Proangiogenic potency of MUC18 in arteriosclerotic disease.

AIM: Stenotic peripheral and dilatative arteriosclerotic diseases have different pathomechanism although associations between both diseases are well known. The adhesion molecule MUC18 is a cell membrane glycoprotein also known as the melanoma cell adhesion molecule. As MUC18 has proangiogenic potency in melanoma and prostate cancer this study investigated the role of MUC18 in patients with stenotic or dilatative arteriosclerotic disease as a putative biochemical marker. METHODS: Using qRT-PCR, Western Blot and immunohistochemistry techniques, the expression of MUC18 in arteriosclerotic arteries from major lower limb amputates (AP, N.=15) as well as specimen from femoral endarterectomies (TEA, N.=20) and in dilatative aortic diseases using abdominal aortic aneurysms (AAA, N.=13) was evaluated. Human visceral arteries without macroscopic arteriosclerosis from liver transplants served as controls (AN, N.=19). RESULTS: MUC18 mRNA and protein expression could be found in AN, AP, TEA and AAA tissues. Immunohistochemical analysis showed that a complete and intact intima was the predominant location of MUC18 expression. Although in stenotic arteriosclerotic disease (AP and TEA) the intima was widely calcified, qRT-PCR analysis showed overexpression compared to normal tissue. Interestingly, MUC18 expression was significantly down-regulated in dilatative compared to stenotic arteriosclerotic disease and normal arteries. CONCLUSION: In peripheral stenotic arteriosclerotic disease the proangiogenic potency of MUC18 may play a role in angiogenesis of collaterals, whereas in dilatative aortic diseases the induction of collaterals is typically not evident. The results support the hypothesis of a role in angiogenesis of MUC18 in stenotic arteriosclerotic disease.

CCR6/CCL20 chemokine expression profile in distinct colorectal malignancies.

Originally, chemokines and their G-protein-coupled receptors were described to regulate multiple physiological functions, particularly tissue architecture and compartment-specific migration of white blood cells. Now, it is established that the chemokine/chemokine receptor system is also used by cancer cells for migration and metastatic spread. Here, we examined the relative levels of CC-chemokine CCL20 and its corresponding receptor CCR6 in resection specimens from patients with different malignant and non-malignant colorectal diseases as well as in colorectal liver metastases (CRLM). CCL20/CCR6 mRNA and protein expression profiles were assessed by quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in resection specimens from patients with ulcerative colitis (UC, n = 15), colorectal adenoma (CRA, n = 15), colorectal adenocarcinoma (CRC, n = 61) and colorectal liver metastases (CRLM, n = 16). Corresponding non-diseased tissues served as control. In contrast to UC tissues, the CCL20/CCR6 system showed a distinct upregulation in CRA, CRC and CRLM related to corresponding non-affected tissues (P < 0.05, respectively). Furthermore, CRA, CRC and CRLM tissue samples displayed significantly higher protein amounts of CCL20 in comparison with UC specimens (P < 0.05, respectively). Our results strongly suggest an association between CCL20/CCR6 expression and the induction of CRA, CRC and the development of CRLM. Therefore, CCL20 and CCR6 may provide potential targets for novel treatment strategies of CRC.

Differential CXC receptor expression in colorectal carcinomas.

In this study, we aimed to assess the expression profile of chemokine receptors CXCR1-4 in inflammatory and malignant colorectal diseases and corresponding hepatic metastases of synchronous and metachronous origin to elucidate their role in colorectal cancer (CRC) progression and metastasis. Chemokine receptor expression was assessed by quantitative real-time PCR, immunohistochemistry (IHC) and Western blot analysis in resection specimens from patients with ulcerative colitis (UC, n = 25), colorectal adenomas (CRA, n = 8), different stages of CRC (n = 48) as well as colorectal liver metastases (CRLM) along with their corresponding primary colorectal tumours (n = 16). While none of the chemokine receptors were significantly upregulated or downregulated in UC or CRA tissues, CXC receptors 1, 2 and 4 demonstrated a significant increase in expression in all tumour stages of CRC specimens with CXCR4 correlating with tumour grading (P < 0.05). On the other hand, CXCR3 showed no significant upregulation in either tumour stage, but significant overexpression in CRLM. While CXCR4 demonstrated significant upregulation in both tumour entities, IHC analysis revealed that the predominate cell type expressing CXCR4 in CRC is represented by tumour cells, whereas in CRLM the majority of positive CXCR4 signals is due to hepatocytes along the tumour invasion front. In conclusion, our findings show a very differential expression pattern of the four receptors in colorectal carcinomas and their corresponding liver metastases with prominent expression profiles that indicate a potential role in the pathogenesis of CRC.

Enhanced expression and clinical significance of CC-chemokine MIP-3 alpha in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent visceral neoplasms worldwide. Using RT-PCR, ELISA, microdissection and immunohistochemistry, we investigated the expression profiles of CCL19, CCL20, CCL21 and CXCL12 and their receptors in tumourous and tumour neighbouring tissues from patients with HCC and in nonmalignant liver lesions, respectively. All chemokines were found to be expressed in normal liver and HCC tissues, yet CCL20 was the only chemokine showing significant upregulation in HCC tissues. Clinicopathological analysis revealed a distinct increase in CCL20 expression rates in HCC tissues of grade III tumours in comparison to HCC tissues from grade II tumours. On mRNA level, only chemokine receptor CCR6 revealed significant upregulation in HCC tissues. However, immunohistochemical studies indicated a marked CCR6 expression accumulated in a streak of normal cells along the tumour invasion front in all our HCC specimens which could provide a stimulative signal for the tumour to further expand. The present findings show significant overexpression of CCL20 in the tumour tissues and marked overexpression of the corresponding receptor CCR6 in the tumour invasion front of HCC patients in comparison to normal liver. Moreover, CCL20 expression was found to correlate with tumour grade and therefore, we suggest that the CCL20/CCR6 system may be involved in hepatocarcinogenesis.

Grief support for informal caregivers of patients with ALS: a national survey.

Providing emotional support to caregivers is integral to comprehensive ALS care. The authors surveyed ALS Association centers and clinics and Muscular Dystrophy Association/ALS centers. Respondents thought that grief and bereavement support was integral to ALS care but thought that the support provided by their centers was often inadequate.

[Psychological adjustment to sterilization--a prospective study (proceedings)]. / Die psychische Verarbeitung der Sterilisation--eine prospektive Studie.

PIP: A study in progress to determine the psychological effect of sterilization on women is reported. Psychologically healthy women who are strongly motivated toward contraception and reach the decision for interval sterilization with their partners, have the best psychological prognosis for sterilization. The preliminary results of the study show that women who undergo interval sterilization respond both physically and psychologically better to the operation. Women who undergo sterilization after an abortion are inclined to have psychological and physical problems afterward, due to a lack of time to make a decision, feeling of lack of choice, and an unfavorable social and psychological situation.^ieng

[The psychological results of tubal ligation as definitive method of contraception (author's transl)]. / Die psychische Verarbeitung der Tubensterilisation als definitive Kontrazeptionsmethode

The cases of tubal ligation at the University Department of Tubingen and the University Department of Giessen during the last few years were reviewed. In most cases the psychological results of the procedure is positive and results in an improved partner relationship in most cases, provided that the procedure was the result of a mature decision by the couple. Tubal ligation in the puerperium is more favorable than in conjunction with the Caesarean Section. Interval sterilization shows the best results. A thorough discussion by the physician and if possible a psychological discussion should take place prior to the tubal ligation since both are important aids in the decision. The social indication should be clearly defined and the responsibility of the couple should be emphasized. A well defined and documented task for the clinical practice of prior physician and psychological discussion of tubal ligation is the basis of a present prospective study at the University Department for Women in Tubingen which is designed to show the positive psychological effects on the couple.

[Loss of libido and frigidity due to ovulation inhibitors from the psychological viewpoint]. / Libidoverlust und Frigidität unter Ovulationshemmem aus psychologischer Sicht

PIP: Reports on the pharmacological effects of oral contraceptives on libido and sexual sensitivity are inconsistent. Recent reports seem to suggest that sociopsychological factors may profoundly influence the side effects of antiovulatory agents. Loss of libido was predominantly observed in women with a contradictory attitude toward a female role on the one hand, and safe prevention of the reproductive function on the other. Other possible factors are insufficient information on the mode of action of hormonal contraceptives and a rejective attitude towards sexuality on the part of the physician.^ieng