Biomedical subjects

D Jager

Publications and source records attributed to D Jager.

7 recordsLinked to original sources

PubMed2006

Multimarker RT-PCR assay for the detection of minimal residual disease in sentinel lymph nodes of breast cancer patients.

The presence of metastases in lymph nodes is the most powerful prognostic factor in breast cancer patients. Routine histological examination of lymph nodes has limited sensitivity for the detection of breast cancer metastases. The aim of the present study was to develop a multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of minimal residual disease in sentinel nodes of breast cancer patients. RNA was extracted from 30 sentinel lymph nodes (SLN) obtained from 28 patients, three primary breast cancers (positive controls), three lymph nodes from patients with benign diseases, and peripheral blood lymphocytes of 10 healthy volunteers (negative controls). RT-PCR was performed using the following markers; cytokeratin (CK)-19, NY-BR-1 and mammaglobin B. RT-PCR results were compared to enhanced histopathologic examination and immunohistochemistry (IHC). All three positive controls showed strong PCR amplification for all three markers. None of the 13 negative controls was amplified by any of the three markers. Among the 30 SLN analysed, breast cancer metastases were detected in six SLNs by routine histology, in eight by IHC and in 15 by RT-PCR. We conclude that a multimarker RT-PCR assay probing for NY-BR-1, mammaglobin-B, and CK-19 is more sensitive compared to enhanced pathologic examination. This method may prove to be of value in breast cancer staging and prognosis evaluation.

Adenocarcinoma↗

PubMed2006

Defining halos.

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AIDS-Related Opportunistic Infections↗

PubMed2003

A Systemic Hyperthermia Oncologic Working Group trial. Ifosfamide, carboplatin, and etoposide combined with 41.8 degrees C whole-body hyperthermia for metastatic soft tissue sarcoma.

BACKGROUND: Based on earlier clinical and preclinical studies, we conducted a phase II trial in metastatic sarcoma patients of the combination of 41.8 degrees C (x60 min) radiant heat (Aquatherm) whole-body hyperthermia (WBH) with 'ICE' chemotherapy. The ICE regimen consists of ifosfamide (5 g/m(2)), carboplatin (300 mg/m(2)) and etoposide (100 mg/m(2)), concurrent with WBH, with etoposide also on days 2 and 3 post-WBH. METHODS: Therapy was delivered every 4 weeks for a maximum of 4 cycles. All patients received filgrastim or lenograstim. RESULTS: Of 108 patients enrolled as of September 2001, 95 are evaluable for response. Of the evaluable patients (mean ECOG performance status approximately 1; mean age 42.3; 58% male) 33 had no prior therapy for metastatic disease, and 62 were pretreated (mean: 1.5 prior regimens). The overall response rate was 28.4% (4 complete remissions and 23 partial remissions) with stable disease (SD) in 31 patients. For no prior therapy, the response rate was 36%; in pretreated patients it was 24%. The median overall survival by Kaplan-Meier estimates was 393 days (95% CI 327, 496); the median time to treatment failure was 123 days (95% CI 77, 164). The major toxicity (287 cycles) was grade 3 or 4 neutropenia and thrombocytopenia seen in 79.7 and 60.6% of treatments respectively; there were 7 episodes of infection (grade 3/4) with 2 treatment-related deaths, bot involving disease progression and ureteral obstruction. CONCLUSION: These results are consistent with continued clinical investigation of this combined modality approach.

Adolescent↗

PubMed2002

Transforming Growth Factor-beta2 protects the small intestine during methotrexate treatment in rats possibly by reducing stem cell cycling.

During chemo- and radiation therapy, the balance between epithelial cell proliferation, differentiation, and cell death at the villus tip is disrupted by premature death of dividing epithelial cells. This will subsequently lead to the onset of mucosal barrier injury in the whole gastrointestinal tract. Up till now there is no validated method to treat side effects occurring due to therapy. An approach to manage this side effect might be to reversibly arrest growth of epithelial stem cells during therapy using Transforming Growth Factor-beta2. A Transforming Growth Factor-beta2 enriched fraction prepared from bovine milk was shown to protect small intestinal epithelial cells against cell cycle specific chemotherapeutic agents by arresting the cells in G1-phase. Secondly, in a rat model for induced small intestinal damage, oral supplementation of rats exposed to methotrexate with the Transforming Growth Factor-beta2 enriched fraction significantly reduced the chemotherapy-associated weight loss and ileal villus atrophy by reducing cell proliferation in the normal stem cell population. Thus oral supplementation with a bovine milk fraction enriched for Transforming Growth Factor-beta2 attenuated the side effects of chemotherapy in the small intestine in rats.

Administration, Oral↗

PubMed1997

High Pressure Coronary Stenting: Efficacy and Safety of Aspirin Versus Coumadin Plus Aspirin Ñ Preliminary Results of a Randomized Study.

The efficacy and safety of treatment after coronary stenting was examined with aspirin alone, 100 mg daily, as compared to coumadin plus aspirin. Data from the first 101 patients, 73 men and 28 women, aged 59.2 +/- 9.3 years, of a prospective randomized study are presented in this preliminary report. Forty-eight patients suffered from one-vessel disease, 32 had two- and 21 three-vessel disease. Indications for stenting were stable angina in 65 patients, unstable angina in 16, threatening myocardial infarction in 4 and restenosis in 16 patients. The stents were implanted by high pressure balloon inflation (14.5 +/- 2.2 atm), 55 of them were Palmaz-Schatz, 31 Micro, 10 Gianturco-Roubin, 2 Wiktor and 3 combined stents. Intravascular ultrasonographic guidance was not performed. The primary end point was defined as the absence of the following events: death, subacute coronary artery closure, acute myocardial infarction, emergency coronary bypass surgery, repeated PTCA, major bleeding or arterio-venous aneurysms needing transfusion or surgery. Eighty out of 101 patients (79.2%), 41 out of 47 (87.2%) in the aspirin group and 39 out of 54 (72.2%) in the coumadin plus aspirin group (p = 0.06) were free of events during hospitalization (9.5 +/- 5.7 days, median: 8 days). Forty-five out of 47 patients (95.7%) in the aspirin and 51 out of 54 (94.4%) in the coumadin plus aspirin group (p = 0.8) were without subacute closure. One death occurred in the aspirin group due to stent abscess two weeks after an angiographically successful stent recanalization. All 7 arterio-venous aneurysms with surgical interventions occurred in the coumadin group (p = 0.01). No emergency bypass surgery had to be performed. If these preliminary results will be confirmed by the final analysis, the combination of coumadin with aspirin does not show more efficacy or safety as compared with aspirin alone in the treatment after high-pressure coronary stenting during the hospital stay.

Journal Article↗

PubMed1988

Purification and characterization of a bacterial dehalogenase with activity toward halogenated alkanes, alcohols and ethers.

An enzyme that is capable of hydrolytic conversion of halogenated aliphatic hydrocarbons to their corresponding alcohols was purified from a 1,6-dichlorohexane-degrading bacterium. The dehalogenase was found to be a monomeric protein of relative molecular mass 28,000. The affinity for its substrates was relatively low with Km values for short-chain haloalkanes in the range 0.1-0.9 mM. The aliphatic dehalogenase showed a much broader substrate range than has been reported for halidohydrolases so far. Novel classes of substrates include dihalomethanes, C5-C9 1-halo-n-alkanes, secondary alkylhalides, halogenated alcohols and chlorinated ethers. Several of these compounds are important environmental pollutants, e.g. methylbromide, dibromomethane, 1,2-dibromoethane, 1,3-dichloropropene, and bis(2-chloroethyl)ether. The degradation of chiral 2-bromoalkanes appeared to proceed without stereochemical preference. Optically active 2-bromobutane was converted with inversion of configuration at the chiral carbon atom, suggesting that the dehalogenase reaction proceeds by a nucleophilic substitution involving a carboxyl group or base catalysis.

Actinomycetales↗

PubMed1987

Degradation of n-haloalkanes and alpha, omega-dihaloalkanes by wild-type and mutants of Acinetobacter sp. strain GJ70.

A 1,6-dichlorohexane-degrading strain of Acinetobacter sp. was isolated from activated sludge. The organism could grow with and quantitatively release halide from 1,6-dichlorohexane, 1,9-dichlorononane, 1-chloropentane, 1-chlorobutane, 1-bromopentane, ethylbromide, and 1-iodopropane. Crude extracts contained an inducible novel dehalogenase that liberated halide from the above compounds and also from 1,3-dichloropropane, 1,2-dibromoethane, and 2-bromoethanol. The latter two compounds were toxic suicide substrates for the organism at concentrations of 10 and 5 microM, respectively. Mutants resistant to 1,2-dibromoethane (3 mM) lacked dehalogenase activity and did not utilize haloalkanes for growth. Mutants resistant to both 1,2-dibromoethane (3 mM) and 2-bromoethanol (30 mM) could no longer oxidize or utilize alcohols and were capable of hydrolytic dehalogenation of 1,2-dibromoethane to ethylene glycol.

Acinetobacter↗