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Biomedical subjects

U Wagner

Publications and source records attributed to U Wagner.

At least 145 records · Page 8Linked to original sources

Magnetization transfer contrast (MTC) and MTC-subtraction: enhancement of cartilage lesions and intracartilaginous degeneration in vitro.

Human articular cartilage from 16 cadaveric or amputated knees was studied using standard magnetic resonance imaging (MRI), on-resonance magnetization transfer contrast (MTC) and MTC-subtraction MRI. Results were compared with subsequent macroscopic and histopathological findings. MTC-subtraction and T2-weighted spin-echo images visualized cartilaginous surface defects with high sensitivity and specificity. MTC and T2-weighted spin-echo images revealed intra-cartilaginous signal loss without surface defects in 80% of the cases, corresponding to an increased collagen concentration. It is concluded that MTC is sensitive to early cartilage degeneration and MTC-subtraction can be helpful in detecting cartilage defects.

Adult↗

False changes in CA 125 levels in ovarian cancer patients after infusion of OC125 fragments for diagnostic and therapeutic purpose.

The influence of human anti-OC125 antibodies formed after multiple infusions of OC125 F(ab')2 fragments on the apparent levels of CA 125 measured with four different tests were examined in two ovarian cancer patients. With the homologous Assay 1, involving only OC125 antibodies, false increases of CA 125 values were observed after infusion of OC125 fragments, which completely covered real CA 125. In contrast, with Assay 2, 3 and 4, which involve no OC125 antibodies as capture antibodies, only slight false increases occurred in the presence of very high anti-OC125 antibody concentrations. Interference was eliminated by addition of non-specific murine IgG in Assay 2 and 4, but not in Assay 1 and 3 indicating that the false increases in Assay 1 and 3 were caused by anti-idiotypic anti-OC125 antibodies. In the presence of elevated real CA 125, with Assay 2 and to a considerably lesser degree with Assay 4, an inhibitory effect of anti-OC125 antibodies became evident leading to false decreases of CA 125 values. In Assay 4 reduction of assay response was eliminated by addition of nonspecific murine IgG. The results confirm that all available CA 125 tests are influenced by interference with human anti-OC125 antibodies. Thus, CA 125 levels in patients who have been treated with OC125 fragments should be interpreted with care.

Adenocarcinoma, Papillary↗

Monoclonal antibodies and idiotypic network activation for ovarian carcinoma.

Antibodies can be processed by the B- and T-cell systems and may lead to a selective activation of the immune system. The network structure of the immune system implicates the possibility of a selective immunization by the activation of idiotypic cascades. In a retrospective analysis, patients with advanced ovarian carcinoma, who had received MAb, against the cancer-associated antigen CA125 for diagnostic purposes, were analyzed for the production of anti-idiotypic antibodies, survival rate, and immunological effects. Furthermore, we started a prospective and randomized study for ovarian cancer patients, using a different antigen, TAG72, for the induction of idiotypic cascades. Our first results on 58 patients with advanced ovarian carcinomas showed that the induction of anti-idiotypic-antibodies against OC125 mimicking the TAA Class III CA125 leads to a prolongation of the survival rate, and, in extended stages, to an induction of antitumoral immunity, and that the induction of idiotypic cascades is also possible for different antigens like TAG72. Summarizing the activation of idiotypic network cascades seems to be a very effective way of intervention in the immune system of patients with advanced stages of ovarian carcinoma. A prospective study of the adjuvant approach seems to be necessary.

Antibodies, Anti-Idiotypic↗

Idiotypic cascades after injection of the monoclonal antibody OC125. A study in a mouse model.

In an animal model, we evaluated the possibility to induce antibodies directed against the tumor-associated antigen CA125 by immunization with the anti-CA125 antibody OC125 via activation of the idiotypic network. Our results show that Balb/c mice, immunized by repeated administrations of F(ab')2-fragments of the OC125 antibody (Ab1), produced anti-idiotypic antibodies (Ab2). The binding of these antibodies to the OC125 could be completely inhibited by the antigen CA125, suggesting that the anti-idiotypic antibodies imitate the original target antigen of the OC125. After induction of these paratope-binding anti-idiotypic antibodies (Ab2 beta), a murine IgG-anti-CA125 (Ab3) response arose in the same mice. The induction of idiotypic cascades offers the possibility of immunization against tumor-associated antigens without using the original antigen and breaking antitumor tolerance.

Animals↗

Brightness matching and colour discrimination in young diabetics without retinopathy.

This study used the methods of the Farnsworth-Munsell 100-hue test (FM-100), heterochromatic brightness matching (HBM) and wavelength discrimination to test the sensitivity and colour vision of 20 juvenile diabetics with no (16) or very mild (4) retinopathy. Their results were compared to an age-matched control group. The FM-100 results showed a significant increase in error scores throughout the spectrum in comparison to the controls. This deterioration in colour vision was confirmed in the results for the wavelength discrimination task, tested between 440 and 640 nm, where the just noticeable difference in colour was, in general, larger for the diabetic group than the control group. Only at 460 nm were the results of the diabetics similar to those of the controls. The diabetic group were also less sensitive than the control group in the HBM task between 480 and 600 nm. The results show that a deficit in sensitivity and colour vision occurs in diabetics before the onset of a clinically visible retinopathy.

Adolescent↗

Diffuse alveolar damage in the rat lung after short and long term exposure to nitrogen dioxide.

In order to quantify parenchymal, vascular and epithelial changes occurring in the exudative and organizing phase of diffuse alveolar damage (DAD) induced by inhaled NO2 groups of 7 rats were continuously exposed to 5, 10 or 20 ppm NO2 for 3 and 25 days alternatively. AgNOR analysis revealed the highest proliferative activity in the epithelium of the respiratory bronchioles. In this region already after 3d exposure to 5 ppm the maximum AgNOR number was reached. In contrast to long-term exposure after 3d exposure to 5 and 10 ppm NO2 the AgNOR number in the respiratory bronchioles was significantly higher than in central airway epithelia. After long-term exposure to 5 and 10 ppm AgNOR number decreased to normal values or showed no further significant increase, long-term exposure to 20 ppm resulted in a further increase of the AgNOR number. A significant increase of the alveolar circumference and decrease of alveolar surface density was found after an exposure to 20 ppm for 3d and long-term exposure to 10 and 20 ppm NO2, whereas the 5 ppm exposure groups disclosed no significant change of these values. Medial hypertrophy was detected after exposure to 10 and 20 ppm NO2 for 25 days, after the exposure to 5 ppm for 3d and 25d medial thickness was significantly decreased due to vasodilation induced by NO, one of the major reaction products of NO2.

Animals↗

Assessment of proliferative activity in type II pneumocytes after inhalation of NO2 by AgNOR-analysis.

Adult male Sprague Dawley rats were exposed to 0.8, 5 and 10 ppm NO, alternatively for 1 or 3 days. After exposure the proliferative activity of the airway epithelium was assessed by means of BrdU incorporation and AgNOR-analysis at three different airway levels--in the bronchial, the bronchiolar epithelium and in Type 2 cells. The BrdU-labeling index (BrdU-LI), and AgNOR-number (AgNOR-N) were used to quantify the epithelial proliferation. Cytologic specimens of Type II cells showed a significant increase of the AgNOR-number and BrdU-LI after exposure to 5 ppm NO2 for 3 days and 10 ppm for 1 and 3 days. In the bronchiolar epithelium both, the AgNOR-number and BrdU-LI were significantly elevated in all the exposure groups. In the bronchial epithelium a significant response of the AgNOR-number was found after exposure to 10 ppm for 3 days. The correlation between AgNOR-number and BrdU-LI was 0.78 (p < 0.005).

Administration, Inhalation↗

Clinical and haemodynamic effects of long-term treatment with torasemide in congestive heart failure.

The clinical and haemodynamic effects of 12 weeks of treatment with torasemide, 5 mg/day, were measured in 24 men aged 51-60 years with symptoms of mild, chronic, congestive heart failure. Clinical status was assessed by NYHA functional class and haemodynamic effects were measured at rest and during supine bicycle exercise at the beginning and end of the 12-week period of study. Torasemide was well tolerated and there was no significant change in any of the measured safety variables. Clinical status was improved in 16 of the 23 patients assessed after 12 weeks of treatment and none experienced symptomatic deterioration. Compared with pretreatment haemodynamic measurements, right atrial and pulmonary vascular pressures were significantly decreased both at rest and during exercise after torasemide. Systemic arterial pressure was reduced at rest, but there were no significant changes in cardiac output, heart rate, or systemic and pulmonary vascular resistances either at rest or during exercise, neither were there any significant changes in systemic arterial blood oxygen saturation, pulmonary arterial blood pH, gas tensions, or bicarbonate concentration either at rest or during exercise at 12 weeks. The results of these studies indicate that the clinical and haemodynamic benefits of torasemide are not subject to the development of tolerance during sustained treatment.

Diuretics↗

Thiaproline reduces glomerular basement membrane thickness and collagen accumulation in the db/db mouse.

Glomerular basement membrane thickening and mesangial expansion are the main pathological features in diabetic nephropathy--glomerulosclerosis with the biochemical correlate of increased collagen accumulation. We studied a new principle to reduce collagen accumulation in the glomerulus: thiaproline, known to inhibit protein synthesis by blocking the elongation, led in our studies to a morphological reduction of the glomerular basement membrane thickening and to a decreased collagen content. As the thiaproline analogue is incorporated into collagen, the mechanism of increased degradation of the modified collagen is being discussed.

Animals↗

Specific interference with the determination of the tumour-associated glycoprotein 72 by human anti-idiotypic antibodies formed after treatment with the anti-tumour-associated glycoprotein 72 antibody B72.3.

Recorded concentrations of the tumour-associated glycoprotein 72 (TAG-72) in ovarian cancer patients after repeated infusion of the antibody B72.3 were found to be falsely elevated when measured with an homologous immunometric assay involving the anti-TAG-72 antibody B72.3 (Test 1), or with an heterologous assay involving CC49 capture and B72.3 detector antibodies (Test 2). Test 1 yielded falsely elevated values up to 10(4) kU/l. Test 2 gave slightly false positive elevations up to 10(2) kU/l for only some of the samples with very high false-positive values in Test 1. The interfering serum components bound to Protein G-Sepharose and could be precipitated with perchloric acid or by heating serum samples to 100 degrees C. Addition of non-specific murine immunoglobulins only partly suppressed false-positive values in both tests. Our results suggest that this interference is caused by human anti-B72.3 IgG induced by B72.3 application, which to some extent specifically binds to determinants of the B72.3 antibody. Heat extraction of serum samples effectively eliminated interferences probably caused by anti-idiotypic antibodies, but did not affect real TAG-72.

Animals↗

The tuberomammillary nucleus region as a reinforcement inhibiting substrate: facilitation of ipsihypothalamic self-stimulation by unilateral ibotenic acid lesions.

The tuberomammillary nucleus (TM), located in the posterior hypothalamic region, consists of five subgroups and is the only known source of brain histamine. Knowledge about the function of this nucleus is still scarce. In a previous study we found an increase in the rate of ipsihemispheric hypothalamic self-stimulation following a dc lesion in the rostroventral part of this nucleus, suggesting that this region has an inhibitory action on a neuronal reward system or on the brain's reinforcement mechanism. In the present study we examined whether this facilitating effect on reinforcement was due to the destruction of fibers passing through the lesion area or of intrinsic cells, by lesioning subgroups of the TM with ibotenic acid, an excitatory amino acid, that selectively destroys neural cell bodies, leaving fibers largely intact. Following such lesions in the rostroventral part of the TM the operant response rates increased over the six days of testing when the animals stimulated themselves in the lateral hypothalamus in the hemisphere located ipsilateral but not contralateral to the lesion. No significant changes in response rate occurred following the lesion in the caudal part of the ventral TM. The results indicate that the region influenced by the lesion exerts inhibitory control over lateral hypothalamic self-stimulation, and that it is possible that histamine-containing neurons are involved in this effect.

Animals↗

Tissue culture of bovine subcommissural organ.

Tissue of the secretory, glial subcommissural organ (SCO) of adult, male cattle was cultured in serum-free medium for 70 days in vitro. Only minor alterations in the histoarchitecture and the cytology of the explanted SCOs could be observed by light and electron microscopy. Light- and electron-microscopic immunocytochemical investigations with an antiserum raised against bovine SCO secretory proteins revealed intra- and extra-cellularly localized immunoreactive material in tissue sections of SCO explants cultured up to 69 days in vitro. An indirect competition enzyme-linked immunosorbent assay (ELISA) was developed to detect minor quantities of SCO secretory products. By means of this assay, approximately 35 ng RF protein per ml was detected in culture medium supernatants conditioned for 3 days in SCO tissue cultures at 3, 38, and 69 days in vitro. These studies demonstrate that the bovine SCO can maintain its secretory activity throughout long periods in vitro.

Animals↗

Pulmonary arteritis with pulmonary arterial thrombosis and recurrent endopulmonary embolization.

A 41-year-old woman underwent medical examination for superficial thrombophlebitis of both lower legs. Incidentally a chronic myelogenous leukemia was diagnosed and chemotherapeutically treated. Three weeks after the first attendance the patient again suffered superficial thrombophlebitides of all extremities. Clinically she exhibited symptoms of recurrent mild pulmonary embolization. Contrast venography revealed no signs of deep venous thrombosis of legs, pelvis, or cava inferior. Despite continuous full-dose intravenous heparin administration the patient died, with signs of fulminant pulmonary embolization. Surprisingly, necropsy revealed a complete thrombotic occlusion of the pulmonary arterial system caused by pulmonary arteritis with signs of recurrent pulmonary embolization from a parietal truncus pulmonalis thrombosis. In addition, an appositional growth of parietal thrombi central from peripheral arterial ramifications had occurred. Simultaneously, superficial thrombophlebitis of all extremities was observed without any additional signs of general vasculitis. There was no strong evidence for a causal relationship between the chronic myelogenous leukemia and pulmonary arteritis nor for any other underlying systemic disorder. Therefore we consider the pulmonary arteritis a possibly primary one. This very rare disease is discussed with respect to the literature.

Adult↗

The stimulatory effect of amylin on mucus secretion in isolated rat trachea.

A modified Ussing chamber technique was used to characterize the effects of amylin on rat tracheal mucus secretion. The effects of amylin were studied at both the mucosal and the submucosal side of isolated rat trachea. Applied at the mucosal side, amylin had no direct effect on mucus secretion, but significantly decreased the acetylcholine (1 mM)-induced tachyphylaxia when this substance was presented a second time (first stimulation: 490%; second stimulation: 334%; second stimulation plus amylin: 407%). At the submucosal side, amylin significantly stimulated mucus secretion (controls: 100%; 1 microM amylin: 193%; 100 nM amylin: 170%; 10 nM amylin: 127%; 1 nM amylin: 127%). Together with the recent observation of specific amylin receptors in rat lung membranes, these data suggest a physiological role for amylin in the regulation of tracheal mucus secretion.

Acetylcholine↗

Amplification of rewarding hypothalamic stimulation following a unilateral lesion in the region of the tuberomammillary nucleus.

The tuberomammillary nucleus, a cluster of cells in the posterior hypothalamus, is the only known source of brain histamine. Although this nucleus is well described in terms of anatomy and neurochemistry, only little is known about its function. In the present study, the effect of a lesion in the region of this nucleus on intracranial self-stimulation was examined. Rats were implanted bilaterally with stimulating electrodes in the lateral hypothalamus and unilaterally with one lesion electrode in the region of this nucleus. After three days of baseline testing, half of the animals were given an electrolytic lesion. The animals were retested for six consecutive days, and thereafter weekly for another seven weeks. From the second day postlesion on, we unexpectedly found a gradual increase in response rate, which peaked on day 13 in the ipsilateral hemisphere only. Although there was no further increase over subsequent days, response rates remained elevated during the following seven weekly tests. The observed increase in lateral hypothalamic self-stimulation after an electrolytic lesion of the tuberomammillary nucleus is discussed in terms of an inhibitory system, possibly located in the region of this nucleus which, when removed by the lesion, increased reinforcing effects of the electrical brain stimulation. The fact that the effects on self-stimulation were lateralized to one hemisphere rules out an interpretation in terms of unspecific "performance" variables that could influence rate of lever pressing.

Animals↗

An improved mathematical approach for the assessment of the medial thickness of pulmonary arteries.

Medial hypertrophy of pulmonary arteries is caused by different acute and chronic diseases complicated by pulmonary hypertension and malformations of the lung. Thus the precise assessment of external radius and relative medial thickness are of importance for clinical and experimental pathology. Different concepts have been proposed to solve this problem. Wall thickness methods which can be applied to obliquely cut arteries suffer from the disadvantage that they require prior injection of vessels. Planimetric methods can be applied to not injected vessels but they fail in assessing the medial thickness of obliquely cut arteries. We describe a mathematical approach which renders even obliquely cut and simultaneously not injected pulmonary arteries able to be assessed accurately for medial thickness and external vessel radius. This method combines the advantages of wall thickness and planimetric methods. This new method and the established wall thickness and planimetric methods were applied to 178 rat pulmonary arteries and 412 injected and 401 not injected human pulmonary arteries. The statistical analysis revealed a satisfying reproducibility (Coefficient of correlation: 0.70-0.90) of the new method. The data assessed by the new method are similar to those of the established methods. We conclude our new method to be a significant tool for the assessment of vessel parameters even in small specimens including only few not injected vessels.

Adolescent↗

The extended family and support for people with AIDS in a rural population in south west Uganda: a safety net with holes?

It is commonly assumed that the extended family in Africa provides a safety net for individuals in times of need. This paper examines this assumption using data on the care of people with AIDS in a rural population in South West Uganda. Over a six month period data were collected by counsellors on the care given to 30 (17 women, 13 men) AIDS patients by their families. In 27 of the 30 cases there was evidence of limited care. Various reasons were given for this by the carers, including lack of food and money for medications and the carer's other family responsibilities. For 17 clients who died during the study period, records of seven cases show that other relatives were asked to help with care but refused on the grounds of poverty or other commitments. However, in all but one of these cases extended families did provide assistance for the funeral. The findings suggest that there is a need to question the assumption that the extended family, in the culture under study, is able to provide adequate support for AIDS patients.

Acquired Immunodeficiency Syndrome↗