Biomedical subjects

Roland Axt-Fliedner

Publications and source records attributed to Roland Axt-Fliedner.

8 recordsLinked to original sources

PubMed2006

First pregnancy and life after preimplantation genetic diagnosis by polar body analysis for mucopolysaccharidosis type I.

Preimplantation genetic diagnosis (PGD) may help couples at risk to avoid pregnancies with known genetic diseases. In Germany, the only option to perform PGD is the analysis of polar bodies (PB). Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder. Q70X is one of the frequent diseases causing mutations of alpha-L-iduronidase (IDUA), leading to a severe phenotype with mental retardation and various somatic abnormalities, and making a request for PGD is understandable. Using five polymorphic DNA markers from the vicinity of IDUA, PGD on first PB was performed for a consanguineous couple, both heterozygotes of the Q70X mutation of IDUA. Sixteen first PB were obtained by laser assisted hatching of the zona pellucida. Genotyping led to the conclusion that 3/16 oocytes carried wild-type IDUA alleles. Only one of these oocytes showed pronucleus formation after intracytoplasmic sperm injection and was transferred on day 2 after oocyte retrieval. A singleton pregnancy was established. Prenatal diagnosis showed a fetus heterozygous for Q70X. For MPS I, PB analysis is a feasible way to perform PGD and it may be an acceptable alternative for couples with moral objections to embryo selection, or for countries in which genetic testing of the embryo is prohibited.

Base Sequence↗

PubMed2006

Detection rate of early fetal echocardiography and in utero development of congenital heart defects.

OBJECTIVE: The purpose of this study was to evaluate the detection rate of early fetal echocardiography and the in utero development of congenital heart defects (CHD). METHODS: Cases were selected from all singleton pregnancies between 1997 and 2003 in which detailed fetal 2-dimensional and color-coded Doppler echocardiography was performed in our prenatal unit between 11 weeks' and 13 weeks 6 days' gestation; 2165 cases with complete outcome parameters were analyzed. RESULTS: During this study period, CHD were diagnosed in 46 fetuses. Between 11 and 13 weeks' gestation, 29 CHD were diagnosed (11 weeks, 9 cases; 12 weeks, 8 cases; and 13 weeks, 12 cases); 9 CHD were found in the second trimester and 2 in the third trimester. The in utero detection rate of fetal echocardiography was 86.96% (n = 40). Six additional CHD (13.04%) were detected postnatally. The spectrum of detected CHD changed with advancing gestational age and was different from the postnatal detected heart defects. CONCLUSIONS: Early fetal echocardiography is feasible and allows the detection of most CHD. Congenital heart defects vary in appearance at different stages of pregnancy and may evolve in utero with advancing gestational age. Therefore, early fetal echocardiography should always be followed by echocardiography at mid gestation.

Adolescent↗

PubMed2003

Granulomatous mastitis.

INTRODUCTION: Granulomatous mastitis (GM) is a rare disease which predominantly occurs in premenopausal women shortly after their last childbirth. ETIOLOGY: Its etiology is unclear, however, the disease has been shown to be correlated with breast-feeding and the use of oral contraceptives. An autoimmune component has also been discussed. PRESENTATION: It presents with the clinical symptoms of galactorrhea, inflammation, breast mass, tumorous indurations and ulcerations of the skin. In mammography and sonography nodular opacities and hypoechoic nodules are found. Very often clinical and radiological findings mimic breast cancer. HISTOLOGICAL DIAGNOSIS: The diagnosis is made by histopathology. Histological features in GM include signs of a chronic granulomatous inflammation with giant cells, leucocytes, epitheloid cells and macrophages as well as abscesses. TREATMENT: Therapy of GM consists of complete surgical excision combined with oral steroid therapy, eventually in combination with anti-inflammatory drugs or colchicine. Use of methotrexate has also been successful. In case of formation of abscesses antibiotic therapy should be applied before steroid therapy. Immune-suppressive therapy should be performed until complete remission as rates of recurrence can be up to 50%.

Adrenal Cortex Hormones↗

PubMedDate not supplied

Analysis of vitamin D-receptor (VDR) and retinoid X-receptor alpha in breast cancer.

The expression of vitamin D-receptor (VDR) and retinoid X-receptor alpha (RXR-alpha) has been analysed immunohistochemically in benign (n = 62 and n = 5 respectively) and malignant (n = 228 and n = 15 respectively) breast tissue samples using a monoclonal antibody 9A7gamma against VDR and a polyclonal antibody against RXR-alpha. A recently developed immunoreactive scoring method (IRS) was employed. The expression of VDR was detected at the RNA-level using the reverse transcriptase-polymerase chain reaction. A statistically significant higher expression of VDR at the protein level was seen in breast cancer compared with benign breast tissue, whereas at the mRNA level no visible differences in the expression of VDR were found. A higher expression of RXR-alpha was seen in breast cancer compared with benign breast tissue. Our findings indicate that breast tissue may be a new target organ for therapeutically applied vitamin D and retinoid analogues. VDR and RXR-alpha are upregulated at the protein level in breast carcinomas as compared to normal breast tissue, indicating a possibly increased sensitivity to therapeutically applied vitamin D analogues. New vitamin D analogues exerting less calcemic side effects may be promising new drugs for the treatment or chemoprevention of breast carcinomas as well as of precancerous breast lesions. Combination therapies of vitamin D and retinoid analogues with fewer side effects seen promising for the treatment of breast cancer.

Antibodies↗

PubMedDate not supplied

Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in cervical tissue.

UNLABELLED: 1,25(OH)2D3 suppresses proliferation and induces differentiation in various cell types, including epithelial cells. Recently, extrarenal activity of 1alpha-hydroxylase for 25(OH)D3 has been reported in various cell types including macrophages, keratinocytes and prostate and colon cancer cells. The aim of this study was to analyze the expression of 1alpha-hydroxylase for 25-hydroxyvitamin D3 in normal cervical samples and in cervical cancer, in order to investigate whether cervical tissue possesses the capacity to produce 1,25(OH)2D3 from 25(OH)D3, indicating that 1,25(OH)2D3 may be a locally produced hormone that controls proliferation in cervical tissue and that alterations in local production of 1,25(OH)2D3 may be involved in tumourigenesis of cervical cancer. MATERIALS AND METHODS: RNA was extracted from normal cervical tissue (n=4), cervical carcinomas (n=8) and HeLa cells using the method of Chomczynski. RNA was reverse-transcribed and RNA-levels were semiquantitatively detected by PCR. RESULTS: mRNA of 1alpha-hydroxylase for 25-hydroxyvitamin D3 was detected in more than 50% of samples analyzed in normal cervical tissue and in cervical cancer with no visible difference between either group. mRNA of 1alpha-hydroxylase for 25-hydroxyvitamin D3 was detected in HeLa cells as well. CONCLUSION: 25(OH)D3-1alpha-hydroxylase is expressed in normal cervical tissue, in cervical cancer and in HeLa cells. Thus, normal cervical and cervical cancer cells seem to be able to synthesize 1alpha, 25(OH)2D3 that may be of significant importance for the growth control in normal and malignant cervical tissue. Normal cervical tissue and cervical cancer cells may be new targets for cancer prevention or cancer treatment with precursors of biologically active vitamin D analogues.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMedDate not supplied

Vitamin D receptor (VDR) expression is not a prognostic factor in cervical cancer.

BACKGROUND: The aim of this study was to analyze whether VDR status is a prognostic factor that may be of importance for the assessment of recurrence in cervical cancer. MATERIALS AND METHODS: VDR-, Ki-67- and p53-status were analyzed immunohistochemically in cervical cancer patients (n=50) and in benign cervical tissue (n=15). The histopathological data of the tumours were evaluated. RNA was extracted from normal cervical tissue (n=4) and cervical carcinomas (n=8) using the method of Chomczynski. RNA was reverse-transcribed and RNA-levels were semiquantitatively detected by PCR. RESULTS: The expression of VDR was significantly increased in cervical cancer compared to normal cervical tissue on the protein-level but not on the RNA-level. No statistically significant correlations were found comparing VDR status with histopathological data (tumour stage, lymph node status, grading, histological tumour type), with the expression of the proliferation marker Ki-67 and of the tumour suppressor gene p53. CONCLUSION: Our findings indicate that VDR protein expression is not a prognostic factor in cervical cancer. The strong I/DR immunoreactivity that we observed in cervical cancer specimens supports the body of evidence that cervical cancer may be a target for therapeutically applied vitamin D analogues.

Adenocarcinoma↗

PubMedDate not supplied

Vitamin D receptor (VDR) expression is not a prognostic factor in breast cancer.

Breast cancer is characterized by its early haematogenous dissemination. Current modalities of risk assessment in lymph node-negative patients, to determine which patients should receive adjuvant chemotherapy, are not effective. The aim of this study was to analyze whether vitamin D receptor (VDR) status is a prognostic factor that may be of importance for the assessment of recurrence in breast cancer. VDR expression was analyzed immunohistochemically in breast cancer patients (n=228). No statistically significant correlations were found comparing VDR expression with histopathological data (tumor stage, lymph node status, grading, histological tumor type), with the expression of estrogen receptors (ER) or progesterone receptors (PR), with the proliferation marker Ki-67, with the tumor suppressor gene p53 or with the S-phase index. Our findings indicate that VDR protein expression is not a prognostic factor in breast cancer. The strong VDR immunoreactivity that we observed in breast cancer specimens supports the body of evidence that breast cancer may be a target for therapeutically applied vitamin D analogues.

Breast Neoplasms↗

PubMedDate not supplied

Immunohistochemical analysis of 1,25-dihydroxyvitamin-D3-receptors, estrogen and progesterone receptors and Ki-67 in ovarian carcinoma.

BACKGROUND: The aim of this study was to analyze immunohistochemically the expression of VDR in normal and carcinomatous ovarian tissue to evaluate whether ovarian tissue may be a new potential target for biologically active vitamin D analogues. MATERIALS AND METHODS: The expression of 1,25-dihydroxyvitamin-D3-receptors (VDR) was immunohistochemically investigated in ovarian carcinomas (n=40). VDR immunoreactivity (mAb 9A7gamma) was compared with the staining pattern of the proliferation marker Ki-67, of the estrogen receptors (ER) and of the progesterone receptors (PR). The percentage of positive tumour cells (PP), the intensity of staining (SI) and a resulting immunoreactivity score (IRS) were determined for the semiquantitative evaluation of VDR-, ER- and PR-expression. RESULTS: A total of 16.7% of the normal surface ovarian epithelium was VDR-negative, while the remaining 83.3% revealed weak to moderate VDR immunoreactivity. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all ovarian carcinomas analyzed. Both the intensity of VDR immunostaining and the number of VDR-positive cells were significantly increased in ovarian carcinomas as compared to normal ovarian tissue. Analyzing coexpression of VDR with the proliferation marker Ki-67 or with the estrogen and progesterone receptors, no significant correlation was found. CONCLUSION: Our findings indicate that: (I) VDR expression is increased in ovarian carcinomas as compared to normal ovarian tissue. (II) Up-regulation of VDR in ovarian carcinomas is not exclusively induced by an increase of proliferation, but by different unknown mechanisms. (III) Expression of VDR in ovarian carcinomas is independently regulated from the expression of ER and PR. (IV) Ovarian tissue may be a new target organ for therapeutically applied vitamin D analogues exerting fewer calcemic side-effects. New vitamin D analogues may be promising drugs for the treatment of advanced ovarian carcinomas.

Cell Division↗