Biomedical subjects

Lars-Christian Horn

Publications and source records attributed to Lars-Christian Horn.

27 records · Page 2Linked to original sources

PubMed2005

Androgen receptors are frequently expressed in mammary and extramammary Paget's disease.

Mammary Paget's disease and extramammary Paget's disease are rare intraepithelial neoplasms. Mammary Paget's disease is almost exclusively associated with underlying invasive breast carcinoma or high-grade ductal carcinoma in situ (DCIS G3). Extramammary Paget's disease arises in areas rich in apocrine glands and is suspected to have apocrine gland origin. The aim of the study was to investigate the presence of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and Her2/neu in a large number of cases. We investigated 58 cases of mammary and 23 cases of extramammary Paget's disease. Formalin-fixed and paraffin-embedded tissues were analyzed using antibodies against AR, PR, ER and Her2/neu according to standardized procedures. In mammary Paget's disease, positive immunoreactions for Her2/neu, AR and ER were observed in 56 of 58 (97%), 51 of 58 (88%), and respectively in six of 58 (10%) cases. All cases of mammary Paget's disease were negative for PR and showed a coexpression of Her2/neu and AR in 51 out of 58 cases (88%). In extramammary Paget's disease, positive immunoreactions for AR, Her2/neu and ER were observed in 18 of 23 (78%), 12 of 23 (52%), and respectively in 1 of 23 (4%) cases. All cases of extramammary Paget's disease were negative for PR and showed a coexpression of AR and Her2/neu in 12 out of 23 cases (52%). In contrast to ER and PR, AR and Her2/neu are commonly expressed in mammary and extramammary Paget's disease. The knowledge about frequent expression of AR in Paget's disease could lead to the development of a new adjuvant therapy, particularly in patients with recurrent disease.

Anus Neoplasms↗

PubMed2005

Three-dimensional reconstruction and quantification of cervical carcinoma invasion fronts from histological serial sections.

The analysis of the three-dimensional (3-D) structure of tumoral invasion fronts of carcinoma of the uterine cervix is the prerequisite for understanding their architectural-functional relationship. The variation range of the invasion patterns known so far reaches from a smooth tumor-host boundary surface to more diffusely spreading patterns, which all are supposed to have a different prognostic relevance. As a very decisive limitation of previous studies, all morphological assessments just could be done verbally referring to single histological sections. Therefore, the intention of this paper is to get an objective quantification of tumor invasion based on 3-D reconstructed tumoral tissue data. The image processing chain introduced here is capable to reconstruct selected parts of tumor invasion fronts from histological serial sections of remarkable extent (90-500 slices). While potentially gaining good accuracy and reasonably high resolution, microtome cutting of large serial sections especially may induce severe artifacts like distortions, folds, fissures or gaps. Starting from stacks of digitized transmitted light color images, an overall of three registration steps are the main parts of the presented algorithm. By this, we achieved the most detailed 3-D reconstruction of the invasion of solid tumors so far. Once reconstructed, the invasion front of the segmented tumor is quantified using discrete compactness.

Algorithms↗

PubMed2005

Alterations in connexin expression in the bladder of patients with urge symptoms.

OBJECTIVE: To compare the formation of gap junctions between detrusor smooth muscle cells in situ and the distribution of connexin (Cx)40, Cx43 and Cx45 expressions in bladder biopsies from a control group (with bladder tumour) and from patients with urge symptoms, as smooth muscle cells of the human detrusor muscle communicate via gap junctions and express several connexin subtypes, alterations of which may be involved in the causes of lower urinary tract symptoms. MATERIALS AND METHODS: Connexin expression is prominent in myofibroblast-like cells, supposedly involved in afferent signalling pathways of the bladder. Their strategic position directly beneath the urothelium suggests they are a link between urothelial ATP signalling during bladder filling and afferent Adelta-fibre stimulation for co-ordination of bladder tonus and initialization of the micturition reflex. Modification of their coupling characteristics may have profound impact on bladder sensation. Bladder tissue probes of patients undergoing cystectomy or transurethral tumour resection for bladder cancer were used as controls. Tissue samples from patients with severe idiopathic urge symptoms were taken for exclusion diagnostics of interstitial cystitis (IC) and carcinoma in situ. The formation of functional syncytia between detrusor smooth muscle cells were examined in dye-coupling experiments by injecting with Lucifer Yellow. The morphology and structure of gap junctions were assessed by transmission electron microscopy and immunogold labelling of Cx43 and Cx45. The expression of connexin subtypes Cx40, Cx43 and Cx45 was compared by indirect immunofluorescence, and confocal laser scanning microscopy used for semiquantitative analysis. RESULTS: There was dye coupling between smooth muscle cells of the detrusor in situ. Electron microscopy and immunogold labelling showed very small gap junctional plaques. These findings were confirmed by confocal immunofluorescence. Semiquantitative analyses showed significantly higher Cx43 expression in the detrusor muscle, and a tendency to higher Cx45 expression in the suburothelial layer associated with urge symptoms, whereas Cx40 expression was unaffected. CONCLUSIONS: Smooth muscle cells of the human detrusor muscle are coupled by classical gap junctions, forming limited local functional syncytia. Both Cx43 and Cx45 are expressed at low levels in normal detrusor. Up-regulation of Cx43 in patients with urge incontinence supports the possibility of functional changes in the syncytial properties of detrusor smooth muscle cells in this condition. In addition, the observed increase of Cx45 in the myofibroblast cell layer supports the idea that alterations in sensory signalling are also involved. Comparison with previous reports implies that the pathophysiology of urgency is distinct from that of the unstable bladder and other forms of incontinence.

Aged↗

PubMed2004

Chorioamnionitis-induced changes of fetal extramedullar hematopoiesis in the second trimester of gestation. Is diagnosis from fetal autopsy possible?

Chorioamnionitis, as the most frequent cause of second trimester abortions, is commonly diagnosed by histomorphological examination of placental tissue. We determined whether chorioamnionitis induces a fetal extramedullary hematopoietic response and estimated whether chorioamnionitis can be diagnosed from fetal liver alone. Clinical data and morphological and histological findings of 39 second trimester abortions, caused by chorioamnionitis, were compared with 32 age-matched control cases. Using hematoxylin and eosin staining, naphtol-ASD-chloracetate esterase and "Berliner Blau" reaction, total hematopoiesis, erythropoiesis, myelopoiesis and intracytoplasmatic iron of fetal liver were examined. In the study group, total hematopoiesis was increased compared with the controls (94.9% versus 84.4%). The same was seen in erythropoiesis (69.2% versus 56.2%, P>0.05). Chorioamnionitis resulted in a significant increase of fetal myelopoiesis with clustering of leukocytes in 56.4% (P=0.001). Neutrophiles were located predominantly intrasinusoidal and periportal (74.4%), while an isolated periportal location was often observed in controls (50.0%). Isolated perivenous iron storing was more often seen with chorioamnionitis (28.3% versus 3.1%) and correlated with the increasing severity of chorioamnionitis. It can be stated that infectious diseases, such as chorioamnionitis, increase fetal intrahepatic myelopoiesis as one defense mechanism. The morphology of fetal intrahepatic hematopoiesis and iron storing might also be helpful in the diagnosis of chorioamnionitis, especially when the placenta is not available for examination.

Abortion, Spontaneous↗

PubMed2004

Identification of the causes of intrauterine death during 310 consecutive autopsies.

OBJECTIVE: Evaluation of causes of death in stillborn infants. METHODS: During a five-year period, 310 consecutive autopsies of stillborn infants were performed using a standardized protocol with systematic examination of all major cranial, thoracic and abdominal organs including microscopic examination. RESULTS: In 71%, the intrauterine death (ID) occurred up to the end of the 37th week of gestation. Thirty-seven percent (115/310) stillbirths represented with maceration and about one-half with minor or major malformations. Thirty-one percent (53/171) of them were responsible for intrauterine death. In 83% (44/53), the intrauterine death of the malformed fetus occurred before the end of 37th week of gestation, most of them (48/53, 90.6%) were small for gestational age infants. In 75.5% (234/310), the placental villous tree and the umbilical cord represented pathologic conditions. In 191 cases (61.1%), utero-placental pathology was responsible for intrauterine death. Intrauterine infections and traumatic lesions were accompanied by intrauterine death in 2.2 and 1.3%, respectively. In 15.2%, unexplained intrauterine death (because of severe maceration, the placenta was not available for autopsy or insufficient clinical data) occurred. CONCLUSIONS: Perinatal autopsy may be valuable in three ways: the confirmation of ante-mortem diagnoses; the identification of unexpected disorders; and exclusion of other (perhaps inheritable) conditions which might be have caused the intrauterine death. Clinically valuable information, obtained from the autopsy, can be improved by high autopsy rate and performing perinatal necropsies by specially trained pathologists.

Autopsy↗

PubMed2002

Smooth muscle cells from human urinary bladder express connexin 43 in vivo and in vitro.

Smooth muscle cells (SMC) of the human urinary bladder are believed to be electrically coupled. However, it has not been successfully demonstrated the nature of the underlying cell-cell communication. Here, we used Western blot technique to demonstrate the gap junction protein connexin 43 (Cx 43) in human bladder musculature and in smooth muscle cell cultures. We found expression of Cx 43 in all samples of the detrusor (Mdv, n=6) and in five of six samples of the internal sphincter (Mv). Cx 43 expression was less in cell cultures, 60% showing Cx 43 expression. Iontophoretic application of the gap junction permeable fluorescent dye lucifer yellow revealed a mean of 2.6+/-2.2 (mean+/-SD, n=8) coupled cells in cultured smooth muscle cells. Our findings support the notion that Cx 43 is constitutively expressed in human bladder SMC in vivo. Thus, the function of the bladder is likely to be influenced by the organisation of smooth muscle cells into functional syncytia.

Aged↗

PubMed2002

Familial cancer history in patients with carcinoma of the cervix uteri.

OBJECTIVES: Several cancers show the tendency to aggregate in families. But the contribution of heredity to the causation of sporadic malignancies, like cervical cancer is unclear. STUDY DESIGN: Seven hundred and thirty-seven women with operative treated cervical cancer (CX) were searched for familiar history of malignant tumours. Positive familial history was stated, if one first degree relative was affected by malignant tumour. The site of malignant tumour was stated and the mean age was compared. RESULTS: Twenty-two percent of the women had malignancies at different sites in first degree relatives. In about one-half the mother, in 30% the father and in 11% more than one first degree relative was affected. Overall, first degree relatives of 21 patients (13%) had malignancies of the lungs or the oro-pharynx. Thirty-seven women had malignant tumours of the lower genital tract and 11 had invasive cervical cancer. Mean age of patients with positive familial history was the same as those without (43 versus 42 years) it. But, women whose first degree female relatives had cervical cancer were significantly younger than those with extragenital malignancies (37 versus 45 years). The mean 5-year survival rate was higher in patients with a positive familial cancer history (85.6% versus 74.6%; P=1.7). CONCLUSIONS: The data suggest, that a small number of patients have a familial susceptibility for cervical cancer and probably for HPV-associated neoplasms. Further studies establishing the immune status and the search for genetic polymorphisms of these patients are required.

Adult↗

PubMed2002

DNA cytometric analysis of surgically treated squamous cell cancer of the uterine cervix, stage pT1b1-pT2b.

OBJECTIVE: To determine the utility of DNA content and DNA-related variables of proliferative activity regarding prognosis in cervical cancer. STUDY DESIGN: DNA image (ICM) andflow cytometry (FCM) were performed to determine the DNA index (DI), 5c-exceeding rate (5c-ER), S-phase fraction (SPF) and proliferation index (PI) in 163 patients with surgically staged pT1b1-pT2b squamous cell cancer of the uterine cervix and treated with primary radical hysterectomy. ICM was performed on imprint cytology, obtained from fresh tumor tissue, which was also used for FCM. Results were analyzed using the chi2 test and Cox regression analysis for risk of pelvic lymph node involvement, tumor recurrence and recurrence-free survival (RFS). RESULTS: ICM was performed on all 163 and FCM on 133 samples. One-third of the tumors showed DNA aneuploidy. Analysis demonstrated prognostic significance of a DI > or = 1.70, with a (70:30) 2.3-fold risk of recurrence (P=.024) and reduced RFS of 10 months (P=.003) in cases of DI > or = 1.70. A high 5c-ER > 11% was associated with pelvic lymph node involvement and decreased RFS (P < or = .04). Significantly more relapses were found in tumors with SPF > 12% (70.8% vs. 29.2%, P=.007). RFS was markedly reduced in tumors with high SPF (52.3 vs. 61.1 months, P=.011). Low proliferative tumors (PI<25%) were associated with lower stage (P=.036) and increased RFS (61.2 vs. 47.1 months, P=.028). In multivariate analysis of clinicopathologic variables (pT category, nodal status, lymphovascular space involvement) and DNA related variables, pelvic lymph node involvement was the only significant predictor of RFS. In patients with nodal involvement, tumors with DI >1.70 were associated with lessfavorable outcomes. CONCLUSION: DNA-related variables of cell cycle analysis were valuablefor predicting prognosis in cervical cancer patients. Tumors with DI>1.70, 5c-ER >11% and high proliferative activity (SPF>12%, PI>25%) represent a subgroup with a poor prognosis.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Secondary cutaneous aspergillosis due to Aspergillus flavus in an acute myeloid leukaemia patient following stem cell transplantation.

In a 64-year-old man suffering from hypoblastic myelodysplastic syndrome a secondary acute myeloid leukaemia developed. After induction chemotherapy with resulting partial remission he received an allogenic (related) peripheral blood stem cell transplantation conditioned with 2 Gy total body irradiation. After haematopoietic reconstitution chest pain and dyspnoea appeared. Computer tomography revealed diffuse bilateral infiltrates which were considered to be suspicious for an invasive pulmonary aspergillosis of the left upper lobe. Respiratory and circulatory insufficiency occurred. In bronchoalveolar lavage fluid Aspergillus antigen was detected. In addition, Aspergillus flavus was isolated on Sabouraud-dextrose agar. Ambisome (liposomal encapsulated amphotericin B) was applied in high dosages. On the skin of the sides and the back five livid red stained nodular lesions with haemorrhagic infarctions appeared. Pathohistologically, both in PAS (periodate acid Schiff) and Grocott-Gomori staining conglomerates of septated hyphae were detected in corium and subcutis. In addition, Aspergillus flavus grew from skin tissue. Despite antifungal treatment the patient died from Aspergillus pneumonia and generalized aspergillosis with dissemination to heart, brain, and skin.

Acute Disease↗