Biomedical subjects

J Packeisen

Publications and source records attributed to J Packeisen.

10 recordsLinked to original sources

PubMed2003

Demystified...tissue microarray technology.

Several "high throughput methods" have been introduced into research and routine laboratories during the past decade. Providing a new approach to the analysis of genomic alterations and RNA or protein expression patterns, these new techniques generate a plethora of new data in a relatively short time, and promise to deliver clues to the diagnosis and treatment of human cancer. Along with these revolutionary developments, new tools for the interpretation of these large sets of data became necessary and are now widely available. Tissue microarray (TMA) technology is one of these new tools. It is based on the idea of applying miniaturisation and a high throughput approach to the analysis of intact tissues. The potential and the scientific value of TMAs in modern research have been demonstrated in a logarithmically increasing number of studies. The spectrum for additional applications is widening rapidly, and comprises quality control in histotechnology, longterm tissue banking, and the continuing education of pathologists. This review covers the basic technical aspects of TMA production and discusses the current and potential future applications of TMA technology.

Animals↗

PubMed2003

High mobility group protein HMGA1 expression in breast cancer reveals a positive correlation with tumour grade.

Members of the HMGA protein (high mobility group protein A) family act as master switches of the chromatin structure by bending DNA and thus modulating the formation of transcription factor complexes of a number of target genes. Accordingly, HMGA proteins have been shown to be associated with the development and/or progression of a variety of benign and malignant tumours. Nevertheless, the HMGA1 expression studies published so far have not included primary breast cancer samples. In this study we have investigated the HMGA1 expression patterns in a series of 170 breast cancer samples by immunohistochemistry. We have found a strong variation in HMGA1 expression between the tumours. Based on an immunoreactive score (IRS) 14.1% of the tumour samples were scored to IRS 8-12 (strong positivity for HMGA1), 24.7% were scored to IRS 4-6 (moderate positivity), 25.3% were scored to IRS 1-3 (weak positivity), and 35.9% showed no positivity at all. Immunoreaction could be detected in all histological types of breast cancers analysed with the exception of invasive papillary and cribriform carcinoma. Statistical analysis revealed a strong correlation between tumour grade and HMGA1 expression (rs=0.3516, p<0.0001). Thus, the HMGA1 expression level can be considered a potential prognostic marker for breast cancer.

Breast Neoplasms↗

PubMed2002

[Epulis in a newborn. histogenetic comparison with a granular cell tumor in adults].

The congenital granular cell tumor is a rare lesion of newborns located on the alveolar ridge with a marked predilection for female infants. Histologically these tumors are characterized by large eosinophilic granular cells, similar to granular cell tumors in adults which are often seen as Abrikossoff tumors. Immunohistochemical studies revealed the different histogenesis and evolution of both these tumor entities. We report on a female newborn infant with a congenital epulis of the left anterior maxillary alveolar ridge. This case demonstrates a rare congenital tumor of newborns and reveals the histogenetic differences to granular cell tumors in adults.

Adult↗

PubMed2002

Tissue microarrays: a new approach for quality control in immunohistochemistry.

AIMS: To improve the interpretation of immunohistochemistry (IHC) staining results the use of a tissue microarray technique was established in a routine setting. METHODS: A tissue microarray was constructed by harvesting 600 microm tissue cores from paraffin wax embedded samples available in a routine pathology department. The punches originating from non-tumorous tissue were placed on host paraffin wax blocks. The microarray contained 12 different tissue samples, with a wide antigen profile and a dimension of 3.5 x 3 mm. One section of the multitissue array was placed as an "internal" positive control on each slide of the patient tissue to undergo identical immunohistochemical procedures. RESULTS: Using the tissue microarray technique as a tool for internal quality control, the interpretation of immunohistochemical staining of more than 20 different antigens in routine IHC was improved. The tissue microarray did not influence the staining results in conventional IHC or in different automated IHC settings. CONCLUSION: The regular use of an institution adapted tissue microarray would be useful for internal positive control in IHC to enable different laboratory demands. Furthermore, this technique improves the evaluation of staining results in IHC.

Antigens↗

PubMed2001

[Spontaneous rupture of a pancreatic pseudocyst into the portal vein].

HISTORY AND ADMISSION FINDINGS: A 69-year-old woman complained of recurrent cramp-like symptoms in the upper abdomen. She admitted excessive alcohol intake. Physical examination revealed swelling and inflammation of both ankles. All other findings were unremarkable. INVESTIGATIONS: Sonography and computed tomography scan showed a cystic structure (5 cm) in the head of the pancreas. Biochemical testing revealed an anemia (Hb 7,5 mg/dl) and an elevated serum lipase (4494 U/l). Intestinal hemorrhage could not be confirmed by endoscopy. An involvement of parapancreatic structures with the pseudocyst could not be demonstrated by combination of endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT). COURSE: The patient died unexpectedly. Autopsy showed a rupture of the pancreatic pseudocyst into the portal vein leading to portal vein thrombosis. The cause of death was an embolism of the pulmonary arteries. Postmortal reevaluation of CT and ERCP clarified diagnostic features. CONCLUSION: Erosion of peripancreatic vessels is one of the life threatening complications in chronic pancreatitis. The complication is uncommon but should be included into differential diagnosis of recurrent intestinal bleeding.

Aged↗

PubMed1999

[Acute appendicitis caused by pregnancy-associated ectopic decidua. Case report and discussion of pathogenesis].

The occurrence of pregnancy-associated ectopic decidua is a well-documented phenomenon. It has been observed most often in the ovaries, uterus, and cervix. An extragenital localization is less frequent and usually an asymptomatic, incidental finding. We report on a 32-year-old woman in her third trimester of pregnancy who developed acute appendicitis caused by ectopic decidua. This case illustrates a rare differential diagnosis of acute appendicitis and discusses the pathogenesis of pregnancy-associated ectopic decidua in such cases.

Acute Disease↗

PubMed1999

Detection of surface antigen 17-1A in breast and colorectal cancer.

Substantial progress has been made in detecting cell surface or intracytoplasmatic antigens to identify spread tumor cells with monoclonal antibodies (MAbs). The 17-1A antigen is already used as a target for specific immunotherapy in colorectal cancer. The purpose of this study was to compare the expression of 17-1A antigen in colorectal tumors versus breast cancers. MAb against the epithelial-specific antigen (ESA) and a routine staining technique were used to detect the 17-1A antigen in 100 cases of colorectal and 111 cases of breast cancer. The antigen expression of each tumor entity was examined by light microscopy on paraffin sections. Thirty six of the formalin-fixed paraffin sections of breast cancer were compared with their corresponding frozen sections. Evaluation was realized by a histological score (grade 0-9) considering the distribution and the staining intensity. We found an antigen expression of 17-1A in colorectal cancer quantified at 7.1+/-1.8 and at 4.5+/-2.5 for breast cancer in our score. Comparing paraffin sections and frozen sections in the 36 cases of breast cancer, the score was 5.5+/-2.3 in the paraffin and 8.1+/-1.9 in the frozen section group. Our results confirmed the high expression of 17-1A cases of in colorectal carcinoma. Furthermore, 17-1A is expressed in the majority of breast carcinomas, revealing a high difference between paraffin and frozen sections. As a result, a specific immunotherapy with MAbs against 17-1A antigen in minimal residual stages of breast cancer might be considered.

Antibodies, Monoclonal↗

PubMed1995

Interleukin-10 directly inhibits the interleukin-6 production in T-cells.

IL-6 is a potent regulator of T-cell activation, proliferation and differentiation. Since IL-10 inhibits cytokine production by T cells, the effect of IL-10 on IL-6 production by T cells was investigated. IL-6 production by purified monocytes or T cells was detected from cell-free culture supernatants by ELISA after stimulation of the cells with LPS or an anti-CD3 monoclonal antibody for 3 days. Although the main source of IL-6 are LPS activated monocytes (29.6 +/- 10 ng/ml), T cells secreted sufficiently high levels of IL-6 (790 +/- 200 pg/ml) to stimulate the high affinity IL-6 receptor. IL-10 decreased anti-CD3 induced IL-6 mRNA expression by up to 80%. In addition, IL-10 significantly inhibited IL-6 release from T-cells. Highly purified, anti-CD3 activated T-cells secreted 600 +/- 150 pg/ml IL-6 compared to 21 +/- 2 pg/ml IL-6 following addition of IL-10 (10 ng/ml; P < 0.001). FACS analysis revealed a monocyte contamination of the T-cell preparations of less than 0.5%. In addition, no IL-1 production was detectable. Thus, in our experiments the effect of IL-10 on IL-6 production was independent of the presence of monocytes. Finally, inhibition of IL-6 production was not reversed by IL-2 (100 U/ml). In conclusion, IL-10 suppressed the synthesis of IL-6 by T-cells via a monocyte- and IL-2-independent mechanism. These results may help to understand the complex regulation of T-cell mediated cytokine production by IL-10.

Cells, Cultured↗

PubMedDate not supplied

[Significance of interleukin 10 for acute graft versus host disease in children and adolescents after allogenic bone marrow transplantation].

BACKGROUND: It has been shown that Interleukin 10 (IL-10) is able to inhibit alloreactivity in a mixed lymphocyte culture. Therefore, here IL-10 production in patients after allogeneic BMT was investigated and correlated with the incidence of acute GvHD. PATIENTS: 14 patients after allogeneic BMT have been investigated. Patients' age ranged from 2.6 to 22 yrs. (median 7 yrs.). Patients were diagnosed with Ewing's sarcoma (1), ALL (4), AML (3), CML (2), Wiskott-Aldrich Syndrome (WAS;1), MDS (1) and SAA (2). GvHD > II degrees occurred in 5/14 patients. As control served 20 healthy volunteers. METHODS: Mononuclear cells (MNC's) isolated from patients and 20 healthy controls were stimulated with an anti-CD3 monoclonal antibody for 72 hr. IL-10 was detected in cell-free supernatants by ELISA. RESULTS: Anti-CD3-induced IL-10 production in MNC's isolated from patients (range/median: 0-1579 pg/10(6) MNC; 221 pg/10(6) MNC) was significantly reduced compared to healthy controls (160-5093 pg/10(6) MNC; 1250 pg/10(6) MNC; p < 0.01). 4/5 patients with low IL-10 production, but only 1/9 with a normal IL-10 production presented with GvHD > II degrees (p < 0.05). CONCLUSION: Ex vivo IL-10 production was decreased in about one third of patients early after allogeneic BMT. The low IL-10 production was associated with a significantly increased risk of severe GvHD. Thus, supplementation of IL-10 might become a useful therapy to prevent GvHD.

Adolescent↗

PubMedDate not supplied

Interaction between interleukin 10 and interleukin 6 in human B-cell differentiation.

Contrary to their opposing action on human T-lymphocytes and monocytes, both Interleukin (IL-)10 and IL-6 are potent differentiation factors of human B-cells. Both are known to induce immunoglobulin (Ig) production. The precise mechanism of this converging effect of IL-6 and IL-10 remains elusive, however. Here we investigated the role of IL-6 in the IL-10 dependent B-cell differentiation into Ig secreting cells. We found that co-stimulation of SAC-stimulated human peripheral B-lymphocytes with IL-10 and IL-6 exhibited no additive effect on Ig production over stimulation with IL-10 alone, and that IL-6 receptor blockade only mildly inhibited IL-10 induced Ig synthesis. In fact, we could show that stimulation of B-cells with IL-10 somewhat suppressed SAC induced autocrine IL-6 production. Despite this suppression IL-6 levels remained sufficiently high to stimulate its receptor, and IL-6 binding to the B-cell surface was not affected. The failure of IL-6 to exert an additional effect on SAC+IL-10 induced Ig production suggests that IL-10 may recruit components of the IL-6 intracellular pathway for Ig induction. In conclusion we could demonstrate that IL-10 acts on B-cell differentiation independently of autocrine IL-6 and that it had a considerably mild effect on B lymphocytic autocrine IL-6 secretion. This still allows an IL-6 effect in the presence of IL-10 which appears adaptive with a view to the converging effects of these two cytokines on human B lymphocytes. Our study thus adds to the appreciation of the complex cytokine regulation of the immune system.

Antibodies↗