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K Janssen

Publications and source records attributed to K Janssen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Activity of O6-methylguanine DNA methyltransferase in mononuclear blood cells of formaldehyde-exposed medical students.

A recent study reported that exposure of student embalmers in Cincinnati to high concentrations of formaldehyde (2 mg/m3) reduced the activity of the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT). Reduction in a DNA repair enzyme may strongly increase the cancer risk not only with respect to the repair-enzyme causing agent but with respect to all carcinogens causing lesions subject to repair by the enzyme in question. Thus, we examined whether formaldehyde exposure of 57 medical students during their anatomy course at two different Universities in Germany influenced MGMT activity in mononuclear blood cells. Mean formaldehyde exposure of 41 students was 0.2 +/- 0.05 mg/m3 for 6 h per week. MGMT activity was 133.2 +/- 14.9 fmol MGMT/10(6) cells before the beginning of the formaldehyde exposure, 131.1 +/- 15.8 fmol MGMT/10(6) cells after 50 days (P = 0.56) and 128.2 +/- 19.0 fmol MGMT/10(6) cells after 111 days of exposure (P = 0.92). Similarly, no significant influence of formaldehyde exposure was observed, when smoking habits, alcohol consumption, allergic disease and sex of students were considered. In addition no significant difference was obtained in MGMT activity between 16 students with mean formaldehyde exposure of 0.8 +/- 0.6 mg/m3 and students without formaldehyde exposure (n = 51; P = 0.37). In conclusion, exposure of the medical students in western Europe to formaldehyde did not decrease MGMT activity in mononuclear blood cells.

Adult↗
PubMed1999

Gene gun-mediated IL-12 gene therapy induces antitumor effects in the absence of toxicity: a direct comparison with systemic IL-12 protein therapy.

Using three murine tumor models, we compared the antitumor efficacy and certain physiological effects of an in vivo interleukin-12 (IL-12) gene therapy protocol and a systemic IL-12 protein therapy protocol. An IL-12 cDNA gene construct was administered in situ into skin tissue via gene gun delivery, and recombinant IL-12 protein was administered subcutaneously at a dose of 1 microgram/mouse/treatment. Both treatment regimes induced a comparable level of regression of established intradermal MethA sarcomas. In B16 melanoma and P815 mastocytoma models, antitumor efficacy of IL-12 protein therapy appeared to be slightly higher than that of IL-12 gene therapy; however, the protein therapy protocol in this comparative study resulted in a high level of mortality of mice. It was also demonstrated that IL-12 gene therapy, in contrast to the IL-12 protein therapy, was not associated with weight loss, splenomegaly, increased Ly6 antigen expression in the spleen, or visible signs of toxicity, such as fur ruffling and lethargy. Moreover, serum levels of interferon-gamma (IFN-gamma) induced in response to IL-12 gene therapy were 300-1000 times lower than those induced by the systemic IL-12 protein administration. Together, these results suggest that gene gunmediated in vivo delivery of IL-12 cDNA may be considered as a safer alternative to IL-12 protein therapy for certain human cancers.

Animals↗
PubMed1998

Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study.

Intake of dietary flavonols and flavones was inversely associated with risk for cardiovascular disease in several epidemiologic studies. This may have been due to effects on hemostasis because flavonoids have been reported to inhibit platelet aggregation in vitro. We indeed found that 2500 micromol/L of the flavonol quercetin and the flavone apigenin significantly inhibited collagen- and ADP-induced aggregation in platelet-rich plasma and washed platelets by approximately 80-97%. However, lower concentrations, such as might occur in vivo, had no effect. To test this in vivo we fed 18 healthy volunteers 220 g onions/d providing 114 mg quercetin/d, 5 g dried parsley/d providing 84 mg apigenin/d, or a placebo for 7 d each in a randomized crossover experiment with each treatment period lasting 2 wk. Onion consumption raised mean plasma quercetin concentrations to 1.5 micromol/L; plasma apigenin could not be measured. No significant effects of onions or parsley were found on platelet aggregation, thromboxane B2 production, factor VII, or other hemostatic variables. We conclude that the antiaggregatory effects of flavonoids seen in vitro are due to concentrations that cannot be attained in vivo. Effects of dietary flavonols and flavones on cardiovascular risk are possibly not mediated by hemostatic variables.

Adult↗
PubMed1997

Cytokine gene therapy of cancer using gene gun technology: superior antitumor activity of interleukin-12.

We compared the antitumor effect of several transgene expression plasmids encoding specific cytokines, including interleukin-2 (IL-2), IL-4, IL-6, IL-12, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF), following gene gun-mediated DNA delivery into the epidermis overlying an established intradermal murine tumor. IL-12 gene therapy was much more effective than treatment with any other tested cytokine gene for induction of tumor regression. Strong activation of antitumor immunity in response to IL-12 gene therapy was evidenced by an augmented CD8+ T cell-mediated cytolytic activity in the draining lymph nodes of tumor-bearing mice. Furthermore, following the IL-12 gene therapy protocol, test mice were able to eradicate not only the treated but also the untreated solid tumors at distant sites. This systemic antitumor effect of IL-12 gene therapy was not associated with visible signs of toxicity or significantly elevated systemic levels of IFN-gamma. These results show that gene gun-mediated in vivo delivery of IL-12 cDNA clearly distinguishes itself from the other cytokine gene therapy approaches tested in parallel, suggesting that this delivery system may be employed as an efficient model for comparative studies of in vivo cytokine gene therapy. The results also suggest that the current IL-12 gene therapy strategy may provide a safer alternative to IL-12 protein therapy for clinical treatment of cancers.

Animals↗
PubMed1997

p53 abnormalities are rare events in neuroendocrine (Merkel cell) carcinoma of the skin. An immunohistochemical and SSCP analysis.

The aim of the present study was to assess a possible role of the tumour suppressor gene p53 in neuroendocrine (Merkel cell) carcinoma of the skin with regard to tumour development and tumour progression. p53 was investigated in a series of routinely processed Merkel cell carcinomas, with application of four different p53 antibodies (CM-1, PAb1801, DO7, and PAb240) to 25 carcinomas and screening for p53 mutations of exons 4-8 by single-strand conformation polymorphism (SSCP) analysis in 9 cases. All 25 tumours in the present series showed the characteristic microscopic and immunohistochemical features of Merkel cell carcinoma of the skin. In 5 of the 25 Merkel cell carcinomas investigated 5-10% of tumour cell nuclei showed a positive p53 reaction with at least one anti-p53 antibody. A few scattered p53 positive nuclei were found in an additional 9 cases. The remaining 11 cases completely lacked p53 immunostaining. SSCP analysis of exons 4-8 revealed no significant alterations in the mobility shift of the single strand DNAs in the five cases with 5-10% p53-immunoreactive tumour nuclei or in five cases lacking p53 accumulation significant. Our results suggest that alterations of the p53 gene play only a minor part in the development or progression of Merkel cell carcinoma of the skin.

Aged↗
PubMed1996

p53 oncoprotein overexpression in choroidal melanoma.

This study immunohistochemically demonstrates p53 oncoprotein overexpression on routinely processed choroidal melanomas by means of four different anti-p53 antibodies after high-temperature antigen retrieval. The results were correlated both with morphologic and clinical parameters. Routinely formalin-fixed and paraffin-embedded tumor tissues from 43 choroidal melanomas were immunohistochemically investigated with four different anti-p53 antibodies directed against four different epitopes (CM-1, DO-7, PAb1801, PAb240) after wet autoclave antigen retrieval. The application of this technique is of outstanding importance for the demonstration of p53 protein on routinely processed tissues. Five patients (11.6%) of 43 showed more than 10% p53-positive tumor cell nuclei, which was regarded as p53 overexpression; these five patients underwent preoperative telecobalt or ruthenium irradiation. An additional 18 patients (41.9%) showed a few positively stained nuclei with at least one of the antibodies applied. p53 expression was more often found in epithelioid cell tumors; there was no statistical correlation between p53 overexpression and the clinical outcome. Our results suggest that p53 oncoprotein overexpression in choroidal melanomas indicates a late event in the progression rather than a crucial step in the development of these tumors. This conclusion is supported by the finding that all tumors with immunohistochemical p53 overexpression underwent preoperative irradiation, which might have caused p53 alteration(s) and thus enabled its immunohistochemical demonstration.

Adult↗
PubMed1995

[Subretinal manifestations as the chief findings in parasitic diseases in germany].

The most frequent intraocular manifestations of parasitoses in Germany and world-wide are retinochoroidal lesions of Toxoplasma gondii; worms are less frequent. In reports of four cases it is shown that demographic data, biomicroscopical hallmarks and the fecal wet-mounts are the most important parameters for a presumptive diagnosis, if no intraocular material can be isolated. The patients in this series lack systemic features and changes in the blood differential, probably due to the adequate alimentary state and lack of reinfestations.

Adult↗
PubMed1993

[Recurrent canaliculitis and dacryocystitis as a sequela of persistent infection with Chlamydia trachomatis].

We report on 4 patients aged 39-62 years with follicular conjunctivitis, canaliculitis, canalicular obstruction, dacryocystitis and nasolacrimal duct obstruction caused by chronic oculogenital infection with Chlamydia trachomatis. Microbiological diagnosis was accomplished by means of the McCoy cell culture technique as a highly specific tool for detection of the chlamydial infection. In addition, serological tests (IgA-IPA and IgG-IPA techniques) were performed. Bacteriological examination of conjunctival smears showed coinfection in 3 patients (Proteus mirabilis in 1, Staphylococcus aureus coagulase-positive in 3). Despite successful operation techniques, the obstructive inflammation caused by oculogenital chlamydial infection could only be cured by systemic treatment with specific antibiotics, such as doxycycline or erythromycin. All cases of chronic follicular conjunctivitis with lacrimal inflammation that are resistant to topical antibiotics should suggest the possibility of infection with Chlamydia trachomatis.

Adult↗
PubMed1983

Treatment of sinus tachycardia with heart-rate feedback.

A 23-year-old male with a history of sinus tachycardia was treated with heart-rate feedback in eight sessions. From a pretreatment average of 103 beats per minute (BPM) as recorded in two separate baseline sessions, the heart rate dropped to 66 BPM in the last treatment session. At follow-up the heart rate seemed stabilized within the normal range, averaging 68 BPM after 1 month and 73 BPM after 12 months. Simultaneous EMG recordings of m. frontalis suggest a generalized effect of this treatment. Results are discussed in terms of somatic and respiratory mediation.

Adult↗
PubMed1983

Differential effectiveness of EMG-feedback versus combined EMG-feedback and relaxation instructions in the treatment of tension headache.

After a 2 1/2 week baseline period 18 muscle tension headache patients were randomly assigned to one of three conditions: waiting list, formal EMG-feedback training, combined training of EMG-feedback and progressive relaxation. Patients in the two treatment conditions obtained 12 training sessions and returned 3 months after treatment for a follow-up session. Both treatment conditions were equivalent in their effect on EMG of m. frontalis and on headache scores, against stability for waiting list patients as observed in a separate analysis. Changes over treatment in both parameters were significantly correlated. Among changes in headache subparameters, the only significant correlation with changes in frontalis EMG was found for duration of pain. In both treatment conditions a generalizing effect to neck muscles was observed. Among personality variables decreases were found in neuroticism and somatization at follow-up for the combined training conditions, whereas the EMG-feedback alone condition remained unaltered. The combined training condition also proved superior in reducing operant pain behavior.

Adolescent↗