotherapy-based eradication programs are aimed at stopping transmission of Wuchereria bancrofti by its obligatory mosquito vector. This study compares one year post-treatment W. bancrofti infection rates of Anopheles punctulatus, the main vector of lymphatic filariasis in Papua New Guinea, using traditional dissection techniques and a polymerase chain reaction (PCR)-based ELISA of a parasite-specific Ssp I repeat. A total of 633 mosquitoes in 35 batches were dissected. Six batches contained W. bancrofti-infected mosquitoes, giving a minimum infection rate of 0.9%. This value was not different than the actual infection rate, which was 9 (1.4%) of 633 mosquitoes (P = 0.48). The DNA was extracted from 47 pools containing a mean of 13.2 mosquitoes per pool. A total of 621 mosquitoes were processed for the PCR-ELISA, including 486 caught by human bait and 135 by light trap, which included both dead and live mosquitoes. Of 23 pools of alcohol-preserved human-bait mosquitoes, seven were positive by the PCR-ELISA, giving an infection rate identical to that obtained by dissection of individual mosquitoes (1.4%). The minimum infection rates for pools of light-trap mosquitoes found dead and alive were 2.7% (2 of 74) and 4.9% (3 of 61), respectively. These values did not differ from each other (P = 0.84), but the overall infection rate of light-trap mosquitoes was greater than that of mosquitoes captured by human bait (3.7% versus 1.4%; P = 0.09). These data indicate that the PCR-ELISA of a W. bancrofti Ssp I repeat using pools of mosquitoes is comparable to traditional dissection techniques for monitoring transmission intensity following introduction of mass chemotherapy. This approach may also be useful for rapid and cost-effective assessment of transmission in endemic areas where the frequency of overt lymphatic pathology is low.

Animals↗
PubMed2000

Expression of messenger RNA of the cardiac isoforms of troponin T and I in myopathic skeletal muscle.

In the absence of clinical signs, elevated values of the cardiac isoforms of troponin T (cTnT) and I (cTnI) can be found in the serum samples of some patients with skeletal muscle myopathies; the cause is unclear. We studied the messenger RNA (mRNA) expression of cTnT and cTnI in the skeletal muscles of 24 patients with histologically proven myopathies and in 18 patients in whom a myopathy could be excluded. For cTnT- and cTnI-mRNA determination, we designed specific primer pairs for nested polymerase chain reaction. After amplification, the products were digested with 2 restriction enzymes and visualized. We found cTnT mRNA in 7 skeletal muscle biopsy specimens (6 patients with Duchenne muscular dystrophy, 1 patient with a primary sarcoglycanopathy) and cTnI mRNA in 6 (5 with Duchenne muscular dystrophy, 1 patient with a histologically negative biopsy). The mRNA of the cardiac isoforms, cTnT and cTnI, is expressed in the skeletal muscles of patients with Duchenne muscular dystrophy, but also in some other myopathies. Further studies are needed to show whether the mRNA is translated into the protein, but serum levels of cTnT and cTnI in patients with Duchenne muscular dystrophy would seem to indicate this.

Biomarkers↗
PubMed1999

Correolide and derivatives are novel immunosuppressants blocking the lymphocyte Kv1.3 potassium channels.

The voltage-gated potassium channel, Kv1.3, is specifically expressed on human lymphocytes, where it controls membrane potential and calcium influx. Blockade of Kv1.3 channels by margatoxin was previously shown to prevent T cell activation and attenuate immune responses in vivo. In the present study, a triterpene natural product, correolide, was found to block Kv1.3 channels in human and miniswine T cells by electrophysiological characterization. T cell activation events, such as anti-CD3-induced calcium elevation, IL-2 production, and proliferation were inhibited by correolide in a dose-dependent manner. More potent analogs were evaluated for pharmacokinetic profiles and subsequently tested in a delayed-type hypersensitivity (DTH) response to tuberculin in the miniswine. Two compounds were dosed orally, iv, or im, and both compounds suppressed DTH responses, demonstrating that small molecule blockers of Kv1.3 channels can act as immunosuppressive agents in vivo. These studies establish correolide and its derivatives as novel immunosuppressants.

Animals↗
PubMed1999

PI3-kinase is involved in mitogenic signaling by the oncogenic receptor tyrosine kinase Xiphophorus melanoma receptor kinase in fish melanoma.

Overexpression of the mutationally activated receptor tyrosine kinase Xiphophorus melanoma receptor kinase (Xmrk) initiates formation of hereditary malignant melanoma in the fish Xiphophorus. In melanoma as well as in a melanoma-derived cell line (PSM) this receptor is highly activated resulting in constitutive Xmrk-mediated mitogenic signaling. In order to analyze mitogenic signaling triggered by Xmrk a possible involvement of phosphatidylinositol 3 (PI3)-kinase in Xmrk signal transduction was examined. Constitutive binding of the p85 adapter subunit of PI3-kinase to the Xmrk receptor was detected in PSM melanoma cells. Further analyses in BHK cells expressing a Xmrk chimera (HER-mrk) showed that p85 association with the intracellular part of Xmrk was dependent on autophosphorylation of the receptor. In vitro binding studies revealed that the interaction is mediated mainly through the N-terminal SH2 domain of p85 which directly binds to a sequence motif around phosphorylated Tyr-983 in the Xmrk carboxy-terminus. In accordance with recruitment of p85 by Xmrk in PSM cells, the PI3-kinase downstream target Akt was found to be highly phosphorylated on Ser-473, indicating efficient PI3-kinase signaling in melanoma cells. PI3-kinase activation was also detected in Xiphophorus melanoma. Moreover, malignant melanomas exhibited an increased level of PI3-kinase activity which was about three times higher than that in benign pigmented lesions. Inhibition of PI3-kinase activity in PSM melanoma cells by both Wortmannin and LY294002 blocked entry into S-phase. Together these data demonstrate that PI3-kinase is a substrate of the oncogenic Xmrk receptor and plays a significant role in mitogenic signaling of melanoma cells and the formation of malignant melanoma in Xiphophorus.

Amino Acid Sequence↗
PubMed1999

[Differential diagnosis in anorexia nervosa: glycogenosis II (the Pompe type)].

HISTORY AND ADMISSION FINDINGS: A 29-year-old woman had since early childhood been smaller and thinner than her contemporaries. Her weight was now 36.5 kg, height 158 cm. Anorexia nervosa being suspected she was to be admitted to a psychosomatic clinic. A few days before the date she developed respiratory failure which required mechanical ventilation for a month. Physical examination revealed markedly reduced musculature. INVESTIGATIONS: Muscle biopsy and fibroblast culture indicated acid maltase deficiency (glycogen storage disease Type II [Pompe's disease]). Lung functions were markedly reduced, blood gas analysis revealing global respiratory insufficiency. TREATMENT AND COURSE: Intermittent patient-controlled ventilation (at night by intermittent positive pressure ventilation) clearly improved both her general condition and blood gases. CONCLUSIONS: Acid maltase deficiency should be included as a possible cause of the differential diagnosis of anorexia nervosa. This diagnosis should strictly follow the criteria listed in ICD-10 (International Classification of Diseases), but also after exclusion of other causes.

Adult↗
PubMed1999

Birth weight and length as predictors for adult height.

Adult height has been found to be inversely associated with mortality. Recently, it has been suggested that growth in utero is linked with adult risk of several chronic diseases. The authors examined possible associations between birth weight, birth length, and adult height in young Danish men. They conducted the study in the fifth conscription district of Denmark including all the men born after January 1, 1973 who were residents in the study area during the period August 1, 1993 to July 31, 1994. The Danish Medical Birth Register contains information on all births in Denmark since January 1, 1973. Data on height from the Conscription Register were linked to the Danish Medical Birth Register in 4,300 conscripts examined. Nearly all Danish men have to register with the draft board around age 18 years of age where they undergo a physical examination. There was a strong positive association between birth weight and adult height; for subjects with birth weight < or = 2,500 g, mean height was 175.7 cm, while for those with birth weight > or = 4,501 g, mean height was 184.1 cm. A positive association was also found between birth length and adult height. For subjects with birth length < 47 cm, mean adult height was 175.2 cm, increasing to 184.3 cm at birth length > 56 cm. The associations between birth length and adult height persisted after adjustment for birth weight, gestational age, and other confounders, while the associations between birth weight and adult height almost disappeared when adjusting for birth length and the same confounders. Genetic and/or environmental factors operating both during the pre- and postnatal period may be responsible for the association between birth length and adult height.

Adolescent↗