We have examined integrin expression and function in the human colon carcinoma cell line HT29, and in clonal sublines derived from the HT29 line. These cells express several different integrin subunits including beta 1, alpha 2, 3, 6 and alpha v, but do not express the classic alpha 5/beta 1 fibronectin receptor. Clonal variation in the pattern of integrin expression was quite limited. The profile of integrin expression correlates well with the adhesive behavior of HT29 cells. Thus the cells adhere well to vitronectin, laminin and type IV collagen, but not at all to fibronectin. Adhesion to collagen was completely blocked by an anti-beta 1 monoclonal antibody, indicating that beta 1 integrins mediate this process. Adhesion to laminin was strongly blocked by anti-beta 1 monoclonal or anti-beta 6 monoclonal, suggesting that the alpha 6/beta 1 complex functions in attachment to laminin; this was somewhat surprising since immunoprecipitation experiments indicate that most of the alpha 6 subunit seems to be associated with the beta 4 subunit. Despite their strong adherence to laminin, collagen and vitronectin, HT29 cells are not very motile and, in response to gradients of these proteins, do not migrate nearly as well as CHO cells tested under similar conditions. Since HT29 cells can undergo an enterocyte-like differentiation in glucose-free medium, we compared integrin expression in HT29 and its subclones during the process of differentiation. There was no correlation between the state of differentiation, as assessed by expression of brush-border hydrolases, and the level of expression of any of the integrin subunits measured. Thus the pattern of integrin expression in these colonic tumor cells seems to be a characteristic of the cell line, and is not readily modified by changes in cell growth or differentiation.

Carcinoma↗

PubMedDate not supplied

Fenestration in extracardiac conduits in children after modified Fontan operation by implantation of stent grafts.

Three patients (ages 3, 5, and 8 years) with various forms of functionally univentricular heart lesions received a total cavopulmonary connection with an extracardiac conduit as a final reconstructive procedure. Failure of the Fontan circulation occurred immediately after surgery because of spontaneous closure of surgical fenestrations in two children and absent fenestration in one. As an emergency procedure, in all patients the conduit was perforated by transcatheter intervention in order to create a connection to the anatomical right atrium. Following balloon dilatation of the perforated conduit, in all three patients covered stent grafts were placed in the newly created defect to attain a reliable communication. Patency of the fenestration was demonstrated by angiogram and any leakage was ruled out. Cardiac output improved and severe pleural effusion and ascites subsided. Right-to-left shunt could be demonstrated by echocardiography at follow-up after 7 months (median) in all three patients. Oxygen saturation remained stable between 85 and 90%. These preliminary results suggest that stent graft fenestration can serve as a valuable tool in failing Fontan circulation, particularly in patients with an extracardiac conduit. Covered stents have the potential to reduce the acute risk of bleeding and they help to prevent early spontaneous closure of the newly created fenestration.

Blood Vessel Prosthesis Implantation↗

PubMedDate not supplied

Treatment of an aneurysmal dilatation of the ductus arteriosus with indomethacin in a premature infant.

A large ductus arteriosus aneurysm can lead to potentially serious and life-threatening complications. We report a case of aneurysmal dilatation of the ductus arteriosus in a premature infant that was successfully treated with indomethacin. Thus, surgical intervention with general anesthesia could be avoided.

Aneurysm↗

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Mycotic pseudoaneurysm of the aorta in children.

Mycotic pseudoaneurysm of the aorta is a rare disease in childhood. We report on two cases which were diagnosed in an unselected general pediatric population within an 8-month period. The first case was a 16-month-old toddler with a normal cardiac history who presented with purulent pericarditis due to group A streptococcus and subsequent pseudoaneurysm formation of the ascending aorta while convalescing from varicella infection. The second case was a 14-year-old girl with a previously undiagnosed coarctation of the aorta who developed a Staphylococcus aureus aortitis in the dilated poststenotic segment with pseudoaneurysm formation and infiltration into the adjacent lung tissue. In both cases parenteral antibiotic therapy was administered over 10 and 4 days, respectively, followed by emergency surgery consisting of aneurysmectomy, coarctectomy (case 2), and in situ homograft implantation. Recovery was uneventful. In both cases early institution of a femorofemoral cardiopulmonary bypass prevented a fatal outcome despite intraoperative rupture of the pseudoaneurysm.

Adolescent↗

PubMedDate not supplied

Interleukin-6 and selected plasma proteins in healthy persons of different ages.

In the present study, interleukin-6 (IL-6) and several acute phase proteins were measured in healthy participants (23-87 years of age). A linear correlation between IL-6 and age was established with an increase of 0.016 pg/ml (0.004) per year of life. Whereas CRP remained below 0.5 mg/dl in all participants, an increase with age for fibrinogen and an inverse relation for albumin as well as transferrin were obtained. However, the increase of IL-6 did not correlate with any of these changes. IL-6 associated diseases may therefore occur more often with advancing age, but in healthy participants IL-6 does not explain the changing plasma protein pattern resembling that of an acute phase reaction.

Acute-Phase Proteins↗

PubMedDate not supplied

Interleukin-6-associated inflammatory processes in Alzheimer's disease: new therapeutic options.

The cytokine interleukin-6 is consistently detected in the brains of Alzheimer's disease patients but not in the brains of nondemented elderly persons. Until recently it was unclear whether an interleukin-6-associated inflammatory mechanism is an early or late event in the pathological cascade of Alzheimer's disease. We investigated whether interleukin-6 could be detected in plaques of Alzheimer's disease patients prior to the onset of neuritic degeneration. We found interleukin-6 mostly in plaques where neuritic pathology has not yet developed. This indicates that the appearance of interleukin-6 may precede neuritic changes and is not just a consequence of neuritic degeneration. Therefore, one may hypothesize that activation of inflammatory mechanisms may cause neuritic degeneration in plaques. A suppression of interleukin-6 synthesis could, therefore, be of therapeutic value. Upon screening a number of substances, we found that a small number of nonsteroidal antiinflammatory drugs, including tenidap, were able to inhibit interleukin-6 synthesis in cultured human astrocytoma cells. These substances may be therapeutically useful in Alzheimer's disease and should be evaluated in clinical studies.

Aged↗

PubMedDate not supplied

The participation of interleukin-6 in the pathogenesis of Alzheimer's disease.

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Acute-Phase Proteins↗

PubMedDate not supplied

Inflammation and Alzheimer's disease.

Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid beta peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder.

Alzheimer Disease↗

PubMedDate not supplied

Isolation of human B-cell subpopulations for pharmacological studies.

Three groups of human peripheral blood B-lymphocytes were separated from each other by countercurrent centrifugal elutriation and free-flow electrophoresis. They differed in their state of maturation and in their capability to produce antibodies in vitro. These B-cell subpopulations were used to study features of a drug such as BAY R 1005. BAY R 1005 is a synthetic glycolipid analogue (GLA), which is supposed to modulate antibody synthesis. Mature, immunoglobulin- (Ig-) secreting B-lymphocytes secreted equal quantities of antibodies in the presence and in the absence of the GLA. BAY R 1005 was found to be without mitogenic activity on resting B-cells and did not induce them to produce antibodies. However, it supported the antibody production of preactivated B-lymphocytes. The in vitro preactivated B-cells were affected via monocytes. Only in vivo preactivated B-lymphocytes increased their antibody production under the direct influence of BAY R 1005.

Antibody Formation↗

PubMedDate not supplied

Techniques for studies on growth characteristics of human prostatic cancer cells.

The methods described in this article seem to be useful for studies on the growth characteristics of malignant epithelial prostate cells which are still under the influence of healthy cells. Before establishing primary cultures, pieces of tissue were sectioned in such a way that they could be unfolded to obtain a large surface. These pieces were treated enzymatically and then incubated for at least 4-6 weeks. In this time, cells grew or migrated out of the tissue and spread over the surface of the culture flasks. The viable single cells harvested from these primary cultures were characterized flow cytometrically, fractionated by countercurrent centrifugal elutriation, or further incubated above agarose so that they formed three-dimensional spheroids. Cytometric determinations of cellular cytokeratin, vimentin, and DNA were performed before and after incubation. They suggested that the percentages of cytokeratin-positive (epithelial) cells, vimentin-positive cells (fibroblasts), and aneuploid cells remained at levels (in vitro) similar to those within the pieces of tissue used for the culturing experiments, respectively. Since our culture technique allows the propagation of human epithelial prostate cells in vitro as they would grow in vivo under the control of the surrounding tissue, the method should help to investigate which particular treatment of the cells influences the growth of the malignant cells, while they are still surrounded by other cells of the same prostatic organ.

Antigens, Neoplasm↗

PubMedDate not supplied

[Prognosis of labour force participation after multidisciplinary outpatient and inpatient rehabilitation for chronic back pain].

UNLABELLED: In a one-year prospective study of patients participating in a multidisciplinary outpatient or inpatient rehabilitation program (OPR/IPR) for chronic back pain the following issues were investigated: (i) the frequency of low labour force participation (LFP), i. e., work loss due to the disease or total duration of sick leave (SL) of 6 weeks or more; (ii) prognostic indicators at the beginning of the rehabilitation program (T1) for low LFP after one year (T2); (iii) the significance of the type of rehabilitation IPR vs. OPR in relation to the identified prognostic indicators for LFP. A total of 413 patients participating in OPR (n = 299) or IPR (n = 114) for chronic back pain returned a postal questionnaire after one year. Low LFP was found in 30 % of all patients without significant differences between OPR (32 %) and IPR (25 %). Compared to the year before T1 the proportion of patients without SL between T1 and T2 increased from 12 % to 48 % after OPR, from 15 % to 47 % after IPR, respectively. In multivariate logistic regression analyses adjusted for type of rehabilitation the following prognostic indicators of T1 for low LFP were identified (p </= 0,05): SL of 6 weeks or more in the year before T1 with an odds ratio (OR) of 11.1; intended termination of employment (OR = 3.2), household income of less than 3300 DM per month (OR = 2.2); reduced social functioning (SF-36) (OR = 2.0). Regarding LFP no significance of the type of rehabilitation (IPR vs. OPR) was found in relation to the identified prognostic indicators or after adjustment for differences (i) in the characteristics of the patients at T1, and (ii) in the duration and number of single measures of the rehabilitation program. CONCLUSIONS: One year after IPR or OPR the rate of return to work is similar (about seven out of ten patients). The identified prognostic indicators may stimulate further research of the improvement of the rehabilitation processes. No evidence was found against the expansion of OPR.

Adult↗