Search PubMed⌕ Search

Biomedical subjects

L Jansen

Publications and source records attributed to L Jansen.

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

Lymphatic mapping and sentinel lymph node biopsy in breast cancer.

Lymphatic mapping with selective lymphadenectomy is an attractive approach in breast-cancer patients. It uses existing technology to exploit logical anatomic and physiological principles to identify occult regional lymph-node metastases. The lymphatic flow is visualized and the first (sentinel) lymph node on a direct drainage pathway from the primary tumour is identified. This is the node at greatest risk of harbouring metastatic deposits. Retrieving this node requires a concerted effort from the nuclear medicine physician, surgeon and pathologist. Lymphoscintigraphy can indicate the number of sentinel nodes and their location. The surgeon can use two techniques to find the node. A vital dye injected at the tumour site will stain the lymphatic duct as well as the sentinel node and allow their visual identification. Alternatively, a lymph-node-seeking radiopharmaceutical will also migrate from the tumour site to the sentinel node and will enable its retrieval with the use of a gamma detection probe. The pathologist has a number of techniques to identify tumour deposits in the lymph node. A review of the literature shows that the sentinel node can be found in more than 90% of the patients. With experience, the false-negative rate can be kept down to about 5%. This novel approach of lymphatic mapping with selective lymphadenectomy may lead to a substantial reduction in the need for axillary node dissection in patients with breast cancer without compromising survival and regional control, and without loss of prognostic and staging information. This development will translate into a great reduction in patient morbidity and medical expenses.

Breast Neoplasms↗
PubMed1999

HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions.

Cancer predisposition in hereditary non-polyposis colon cancer (HNPCC) is caused by defects in DNA mismatch repair (MMR). Mismatch recognition is attributed to two heterodimeric protein complexes: MutSalpha (refs 2, 3, 4, 5), a dimer of MutS homologues MSH2 and MSH6; and MutSbeta (refs 2,7), a dimer of MSH2 and MSH3. These complexes have specific and redundant mismatch recognition capacity. Whereas MSH2 deficiency ablates the activity of both dimers, causing strong cancer predisposition in mice and men, loss of MSH3 or MSH6 (also known as GTBP) function causes a partial MMR defect. This may explain the rarity of MSH6 and absence of MSH3 germline mutations in HNPCC families. To test this, we have inactivated the mouse genes Msh3 (formerly Rep3 ) and Msh6 (formerly Gtmbp). Msh6-deficient mice were prone to cancer; most animals developed lymphomas or epithelial tumours originating from the skin and uterus but only rarely from the intestine. Msh3 deficiency did not cause cancer predisposition, but in an Msh6 -deficient background, loss of Msh3 accelerated intestinal tumorigenesis. Lymphomagenesis was not affected. Furthermore, mismatch-directed anti-recombination and sensitivity to methylating agents required Msh2 and Msh6, but not Msh3. Thus, loss of MMR functions specific to Msh2/Msh6 is sufficient for lymphoma development in mice, whereas predisposition to intestinal cancer requires loss of function of both Msh2/Msh6 and Msh2/Msh3.

Alleles↗
PubMed1999

[Contribution of nuclear medicine to lymphatic mapping and sentinel node identification in oncology].

An overview of the current applications of nuclear medicine for lymphatic mapping and sentinel node identification is given. The validation of the sentinel node concept in oncology has led to the rediscovery of lymphoscintigraphy. By combining preoperative lymphatic mapping with intraoperative gamma probe detection this nuclear medicine procedure is increasingly used to identify and detect the sentinel node in melanoma, breast cancer, and in other malignancies such as penile cancer and vulvar cancer. In melanoma, the adequate combination of dynamic and static gamma camera images enables lymph node visualization with identification of the sentinel node in more than 97% of the cases. The variability in drainage in areas such as trunk, head and neck makes lymphoscintigraphy indispensable in protocols of sentinel node biopsy. The reproducibility of lymphoscintigraphy for sentinel node detection varies from 85% to 88% and the method appears to have a high interobserver agreement. In contrast to the procedure of lymphoscintigraphy for melanoma, for which the only dilemma remaining is probably the choice of the tracer, in breast cancer there has not yet been reached a consensus for many topics such as tracer characteristics, injection volume, and principally the site of administration. Lymphoscintigraphy by subdermal tracer administration is able to detect axillary lymph nodes in 98% of the cases but the method is accompanied by a low visualization incidence (2%) of drainage outside the lower axilla such as the internal mammary chain. This latter aspect appears to occur in 16% to 35% in the series using peri- or intratumoural administration with an axillary rate of visualization of 75% to 98%. Although peritumoural administration is predominantly associated with late lymph node detection, the early appearance observed after subdermal and intratumoural tracer injection justifies the obtention of early gamma camera images. The strategies of identification of the sentinel node depend strongly on the results of lymphoscintigraphy. In melanoma, the rapid lymphatic drainage and the visualization of afferent lymphatic vessels enables sentinel node identification by lymphoscintigraphy in almost the totality of the cases and intraoperative probe detection may subsequently be performed. In breast cancer, the slower drainage pattern may hamper image interpretation and diagnostic conclusion. Considering the first appearing node and the visualization of an afferent lymphatic vessel as the major criteria to identify the sentinel node, scintigraphy may be considered conclusive in approximately 75% of the cases, and not conclusive in about a fourth part of the cases in which 2 or more lymph nodes appear simultaneously without lymph vessel delineation. When lymphoscintigraphy is not conclusive, additional lymphatic mapping with blue dye is recommended to definitively identify the sentinel node. The use of nuclear medicine techniques for the sentinel node procedure will become an important part of clinical work in the nuclear medicine and surgical oncology practice of the next years. Principally mammary lymphoscintigraphy demands from the nuclear medicine community and allied disciplines a prompt standardization of the technique to solving some controversial aspects such as tracer requirements, administration route and interpretation criteria.

Biopsy↗
PubMed1998

Improved staging of breast cancer through lymphatic mapping and sentinel node biopsy.

Sentinel node biopsy is a less invasive technique for staging breast cancer than complete axillary lymph-node dissection and may be as accurate. In the case of a 71-year-old woman with a T1 breast cancer, sentinel node biopsy improved staging. Metastases were discovered in sentinel nodes outside the axilla while the axillary nodes were tumour-free.

Aged↗
PubMed1998

Technique of lymphatic mapping and sentinel node biopsy for melanoma.

AIMS: An increasing number of surgeons perform sentinel node biopsy to identify melanoma patients with early lymphatic dissemination who may benefit from regional node dissection or adjuvant therapy. The addition of lymphoscintigraphy and intraoperative gamma-ray detection with a hand-held probe increases the sensitivity of the surgical technique substantially. METHODS: The value of lymphoscintigraphy is discussed. The operative technique of lymphatic mapping and sentinel node biopsy is described, including the use of a vital dye and a gamma-ray probe. CONCLUSIONS: Close to 100% of first-tier lymph nodes can be identified with this combined approach without the unnecessary removal of too many higher-echelon nodes.

Adult↗
PubMed1996

Human APOE protein localized in brains of transgenic mice.

Transgenic mice carrying the three common human apolipoprotein E (APOE) alleles have been developed. In this study, brains of the transgenic mice have been analyzed by in situ histohybridization, immunohistochemistry, and immunoblots to determine sites of gene expression, to identify specific brain cells associated with human apoE protein, and to determine the relative concentrations of the human apoE. Results indicate that (1) human APOE mRNA and apoE protein occur in the gray and white matter of transgenic mouse brains; (2) in the hippocampus of transgenic brains, human apoE protein reacts immunologically within the same cells as the glial fibrillary acidic protein (GFAP), a specific marker for astrocytes; and (3) concentrations of the apoE isoforms determined in three heterozygous transgenic brains range from 22 to 250 pmol/g wet weight of brain.

Alleles↗
PubMed1995

Discovery of a brain promoter from the human transferrin gene and its utilization for development of transgenic mice that express human apolipoprotein E alleles.

Transgenic mice carrying heterologous genes directed by a 670-bp segment of the regulatory sequence from the human transferrin (TF) gene demonstrated high expression in brain. Mice carrying the chimeric 0.67kbTF-CAT gene expressed TF-CAT in neurons and glial cells of the nucleus basalis, the cerebrum, corpus callosum, cerebellum, and hippocampus. In brains from two independent TF-CAT transgenic founder lines, copy number of TF-CAT mRNA exceeded the number of mRNA transcripts encoding either mouse endogenous transferrin or mouse endogenous amyloid precursor protein. In two transgenic founder lines, the chloramphenicol acetyltransferase (CAT) protein synthesized from the TF-CAT mRNA was estimated to be 0.10-0.15% of the total soluble proteins of the brain. High expression observed in brain indicates that the 0.67kbTF promoter is a promising director of brain expression of heterologous genes. Therefore, the promoter has been used to express the three common human apolipoprotein E (apoE) alleles in transgenic mouse brains. The apoE alleles have been implicated in the expression of Alzheimer disease, and the human apoE isoforms are reported to interact with different affinities to the brain beta-amyloid and tau protein in vitro. Results of this study demonstrate high expression and production of human apoE proteins in transgenic mouse brains. The model may be used to characterize the interaction of human apoE isoforms with other brain proteins and provide information helpful in designing therapeutic strategies for Alzheimer disease.

Alleles↗
PubMed1995

A human (3.3 kb) haptoglobin-CAT transgene is modulated in lungs of transgenic mice by inflammation.

Four independent lines of transgenic mice were produced carrying integrated copies of a chimeric gene composed of 3.3 kb of the human haptoglobin 5' regulatory region fused to the CAT (chloramphenicol acetyl transferase) reporter gene. Although the endogenous mouse haptoglobin (Hp) and human haptoglobin (HP) genes express mainly in liver and lung, expression of the human 3.3-kb HP-CAT transgene was not detected until after induction of inflammation and then only in lungs. The results indicated that the transgene maintained the regulatory DNA elements required for lung specific responsiveness to inflammation in vivo but lacked the DNA sequence required for robust expression in liver. The DNA sequence(s) responsible for the normally high level of HP expression in liver either reside outside the 3.3-kb regulatory region of the HP chimeric gene or this region contains a suppressor sequence affecting tissue specific expression in the liver.

Animals↗
PubMed1993

IL-1 beta decreases expression of amyloid precursor protein gene in human glioma cells.

In Alzheimer's disease a small fragment of the amyloid protein precursor (APP), called beta 4, is a characteristic component of senile plaques in brains of affected patients. Efforts to intervene in Alzheimer's disease include approaches by which APP levels can be decreased in brain. The study described here demonstrates the expression of APP gene in four cell lines that originated from human brain glioblastomas. In one line, HTB 17, APP mRNA level was approximately 25% the APP mRNA found in human brain and 150% that found in human liver. To ascertain whether or not APP expression in HTB 17 cells could be modulated by a cytokine associated with the inflammatory response, cells were cultured in the presence of IL-1 beta. A significant decrease in APP mRNA accompanied treatment of glioma cells with IL-1 beta.

Amyloid beta-Protein Precursor↗
PubMed1985

Comparison of the crystallin mRNA populations from rat, calf and duck lens. Evidence for a longer alpha A2-mRNA and two distinct alpha B2-mRNAs in the birds.

Total cytoplasmic poly(A)-containing RNA from rat, calf and duck lens was fractionated by electrophoresis in methylmercury hydroxide-containing agarose gels. RNA electrophoresed in parallel lanes was either transferred onto nitrocellulose and hybridized with total cDNA synthesized on the initial mRNA or was recovered from individual gel fractions for in vitro translation in a reticulocyte cell-free system. This allowed the identification and size-characterization of individual mRNA species encoding alpha-, beta-, gamma- and delta-crystallin polypeptides. The 14 S mRNA fraction of rat lens comprises two alpha A2-mRNAs of approximately 1250 and 1350 nucleotides and the alpha AIns-mRNA with a size similar to that of the largest alpha A2-mRNA. The calf lens 14 S mRNA fraction harbors a heterogeneous population of alpha A2-mRNA. In the same fraction another mRNA encoding a polypeptide, designated X, has been found sharing no homology with alpha A sequences. The duck lens alpha A2-mRNA appears to be 400-450 bases longer than the rat and calf lens alpha A2-mRNAs. Furthermore, in contrast to the single alpha B2-mRNA in rat and calf lens, two alpha B2-mRNAs have been identified in duck lens, one, the major species, similar in size to the alpha B2-mRNA in rat and calf lens (800 bases), and the other species 700 nucleotides longer. The large size differences among the alpha A2- and alpha B2-mRNAs most likely reside in their 3'-untranslated sequences.

Animals↗