Biomedical subjects

C Wilkens

Publications and source records attributed to C Wilkens.

13 recordsLinked to original sources

PubMed2005

Association between the promoter polymorphism T/C at position -159 of the CD14 gene and anti-inflammatory therapy in patients with inflammatory bowel disease.

Immune response to intestinal bacteria and genetic predisposition seem to play a crucial role in the pathogenesis of inflammatory bowel disease. A single nucleotide polymorphism in the promoter of the lipopolysaccharide-receptor CD14 gene (T/C at position -159) has recently been described. To evaluate the role of the CD14 gene in anti-inflammatory therapy, the functionally relevant T(-159)-->C promoter polymorphism has been genotyped in 72 patients with inflammatory bowel disease and associated with the cumulative steroid dose. Cumulative corticosteroid dose was significantly higher in ulcerative colitis patients with the TT genotype (2447.7 +/- 927.0 mg/yr) compared with the CT genotype (142.3 +/- 142.3 mg/yr, p=0.016) and the CC genotype (391.7 +/- 272.7 mg/yr, p=0.047). In contrast, in patients with Crohn's disease there was no significant difference of the cumulative corticosteroid doses between the various T(-159)-->C promoter CD14 genotypes. An altered immune response to lipopolysaccharides with influence on the anti-inflammatory therapy seems to play a role in the genetic predisposition to ulcerative colitis. Genetic stratification will lead to the development of individualized therapies in inflammatory bowel disease.

Adrenal Cortex Hormones↗

PubMed2000

A carboxyl-terminal region important for the expression and targeting of the skeletal muscle dihydropyridine receptor.

We have used the yeast two-hybrid technique and expression of truncated/mutated dihydropyridine receptors (DHPRs) to investigate whether the carboxyl tail of the DHPR is involved in targeting to junctions between the sarcolemma and sarcoplasmic reticulum in skeletal muscle. The carboxyl tail was extremely reactive in yeast two-hybrid library screens, with the reactivity residing in amino acids 1621-1647 and abolished by a point mutation (V1642D). Dysgenic myotubes were injected with cDNA encoding green fluorescent protein fused to the amino terminus of DHPRs truncated after either residue 1620 (Delta1621-1873) or residue 1542 (Delta1543-1873) or of full-length DHPRs with the V1642D mutation (V1642D). For either Delta1621-1873 or V1642D, the restoration of excitation-contraction coupling was reduced approximately 40%, and the number of functional DHPRs in the sarcolemma was reduced approximately 30%, compared with the wild-type DHPR. The restoration of excitation-contraction coupling and surface expression was more drastically reduced (by approximately 90 and approximately 55%, respectively) for Delta1543-1873. Fluorescence microscopy revealed that Delta1621-1873 and V1642D were concentrated in a longitudinally restricted region near the injected nucleus, whereas wild-type DHPRs were present relatively uniformly along the length of a myotube. The intensity of fluorescence was greatly reduced for Delta1543-1873, indicating a low level of protein expression. Thus, residues 1543-1647 appear to play a role in the biosynthetic processing, transport, and/or anchoring of DHPRs, with residues 1543-1620 being particularly important for expression.

Animals↗

PubMed1998

C-myc mRNA expression in epithelial ovarian carcinomas in relation to estrogen receptor status, metastatic spread, survival time, FIGO stage, and histologic grade and type.

Recently, it has been suggested that c-myc expression might correlate with estrogen receptor (ER) status and metastatic spread in ovarian cancer. In this study, expression of c-myc mRNA in 90 epithelial ovarian carcinomas was determined using the S1 nuclease protection assay. Expression of c-myc mRNA was detectable in 27 of 90 tumors. There was no significant association between c-myc mRNA expression and metastatic spread, survival time, FIGO stage, or histologic grade and type. C-myc mRNA was expressed in 45% of ER-positive tumors but only 24% of ER-negative tumors (p = 0.094; Fisher's exact test). Similarly, 44% of progesterone receptor (PR)-positive and 23% of PR-negative tumors expressed c-myc mRNA (p = 0.098). However, the association between c-myc mRNA expression and ER and PR status was not statistically significant. The ratio of mean expression of c-myc mRNA in patients with FIGO stages III/IV compared with patients with FIGO stages I/II was 2.1:1, an insignificant difference (p = 0.57, Wilcoxon rank sum test). In conclusion, c-myc was not significantly associated with the clinical parameters investigated in this study.

Carcinoma↗

PubMed1997

Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement.

Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this project to: (a) examine the relationship between contrast-enhanced dynamic MRI-derived characteristics and histological microvessel density counts, a recognized surrogate of tumor angiogenesis, from primary or recurrent cancers of the uterine cervix; and (b) correlate these parameters with lymphatic involvement to characterize tumor aggressiveness in terms of lymphatic spread. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) were calculated from a contrast-enhanced dynamic MRI series in 55 patients (ages 25-72 years; mean, 50 years) with biopsy-proven primary (n = 42) or recurrent (n = 13) uterine cervical cancer. Both pharmacokinetic parameters were correlated to histologically determined microvessel density counts (factor VIII-related antigen) and other pathological tumor characteristics obtained from the operative specimens after radical surgery. In addition, the magnetic resonance and histological data were correlated to the presence or absence of lymphatic system involvement. Pharmacokinetic MRI-derived parameters (A and k21) increased with increasing histological microvessel density counts with r = 0.41 and 0.50, respectively. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k21 compared with histological microvessel density, resulting in a higher sensitivity, overall accuracy, and comparable specificity. Contrast-enhanced MRI parameters might prove to be applicable for estimation of tumor angiogenesis in uterine cervical cancer; thus, MRI may become an additional tool to characterize malignant progression in terms of lymphatic involvement in uterine cervical cancer.

Adenocarcinoma↗

PubMed1996

Cytokeratin and vimentin expression in primary and recurrent carcinoma of the vulva: correlations with prognostic factors and the course of disease.

Radical vulvectomy for the treatment of a vulvar carcinoma inevitably entails severe psychosexual consequences for the patients. Thus, for such tumors, reliable histological prognostic parameters are needed to allow; when appropriate, the use of less radical operative measures. One possible approach to this problem might be to examine tumors immunohistochemically for the presence of cytoskeletal components. To assess the utility of this method, we applied a panel of antibodies directed against cytokeratins (CKs) and vimentin to a groups of vulvar carcinomas (62 primary and 35 recurrent tumors) and examined the results for possible correlations with the course of disease and various clinical parameters. all of the investigated CKs typical of squamous epithelia had no prognostic relevance. In contrast, the present of CKs typical of glandular differentiation as well as vimentin, suggesting early dedifferentiation, resulted in a less favorable prognosis. Thus, the procedures applied in the present study may have a role to play a decisions concerning the appropriate therapy for such tumors.

Female↗

PubMed1995

Usefulness of immunohistochemical staining for p53 in the prognosis of breast carcinomas: correlations with established prognosis parameters and with the proliferation marker, MIB-1.

Mutations of the p53 gene often result in the overexpression of p53 protein. Previous studies have suggested that the function of p53 and its mutant protein forms may be linked with the disease course of patients with a breast carcinoma. In the present study, we tested 462 primary breast carcinomas for the presence of p53 antigen using immunohistochemical methods employing antibodies against the clone, DO-1. These tumors were also immunohistochemically stained using the monoclonal antibody, MIB-1, in order to demonstrate the presence of Ki67. Comparison of the presence of p53 with other prognostic parameters revealed highly significant negative correlations with estrogen- and progesterone-receptor status (P < 0.001 and P = 0.001, respectively) as well as positive correlations with both the presence of MIB-1 (P < 0.001) and the histological grading (P = 0.008). The presence of p53 was not correlated with tumor stage and node status. Evaluation of the findings for all 462 tumors as well as for node-positive and -negative subgroups revealed less favorable findings for overall survival and the disease-free period for both p53-positive tumors (for total group, overall survival, P = 0.0002, disease-free period, P = 0.02; for node-positive group, overall survival, P = 0.0004, disease-free period, P = 0.1045) and breast carcinomas with higher proportions of cell nuclei positive for MIB-1 (total, overall survival, P = 0.0026, disease-free period, P = 0.0022; node-positive, overall survival, P = 0.021, disease-free period, P = 0.0882). We were able to demonstrate that p53 expression in breast carcinomas means a significantly worse prognosis for grade II tumors (overall survival, P = 0.0002; disease-free period, P = 0.0116), for overall survival in the case of estrogen-receptor-positive tumors (P = 0.014), and for tumors showing increased proliferation activity (overall survival, P = 0.0477).

Antibodies, Monoclonal↗

PubMed1995

[Hormone receptor determination in breast carcinoma tissue. Comparison of recent immunohistologic techniques with biochemical receptor testing].

For evaluation of the hormone receptor status in breast cancer tissues two methods are mainly used: immunohistochemical detection by monoclonal antibodies on frozen sections (ER-ICA, PgR-ICA) and the biochemical radioligand-binding assay (DCC) of fresh tissue. Using new antibodies makes it possible to evaluate the estrogen and progesterone receptor status in formalin-fixed and paraffin-embedded tissue. In the present retrospective study, tissues from 223 primary breast carcinomas or breast carcinoma recurrences were re-evaluated with the three methods mentioned above and the results were compared. We used antibody 1D5.26 reacting with the estrogen receptor and mPR1 specific for the progesterone receptor in paraffin-embedded tissue. The agreement of positive and negative cases between these two immunohistochemical procedures was 97.8% for the estrogen receptor and 85.7% for the progesterone receptor. Comparison of immunohistochemistry on paraffin-embedded tissue and biochemical evaluation showed an agreement of 74.7% for the estrogen receptor and 68.7% for the progesterone receptor. These results are comparable to the correspondence between ER-ICA and PgR-ICA and the DCC method. This study proves that the prognostically and therapeutically important hormone receptors can be reliably determined in formalin-fixed and paraffin-embedded tissues. These results are not only important for the evaluation of hormone receptors of a small breast carcinoma that is not found in the frozen section, but for the considerable difference in costs among the different methods.

Antibodies, Monoclonal↗

PubMed1995

[Myoperitoneal composite flaps: a new surgical principle for vaginal reconstruction].

In spite of the development of various techniques for the formation of a neovagina, the longterm results are often disappointing, especially if the simpler methods (dilation, ectopic pouch formation, epithelium transfer) have been applied. The more complex surgical techniques such as musculo/fasciocutaneous and colon flaps are associated with a significant risk of severe complications. For certain operative situations necessitating vaginal reconstruction, adequate procedures are still missing. Based on surgico-anatomic investigation of the vascular territories of the myoperitoneal anterior abdominal wall, we introduce the use of myoperitoneal composite flaps from the deep inferior epigastric artery angiosome as a novel surgical principle for vaginal reconstruction and report on the experience with the first two patients.

Adenocarcinoma↗

PubMed1995

[Immunohistochemical detection and prognostic significance of p53 in the primary tumor of breast carcinoma patients].

The occurrence of the p 53 gene mutation in breast carcinoma tumour cells, leads to the accumulation of mutant p 53 protein types, whose consequence is the loss of the negative regulation normally exercised by the p 53 gene, which is considered to act as a tumour suppressor. It is possible to demonstrate the presence of mutant p 53 protein types in tumour cell nuclei by applying immunohistochemical procedures to paraffin sections (Clon DO 1, Dianova). We tested 482 primary breast carcinomas for the presence of these proteins, and positive immunohistochemical findings for mutant p 53 proteins were recorded in 21.6% of the cases. In another 14.3% of these breast carcinomas, less than 10% of the tumour cells exhibited positive staining. In the other 64.1% of cases, the immunohistochemical findings for p 53 proteins were entirely negative. Independent of the immunohistochemical staining results, we performed a retrospective analysis of the disease course of this group of primary breast carcinomas: it emerged, that p-53-positive breast carcinomas had a significantly less favourable prognosis as compared to primary tumours, which were negative or weakly positive for this protein group. The accumulation of p 53 proteins in tumour cell nuclei is correlated with negative oestrogen- and progesterone-receptor status, as well as with the degree of proliferation exhibited by the breast carcinoma. Such accumulation is, in contrast, unaffected by the tumour stage, its histological grading, menopausal status, and the overexpression of c-erb B2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Growth fractions (Ki-67) in primary breast cancers, with particular reference to node-negative tumors.

We determined the growth fraction in 549 primary breast carcinomas using monoclonal antibody Ki-67. With respect to the course of disease, significant differences emerged for the whole collective as well as among the node-positive tumors. We paid special attention to the node-negative (N0) carcinomas in the group, the aim being to differentiate a prognostically unfavorable subgroup in this otherwise favorable collective. Owing to the comparative rarity of clinical events, our findings for such tumors failed to attain statistical significance; however, a strong clinical trend indicating an adverse prognosis for both overall and disease-free survival emerged for tumors exhibiting a high growth fraction. One-quarter of these patients had received adjuvant treatment. In the group exhibiting high levels of Ki-67 reactivity, significantly less favorable findings with respect to overall survival were observed among the untreated patients. The present results seem to confirm previous indications that antibody Ki-67 is of value in assessing the prognosis of N0 breast cancer.

Breast Neoplasms↗

PubMed1994

Immunohistochemical detection of hormone receptors in breast carcinomas (ER-ICA, PgR-ICA): prognostic usefulness and comparison with the biochemical radioactive-ligand-binding assay (DCC).

In a prospective study conducted since 1983, the hormone-receptor status of primary breast carcinomas was investigated using immunohistochemical (ER-ICA, PgR-ICA) and biochemical (DCC) methods. The degree of immunohistochemical staining was evaluated according to the immunoreactive score (IRS) devised by Remmele and Stegner [Frauenarzt 28, 41-43 (1987)]. The findings obtained using the biochemical radioactive-ligand-binding assay (cutoff level, 20 fmol/mg) and those obtained using qualitative immunohistochemical methods were in agreement in 72.5% (ER-ICA) and 72.2% (PgR-ICA) of cases. For the 789 cases of primary breast carcinoma examined, postoperative data were available for a mean follow-up period of 48 months. Using the statistical procedure of Kaplan-Meyer to analyze the probability of disease-free and overall survival, it emerged that ER-ICA- and PgR-ICA-positive breast carcinomas exhibited the most favorable course of disease. Breast carcinomas with negative immunohistochemical findings for both types of receptor were found to have a significantly less favorable disease course. Semiquantitative evaluations of the staining results using the IRS failed to yield significant differences among the 12 IRS groups. Neither the percentage of positive tumor cells nor the immunohistochemical staining intensity proved to be prognostically useful parameters for predicting the course of disease. In comparison to the established biochemical method for the demonstration of hormone receptors, however, the immunohistochemical procedure was found to be superior with respect to prognostic meaningfulness, particularly in the group with conflicting biochemical and immunohistochemical findings with respect to hormone-receptor status. Using Cox analysis, the prognostic usefulness of the immunohistochemical test was compared with that of certain established prognosis parameters (pT, pN, grading, Ki-67), from which it became apparent that PgR-ICA has the greatest prognostic value, with the most lasting influence on the course of disease. The results of the present study demonstrate that, with respect to the prognostic value of its findings, the immunohistochemical test for hormone receptors is superior to the biochemical procedure.

Breast Neoplasms↗

PubMed1994

[Minimally invasive therapy of peritoneal leiomyomatosis. A case report of diagnostic and therapeutic problems].

Leiomyomatosis peritonealis disseminata (LPD) is a rare benign disease characterised by the presence of multiple intraabdominal nodules, consisting of benign smooth muscle. LPD has only been found in women, predominantly in their late reproductive age. There is a very high association with excess exogenous and endogenous female gonadal steroids, specifically oestrogen and progesterone. Since it is grossly indistinguishable from diffuse carcinomatosis of the peritoneum, several unnecessary radical procedures have resulted. We describe the 44th documented case and the first case of minimal invasive surgery in a 42-year-old women with peritoneal leiomyoma on the right pelvic wall and uterine subserous and submucous leiomyoma.

Biopsy↗

PubMed1979

Joint nursing-pharmacy program helps reduce medication errors.

A hospital's nursing and pharmacy staffs have substantially reduced errors in medication administration, especially errors of omission. They have achieved the reductions partly through primary nursing, which demands greater accountability for total patient care, including medication, from each nurse. Other methods and aids include corrective action, special reports and audits, "remainder" cards, and a computer system.

California↗